This article systematically studied the A-optimal designs of a high-order mixture central polynomial model, which is an advancement of the research results for the A-optimal design of the most recent third-order mixture central polynomial model and a more accurate response surface model. This article is based on the simplex center design, obtaining measurement values at various design points, and verifying them through the A-optimal equivalence theorem. We also compare the A-efficiency of designs through examples, which can be applied to the A-optimal precise design of the fourth-order mixture model.

Vision impairment may delay responses to hazards when driving. In a proof-of-concept driving simulator study, we evaluated a hazard warning device designed for vision impaired drivers. Three groups participated: 11 persons with central vision loss (CVL; median age 60 years), 12 with homonymous field loss (HFL; 52 years) and 11 with normal vision (NV; 60 years). CVL is characterised by impaired visual acuity and contrast sensitivity while HFL is a loss of vision in the same half of the visual field (blind side) in both eyes. Participants completed drives with and without the device which gave a directional vibro-tactile warning for an approaching pedestrian hazard when collision risk exceeded a pre-defined threshold. Warnings significantly (p< 0.001) reduced brake response times for CVL (∆= 0.54s) and HFL (∆= 0.30s), but not NV participants. For HFL participants, the reduction was greater (p = 0.02) for hazards on the blind (∆= 0.57s) than seeing side (∆= 0.10s). The warnings significantly reduced collision rates for CVL participants from 11 to 0% (all hazards) and for HFL participants from 30 to 1.7% (blind side hazards). Thus, hazard warnings may be beneficial in improving safety of vision impaired drivers; further research is warranted.

The Badenian/Sarmatian boundary in the Central Paratethyan basins is characterized by a change from open marine conditions during the late Badenian to the assumed brackish conditions during the early Sarmatian. Foraminiferal and palynological results of the Badenian/Sarmatian boundary interval in the Babczyn 2 borehole (SE Poland) showed that the studied interval accumulated under variable, unstable sedimentary conditions. The Badenian/Sarmatian boundary as correlated with a sudden extinction of stenohaline foraminifera is interpreted as due to the shallowing of the basin. The lack of foraminifera and palynomorphs just above the Badenian/Sarmatian boundary can reflect short-term anoxia. The composition of euryhaline assemblages characteristic for the lower Sarmatian part of the studied succession indicates marine to hypersaline conditions.

Considering future tasks in soil health, resources management and environmental protection, farmers are challenged to develop sustainable strategies for managing soil and land resources. In this study, the long-term sustainability of two fertilization strategies, - current, with synthetic fertilizers (SYN) vs conservative, with organic sources of nitrogen (organic amendments plus green manure with a legume - CONS) - was assessed in a processing tomato/durum wheat rotation. The EPIC model was used, validated with field data then run to simulate the management for 30 years under 3 current and future climates. Yield, soil organic carbon (SOC) stock change, nitrogen use efficiency (NUE), water use efficiency (WUE) and nitrate leaching were considered as sustainability indicators. Under all the future climate scenarios, tomato yield increased in CONS, remaining almost stable in SYN. Wheat yield increased both in CONS and SYN, but the average yield in CONS was considerably lower than in SYN. NUE and nitrate leaching followed the same trend, both decreasing in CONS, while WUE was higher in CONS compared to SYN. The effect of CONS on SOC was always positive. Thus, the alternative N fertilization strategy proposed can be a favorable option for maintaining soil health and a sustainable crop production.

In Africa, vector-borne diseases (VBDs) are still a major public health issue especially in cities that gather an increasing human population. Market gardening practices, for example, can favor the transmission of urban malaria, while insufficient water supply and waste management favor the circulation of arboviroses related to Aedes mosquitoes. Urban planning is a major challenge to mitigate vector risks. As a planning strategy, greening is a concept that is increasingly considered as a major element impacting the well-being of inhabitants, but also for the restoration of biodiversity in cities. Nevertheless, the impact of urban green spaces on vector risk remains poorly investigated, as they may serve as refuge for vectors. This is why the diversity of mosquitoes in terms of species and larval habitat, through larval prospections in environmental water collections and human landing catches, is studied here at an intra-urban interface area between a forest and an urban ecosystem in order to assess the vector risk generated by preserving a forest patch in the heart of Libreville, capital of Gabon, central Africa. Out of 104 water containers explored, 94 (90.4%) were artificial, mainly comprising gutters, used tires, and plastic bottles, while 10 (9.6%) were natural, comprising a puddle, streams, and tree holes. The majority of the water collections recovered (73.1%) were found outside of the forested area, natural and artificial ones considered together. A total of 770 mosquitoes belonging to 14 species were collected from water collections. The mosquito community was largely dominated by anthropophilic species like Aedes albopictus (33.5%), Culex quinquefasciatus (30.4%), and Lutzia tigripes (16.5%). The Shannon index of diversity showed that mosquitoes were almost twice less diversified inside the forest (0.7) than outside (1.3). However, both communities were quite similar in terms of common species and relative abundance (Morisita-Horn index = 0.7). Regarding Human landing catches, Aedes albopictus (86.1%) was the most aggressive species, putting people at risk of Aedes-borne viruses. This study uncovered the importance of considering urban forested ecosystems as potential drivers of disease emergence and spread in urban areas, as they might locally boost urban mosquito densities due to poor environmental practices, mainly maintained by humans through poor environmental practices. In Gabon, this study should contribute to guide targeted vector control strategies, especially regarding the implementation of policies for a better environmental management and vector surveillance in urbanized areas.

Accurate knowledge of the rain amount is an crucial driver in several hydro-meteorological applications. This is especially true in complex orography territories, which are typically impervious, thus leaving ungauged most of the mountain areas. Thanks to their spatial and temporal coverage, weather radars can potentially overcome such an issue. However, weather radar, if not accurately processed, can suffer from several limitations (e.g., beam blocking, altitude of the observation, path attenuation, indirectness of the measurement) that can hamper the reliability of the rain estimates performed. In this study, a comparison between rain gauge and weather radar retrievals is performed in the target area of the Abruzzo region in Italy, which is characterized by a heterogeneous orography ranging from the sea side to Apennine ridge. Consequently, the Abruzzo region has an inhomogeneous distribution of the rain gauges, with station density decreasing with the altitude reaching up to approximately 1500 m a.s.l. Notwithstanding, pluviometric inflow spatial distribution shows a sub-regional dependency as a function of four climatic and altimetric factors: coastal, hilly, mountain, and inner plain areas (i.e., Marsica). Such areas are used in this analysis to characterize the radar retrieval vs. rain gauge amounts in each of those zones. Compared to previous studies on the topic, the analysis presented an attention to the importance of an accurate selection of the climatic and altimetric sub-regional areas where undertake the radar vs. rain gauge comparison. This aspect is not only of great importance to correct biases in radar retrievals in a more selective way, but it also paves the way for more accurate hydro-meteorological applications (e.g., hydrological model initialization, quantify the aquifers recharge etc.) which, in general, require the accurate knowledge of rain amounts upstream of a basin. To fill the gap caused by the uneven rain gauge distribution, Ordinary Kriging has been applied on a regional scale to obtain 2D maps of rainfall data, which are cumulated on a monthly and yearly base. Weather radar data from the Italian mosaic are considered as well, in terms of rain rate retrievals and cumulations performed on the same time frame used for rain gauges. The period considered for the analysis is two continuous years: 2017 and 2018. The output of the elaborations are raster maps for both radar and interpolated rain gauges, where every pixel contains a rainfall quantity. Although the results show a general underestimation in the weather radar data especially in mountain and Marsica areas, even though within the 95% confidence interval of the OK estimation. Our analysis highlights that the average bias between radar and rain gauges, in terms of precipitation amounts, is a function of altitude and is almost constant in each of the selected areas. This achievement suggests that after a proper selection of homogeneous target areas, the radar retrievals can be corrected using the denser network of rain gauges typically distributed at lower altitudes and extend such correction at higher altitudes without loss of generality.

UEDVT still remains an underdiagnosed entity due to a significant percentage of patients who remain asymptomatic. The etiology of UEDVT is overwhelmingly attributed to secondary causes including but not limited to central venous access devices and malignancy. Treatment modalities include anticoagulation, catheter directed thrombolysis, percutaneous mechanical thrombectomy or a multimodality approach along with the management of underlying etiology. We describe a case of a female with breast cancer, who came with left UEDVT and CVC malfunction and was successfully treated using the ClotTriever system to maintain continuous intravenous access.

In order to follow the Preventive Chemotherapy for the transmission control as recommended by WHO, Gabon initiated in 2014 the mapping of Schistosomiasis and Soil Transmitted Helminthiasis (STH). Here we report the results of the Northern and Eastern health regions, representing a third of the land area and 12% of its total population. All the 9 departments of the two regions were surveyed and from each, 5 schools were examined with 50 schoolchildren per school. The parasitological examinations were realized using the filtration method for urine and the Kato-Katz technique for stool samples. Overall 2245 schoolchildren (1116 girls and 1129 boys), mean aged 11.28 ± 0.04 years, were examined. Combined schistosomiasis and STH affected 1270 (56.6%) with variation between regions, departments and schools. For schistosomiasis, prevalence were 1.7% across the two regions, with no significant difference (p>0.05) between the Northern (1.5%) and the Eastern (1.9%). Schistosomiasis is mainly caused by Schistosoma haematobium with a prevalence of 1.5%, 1.9% and 1.7%, respectively in the North, East and globally. STH are more common than schistosomiasis, with an overall prevalence of 56.1% significantly different between the Northern (58.1%) and Eastern (53.6%) regions (p = 0.034). Trichuris trichiura is the most abundant infection with a prevalence of 43.7% followed by Ascaris lumbricoides 35.6% and hookworms 1.4%. According to these results, an appropriate mass drug administration strategy is given for the control of each neglected tropical disease group surveyed.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

The pathophysiologic substrate of pediatric hydrocephalus has not been thoroughly explained. Because of that, the available treatment options and protocols will be largely based on expert opinions or the results of single-center databases, until a more comprehensive knowledge of the various subcategories of hydrocephalus is undertaken. In retrospect, we mention that valve-based shunt systems have been constituting the mainstay of therapy since the late 1950s. The initially used shunt systems were concerning the ventricular system and the atrium. In the 1970s, VA shunts were not the main stay of treatment, as the primary location for the distal end was substituted by the peritoneum, due to the emergence of the ventriculoperitoneal shunts. Several types of one-way valve-based shunt systems have been developed. The ultimate goal was the drainage of the appropriate amount of CSF, in order to avoid either overdrainage or underdrainage, without interfering with normal brain development or cognition. Our review briefly analyzes these valve types and attempts a comparison, based on their functional characteristics. In addition to the peritoneum, other distal locations for shunt placement have been explored, including the pleural space and gallbladder. A separate subcategory includes the shunt systems which incorporate the lumbar subarachnoid space as the proximal location for the central catheter. Nowadays, the only available surgical alternative for the treatment of hydrocephalus is ETV. Since 2000, approximately 50% of children suffering hydrocephalus have been considered to be candidates for the execution of ETV. The potential benefits are that it closely resembles to the normal, physiological pathway of CSF absorption, thus circumventing the need for an artificial shunt system. Moreover, this technique is associated with lower infection rates, as well as on average, with a lower reoperation rate. Attempts of future progression are largely based on the development of improved shunt valve systems that could be affordable worldwide, as well as with the constant availability of ETV in developing countries. Another term that deserves special mention is related with the outcome of ETV in children who had a medical history of previously incorporated shunts and who were subsequently experiencing shunt dysfunction. This subset of patients is discussed in terms of efficacy (success rate from 40% to 80%) and safety (0%–32.5% of complications). Based on literature reviews, well-recognized predictive factors associated with secondary ETV failure include age, early onset of hydrocephalus, and prematurity. Currently, there is no consensus when the optimum surgical strategy is concerned in the different subgroups of patients, who are suffering from shunt dysfunction. Therefore, another issue that this review attempts to elucidate is the identification of subgroups of patients in whom shunt treatment is associated with a favorable outcome, compared to ETV, and vice versa. The objective of our study is to evaluate the comparative safety and efficacy, as well as the outcomes, of shunting and ETV in pediatric hydrocephalus cases. Anatomic and molecular substrate of hydrocephalus need to be better elucidated, so that medications or genetic modifications become more effective in order to offer a potential cure for hydrocephalus. Advancements in the treatment of hydrocephalus will depend on research into the shared molecular mechanism underlying various forms of the condition, paving the way for new therapeutic strategies.

Human activities continuously alter the delivery of ecosystem services (ESs), which play a crucial role in human well-being. There is a pressing need for effective ecological management strategies that consider the spatial heterogeneity of ESs to support the transition from trade-offs to synergies. This study focuses on the Haba River Basin and examines characteristics of land use change and the shift from trade-offs to synergies. The results indicate that from 1990 to 2000, the initial phase of land development, 10.65% of the land experienced change. Subsequently, during the intensive period of land development from 2000 to 2010, 30.29% of the land underwent significant transformation, with approximately 78% of grassland, sparse grassland, forested land, and desert converted into arable land. However, between 2010 and 2020, as the focus shifted towards the establishment of native vegetation and the intensity of land development decreased, only a small percentage (3.65%) of the total area underwent changes. Based on an in-depth analysis of spatial heterogeneity from 1990 to 2020, it is believed there has been a shift from trade-offs to co-benefits between 2000-2010 and 2010-2020. The years 2010 and 2020 were pivotal time nodes for the transition from trade-offs to synergies and for reducing trade-offs, with NPP identified as a critical driving factor for Comprehensive ES （CES） functions. By considering the trade-offs/synergies relationship and hotspots of ecological service functions, combined with unified water resource management policies, comprehensive ecological management measures tailored to different regions are proposed. These measures have facilitated the implementation of robust ecological protection policies to shift ES development from trade-offs to synergies in arid areas, thereby enhancing overall ecosystem service functions in the Haba River Basin. The research findings offer crucial scientific support and guidance for ecosystem management in arid areas, particularly within Central Asia.

An untrained couch potato involuntarily forced to undergo a long strenuous exercise towards exhaustion will feel it at the end as a discomforting fatigue. A well-trained athlete will feel the same but after a longer time. Patients of various neurological diseases will do so much earlier. All may also finally experience muscle pain and soreness the next day.Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. Muscle fatigability varies with muscle use, age and sex. It is commonly divided into two broad categories: peripheral and central fatigue. The first refers to the many processes in the fatiguing muscle(s), the second to subsequent processes in the central nervous system (CNS). Peripheral muscle fatigue can be caused by numerous different mechanisms, ranging from the accumulation of metabolites within muscle fibers to their damage. Central fatigue involves the inadequacy of the CNS to generate and maintain sufficiently strong motor command. There must of course be a mediator relating the two fatigue types, and this is the collection of small-diameter group III (Aδ) and IV (C) nerve fibers emanating from the muscle and distributing their activation effects throughout the CNS.Muscle fatigue develops during eventually exhausting exercise that goes along with activations of the cardio-vascular and respiratory system to supply oxygen and energy resources. While these functions are supported by a number of sensory afferents, fatigue-activated group III/IV muscle afferents have been proposed to contribute their share to cardio-vascular and ventilatory reflex responses that are mediated in the brainstem. Neural feedback from working skeletal muscle is a vital component in providing a high capacity for endurance exercise because muscle perfusion and O₂ delivery determine the fatigability of skeletal muscle (Amann 2012).The development of chronic muscle fatigue is related to muscle wasting mediated by aging, myopathies, muscle dystrophies, immobilization, insulin resistance, diseases associated with systemic inflammation (arthritis, sepsis, infections), trauma, cardio-vascular (heart failure) and respiratory disorders (chronic obstructive pulmonary disease (COPD)), chronic kidney failure, multiple sclerosis (MS), and, more recently, coronavirus disease 2019 (COVID-19).

The use of educational robotics has become increasingly popular in STEM education, offering motivating and hands-on learning experiences. This paper explores the potential of educational robotics for teaching plane curves at the university level. Specifically, it investigates the development and implementation of a LEGO SPIKE Prime robot designed to draw various central trochoids, including epicycloids and hypocycloids. The robot’s construction and programming are described, emphasizing the relationship between the robot’s physical movements and the mathematical equations of the curves it produces. The study also examines the integration of dynamic geometry software, which allows for visualization of the curves and verification of the robot’s accuracy. The paper concludes that educational robotics can serve as a valuable tool for enhancing both theoretical and practical understanding of mathematical and engineering concepts, offering a more engaging and interactive approach to learning.

In this study, the team employed full-scale crash tests to investigate the impact of post-densification technology on the safety performance of separated central median W-beam barriers under low compaction conditions. By precisely simulating the design and construction environment of the central median, the study comprehensively evaluated the barrier's containment, redirection, buffering, and anti-intrusion performances, as well as the deformation of both the barrier and vehicles under various collision scenarios. The results indicate that under low compaction soil conditions, the A-level separated central median barriers reinforced with post-densification technology effectively meet the specified protection requirements. By comparing the influence of soil strength variations on barrier performance under simulated rainfall conditions, it was confirmed that enhancing soil compaction significantly improves soil stability, effectively increases the overall strength and stability of the barriers, reduces deformation, and significantly enhances safety performance. This study not only validates the effectiveness of the reinforcement scheme but also provides new perspectives for the scientific research of safety barriers and offers crucial technical support for the optimal design of road safety protection facilities.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

The aim of this study was to examine the relationship of the distance between the apex tip of the upper central tooth (U1A) and the anterior nasal spine (ANS) and the nasal floor (NF) with the vertical cephalometric values using cone-beam computerized tomography (CBCT). A total of 122 patients who applied to Department of Orthodontics between January 2011-June 2019 were included. On the CBCT’s, distances between the U1A and the NF and ANS were measured. Statistical significance was considered as p&lt;0.05. Of 122 individuals 73.8% (n=90) were female and 26.2% (n=32) were male with an mean age of 22,8±3,3 years. A statistically significant moderate positive correlation was found between the NF-U1A mean values and the measurements of N-Me, ANS-Me and ANS-Gn, S-Go, and N-ANS measurements (p &lt;0.01). A statistically significant positive correlation was found between the ANS-U1A mean values and Ar-Go-Me, total posterior angles, N-Me, SN/GoGn and Y-axis angle, ANS-Me and ANS-Gn (p &lt;0.01). In this study, we found that the distance of U1A from ANS and NF points was related to orthodontic vertical direction parameters. It was demonstrated that the ANS-U1A and NF-U1A points can serve as reference points for identifying the orthodontic vertical growth pattern on CBCT scans.

Phantom Limb Pain (PLP) is a challenging condition affecting a significant proportion of amputees. In this article we describe the case of a 54-year-old Paralympic athlete with Phantom Limb Syndrome following right leg amputation and widespread sports-related enthesitic pain, who underwent a Whole Body Cryostimulation (WBC) cycle, an emerging treatment known for its rapid pain-relieving and anti-inflammatory effects. Assessments were conducted before and after a 10-session WBC cycle, including pain and quality of life assessment, and use of medications. A substantial reduction in enthesitic pain, PLP intensity, paresthesia, tingling related to atmospheric events and an improved function and quality of life were reported after the WBC cycle and lasted for two weeks. One month after WBC, the enthesitic pain following sports activity and PLP gradually returned but with lesser intensity. Similarly, the stump's sensitivity to atmospheric changes returned but with lower frequency. Pain at night remained lower than before WBC with significantly improved quality of sleep. This case study suggests that WBC could be a valuable adjuvant treatment for alleviating PLP. Controlled studies are warranted to validate the findings of this case-report and elucidate the mechanisms underlying the positive effects of WBC in this condition.

Background: As the world tends to recover from the crisis created by the COVID-19 pandemic, vaccines have served as one of the most valuable tools of combat and large-scale immunization has helped to tide over the catastrophe. However, several reports of post -vaccination neurological complications around the globe have surfaced up in recent literature. This study was conducted with an aim to describe the spectrum of neurological ailments requiring hospitalization following COVID-19 vaccination.Methods: An ambispective observational study was carried out from March 2021 to February 2022 at a tertiary care institute with 25 patients who satisfied the inclusion criteria of a new onset neurological illness requiring hospitalization within 4 days to 42 days of vaccination. The patients were duly followed upto months after discharge.Results: The median age of the sample was 36 years and the median latency of onset of neurological events was 14 days. Guillain-Barré syndrome was documented in 11 patients; majority were acute motor axonal neuropathy (45.45%) followed by acute inflammatory demyelinating polyradiculoneuropathy (36.36%) and acute motor sensory axonal neuropathy (18.18%). Central nervous system demyelination was reported in 9 patients; two patients had acute disseminated encephalomyelitis, 2 patients were diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease, one patient with aquaporin-4 positive neuromyelitis optica spectrum disorder , and the rest were labelled as seronegative central nervous system demyelination. Vascular events were noted in 5 patients comprising of 2 cases each of cerebral venous sinus thrombosis and intracerebral hemorrhage and a case of Moyamoya angiopathy. All patients were conservatively managed and had a complete to partial recovery suggestive of a favorable outcome after 3 months. Conclusion: The pathomechanisms of post -vaccination neurological complications is yet to be elucidatedand any causal association attributable to vaccination warrants further research. Compared to the enormity of the vaccinated population, the adverse effects are miniscule to hinder and discourage vaccination.

New antibiotics are unquestionably needed in the fight to the emergence and spread of multidrug-resistant bacteria. So far, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety re-placing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e. Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All tested compounds were more effective when assayed in chemically defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 μg/mL), at a concentra-tion between the non-desmethytaled (0.1 μg/mL) and the phosphonic (80 μg/mL) analogues. Also in Bacillus subtilis the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues to the development of novel antimicrobial drugs containing the phosphinic moiety.

Mediterranean Sea are dynamic habitats in which human activities have been conducted for centuries and which feature micro-tidal environments with about 0.40 m of range. For this reason, human settlements are still concentrated along a narrow coastline strip, where any change in the sea level and coastal dynamics may impact anthropic activities. We analyzed light detection and ranging (LiDAR) and Copernicus Earth Observation data. Aim of this research is to provide estimates and detailed maps (in three coastal plain of Sardinia (Italy) and in the Pontina Plain (southern Latium, Italy) of: i) the past marine trasgression occurred during MIS 5.5 higstand 119 kyrss BP; ii) the coastline regression occurred during the last glacial maximum MIS 2 (21.5 krs cal BP) and iii) the potential marine submersion for 2100 and 2300. The objective of this multidisciplinary study is to provide maps of sea-level rise future scenarios using the IPCC RCP 8.5 2019 [1]projections and glacio-hydro-isostatic movements for the above selected coastal zones, which are the locations of touristic resorts, railways, and heritage sites. We estimated a potential loss of land for the above areas of between about 146 km² (IPCC 2019-RCP8.5 scenario [1]) and 637 km² along a coastline length of about 268 km.

Dust storms originating from Central Australia and western New South Wales frequently cause high particles concentration at many sites across New South Wales, both inland and along the coast. This study focussed on a dust storm event in February 2019 which affect air quality across the state as detected at many ambient monitoring stations in the Department of Planning, Industry and Environment (DPIE) air quality monitoring network. The WRF-Chem (Weather Research and Forecast Model – Chemistry) model is used to study the formation, dispersion and transport of dust across the state of New South Wales (NSW, Australia). Wildfires also happened in northern NSW at the same time of the dust storm in February 2019, and their emissions are taken into account in WRF-Chem model by using Fire Inventory from NCAR (FINN) as emission input. The model performance is evaluated and is shown to predict fairly accurate the PM2.5 and PM10 concentration as compared to observation. The predicted PM2.5 concentration over New South Wales during 5 days from 11 to 15 February 2019 is then used to estimate the impact of the February 2019 dust storm event on three health endpoints namely mortality, respiratory and cardiac diseases hospitalisation rates. The results show that even though as the daily average of PM2.5 over some parts of the state, especially in western and north western NSW near the centre of the dust storm and wild fires, are very high (over 900 µg/m3), the population exposure is low due to the sparse population. The top five Statistical Area Level 4 regions with the most impact in term of mortality, respiratory diseases hospitalisation and cardiac disease hospitalisation are Far West and Orana, Newcastle and Lake Macquarie, New England and North West, Sydney – Inner South West and either Central Coast (mortality) or Sydney – Parramatta (respiratory diseases hospitalisation) or Sydney – Inner West (cardiac diseases hospitalisation). Generally, the health impact is similar in order of magnitude to that caused by biomass burnings events from wildfires or from hazardous reduction burnings (HRBs) near populous centres such as in Sydney in May 2016. One notable difference is the higher respiratory diseases hospitalisation for this dust event (161) compared to fire event (24).

The ultramafic-hosted Kairei vent field, located at 25°19′S, 70°02′E towards the northern end of the segment 1 of the Central Indian Ridge (CIR-S1) in a water depth of ~2450 m. This study aims to investigate the distribution of trace elements among sulfides of differing textures, and discuss the possible factors controlling the trace element distribution in those minerals by using LA-ICP-MS spot analyses as well as line scans. Our results show that there are distinct systematic trace element distributions throughout the different minerals：(1) Pyrite is divided into three types at the Kairei, including early-stage euhedral pyrites (py-I), sub-euhedral pyrites (py-II), and colloform pyrites (py-III). Pyrite is generally enriched in Mo, Au, As, Tl, Mn, and U. py-I have higher contents of Se, Te, Bi, and Ni, py-II are enriched in Au relative to py-I and py-III, but poor in Ni, py-III are enriched in Mo, Pb, and U but are poor in Se, Te, Bi, and Au. Variations in the concentrations of Se, Te, and Bi in pyrite are likely governed by the strong temperature gradient. Ni is generally lower than Co in pyrites, indicates that our samples precipitated at a high-temperature condition, whereas the extreme Co enrichment is likely from a magmatic heat source combined serpentinization reactions underlie the deposits. (2) Chalcopyrite is characterized by high concentrations of Co, Se, Te. The abundant of Se and Te in chalcopyrite cause by the high solubilities of Se and Te incorporated into chalcopyrite lattice at high temperature fluids. The concentration of Sb, As and Au is relatively low in chalcopyrite from the Kairei vent field. (3) Sphalerite from both the Zn-rich chimney is characterized by high concentrations of Sn, Co, Ga, Ge, Ag, Pb, Sb, As, and Cd, but depleted in Se, Te, Bi, Mo, Au, Ni, Tl, Mn, Ba, V, and U in comparison with the other minerals. The high concentration of Cd and Co is likely caused by the substitution of Cd2+ and Co2+ for Zn2+ in sphalerite. A high concentration of Pb accompanied by high Ag concentration in sphalerite indicating the Ag occurs in the microinclusions of Pb-bearing minerals such as galena. Au is generally low in sphalerite and strong correlate with Pb suggesting its presence in the microinclusions of galena. The strong correlation of As with Ge in sphalerite from Kairei suggests that they might precipitate under medium- to low-temperature with moderately reduced conditions. (4) Bornite-digenite is very low in most trace elements, except for Co, Se, and Bi. The high concentration of Se and Bi in all the sulfide minerals was observed in bornite-digenite can be explained by abundant Bi-selenide inclusions. Serpentinization in ultramafic-hosted hydrothermal systems might play an important role on Au enrichment in pyrite with low As contents. Compared with felsic-hosted seafloor massive sulfide (SMS) deposits, sulfide minerals from the ultramafic-hosted deposits show higher concentrations of Se and Te, but lower As, Sb, and Au concentrations attributed to the contribution of magmatic volatile input. Significant Se enrichment in chalcopyrite has been found from mafic-hosted SMSs indicate that the primary factor that controls the Se enrichment is its temperature-controlled mobility in fluids.

Abstract: Although the pathophysiology of fibromyalgia syndrome has been better understood in recent decades, a unified model of its pathogenesis and an effective therapeutic approach are still far from being realized. The main aim of this article will be to delve into the fundamental mechanisms of the pathophysiology of fibromyalgia conceptualized as stress intolerance syndrome. Using the biopsychosocial model of chronic pain syndromes, we will describe the potential role of the attachment system, C tactile fibers, and oxytocinergic system dysfunction in the pathophysiology of fibromyalgia syndrome and other central sensitivity syndromes. At the end of the article, the therapeutic implications of this new global and translational pathophysiological model will be briefly discussed.

Background: Central and branch retinal artery occlusion (CRAO and BRAO) are critical causes of acute vision loss, predominantly affecting older adults with systemic vascular pathology. These occlusions typically result from embolic events, leading to partial or complete retinal ischemia; Methods: This retrospective case series report details of our ten-year experience using the 1064 nm Nd:YAG laser for Transluminal Nd:YAG Embolysis (TYE) in order to lyse visible emboli whitin the retinal arteries; Results: We conducted a retrospective case series involving 18 patients treated by TYE for different retinal arteries occlusions between 2014-2024. TYE effectively restored blood flow in the occluded arteries, with variable but generally favorable visual outcomes. Our article highlights significant clinical and interventional aspects of three treated patients: a BRAO case with multiple transluminal emboli, a case of double BRAO and a CRAO case. We also report the successful use of TYE for intraluminal lysing of an embolus located outside the optic disc. The procedures were well-tolerated, with minor complications such as preretinal or vitreous hemorrhages resolving spontaneously; Conclusions: TYE is a minimally invasive therapeutic option for retinal artery occlusion with visible emboli, particularly when intervention occurs shortly after the onset of symptoms. Compared to observation, TYE can improve visual outcomes and reduce the risk of permanent vision loss, presenting a significant advancement in the management of this ophthalmic emergency. The worldwide experience with TYE is continuously increasing. Further research with larger cohorts is recommended to validate these results and refine the treatment protocol.

Treating central giant cell granuloma (CGCG) is challenging due to high recurrence rates and variable therapy responses. This study examines the efficacy of various treatments in reducing CGCG recurrence. A literature review explored outcomes of surgical excision, curettage, intralesional corticosteroid injection, and adjuvant therapy, considering factors like lesion location, size, and histological features. Aggressive surgical techniques such as en bloc resection were found to potentially lower recurrence rates compared to conservative approaches. However, treatment should be tailored to individual patient needs. Further research is needed to confirm these findings and improve treatment strategies. A concise literature review was conducted using PubMed, MEDLINE, and Google Scholar, focusing on papers published from 1986 to 2024. Search terms included "central giant cell granuloma," "recurrence," "treatment modalities," and "surgical excision". Studies reporting recurrence rates and treatment outcomes for CGCG were analyzed. Twenty-nine studies were reviewed, including six studies on surgical excision and curettage, eight studies on intralesional corticosteroid injections, six studies on calcitonin therapy, five studies on interferon alpha therapy and four studies on the therapy with denosumab. Analysis indicated that aggressive surgical treatments like en bloc resection were associated with lower recurrence rates compared to conservative methods. Predictors of recurrence included lesion size (&gt;3 cm), location (mandible), and aggressive histopathological features. Aggressive surgical excision combined with nonsurgical methods may lower recurrence rates, while conservative techniques remain viable in some cases. Further prospective research is needed to validate these findings and enhance CGCG treatment options.

Airborne distributed position and orientation system (ADPOS), which integrates multi-inertia measurement units(IMUs), data-processing computer and Global Navigation Satellite System (GNSS), serves as a key sensor in new higher-resolution airborne remote sensing, such as array SAR, multinode imaging loads and so on. ADPOS can provide multinode high accuracy spatio-temporal reference information to realize multinode motion compensation with the various state estimation methods such as Central Difference Kalman Filtering (CDKF), modifed CDKF. However, these methods focus on noise optimization based on known nonlinear models and its linear minimum variance estimation criterion, which cannot gain better estimation performance for high-dimensional nonlinear systems. For this reason, the variational optimization process based on conjugate gradient algorithm is proposed for the estimation of filtering update step, which is more efficient than linear minimum variance estimation criterion. Therefore, aiming at ADPOS with high-dimensional and nonlinearity, Central Difference Variational Filtering (CDVF) using variational optimization based on conjugate gradient algorithm for mean correction in the filtering update stage is devoted to advancing the estimation accuracy of multinode motion parameters. A real ADPOS flight test has been conducted, the experimental results show that the accuracy of the slave motion parameters has a distinct progress than the up to date CDKF, and the compensation performance is distinct.

Whether and how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus regarding behavioral, molecular, and electrical recording parameters remains unclear. Following the experimental protocols of a rat hemorrhage CPSP model, the VBC of the thalamus of wild-type and P2X7 receptor KO mice was injected with 10 mU/0.2 μl type IV collagenase to produce an animal model of stroke-like thalamic hemorrhage. Behavioral data showed that the CPSP group induced thermal and mechanical pain, while the P2X7 receptor KO group showed reduced thermal and mechanical pain behaviors. Molecular assessments revealed that the CPSP group had lower expression of NeuN and KCC2 and higher expression of GFAP, IBA1, and BDNF. The P2X7 KO group showed lower expression of GFAP, IBA1, and BDNF and higher expression of KCC2 than the CPSP group. The expression of NKCC1, GABAa receptor, and TrkB did not differ significantly between the control, CPSP, and P2X7 receptor KO groups. Muscimol application increased multiunit numbers and [Cl-] influx in the membrane in the CPSP group, while P2X7 receptor KO reduced multiunit activity and [Cl-] outflux. P2X4 receptor expression was significantly decreased in the 100 kb but not the 50 kb site in the P2X7 receptor KO group. Altogether, the P2X7 hypothesis of CPSP was proposed, wherein P2X7 receptor KO changed the CPSP pain behavior, numbers of astrocytes and microglia, CSD amplitude of the anterior cingulate cortex and the medial dorsal thalamus, BDNF and KCC2 expression, [Cl-], and P2X4 activation in 100 kb with P2X7 receptors. The present findings have implications for the clinical treatment of CPSP symptoms.

Rapid urbanization has led to many ecological problems such as landscape fragmentation, decreased landscape connectivity, and decreased biodiversity. Building an ecological security pattern is an important way to ensure ecological security and maintain sustainable urban development. Harbin is an important large-scale city in northeastern China, and the urban central district of Harbin is used as the study area. Ecological sensitivity assessment, MSPA, gravity model, landscape connectivity assessment and MCR model were used to extract ecological source areas, ecological corridors and ecological nodes in the study area to construct and optimize the ecological security pattern. Research shows that: A total of 23 ecological source areas were identified, mainly located along the Songhua River in the central part of the study area and in the mountain forest areas within the A-cheng District in the southeastern part of the study area. 48 ecological corridors were extracted, mainly in Daowai District, A-cheng District and the eastern part of Xiangfang District. There are 8 important ecological corridors and 10 important connecting corridors. 61 ecological nodes of the first level and 65 ecological nodes of the second level were extracted. High, higher, medium, lower and low security areas were classified based on the minimum cumulative resistance surface, with the highest proportion of high ecological security areas accounting for 45.75% of the study area. 65 ecological breakpoints were extracted and restoration measures were proposed. Finally, The structure of the ecological security pattern optimization of "two axes, two belts and four areas" is proposed, and corresponding ecological management measures are put forward. The experimental system of this study can provide new ideas for the construction of ecological security patterns in other regions and provide scientific support for the ecological sustainable development of similar urban areas.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induce the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted in the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions which share high identity between SARS-Cov-2 anti-gens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

Carbon (C) cycle n inland waters, including its concentrations and carbon dioxide (CO2) emis-sions from water surfaces are at the forefront of biogeochemical studies, especially in the re-gions, strongly impacted by on-going climate change. Towards better understanding of C stor-age, transport and emission in Central Asian mountain regions, extremely poorly studied until now, here we carried out systematic measurements of dissolved C and CO2 emissions in 15 riv-ers and 5 lakes located along a macro-transect of various natural landscapes in the Sayan-Altai mountain region, from high mountains of the Western Sayan in the northwest of Tyva to arid (dry) steppe and semi-deserts in intermountain basins of the southeast of Tyva, the border with Mongolia. New data on major hydrochemical parameters, CO2 fluxes by floating chambers, dis-solved organic and inorganic carbon concentrations collected over four main hydrological sea-sons allowed to assess the current C biogeochemical status of these water bodies in order to judge possible future changes under climate warming. We further tested the impact of perma-frost, river watershed size, lake area and climate parameters as well as ‘internal’ biogeochemical drivers (pH, mineralization, organic matter quality and bacterial population) on CO2 concentra-tion and emissions in lakes and rivers of this region, and compared them with available data on other subarctic and mountain settings.

This paper uses preliminary studies of archaeological sites (burial mounds and settlements) from the Iron Age through Medieval periods (ca. 800 BCE to 1200 CE) in the Juuku Valley on the South side of Lake Issyk-Kul to model land-use across vertical mountain zones. To do so, we have established a radiometric chronology, conducted test excavations of an Iron Age settlement and a Turkic period burial, undertaken preliminary archaeobotanical research, and pedestrian surveys. Seed remains of wheat (Triticum aestivum), barley (Hordeum vulgare), broomcorn millet (Panicum milaceum) and foxtail millet (Setaria italica) and legumes were recovered in very small quantities from an Iron Age upland settlement at 2100 m asl and a Turkic period burial mound at 1934 m asl. These preliminary archaeobotanical results are compared to the Talgar Iron Age settlements on the north side of the Tian Shan Mountain range in Kazakhstan studied earlier by Robert Spengler. Small samples of faunal remains found at the Turkic period kurgan and from a profile at the upland Iron Age settlement indicate livestock herding of sheep/goats, cattle, and horses in Juuku Valley. The goal of this paper is to test the hypothesis that pastoral transhumance and agropastoralism were economic strategies used by ancient societies during the Iron Age through Medieval periods in mountain-river valley areas between 750 m to 2500 m asl. These economic strategies that combined the pasturing of sheep, goats, cattle and horses with the cultivation of cereals were adapted to the use of different vegetational zones along a vertical gradient. This paper based on preliminary research of upland sites of the Juuku Valley in Kyrgyzstan, initiates a long-term research study of four millennia of settlements that ranged from pastoral transhumance, pastoral nomadism, and combined mountain agriculture using survey data and test excavations.

The central coast is one of the importantly livable regions in China, and green land plays a meaningful role in improving human settlements through regulating ecosystem services. However, the research on spatiotemporal heterogeneity of green land in different urbanized areas are still lacking in this region, which limits the timeliness of reporting on the land-surface thermal properties of residential environment from green land perspective. To address this issue, the synergistic methodology of “artificial numerical technology -- urban interior mixed pixel classification -- surface radiation energy balance model” was applied to investigate the green land change and its impact on human settlements in Rizhao region, which is known for its coastal ecology and greenery in China and obtained the United Nations habitat award. Main conclusions of this study are below: (1) Although total green land decreased by 474.05 km2, resulting in a decrease of 9.17% in its share of the entire study area from 2000-2022 during the urbanization process, but the greening levels improved within the built-up area, with the greening proportion of 25.34% in 2000 and 42.98 km2 in 2022. (2) Differences in green land at different urbanized regions were first observed, namely, urban greening rate was 37.78% in the old urban areas of 2022, while it was up to 46.43% in new urban areas. More attention was paid to the construction of urban green space during urban expansion, which will inevitably bring better visual and comfort experience to residents. (3) Thermal comfort indicators for urban residents were evaluated in latent heat flux (0-457.83 W/m2), sensible heat flux (0-645.09 W/m2), total available energy (254.07-659.42 W/m2) and others. (4) The lowered cooling temperature effect in the middle, high green land density region was 1.05 ℃ and 2.12 ℃ compared to the low-density region, and the average air temperature was 25.86 ℃. Also, spatial patterns of hot and cold uncomfortable areas were displayed in this study. Overall, this study provides the meaningfully practical reference for exploring the spatiotemporal heterogeneity of green land and its impact on residents' environments from the perspective of land-surface thermal properties in coastal areas of China and around the world.

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

A quite energetic seismic excitation consisting of one main and additional three distinctive earthquake clusters that occurred in the transition area between the Kefalonia Transform Fault Zone (KTFZ) and the continental collision between Adriatic and Aegean microplates, is thoroughly studied after high–precision aftershocks’ relocation. The activated fault segments are in an area where historical and instrumental data have never claimed the occurrence of a catastrophic (M>6.0) earthquake. The relocated seismicity initially defines an activated structure extending from the northern segment of the Lefkada branch of KTFZ with the same NNE–SSW orientation and dextral strike-slip faulting and then keeping the same sense of motion its strike becomes NE–SW and its dip direction NW. This provides unprecedented information on the link between the KTFZ and the Collision front and sheds more light on the regional geodynamics. The earthquake catalog, which is specially compiled for this study, starts one year before the occurrence of the Mw5.4 mainshock and adequately provides the proper data source for investigating the temporal variation of the b–value, which might be used for discriminating foreshock and aftershock behavior.

The life and work of Ignacio Ellacuría, S.J. is of radical vision, and revolutionary change. His dynamic life and works accompanied El Salvador and the Universidad Centroamericana through perhaps the most tumultuous years of the country’s history, yet there has been limited work done to examine his contributions. This paper shows how Ellacuría viewed the role of a Christian intellectual, and a Christian university within his philosophical and theological framework. I argue that Ignacio Ellacuría held, similarly to his soteriological views, that the intellectual must also be willing to sacrifice all for the sake of his/her work in a pattern of discipleship/martyrdom prefigured by his exemplars Christ and Socrates. It was this dedication to praxis and theory that western theology and philosophy had respectfully lost since their foundations which he sought to restore to a central role. In conclusion, the Christian intellectual and institution, according to Ellacuría, must use its voice and life in service of the people even to the point of martyrdom; he would argue, the implicit reason for Christian martyrdom and the crucifixion of Christ himself.

Amyotrophic lateral sclerosis (ALS) is a refractory neurodegenerative disease characterized by the de-generation and loss of motor neurons, leading to death within five years of onset. There have been few effective treatments, making the development of robust therapies an urgent challenge. Genetic mutations have been identified as contributors to ALS, with mutations in superoxide dismutase 1 (SOD1), which neutralizes the harmful reactive oxygen species superoxide, accounting for approximately 2% of all ALS cases. To counteract the toxic gain of function caused by SOD1 mutations, therapeutic strategies aimed at suppressing SOD1 gene expression have shown promise. Antisense oligonucleotide (ASO) is an arti-ficially synthesized short single-stranded DNA/RNA molecule that binds to target RNA to alter gene expression, representing a next-generation therapeutic approach. In 2023, tofersen became the first ASO drug approved by the FDA for ALS. Administered intrathecally, tofersen specifically binds to SOD1 mRNA, inhibiting the production of toxic SOD1 protein, thereby improving biomarkers of ALS. The long-term efficacy and safety of tofersen require further validation, and the development of more opti-mized treatment protocols is essential. A series of studies and therapeutic developments related to SOD1 mutations have advanced the understanding of ALS pathophysiology and significantly contributed to treatment strategies for central nervous system disorders. This review focuses on the overview of SOD1 mutations and the development process of tofersen, aiming to deepen the understanding of advancements in ALS research and discuss future challenges and directions for ASO therapy.

Exploring the spatio-temporal differentiation characteristics and coupling coordination relationship of the composite ecosystem of urban agglomerations is of great significance for promoting the synergistic development and integration construction of urban agglomerations. This paper is based on LUCC data, DEM, temperature, precipitation and other multi-source data, taking the central Yunnan urban agglomeration as an example. The entropy weight method is first used to determine the comprehensive weights to evaluate the regional economic and social development level. Then, the InVEST (Integrated Valuation of Ecosystem Services and Trade-offs)model was used to quantitatively calculate and analyze the spatial and temporal evolution characteristics of the four ecosystem services, including water conservation, soil conservation, carbon sequestration services, and habitat quality. The coupling coordination model was used to quantitatively analyze the evolution of the coupling coordination of the composite ecosystems in the central Yunnan urban agglomeration during the period of 2010-2020, and to reveal its development law. The results show the following: ①During the study period, the socio-economic subsystems in central Yunnan urban agglomeration demonstrated an outward radiative growth from Kunming City, marked by underdeveloped sub-centers and prevalent low-level areas. ②Trends in ecosystem services varied, with water and soil conservation showing fluctuating increases, carbon sequestration remaining stable, and habitat quality declining. The integrated ecosystem services critically important zone is mainly located in the northeastern region and southwestern edge of the study area. ③Economic, social and ecological subsystems are highly coupled, with consistent overall development trends and strong interactions. ④The increase in the degree of harmonization amounted to 7.82%, with lagging subsystems varying in different degree of harmonization subregions. The study can provide a scientific basis for urban agglomerations to formulate scientific and reasonable development policies, promoting regional sustainable development and optimizing the spatial pattern of the national territory.

Micro-nanoparticles' characteristics in geothermal fluids can be applied to detect of deep hidden geothermal resources. Observations using a nanoparticle tracking analyzer (NTA) indicated that the karst geothermal water collected in the central area of Shandong Province (Jinan and Zibo) contains many natural micro-nanoparticles with sizes primarily ranging between 100 nm and 5 μm. The micro-nanoparticles’ type, shape, crystal form, and chemical composition in the samples were analyzed using transmission electron microscopy (TEM). TEM images and energy dispersive spectroscopy showed that the micro-nanoparticles in geothermal water samples were mostly amorphous, irregular, or nearly spherical, with rough edges. The micro-nanoparticles were mainly carbonates, sulfates, and chlorine-containing Fe, Ca, Na, and Mg. The characteristics of the particles can reveal the properties of the deep, hot reservoirs and aquifers from where they originate. Therefore, we believe that natural micro-nanoparticles can be essential to detecting and studying deep, hidden geothermal resources, which is a novel approach to exploring deep, hidden geothermal resources.

Cerebrospinal fluid contacting neurons (CSF-cNs) are a specific type of neurons located around the ventricles in the brain and the central canal in the spinal cord and have been demonstrated to be intrinsic sensory neurons in the central nervous system (CNS). One of the important channels responsible for the sensory function is polycystic kidney disease 2-like 1 (PKD2L1) channel. Most of the studies concerning the distribution and function of the PKD2L1-expressing CSF-cNs in the spinal cord have previously been performed in non-mammalian vertebrates. In the present study immunohistochemistry was performed to determine the distribution of PKD2L1-immunoreactive (IR) CSF-cNs in the spinal cords of 4 mammalian species: mouse, rat, cat, and macaque monkey. Here, we found that PKD2L1-expressing CSF-cNs were present at all levels of the spinal cord in these animal species. Although the distribution pattern was similar across these species, differences existed. Mice and rats presented a clear PKD2L1-IR cell body labeling, whereas in cats and macaques the PKD2L1-IR cell bodies were more weakly labeled. Ectopic PKD2L1-IR neurons away from the ependymal layer were observed in all the animal species although the abundance and the detailed locations varied. The apical dendritic protrusions towards the lumen of the central canal were clearly seen in all the animal species, but the sizes of protrusion bulbs were different among the species. PKD2L1-IR cell bodies/dendrites were co-expressed with doublecortin, MAP2 (microtubule-associated protein 2) and aromatic L-amino acid decarboxylase, but not with NeuN (neuronal nuclear protein), indicating their immature property and ability to synthesis monoamine transmitters. In addition, in-situ hybridization performed in rats revealed PKD2L1 mRNA expression in the cells around the central canal. Our results indicate that the intrinsic sensory neurons are conserved across non-mammalian and mammalian vertebrates, and that this may play an essential role in the regulation of motor and sensory functions as well as in the maintenance of homeostasis in the CNS.

Turbo-roundabouts are one of the most frequently recommended road junction design options when it comes to increasing traffic capacity and traffic safety. This is in particular true of suburban areas, with dominant traffic flow on the main road and moderate traffic flow on the side road. Other intersections handling local traffic and considerably constricting the availability of space are usually located in the vicinity of such intersections. Another factor contributing to less availability of land for construction in these locations is the presence of surrounding residential housing. Then choosing the suitable turbo-roundabout type becomes the main issue. The article presents a case study for the selection of a type of turbo roundabout under the conditions of considerably constricted land availability, based on analyses of provision of swepth path for the chosen design vehicles. The article considers the typical Egg type turbo roundabouts, "flattened" turbo roundabouts and ellipse based roundabouts, with unconventional geometries of the truck apron and central island. For each of the analysed roundabout types setting out methods were described in detail, which enable designers to quickly select a type of roundabout suitable for specific constrained site conditions.

We assessed true bugs among above-groundand and soil inhabitants of four different biocoenosis of pine forests representing the intra-zone areas of flora and fauna of the Kazakh upland. 15 species of three families were listed for the Central Kazakhstan region for the first time. Species Eremocoris podagricus was not registered for the territory of Kazakhstan earlier. Fifteen species (50 %) were true above-ground inhabitants or ones living on grasses, whereas other species use soil surface and ground litter as temporary habitats. Drymus brunneus and Eremocoris fenestratus play a key role in the structure and function of the true bugs assemblages in the in biotopes studied. The ecological success of typically forest and boreal inhabitants in biotopes of arid region is explained by relict nature of forests and ancient connections with the taiga zone of Western Siberia and mountain forests of the Urals and Altai. The results of a comparative analysis of the similarities and differences of the dominant and ecological structures of Heteroptera complexes of aboriginal studied forests and derived type of forest are presented.

This research illustrates modification of multi-walled carbon nanotubes (MWCNT) by ZrO2/Pb to construct nanocomposites (MWCNT/ZrO2/Pb-NCs) by simple precipitation technique and subsequently examine its ability for adsorption of Amido black (AB) and Eosin B (EB) dyes in binary system. The present nanocomposites investigation by FESEM, XRD, FTIR, and EDX analysis, reveal its as-synthesized crystalline nature with cubic morphology and average particle size 30–50 nm. The present nano-adsorbent represent high efficiency for AB and EB adsorption from aqueous solution, while dependency of variables including pH, initial concentration of dyes, contact time and MWCNT/ZrO2/Pb-NCs mass were analyzed by central composite design (CCD). The predicted maximum removal percentage was 95% removal for both dyes is consequence of adjustment of operational conditions at pH of 6.0; 0.05 g MWCNT/ZrO2/Pb-NCs; 15 min stirring at 15 mg L-1 for both dyes. The Langmuir as applicable for representation and description of reveal data of adsorption with adsorption capacity of 15.46 and 16.92 mg g-1 for AB and EB, respectively. Pseudo-first order model owing to its high correlation coefficient and closeness of experimental and theoretical data well represented behavior of corresponding adsorption system. Mechanism examination strongly proof high contribution of external mass transference as the main rate-controlling step. The successful regeneration of MWCNT/ZrO2/Pb-NCs suggested their usefulness in wastewater treatment and its ability of environmental management.

Intranasal (i.n.) administration became an alternative strategy to bypass the blood-brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions and thus, they could be beneficial in the treatment of different medical conditions.

Both climate change and anthropogenic activities contribute to the deterioration of terrestrial water resources and ecosystems worldwide. Central Asian endorheic basins are among the most affected regions through both climate and human impacts. Here, we used a digital elevation model, digitized bathymetry maps and Landsat images to estimate the areal water cover extent and volumetric storage changes in small terminal lakes in Burabay National Nature Park (BNNP), located in Northern Central Asia (CA), for the period of 1986 to 2016. Based on the analysis of long-term climatic data from meteorological stations, short-term hydrometeorological network observations, gridded climate datasets (CRU) and global atmospheric reanalysis (ERA Interim), we have evaluated the impacts of historical climatic conditions on the water balance of BNNP lake catchments. We also discuss the future based on regional climate model projections. We attribute the overall decline of BNNP lakes to long-term deficit of water balance with lake evaporation loss exceeding precipitation inputs. Direct anthropogenic water abstraction has a minor importance in water balance. However, the changes in watersheds caused by the expansion of human settlements and roads disrupting water drainage may play a more significant role in lake water storage decline. More precise water resources assessment at the local scale will be facilitated by further development of freely available higher spatial resolution remote sensing products. In addition, the results of this work can be used for the development of lake/reservoir evaporation models driven by remote sensing and atmospheric reanalysis data without the direct use of ground observations.

Trichiurus japonicus is the most productive fish caught in our country. In order to understand the seasonal distribution of Trichiurus japonicus in the central and southern parts of the East China Sea and Yellow Sea, three species distribution models were adopted, namely Random Forest Model, K-nearest neighbor algorithm and gradient ascending decision Tree model, based on the data of trawling surveys in the central and southern parts of the East China Sea and Yellow Sea from 2008 to 2009. Combined with variance inflation factor and cross-check, the distribution model of Trichiurus japonicus was screened and constructed to analyze the influence of environmental factors on the distribution of Trichiurus japonicus in the central and southern parts of the East China Sea and the Yellow Sea. The results showed that the random forest model had the advantages of fitting effect and prediction ability among the three models. The analysis of this model showed that the water depth, bottom water temperature and surface salinity had a great influence on the habitat distribution of Trichiurus japonicus. The relative resources of Trichiurus japonicus increased with the increase of bottom water temperature and reached the maximum at 23.8℃, and first increased and then decreased with the increase of water depth and surface salinity, reaching the maximum at 72 m and 31.2‰, respectively. The random forest model was used to predict the spatial distribution of Trichiurus japonicus in the East China Sea and the central and southern Yellow Sea during 2008-2009, and the results showed that the predicted results were close to the actual situation. The research results can provide reference for the exploitation and protection of Trichiurus japonicus resources in the East China Sea and the central and southern Yellow Sea.

Background Corpus callosum abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosum abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications on the postnatal outcome. Methods In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies. Results The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%) and hypoplasia with dysplasia (4.2%). Amongst them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both. Conclusion The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a diagnosis suspected on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in the cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demye-lination and motor and cognitive impairment due to the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intrave-nously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.

We are in amidst of COVID-19 pandemic. Since Dec 2019, severe acute respiratory corona virus (SAR-CoV-2) has infected more than half a billion people killing nearly 7 million people worldwide. Now the BA.5 variant of SARS-CoV-2 is causing mayhem and driving the global surge. Epidemiologist are aware of the fact that this virus is capable of escaping immunity and likely to infect the same person multiple times despite adequate vaccination status. Elderly people of age more than 60 years and those with underlying health conditions are considered as high-risk who are likely to suffer complications and death. While it is tempting to frame complications and mortality from COVID-19 as a simple matter of too much of a virulent virus in too weak of a host, much more is at play here. Framing the pathophysiology of COVID-19 in the context of the Chrousos and Gold model of the central stress response system can shed insight into its complex pathogenesis. Understanding the mechanisms by which pharmacologic modulation of the central stress response system via administration of clonidine and/or dexamethasone may offer an explanation as to why a viral pathogen can be well tolerated and cleared by one host while inflaming and killing another.

Background: Central serous chorioretinopathy (CSC) is a common macular condition characterized by detachment of the neuroretina and is a frequent cause of central vision loss in adults. Among the various therapeutic strategies, subthreshold microsecond pulsed laser (SML) treatment has become a useful option. Despite the suggested involvement of choroidal circulatory disturbances in CSC, effects of this treatment on macular microperfusion have not been fully evaluated yet. Herein, we report the impact of SML on retinal and choroidal microvascular flow using non-invasive optical coherence tomography (OCT) angiography (OCTA). Methods: In this study, CSC patients with persistent subretinal fluid (SRF) with or without secondary choroidal neovascularization (CNV) were included (referred to as pachychoroid neovasculopathy (PNV) group and CSC group, respectively). SML was conducted using a yellow (577 nm) laser with duty cycle of 10%, spot size of 200 µm and duration of 200 ms. Best corrected visual acuity (BCVA) as well as OCT and OCTA images were evaluated at baseline and 4 weeks after SML. OCTA parameters of interest included full retinal perfusion (FRP), choriocapillaris perfusion (CCP), Sattler’s layer perfusion (SLP), and Haller’s layer perfusion (HLP), which were evaluated longitudinally and compared to unaffected fellow eyes. Results: 27 affected eyes and 17 fellow eyes from 27 patients were included. Before treatment, central retinal thickness (CRT) and subfoveal choroidal thickness (SFCT) of affected eyes were significantly larger than in fellow eyes. Four weeks after SML, CRT decreased significantly, whereas perfusion parameters did not change. In subgroup analyses, the CSC group showed a significant decrease of SFCT, whereas the PNV group did not despite the decrease of CRT. Conclusion: Our results suggest that the SML may SFCT of CSC, but not of PNV patients at least within four weeks following treatment. This effect seems to be independent of the change in choroidal perfusion measured with OCTA.

Purpose: To evaluate the impact of intravitreal bevacizumab (IVB) therapy on anatomical and visual outcomes in patients with macular neovascularization (MNV) secondary to chronic cen-tral serous chorioretinopathy (cCSC). Methods: This retrospective observational study reviewed the medical records of treatment-naïve patients diagnosed with cCSC complicated by MNV, treated with IVB injections over a 5-year period. The presence of MNV was confirmed using op-tical coherence tomography angiography (OCTA). Best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SFCT), and subretinal fluid (SRF) were recorded pre- and post-IVB treat-ment. Results: Twenty-two eyes of 22 patients (mean age, 68 ± 11 years) were included. After a mean follow-up of 21.0 ± 14.6 months, SRF significantly decreased from baseline (176.86 ± 115.62 µm) to the final follow-up (80.95 ± 87.32 µm, P = 0.003). Greater SRF reduction was associated with more injections (>7) (P = 0.047). However, no significant changes were observed in BCVA (P > 0.05) or SFCT (P > 0.05), irrespective of follow-up duration or injection frequency. Complete res-olution of SRF was achieved in 9 patients (40.9%), and a significantly greater reduction in SFCT was observed in complete responders compared to non-responders (P = 0.03). Conclusion: IVB therapy significantly reduced SRF in cCSC patients with secondary MNV, though it did not lead to visual improvement or significant changes in SFCT. However, greater choroidal thinning in patients with complete fluid resorption may suggest distinct underlying mechanisms or alterna-tive sources of subretinal fluid beyond the MNV itself.

Background/Objectives: The study outlines the systematic approach taken to develop and apply a robust NLP algorithm to determine the necessity of performing routine imaging after central venous catheter (CVC) placement and removal, based on the incidence of pneumothorax observed. Methods: Electronic health records from four university hospitals in Salzburg, Austria, on X-rays performed between 2012 and 2021 following CVC procedures, were analyzed using an NLP al-gorithm. The algorithm detected a pneumothorax in radiologists' reports and clinician requests, while excluding cases with contraindications such as chest injuries, prior pneumothorax, missing data, or unrelated follow-up X-rays. Chi-square tests were used to compare pneumothorax rates between CVC insertion and removal, and multivariate logistic regression identified risk factors, with a focus on age and gender. Results: The study analyzed 17,175 cases of patients aged 18 and older, with 95.4% involving CVC insertion and 4.6% involving CVC removal. Pneumothorax was identified in 106 cases after insertion (1.3%) and in 3 cases after removal (0.02%). The Chi-square test showed no statistically significant difference in pneumothorax incidence between insertion and removal (p = 0.4797), in-dicating no substantial difference in pneumothorax risk between these procedures. Conclusions: Given the lack of significant difference in pneumothorax incidence between CVC insertion and removal, and the established consensus that routine imaging is unnecessary after CVC removal, these findings indicate that routine imaging following CVC insertion may also be unnecessary in asymptomatic patients.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p &lt; 0.0001; and WMH: 0.0004±0.0007; p &lt; 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p &lt; 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

White adipose tissue (WAT) and gut are involved as inducers of neuroinflammation when they detect injury and trigger inflammation. The autonomous nervous system innervates both tissues, although the roles of the sympathetic, parasympathetic and enteric nervous systems have not been fully elucidated. Here, we revisited the participation of both types of inflamed peripheral tissue in neuroinflammation. We first analyzed how inflamed peripheral WAT plays a key role in neuroinflammation once metainflammation is installed. Second, we described the impact of insulin resistance (IR) on hypothalamic dysfunction, T2DM and neurodegenerative diseases. Finally, we analyzed the gut-brain axis, examining cell interactions, soluble factors, the sensing of microbes and the role of the intestinal microbiota and mucosal barriers in neuroinflammation. Since intestinal mucosa and secondary lymphoid organs are densely innervated by the sympathetic, parasympathetic, and enteric nervous systems, we analyzed bidirectional crosstalk between different tissues, neurons, and immune systems in healthy and pathological circumstances to restore normal tissues functions, and consequently homeostasis.

Vector-borne disease (VBD) accounts for more than 17% of the global infectious disease burden, disproportionately affecting developing nations within tropical and subtropical areas. As Aedes aegypti mosquitoes are the principal vector for the transmission of many Public Health pathogens, our study examined their population dynamics within the seasonal context of tropical dry biomes in El Salvador as incidence of VBD in this region has increased in recent years. Species that rely on sexual reproduction must maintain a balanced sex ratio (1:1) to support their population dynamics, however, our phenological analysis of field-collected A. aegypti specimens revealed significant sex ratio variations during dry and wet seasons. Interestingly, we detected a seasonal shift that favored female mosquitoes during the dry season, highlighting the dynamic nature of mosquito populations in highly urbanized environments like El Salvador. By linking sex ratio distortions to anthropogenic factors, our study underscores the importance of comprehensively characterizing the urban ecology of vectors for the development of effective biocontrol strategies. As such, we advocate for more nuanced vector control approaches that consider ecological factors as well as the human behaviors that influence mosquito breeding habitats to effectively combat the rise of VBDs amid global climate changes.

Ecuador is the world's fifth largest cocoa producer, generating hundreds of annual tons of residues from this fruit. This research aims to value this residual (cocoa pod husk) by using it as raw material to obtain pectin, which is widely used in the food and pharmaceutical industries. For them, the extraction of three different organic acids with GRAS status (and therefore safe for their use), citric, malic and fumaric acids, were studied. In addition, two other factors, temperature (70-90°C) and extraction time (60-90 min), were explored in a central composite design of experiments. Under the conditions of the experiment, it was obtained that the best yields were reached for citric acid, malic acid and fumaric acid and for ~86 min of extraction time. The temperature did not show a significant influence on the yield. The pectins obtained under optimal conditions were characterised, showing their similarity with commercial pectin. However, the equivalent weight and the esterification degree of the pectin obtained with fumaric acid classify it as having a high equivalent weight and a low degree of esterification. It differs significantly from the other two acids, perhaps due to the limited solubility of fumaric acid.

For each $t\in(-1,1)$, exact values of the least upper bounds $$ H(t)=\sup_{\E X=t,\,\E X^2=1} \frac{\E\abs{X}^3}{\E \abs{X-t}^3},\quad \sup_{\E X=t,\,\E X^2=1} \frac{L_1(X)}{L_1(X-t)} $$ are obtained, where $L_1(X)=\E|X|^3/(\E X^2)^{3/2}$ is the non-cental Lyapunov ratio. It is demonstrated that these values are attained only at two-point distributions. As a corollary, S.\,Shorgin's conjecture is proved that states that the exact value is $$ \sup\frac{L_1(X)}{L_1(X-\E X)}= \frac{\sqrt{17 + 7\sqrt7}}{4} = 1.4899\ldots, $$ where the supremum is taken over all non-degenerate distributions of the random variable $X$ with the finite third moment. Also, in terms of the central Lyapunov ratio $L_1(X-\E X)$, an analog of the Berry--Esseen inequality is proved for Poisson random sums of independent identically distributed random variables with the constant $$ 0.3031\cdot H\left(\frac{\E X}{\sqrt{\E X^2}}\right) \left(1-\frac{(\E X)^2}{\E X^2}\right)^{3/2} \le 0.3031\cdot \frac{\sqrt{17 + 7\sqrt7}}{4}<0.4517.$$ where $\Law(X)$ is the common distribution of the summands.

Chikungunya virus is an Alphavirus belonging to the family Togaviridae that is transmitted to humans by an infected Aedes mosquito. Patients develop fever, inflammatory arthritis, and rash during the acute stage of infection. Although the illness is self-limiting, atypical and severe cases are not uncommon, and 60% may develop chronic symptoms that persist for months or even for longer durations. Having a distinct periodical epidemiologic outbreak pattern, chikungunya virus reappeared in Thailand in December 2018. Here, we describe a cohort of acute chikungunya patients who had presented to the Bangkok Hospital for Tropical Diseases during October 2019. Infection was confirmed by real-time RT-PCR using serum collected at presentation to the Fever Clinic. Other possible acute febrile illnesses such as influenza, dengue, and malaria were excluded. We explored the sequence of clinical manifestations at presentation during the acute phase and associated the viral load with the clinical findings. Most of the patients were healthy individuals in their forties. Fever and arthralgia were the predominant clinical manifestations found in this patient cohort, with a small proportion of patients with systemic symptoms. Higher viral loads were associated with arthralgia, and arthralgia with the involvement of the large joints was more common in female patients

In this research, univariate and bivariate statistical methods were applied to rainfall, river and piezometric level datasets belonging to 24 years long time series (1986-2009). These methods, that often are used to understand the effects of precipitation on rivers and karstic springs discharge, have been used to assess, piezometric level response to rainfall and river level fluctuations in a porous aquifer. A rain gauge, a river level gauge and three wells, located in Central Italy along the lower Pescara river valley in correspondence of its important alluvial aquifer, provided the data. The statistical analysis has been used within a known hydrogeological framework, which has been refined by mean of a photo-interpretation and a GPS survey. Water-groundwater relationships were identified following the autocorrelation and cross-correlation analyses; the spectral analysis and mono-fractal features of time series were assessed, in order to provide information on multy-year variability, data distributions, their fractal dimension and the distribution return time within the historical time series. The statistical-mathematical results were interpreted through field work that identified distinct groundwater flowpaths within the aquifer and enabled the implementation of a conceptual model, improving the knowledge on water resources management tools.

Traumatic brain injury (TBI) is a global healthcare concern affecting millions, with wide-ranging symptoms including sensory and behavioral changes that can persist long-term. Due to similarities with human brain cytoarchitecture and inflammation, minipig models are advantageous for translational TBI research. However, gaps in knowledge exist regarding their behavioral and sensory sequelae following injury. Therefore, in this study, we assessed changes in approachability using a forced human approach task (FHAT) and mechanical nociception using the von Frey Test in adult male and female Yucatan minipigs for up to one week following a sham or central fluid percussion injury (cFPI). Specifically, the FHAT assessed each animal’s response to a forced interaction with either a known or unknown experimenter. To evaluate changes in nociceptive sensory sensitivity, von Frey monofilaments ranging from 0.008 to 300 grams of force were applied to the pinna of the ear or base of the tail. We found that forced approachability was affected by experimenter familiarity as well as cFPI in a sex-specific manner at subacute timepoints. We also found reductions in sensitivity following cFPI on the ear in male minipigs and on the tail in female minipigs. Overall, the current study demonstrates that cFPI produces both behavioral and sensory changes in minipigs up to one-week post-injury.

Robotics offers innovative possibilities at all levels of education, which should be considered when planning the teaching process for certain topics of engineering mathematics in higher education. In this paper, we present a new teaching-learning technique using STEAM-based methods to explore the properties of cycloidal curves for Computer Science Engineering BSc students. Frontal teaching, which is part of the tradition of higher education, has been complemented with teaching methods that meet the generational needs of students: problem-based learning, integration of STEAM-based methods and project-based learning. We have developed a new methodological model that combines the advantages of the traditional teaching method with new forms of teaching that have proven to be effective in teaching Generation Z. The four-stage methodological model uses a variety of didactical approaches because each stage applies a different type of learning technique to make the learning process interesting, motivating and effective. One of the main pillars of the model is the use of Desmos dynamic geometry software to create animations, and the other is the use of educational robotics to support visualisation. The implementation of educational robotics and its potential for teaching cycloidal curves is discussed in detail. The effectiveness of the method was investigated with first-year undergraduate students in computer science engineering. Quantitative studies were carried out to test the effectiveness of the new teaching technique. The experimental results strongly indicate the value of using the four-stage methodological model to implement active learning in the field of cycloidal curves.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Snow-covered regions are the main source of reflection of incident shortwave radiation (ISR) on Earth’s surface. The deposition of light-absorbing particles (LAPs) on these regions increases the capacity of snow to absorb ISR and decreases surface snow albedo (SSA), which intensifies the radiative forcing leading to accelerated snowmelt and modifications of the hydrologic cycle. In this work we investigate changes in SSA and radiative forcing (RF) induced by LAPs in the Upper Aconcagua River Basin (Chilean central Andes) using remote sensing satellite data (MODIS), in-situ spectral SSA measurements, and the ISR (Chilean Solar Explorer platform) during the austral-winter months (May to August) for the 2004-2016 period. To estimate the changes in SSA and RF, we define two spectral ranges: i) an enclosed range (Ecr) between 841-876 nm, which isolates effects of Black-Carbon, an important LAP derived from anthropogenic activities, and ii) a broadband range (Bbr) between 300-2500 nm. Our results show that percent variations in SSA in the Ecr are higher than in the Bbr, regardless of the total amount of radiation received, which may be attributed to the presence of LAPs as these particles have a greater impact on SSA at wavelengths in the Ecr band than in the Bbr band.

Mesozoic-Palaeozoic marine carbonate rocks are important hydrocarbon reservoirs in the Central Uplift area of the South Yellow Sea Basin (SYSB). Due to the lack of boreholes and the great heterogeneity of carbonate reservoirs, the distribution of porous carbonate reservoirs and their related key controlling factors remain unclear. Based on seismic inversion and isotope analysis, this study explores the factors affecting the distribution of porous Carboniferous-Early Permian carbonate reservoirs in the SYSB. In this study, the log-seismic characteristics of porous carbonate reservoirs, sensitive lithology parameters, and physical property parameters are extracted and analyzed. The pre-stack simultaneous inversion technique is applied to predict the lithology properties and physical properties of the porous carbonate reservoirs. Moreover, the sedimentary of carbonate is analyzed using isotopes of carbon, oxygen, and strontium. The results indicate that porous carbonate reservoirs with porosities of 3%~5% mainly occur at the paleo-highland (Huanglong Formation and Chuanshan Formation) and the slope of paleo-highland (Hezhou Formation). The porous carbonate reservoirs of the Qixia Formation are only locally developed. In addition, the study area was dominated by a warm and humid tropical climate from the Carboniferous to Early Permian, with four sea-level eustatic fluctuation indicated by the negative and positive δ13C excursions. When the sea level fell, the study area was exposed and denuded, and the supply of terrigenous detrital was dominated, which significantly influenced the carbonate deposit and diagenesis. This study highlights that sedimentation was a key factor in controlling the quality of Carboniferous-Early Permian carbonate reservoirs. The methods proposed in this study can be used in other carbonate-dominated strata worldwide.

The genetic pool of valuable old ornamental cultivars and their in situ maintenance may be threated by climate change. Meanwhile, the ornamental plants like roses make up an important share of both gardens and urban green spaces, where they are particularly vulnerable to multistress growth conditions. The aim of this research was to evaluate the effect of changing climatic conditions on growth and flowering of 11 historic climber roses through long-term studies (2000-2017) conducted in Central Europe. The evaluation of plants consisted of assessment of frost damage and the timing of early phenological stages (starting of bud break, leaf unfolding) as well as gathering data on beginning, fullness and end of flowering and its abundance. Frost damage was not recorded in any year only in ‘Mme Plantier’, and did not occur for any cultivar after the winter in the years 2007, 2008, and 2014. Only a little damage to one-year shoots was recorded after the winter in the years 2015-2017. Frost damage to ‘Alberic Barbier’, ‘Albertine’, ‘Chaplin's Pink Climber’, ‘Orange Triumph clg’ and ‘Venusta Pendula’ led to pruning to ground level in every year excluding those listed above. Frost damage of once blooming roses limited their flowering; however, the many-year data-sets showed a trend for decreased frost damage and improved abundance of flowering, and these results can be interpreted as a response to the increase of average air temperature. The timing of bud breaking and leaf development in all climber roses was strictly correlated with average air temperature in the dormancy period. The reactions of climber roses to weather conditions confirmed the influence of climatic changes on ornamental crop plants in Central Europe, introducing the potential possibility for the wider application of climber roses, but without certainty of flowering every year.

Mercury has a strong environmental impact since both its organic and inorganic forms are toxic and it represents a pollutant of global concern. Liquid Hg is highly volatile and it can be released during natural and anthropogenic processes in the hydrosphere, biosphere and atmosphere. In this study the distribution of Gaseous Elemental Mercury (GEM) and the total and leached mercury concentrations on paints, plasters, roof tiles, concretes, metals, dust and wood structures were determined in the main buildings and structures of the former Hg-mining area of Abbadia San Salvatore (Siena, Central Italy). The mining complex (divided into 7 units) covers a surface of about 65 ha and contains mining structures and managers and workers buildings. In this work, nine surveys of GEM measurements were carried out from July 2011 to August 2015 for the buildings and structures located in the units 2, 3 and 6. Moreover, detailed measurements were performed in February, April, July, September and December 2016 in the edifices and mining structures of Unit 6. GEM concentrations showed a strong variability in terms of space and time mostly depending on the distance from the building hosting driers, furnaces and condensers and ambient temperature, respectively. In the Unit 2 surveys carried out in the hotter period (from June to September) showed GEM concentrations up to 27,500 ng m⁻³, while in the Unit 6 they were on average much higher and occasionally they saturated the GEM measurement device (>50,000 ng m⁻³). Concentrations of total (in mg kg⁻¹) and leached (in μg L⁻¹) mercury measured in different building materials (up to 46,580 mg kg⁻¹ and 4,470 mg L⁻¹ for total and leached mercury, respectively) showed for the same type of material highly variable values in dependence on the edifice or mining structure from which they were collected. The results obtained in this study are of relevant interest for the operational cleanings to be carried out during the reclamation activities.

This study aimed to assess the predictive performance of first and second-order regression models in optimizing bedaquiline (BQ) solid lipid nanoparticles (SLNs) formulations. Employed a central composite design and graphical optimization process using three steps. A design of experiments to evaluate the impact of BQ, Tween 80 (T80), polyethylene glycol (PEG), and lecithin on the formulations' response variables: Z-average (PSD), polydispersibility index (PdI), and Zeta potential (ZP). Secondly, quantified the relationship between experimental variables using the regression model coefficients. Lastly, predicted the responses and verified the models’ adequacies to ensure accurate representation and effective optimization. First-order polynomial showed poor model adequacy that required further refinement. The second-order models provided superior fitness, sensitivity to variability, complexity, and prediction consistency. The optimized formulation achieved a desirability value of 0.9998 indicating alignment with the desired criteria. Specifically, the levels of BQ (19.4mg), T80 (25.2mg), PEG (39.2mg), and Lecithin (200mg) corresponded to PdI (0.41), PSD (250.99 nm), and ZP (-25.95 mV). Maintaining BQ concentration between 10-20% and T80 between 15-18% is vital for maximizing ZP and minimizing PdI and PSD, ensuring stable SLN formulations. The study underscores significance of precise model selection and statistical analysis in pharmaceutical formulation optimization for enhanced drug delivery systems.

Neurologic disorders such as traumatic brain injury, multiple sclerosis, Alzheimer’s disease, and drug-resistant epilepsy have a high socioeconomic impact around the world. Current therapies for these disorders are often not effective. This creates a demand for the development of new therapeutic approaches to treat these disorders. Recent data suggest that autoreactive naturally occurring immunoglobulins produced by subsets of B cells called B1 B cells combined with complement are actively involved in the processes of restoration of neuronal functions during pathological conditions and remyelination. The focus of this review is to discuss the possibility of creating specific therapeutic antibodies that can activate and fix complement to enhance neuronal survival and promote central nervous system repair after injuries associated with many types of neurodegenerative diseases.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Interrupting the vicious cycle within neuron-microglia interactions may be a therapeutic goal in DE by limiting the inflammatory response.

Grasping the spatial and temporal patterns of forest fires, along with the key factors that drive them and the ability to forecast such events accurately, is essential for the successful management of forests. In China's southern region, forest fires significantly endanger the ecological system, public safety, and economic well-being. Through the application of Geographic Information Systems (GIS) and LightGBM (Light Gradient Boosting Machine) model, this study investigates the determinants of fire incidents and formulates a predictive model for forest fire occurrences, alongside a zoning strategy, within the Central-South area. The results indicate: (i) Spatially, fire points exhibit significant clustering and autocorrelation characteristics; (ii) The Central-South Forest Fire Prediction Model shows exceptional accuracy, reliability, and predictive power, with high performance metrics across training and validation sets, including over 85% accuracy, precision, recall, and F1 scores, along with AUC values above 89%, underscoring its efficacy in forecasting forest fires and distinguishing between fire events; (iii) Throughout the year, forest fire risks in the Central-South region of China vary by region and season, with risk spikes from March to May in Guangdong, Guangxi, Hunan, Hubei, and Hainan. From June to August, localized risks are observed in Heyuan and Huangshi, while from September to November, an increase in risk is noted in Guangdong (Meizhou, Heyuan, Shaoguan), Guangxi (Nanning, Hezhou, Yulin), and Hunan (Binzhou, Yongzhou, Hengyang) due to cooler, drier conditions and leaf litter accumulation. From December to February, the risk continues in specific areas across Guangdong, Guangxi, Hunan, and Hubei.

Breast cancer is the most common cause of mortality due to cancer for woman both in Lithuania and worldwide. Chances of survival after diagnosis differ significantly depending on the stage of disease at the time of diagnosis and other factors. One way to estimate survival is to construct a Kaplan-Meier estimate for each factor value separately. However, in cases when it is impossible to observe a large number of patients (for example, in case of countries with lower numbers of inhabitants) dividing data into subsets, say, by stage at diagnosis may lead to results where some subsets contain too little data so that results of Kaplan Meier (or any other) method will become statistically incredible. The problem may become even more acute if the researcher would like to use more risk factors, such as stage at diagnosis, sex, place of living, treatment method, etc. Alternatively, Cox models are used to analyse survival data with covariates, and they don’t require dividing the data into subsets according to chosen risks factors (hazards).

Takotsubo syndrome (TTS) is a cardiomyopathy that presents clinically as a transient and reversible left ventricular wall motion abnormality (LVWMA) that can recover spontaneously within hours to weeks. Studies have shown that it mainly affects older people. Postmenopausal women in particular have an increased prevalence. Physical and emotional stress are widely discussed and generally recognized trigger factors. As age also appears to play a major role in the development of TTS, this review will take a closer look at age- and gender-specific aspects. First and foremost, postmenopausal women and the associated lower oestrogen concentration should be mentioned here. Another important role is played by the hypothalamic-pituitary-adrenal (HPA) axis and the associated glucocorticoid-dependent negative feedback and the resulting immune response. Inflammaging is another term that is increasingly used in connection with TTS. In the following, these risk factors are considered in more detail and linked to the increased sympathetic activity as a possible consequence of chronic stress. Based on the imbalance between the sympathetic and parasympathetic nervous system, we venture an explorative proposal and would like to present a new possible therapeutic approach.

This article provides a general overview of the bio-inspired computing method called DNA-Based Computing (DBC), including its theory and applications. The main theme of DBC is the central dogma of molecular biology (once information of DNA/RNA has got into a protein, it can’t get out again), i.e., DNA to RNA (sequences of four types of nucleotides) and DNA/RNA to protein (sequence of twenty types of amino acids) are allowed, not the reverse ones. Thus, DBC transfers few-element information (DNA/RAN-like) to many-element information (protein-like), solving a given cognitive problem. DBC can take many forms; this article elucidates two main forms, denoted as DBC-1 and DBC-2. Using arbitrary numerical examples, it is shown that DBC-1 can solve the following cognitive problems: “similarity indexing between seemingly different but inherently identical objects” and “recognizing regions of an image separated by a complex boundary.” DBC-2 can solve the following cognitive problem: “pattern recognition when the relevant information is insufficient.” Smart manufacturing-based systems (digital twins and big data analytics) must solve the abovementioned problems to make the manufacturing enablers (machine tools and monitoring systems) more self-reliant and autonomous. Consequently, DBC can improve the cognitive problem-solving ability of smart manufacturing-relevant systems and, thereby, can enhance its biologicalization.

Tunneled central venous catheters (CVC) are mainly considered as rescue vascular access option in dialysis but still used in about one quarter of prevalent patients worldwide as being associated with poor performances and higher risks. Study design. In this retrospective single-center study, we aimed to report on clinical performances achieved with high-flow tunneled CVC (DualCath, DCath) and compared it with arteriovenous accesses (AVAs; AV fistula, AV graft, Thomas Shunt) in a hospital-based dialysis unit. Methods. Sixty-eight stage 5 chronic kidney disease dialysis dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-up of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V and total Kt, ultrafiltration volume and percent reduction of ß2-M were measured monthly as part of quality control in our unit. Results. At baseline, effective blood flow with DCath was close to 400 ml/min, similar to AVAs. Recirculation with DCath (7%, 6-13%) was higher than AVAs. Diffusive dialysis dose delivered with DCath (spKt and eKt/V) and convective dialysis dose achieved with DCath were slightly lower than AVAs, but still much higher than recommended by guidelines. Percent reduction of ß2-M achieved with DCath was also 4 to 10% lower than AVAs. On longitudinal follow-up, main clinical performance indicators of DCath (total Kt and total ultrafiltration volume, L/session) were maintained very stable over time and close to those achieved with AVAs. Conclusions. As shown in this study, high-flow DualCath tunneled two single lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performances. These results rely from the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Background: The use of peripherally inserted central catheters and midline catheters is growing due to their potential benefits. These devices can increase patient safety and satisfaction while reducing the use of resources. As a result, many hospitals are establishing vascular access specialist teams staffed by nurses who are trained in the insertion and maintenance of these catheters. Objective: Evaluate ex-ante whether the benefits of replacing peripheral venous catheters, peripherally inserted central catheters and midline catheters with ultrasound-guided peripherally inserted central catheters and midline catheters by a vascular access specialist team outweigh their costs. Methods: Cost-benefit analysis from the perspective of the healthcare provider based on administrative data. The study estimates the reduction in resources used when replacing peripherally inserted central catheters, midline catheters and peripheral venous catheters with ultrasound-guided peripherally inserted central catheters and midlines, as well as the additional resources required for their use. Results: Each ultrasound-guided peripherally inserted central catheter replacing a peripherally inserted central catheter, results in a measurable resource reduction of approximately €31. When 3 peripheral venous catheters are replaced by an ultrasound-guided peripherally inserted central catheter, the saving is €63. Similarly, each ultrasound-guided midline catheter replacing a midline, results in a reduction of €16, while each ultrasound-guided midline catheter replacing 3 peripheral venous catheters results in a reduction of €96. Conclusion: The benefits of replacing peripheral venous catheters, peripherally inserted central catheters and midline catheters by introducing a vascular access specialist team trained in the implantation of ultrasound-guided peripherally inserted central catheters and midline catheters, outweigh its cost mainly because of the decrease in hospital stay due to the lowered risk of healthcare-associated infections. These results motivate the implementation of the service, adding to previous experience suggesting that it is also preferable from the point of view of patient safety and satisfaction.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

Credit rationing, especially prevalent for smaller firms, impedes economic growth. A Central Bank aligned “not for profit” managed business to business “Stable-Coin” (“Synthetic Central Bank Digital Currency”) providing trade debt liquidity can lower small firm credit rationing. It raises growth by reducing monetary transmission imperfections consequent upon asymmetric information, commercial bank underwriting restrictions, market power dynamics and regulatory distortion. A simple framework is developed to contextualise small firm credit rationing and associated monetary transmission imperfections with broader credit flows into both the real and monetary sectors. Evidence is presented regarding US monetary transmission efficacy to firms, paving the way to proposing a trade debt business to business focused stable-coin to help close credit rationing gaps. Designed to minimise “moral hazard”, the proposed stable-coin provides an additional monetary transmission channel that supplies interest free trade debt funding to firms to support economic activity and raise growth. In addition to helping close the small firm financing gap, the stable-coin provides policy makers with an additional contra-cyclical monetary transmission instrument to minimise real economic disruption consequent upon financial system crises and liquidity events.

The VEMoS AXL system is a new optical biometer based on spectral domain optical coherence tomography (SD-OCT) that has been tested in terms of intrasession repeatability and compared with a swept-source optical coherence tomography biometer (SS-OCT), which is considered the gold standard, for an agreement analysis. A biometric analysis was performed three consecutive times in 120 healthy eyes of 120 patients aged between 18 and 40 years with the SD-OCT system and afterwards a single measurement was obtained with the SS-OCT system. Within-subject standard deviations were 0.004 mm, 4.394 µm and 0.017 mm for axial length (AL), central corneal thickness (CCT), and anterior chamber depth (ACD) measures obtained with the SD-OCT biometer, re-spectively. The agreement between devices was good for AL (Limits of agreement, LoA: -0.04 to 0.03 mm) and CCT (LoA: -4.36 to 14.38 µm), whereas differences between devices were clinically relevant for ACD (LoA: 0.03 to 0.21 mm). In conclusion, the VEMoS AXL system provides consistent measures of anatomical parameters, being most of them interchangeable with those provided by the SS-OCT-based gold standard.

Non-ulcerated cutaneous leishmaniasis (NUCL) is an atypical and peculiar clinical form of the disease that was first described by Ponce et al. (1988) in Honduras (Central America), where iso-lated or disseminated popular and/or nodular skin lesions are commonly seen in adolescents and young adults. Leishmania (L.) chagasi was then incriminated as the causal agent of the disease, as well as of American visceral leishmaniasis (AVL), although NUCL has been shown to be more prevalent than AVL in the region. Considering, however, the dubious taxonomic character of the causal agent of NUCL, as there is no evidence of this form of disease associated with L. (L.) cha-gasi in South America, this study aimed to carry out a retrospective taxonomic analysis on a se-ries of studies on the diagnostic approach to the Honduran parasite in loco (El Tigre island, Amapala municipality, west coast of Honduras), where taxonomic characters of a biological (in vitro and in vivo), epidemiological (vector and canine reservoir), clinical-immunological (im-munopathological features of in situ skin lesion and systemic infection) and molecular (ge-nomic/phylogenetic analyses) nature were considered. The findings, particularly those of mo-lecular nature, such as: the Honduran parasite showed to be more ancestral (molecular clock analysis of the DNA polymerase alpha subunit gene) than all viscerotropic ones [L. (L.) chagasi, L. (L.) donovani and L. (L.) infantum], as well as presenting an absolutely unprecedented structural variation on chromosome 17 and the highest frequency of genomic SNPs (more than twice the number seen in the Brazilian parasite), in addition to representing a different phylogenetic lin-eage (mainly in the NJ - RNA Pol II tree) from those viscerotropic ones, have pointed to the characterization of a new leishmanine parasite, Leishmania (Leishmania) poncei n. sp. (Kinetoplas-tea: Trypanosomatidae), in honor of Professor Ponce, who was the first researcher to describe NUCL in Honduras.

Truffles are ascomycete hypogeous fungi belonging to the Tuberaceae family of the Pezizales order that grow in ectomycorrhizal symbiosis with tree roots and are known for their peculiar aromas and flavors. Axenic culture of truffle mycelium is problematic because it is not possible in many cases, and the growth rate is meager when it is possible. This limitation prompts searching and characterizing new strains that can be handled in laboratory conditions for basic and applied studies. In this work, a new strain of Tuber borchii (strain SP1) has been isolated and cultured, and its transcriptome has been analyzed under different in vitro culture conditions. The results show that the best T. borchii SP1 growth was obtained using maltose-enriched cultures made with soft-agar and in static submerged cultures made at 22ºC. The transcriptome analysis of this strain cultured in different media indicated that most of the gene transcription effort is due to a limited number of genes (20% of genes account for 80% of the transcription), that the transcription profile of the central metabolism genes was similar in the different conditions analyzed with a transcription signal detected for around 80% of the annotated genes. The gene expression profile suggests that T. borchii uses a fermentative rather than respiratory metabolism, even in aerobic conditions. Finally, there is a reduced expression of genes belonging to secondary metabolite clusters, whereas there is a significative transcription of those involved in producing volatile aromatic compounds.

This work presents emission line flux and kinematic structure mapping based on IFU data of the planetary nebulae Abell 30 (A30). The IFU has a field of view (FoV) of 16" x 12.3" and was used to partially cover knots J1 and J2, and completely cover knots J3 and J4 of A30. Our emission line flux map shows recombination species C II, C III, He I, O II as well as forbidden line species [O III], [Ne III] and [Ne IV] of high excitation level are all distributed in different parts of the knots. The kinematic structure shows considerable variation in both the velocities and spatial locations of these knots with positive and negative velocity excursions from the systematic value. Forbidden line species [O III], [Ne III] are distributed in both knots J3 and J4 but they are travelling at different speeds in opposite directions. Despite variation in distribution of the species, the velocities of [Ne IV] and [O III] are similar and travelling in the same direction while the other species [Ne III], He I, and O II share similar velocity of 200kms−1 up in the opposite direction. The complexity of distribution and kinematic structure of the knots revealed in this work indicates a strong tendency towards the hypothesis of multiple triggering events in the past history of A30.

Mountain and pastoralist societies around the world have for centuries sustained their livelihoods and cultures by accumulating specialist knowledge about their local and regional socio-ecological environments. Developing traditional knowledge and customary practices takes time, sometimes spanning across generations. As macro-level changes to social and natural environment are now taking place, such as globalization and climate change, local communities could potentially also benefit from complementary, suitably adapted educational opportunities for sustainable development. However, access to education has often required moving to urban centres, which can weaken community structures and cohesion, and could also foster increased dependence on external specialists, providers or decision-makers. Careful introduction of emerging Educational Technologies could alleviate and possibly reverse such trends as mobile Internet access spreads to remote areas. This paper examines the role of education in sustainable development and specifically explores the potential for two educational innovations, open badges and blockchain, to provide a new construct for transformation in sustainable development amongst mountain and pastoralist societies. These technologies could not only facilitate education through online distance learning, but also allow geographically remote populations to highlight the value of their traditional knowledge and to engage more comprehensively in their changing worlds.

This work deals with a numerical implementation of a fifth order CENTRAL WENO-TVD (\textit{Weighted Essentially Non-Oscillatory-Total Variation Dimimishing}) of Haschem (2006) scheme applied to the convective terms of some hyperbolic conservation laws problems, in a volume finite framework. The WENO-TVD scheme is used to solve the 1D advection and Burgers equations. For this case is implemented two different numerical fluxes: The Lax-Friedrichs and TVD fluxes. In the TVD fluxes the schemes applied are in flux-limiter form. The schemes implemented for this flux are: Van Albada-1 (van Albada et al.,1982), van Albada-2 (Kermani et al., 2003), van Leer (Hassanzadeh, 2009) and MINMOD (Hirsch, 2007). The WENO type schemes are characterized for their high order approximation, and do not produce spurious oscilations near discontinuities, shocks and higher gradients. A third order Runge-Kutta TVD for the temporal variable is used. Qualitative and quantitative comparison are presented. The numerical solutions are computed with an in-house computer code developed in MATLAB software. In future works, it will develope a paralelization of computer code for solving systems of conservation laws, e.g. Euler equations of gas dynamics.

Neurodevelopmental disorders are characterised by an amalgam of genetic and epigenetic faults implicating neuronal protein-related loss-of-function and gain-of-function respectively, hence their inclusion into the category of complex diseases. Neurodevelopmental disorders are regarded as autism spectrum disorder due to this reason; that the risk factors and phenotype constitute a spectrum of faults and protein overactivity. One example of an epigenetic factor leading to the onset of neurodevelopmental delays constitutes a set of immune response-based dysregulations, as well as the excessive growth of the adaptive immune memory of the foetus or the baby following significant infectious disease during pregnancy, as well as in babies aged 0-2, given the existence of profound links between developmental immunity and developmental neurology. Given that genetic information very likely represents a form of energy, the intake of excessive pathogen-related information may transiently overload the adaptive immune memory similarly to the manner functional pathogens do whilst inducing significant illness, and if events as such occur during important stages of neuro-immunological development, then there could often be irreversible effects upon the rate of development in neurological networks that normally have a major importance in the modulation of the related cognitive and behavioural phenotype. The full extent of evidence may only be obtained via a thorough study of the applications of physical laws into biology and medicine, given the foundational role of the physical matter in the development and maintenance of life. A common misconception is that neurodevelopmental delays are characterised solely by an accumulation of protein loss-of-function incidences in the central nervous system area, rather than a disruption of neuronal region developmental rates. For example, an overexpression of neuronal proteins related to cognition factors that is accompanied by an underexpression of proteins related to social behaviour is phenotypically manifested in people with sharper rational thinking and poorer communication skills, with an impact on the abilities of decision-making as well, and this tends to be regarded as a classical example of the clinical manifestation of neurodevelopmental delays. More severe forms of autism spectrum disorder tend to implicate a more generalistic impact upon the developmental rates of key human behaviours, including those related with the development and maintenance of social and intimate relationships. Likewise, more severe implications upon regular developmental rates tend to bring a major impact upon the healthy function of related functions. As a result, lower functioning forms of neurodevelopmental delays bring fresh concerns with regards to a possible uncanny increase of incidences of deviated sexuality during years of adulthood, and in the worst cases, such deviations may lead to the planning and development of criminal activity, particularly in individuals who are or become prone to breaking the moral code that established the civilised society. What holds the concerns valid is the exponential increase in the number of lower functioning autism cases throughout the world and the major signs that such an increase will continue with a full force. One major solution to this potential future problem would be a much higher investment into awareness of the exact genetic and environmental factors that directly or indirectly result in the onset of lower-functioning autism and of the current research efforts to develop the matching support for people found in situations as such. The most important aim of future research with regards to such a scenario would be a separation of disease and disability with choices made to step into more severe forms of disease and into areas that are outside of the established moral circle.

The term `motor control´ encompasses a wide range of mechanisms thought to be implicated in the organization of movements. Their study, like that of any other scientific field, must use specific notions to get to grips with them. This review is therefore organized along a series of notions that are frequently used in motor control, and we will discuss them with particular emphasis on neurological conditions, which may disrupt normal motor functioning. We will start with a short description of the roles of space and time, in which movements take place. Subsequently we will deal with kinematics and kinetics (dynamics) of movements. Then, we will list the inputs to motoneurons (MNs), which, in different forms, convey signals from the central nervous system (CNS) to skeletal muscles and muscle spindles, including central pattern generators (CPGs), sensory inputs and supraspinal descending fiber systems. Some helpers in movement organization will be introduced, such as internal models and neuronal network models. A relatively brief section on sensory-motor learning will follow because learning abilities are required to endow the sensory-motor system with flexibility and adaptability. The major emphasis is placed on neurological processes, which result from genetic modifications, autoimmune diseases, neurodegenerative diseases, infections in the nervous system as well as vascular and traumatic lesions. These neurological diseases lead to a variety of impairments and symptoms, particularly movement derangements including cerebellar ataxia, spasticity, and (other) movement disorders such as Parkinson’s syndromes. The conclusion is that there is no unique top controller that controls ´motor control`.

The architecture, organization and functioning of biocatalytic reaction networks, which are coded in the cell specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. The knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary which is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims at outlining advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.

A stable match, an intercuspated maxilla-mandible relation is the universally accepted goal for dental restorative interventions, yet the underlying sensorimotor mechanisms to achieve this goal in the natural jaw closure remains to be elucidated. Dentists have intuitively regarded peripheral sensory innervation from tooth contacts as a significant control element for jaw muscle actions, both in the state of health and in cases of pathological dysfunction. However, therapeutical interventions for reshaping the dental arch anatomy and jaw relations have not always been successful. Repetitive masticatory chewing cycles, swallowing, talking, as well as volitional jaw-opening and -closing involve stereotyped neural commands from the central nervous system that are modulated in reaction to the sensory afferent feedback from the peripheral neurons and their sensor organs. The aim of this article is to describe, on a fraction of a second time-scale, the minuscule tilts and kinematic events of mandible during the making of a stable match with maxilla. Evidence of the importance of tooth contacts as the sensorimotor motivation of each of the successive kinematic steps of the “mandible-meets-maxilla-narrative” are discussed.

The introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology is based on the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In such cases, the fact that the material design methods are based on fundamental scientific principles and have been proven in laboratories and through Accelerated Pavement Testing (APT), may be of little influence. However, the general acceptance of new disruptive technologies, e.g. telecommunications and Information Technologies (IT), have been based on the considerable advantages it presented. The same principles are applicable to the general acceptance and use of NME stabilisation/enhancement of materials in the road construction industry. This article is aimed at the practical cost-effective demonstration of the general application of the use of nanos-silane modified emulsions in the construction of the highest order roads, i.e. inter-city multi-lane highways, lower order roads (including Low-Volume-Roads (LVR)) and even local accesses to farms and in villages/townships. The implementation of NME technologies is directly associated with ease of use, time and cost savings and the addressing and reduction of risks applicable to the use thereof.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

We examined special roles of the Central Nervous System (CNS) in an attempt to resolve the puzzle that chronic diseases cannot be cured by medicine. By exploring a skill-learning model, we found that the CNS is able to remember certain information reflecting biochemical and cellular (B&C) processes in the body. From the skill using ability, we found that the CNS is able to control basic B&C processes that drive and power the skill. From the ability to adjust forces and force direction of a physical act, we found that the CNS is able to adjust B&C processes that drive the physical act. From this adjustment capability, we further inferred that the CNS must also store information on the baseline B&C processes. As a whole, we found that the CNS can maintain information on baseline B&C processes, up-regulate or down-regulate the processes, and make comparisons in performing its regulatory functions. We found that chronic diseases are the results of deviated baseline B&C processes. Per the proved hypothesis, the CNS maintains deviated baseline B&C processes, and thus protects the body states of fully developed diseases. We then used the three CNS roles to explain that cancer progresses with increasing malignancy, cancer quickly returns after a surgery, cancer cells repopulate after chemotherapy and radiotherapy, cancer develops drug resistance inevitably, immune cells rebound after suppression, generally poor benefits of cancer drugs such as beta-blockers, etc. We further showed that long-term exercises generally push most, if not all, baseline B&C processes in diametrical opposing directions against the diseased B&C processes, implying that exercises play unique roles in reversing chronic diseases. Finally, we proposed several strategical approaches to resetting the CNS’ state memory as the essential condition for curing chronic diseases.

The production of particles outside the region of nucleon-nucleon kinematics due to interactions involving dense cold clusters of quark-gluon matter in nuclei is calculated. The possibility of observing this process in the region of central rapidities and large transverse momenta in heavy ion collisions at low energies with MPD detector at the NICA collider has been demonstrated.

Loess provides a valuable terrestrial record of past environmental conditions, including the dynamics of air mass circulation responsible for dust transport. Here we explore variations in the luminescence characteristics of sedimentary quartz and feldspar – dominant minerals in loess-palaeosol sequences (LPS) - as possible tools for identifying changes in source. We investigate luminescence sensitivity, a rapidly measurable index which is the product of interplay between source lithology and the history of the mineral in question. Variations in sensitivity down profile may therefore reflect, among other factors such as pedogenesis and reworking, changes in sediment provenance. We undertake an empirical investigation of the luminescence sensitivity of quartz and feldspar from different grain-size fractions from the climatically sensitive Schwalbenberg LPS in the German Rhine valley, comparing samples from a 30 m core spanning the last full glacial cycle with samples of oxygen isotope stage (OIS) 3-2 age exposed within a c. 6 m profile downslope. The temporal overlap enables comparison of luminescence characteristics with respect to possible provenance change during that timeframe. We find an overall inverse relationship between quartz and feldspar sensitivity, as well as variability in sensitivity between different quartz grain sizes. There is some indication that feldspar sensitivity increases during periods of soil formation down the core. In particular, measurements of IR50 sensitivity on unprocessed sediments show correlation with down-profile trends in more established indicators of provenance. This suggests it may be used to provide a reliable, rapid scan of sensitivity changes, and may suggest source variability over millennial timescales.

Malware detection is a crucial pillar of cybersecurity and aims to identify and neutralize malware threats. This study investigates how three deep learning algorithms - Convolutional Neural Net-works with One-Dimensional Architecture (CNN1D), Neural Networks (NN), and a hybrid model of one dimensional convolutional neural networks (CNN1D) and Long Short-Term Memory (LSTM) - help detect malware in Portable Executable working (.exe) files. Using a large dataset of tagged malware and benign samples, the effectiveness of these algorithms in distinguishing dangerous from harmless executables is extensively tested. In addition, the study evaluates the computational efficiency of the proposed methods for a variety of hardware configurations, including Central Processing Units (CPU), Graphics Processing Units (GPU), Raspberry Pi (IoT device), and Tensor Processing Units (TPU). Performance metrics provide insight into the scalability and effectiveness of the model across different hardware configurations. The results of this study have significant impact on the development of malware detection, particularly in the context of IoT security. By demonstrating the capabilities and limitations of CNN1D, Neural Networks, and CNN1D with LSTM models, the study provides practitioners with efficient and scalable solutions to real-world malware detection difficulties. In addition, insights from performance tests on various hardware platforms provide important assistance in developing robust security measures in IoT contexts, strengthening cybersecurity defenses in an ever-changing digital landscape.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Glial cells provide physical and chemical support and protection for neurons. Secreted neurotrophic factors, scaffolds and vesicles regulate in addition to normal homeostasis, repair following neural tissue injury or degeneration. We previously demonstrated that human CNS glia have revascularization capacity by inducing endothelial cell sprouting and microchanneling driven by glial cell secreted components. The clinical potential of using secreted factors and vesicles generated by glial cells in conditioned media was shown by their re-normalization of pathological blood vessels and 3D tissue wound healing and remodeling capacity. To identify secreted components of glial cells and how CNS and PNS glial cells differentially regulate neural tissue homeostasis, disease and injury response, we developed a novel culture method for various types of glial cells that allow for isolating and characterizing secreted glial components, free of animal factors and contaminants normally associated with serum-based culture conditions. Our culture method will enable to identify secreted components using ultrasensitive RNA, glycoconjugate and protein analysis technologies. The characterization of glial secreted factors involved microchanneling may help in development of new clinical therapies for glial and neural cells or axons to migrate and reform connections.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

Zebrafish have been found to be the premier model organism in biological and biomedical research, specifically offering many advantages in developmental biology and genetics. This unique aquatic species has been found to have the capacity to regenerate their spinal cord after injury. However, the complete molecular and cellular mechanisms behind glial bridge formation in the central and peripheral nervous systems upon glial cell injury remains unclear. This review paper focuses on the molecular mechanisms and cellular processes that underlie spinal cord regeneration in four initial phases: proliferation and initial migration; migration and differentiation; glial bridge formation; and remodeling. We propose that within these four phases the cellular mechanisms that underlie spinal cord regeneration each express a terminating signal that aborts one step of the process and initiates the next. Specifically, future studies would be devoted to investigate transmitting signals in the spinal cord injury micro-environment in hope to contribute to the understanding of underlying cellular mechanisms by connecting each process of spinal cord regeneration in zebrafish.