HybridAC/DC microgrids(HMG) are emerging as an attracting method for integrating the AC/DC distributed energy resources(DERs) with the features of high-performance and low-cost. In the isolated hybrid AC/DC microgrid (IHMG), the key problem is how to balance the power variation and regulate the voltage and frequency. Various energy storage systems (ESS)and interlinking converter (IC) technologies are viable for this application. The present study proposes a novel unified power flow model to evaluate and compare the abilities of the ESS with different connection topologies and ICs with different control approaches to maintain the voltage and frequency stability of the IHMG. In order to investigate the performance of the proposed scheme, five operation modes of the IHMG are defined and explained. The classification is based on the connection topologies and control modes of the ESS/IC in the IHMG. Then, a set of generic PF equations are derived. Moreover, three binary matrices are applied in the construction of the unified power equations. These matrices are used for describing the running state of the IHMG. Finally, in order to verify the proposed scheme, it is applied to several case studies of the IHMG. The operation characteristics of multi-DC subgrids IHMG in different modes, particularly when an external disturbance occurs, are investigated.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

School Feeding Programmes are social safety net interventions providing educational and health benefits to vulnerable children in developing countries. This study assessed the impact of Osun Elementary School Feeding and Health Programme (O-MEALS) on the enrolment and retention of rural primary schools in Osun State. Multi stage sampling technique was used to select 188 respondents while data was collected through interview schedule. Percentages, Chi-square, PPMC and T-test were used for data analysis. Findings revealed that over half (51.6%) of the respondents were male, aged 9.38 ± 1.84 years and majority (83.0%) had a family size of 6-10 people. Food incentives (=1.25), health challenge (=0.69), and peer influence (=0.67) were major factors affecting school attendance. More than half (53.2%) of the respondents had unfavourable perception towards the school feeding programme. Results showed a significant difference between pupils’ enrolment (t = 5.332, p = 0.006) and retention rate (t = 58.386, p = 0.000) before and after the commencement of O-MEALS. Furthermore, pupils’ enrolment and retention (r = 0.993, p = 0.001) after the commencement of O-MEALS was significantly related. Food incentive was a major factor affecting school attendance, which fostered an improvement in the poor enrolment and retention previously experienced. Since a good number of the pupils possessed unfavourably perception towards the school feeding programme, it was recommended that effective monitoring be established to checkmate food vendors’ activities in delivering quality and satisfactory services. Likewise, the Government’s policies on school restructuring and levy, which had proved counterproductive, should be reviewed.

Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signalling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signalling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1β (IL-1β) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC, significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1β in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB) and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn, attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signalling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.

Riverine particulates dominate the transport of vital nutrients like Si, Fe or P to the ocean mar-gins, where they may increase primary production by acting as slow release fertilizer. Further-more, the supply of particulate surface area to the ocean is considered to be a major control or-ganic carbon burial. Taken together, these observations suggest a close link between the supply of riverine particulate material and the organic carbon cycle. To explore this link, we conducted microcosm experiments to measure the growth of the marine diatom Thalassiosira weissflogii in the presence and absence of different types and concentrations of riverine particulate material. Results demonstrate a strong positive effect of riverine particulate material on diatom growth with increased total diatom concentrations and slowed post-exponential death rates with in-creasing particulate concentration. Moreover, SEM and optical microscope investigations con-firm that riverine particulates facilitates organic carbon burial through their role in the aggrega-tion and sedimentation of phytoplankton. The supply of riverine particulate material has been shown to be markedly climate sensitive with their fluxes increasing dramatically with increas-ing global temperature and runoff. This pronounced climate sensitivity implies that riverine particulates contribute substantially in regulating atmospheric CO2 concentrations through their role in the organic carbon cycle.

Background: During the COVID-19 pandemic some family physicians were overburdened and experienced difficulties reaching vulnerable patients and meeting the increased need for psycho-social support. This randomized controlled trial (RCT) tested whether a primary healthcare (PHC) based community health worker (CHW) intervention could tackle psychosocial suffering due to physical distancing measures in patients with limited social networks. Methods: CHWs provided 8 weeks of tailored psychosocial support to the intervention group. Control group patients received ‘care as usual’. The impact on feelings of emotional support, social isolation, social participation, anxiety and fear of COVID-19 were measured longitudinally using a face-to-face survey to determine their mean change from baseline. Self-rated change in psychosocial health at 8 weeks was determined. Results: We failed to find a significant effect of the intervention on the prespecified psychosocial health measures. However, the intervention did lead to significant improvement in self-rated change in psychosocial health. Conclusions: This study confirms partially the existing evidence on the effectiveness of CHW in-terventions as a strategy to address mental health in PHC in a COVID context. Further research is needed to elaborate the implementation of CHWs in PHC to reach vulnerable populations during and after health crises.

In zebrafish inner ear, hair cell orientation in anterior and posterior maculae of the embryonic otic vesicle is different (about 30–40 degrees): this is rather unusual in planar polarity mechanism of action, instead suggests that kinocilia may be rotationally polarized. In mice node, the innermost monociliated cells generate a left-ward fluid flow sensed by the immotile primary cilia of Left peri-nodal cells: the Nodal signaling pathway is then expressed asymmetrically, in the Left lateral plate mesoderm, breaking symmetry in visceral organs (situs solitus); however, Right peri-nodal cells also, if artificially excited by a right-ward flow, break symmetry and activate the Nodal cascade, though inverting visceral organ asymmetry (situs inversus); surprisingly, peri-nodal cells prove to be adept at distinguishing flow directionality. Recently, in the Kupffer vesicle (the zebrafish laterality organ), chiral primary cilia orientation has been described: primary cilia, in the left and right side, are symmetrically oriented, showing a mirror average divergence of about 15–20 degrees from the midline. This finding, taken together with the mirror behavior of mouse perinodal cells and zebrafish hair cells, champions the idea of primary cilia enantiomerism.

To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open-angle glaucoma (POAG) patients. This was a multicenter, retrospective study and included POAG patients with or without visually-significant cataracts. The primary outcome was intraocular pressure (IOP) reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2-years. Success was defined as: 1) IOP < 21 mmHg and at least 20% IOP reduction from baseline after 3 months at any two consecutive visits, and 2) no additional glaucoma surgery required. A total of 42 patients were enrolled; thirteen had a history of failed glaucoma surgery. Twelve patients underwent Trabectome surgery combined with phacoemulsification while the remainder underwent Trabectome surgery alone. Overall, the mean preoperative IOP was 21.4±1.23 mmHg. The Trabectome lowered IOP to 18.5± 0.94 mmHg at 2 years (P<0.05). The number of glaucoma medications also decreased from a baseline of 2.0±0.9 to 1.2± 0.21 at 2 years (P=0.04). The overall success was 78%, with patients undergoing combined surgery having a higher success than those with Trabectome surgery alone (100% vs. 76%). No major complications were seen. The Trabectome appears to be an efficient and safe procedure in Chinese POAG patients in the long-term.

People from Black and Asian backgrounds are more likely to die from Covid-19 but less likely to be vaccinated, threatening to exacerbate health inequalities already experienced by ethnic minority groups. Literature suggests that mistrust rooted in structural inequality may be a key barrier to Covid-19 vaccine uptake. We need to better understand how structural inequalities influence vaccine confidence. Understanding and addressing these processes is likely to lead to longer-term impacts than information alone. We draw on health and sociological theories of structure and agency to inform our understanding of structural factors. We conducted qualitative interviews and focus groups with 22 people from London and surrounding areas in December 2021 to March 2022. Fifteen participants were members of the public from ethnic minority backgrounds and 7 were professionals working with the public to address concerns and encourage vaccine uptake. Our findings suggest that people from ethnic minority backgrounds make decisions regarding Covid-19 vaccination based on a combination of how they experience external social structures (including political authority, social positioning and racial inequality) and internal processes (what they believe and understand about Covid-19 vaccines). We may be able to support knowledge accumulation through the provision of reliable and accessible information, particularly through primary and community care. But we recommend a number of changes to research, policy and practice which address structural inequalities. These include working with communities to improve ethnicity data collection, increasing funding allocation to health conditions where ethnic minority communities experience poorer outcomes, greater transparency and public engagement in the vaccine development process, and culturally adapted research recruitment processes.

The term “conservation,” as it relates to biodiversity in a Western context, has a storied past and as conservation science and societal values have evolved, consensus over its precise meaning has remained elusive. The broad scope of contemporary definitions hampers effective communication during a period of environmental crisis and is troublesome for any derivative concept which aims to empirically quantify the efforts of the conservation sector. This presents an avoidable hindrance to the systematic planning of the conservation field. To help remedy this situation, we provide an outcome separation framework that is based on the expected degree of separation between an action’s proximate outcome, from its intended, ultimate outcome for a habitat and/or species. Framing a definition of conservation through this lens of outcome separation allows for conservation-related actions to be clearly categorized into one of three discrete tiers: primary, secondary, and tertiary. A distillation of this tiered framework also provides a new definition of biodiversity conservation that is more rigorous and adaptable to future conceptual evolutions of the field.

Primary care pediatricians encounter a wide range of complex conditions in their daily clinical practice. It is not uncommon for their patients to get exposed to medical errors. Diagnostic errors, defined as missed, delayed, or wrong diagnosis, are of great importance as they may cause significant harm to the pediatric patient with severe disease. These errors often occur when the symptoms and signs of a disease are atypical or missing. Data on the most frequent misdiagnosed situations in pediatrics is scarce. One of these groups of conditions is that regarding cardiac diseases. The pediatric cardiology field has met rapid development over the past few decades. Primary care providers play a key role in diagnosis, management, and referral of children with heart disease, both congenital and acquired, because many common cardiac complaints are first addressed in the primary care setting. The scope of this review is to investigate the cardiac entities that are often missed by the general pediatricians. In particular, it aims to spot the most common of them, to describe their clinical presentation, their diagnostic options, red flags, and tips, and to provide the ways to avoid erroneous, delayed, or missed diagnosis.

More than 13.5 billion COVID-19 vaccine doses have so far been delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the most likely scenario of continued circulation of SARS-CoV-2 and the need for periodic booster doses, there was a need for countries to plan for more sustainable approaches to provide COVID-19 vaccination. In this context of uncertainty, a global tool for integrating COVID-19 vaccines into immunization programmes and primary health care was published jointly by WHO and UNICEF to respond to country needs. The guidance leveraged existing health system frameworks, proposed four steps for the COVID-19 integration journey, and identified investment areas. The development process maximized robust global stakeholder and country engagement, and the timeframe was aligned with donor funding windows to support the integration of COVID-19 vaccination. The rapid dissemination of guidance allowed its use by countries to ascertain their readiness for integrating COVID-19 vaccination and inform the development of national plans and funding applications. While progress has been made in specific areas (e.g., optimizing cold chain and logistics leveraging COVID-19 vaccination), in the context of decreasing demand for COVID-19 vaccines, reaching adult COVID-19 vaccine high-priority-use groups and engaging and coordinating with other health programmes (beyond immunization) remains a challenge. We share the learning that despite the uncertainties of a pandemic, guidance documents can be developed and used within a short timeframe. Working in partnership with stakeholders beyond immunization towards a common objective is powerful and can allow progress to be made on integrating health services and preparing better for future pandemics.

This paper utilizes a life cycle assessment to evaluate the energy resources and environmental impacts of three heating systems. In the first step, life cycle assessments (LCAs) are prepared for the renewable, conventional, and combined systems. The system boundary of the LCA method is "cradle to gate," which means it includes the entire life cycle of a product or process. This includes energy supply, transport, energy generation, and operational energy use. The system scenarios were compared based on ecological and energy loads in the second step. Primary energy, resources, emissions, and environmental potentials are calculated for the system scenarios using the life cycle assessment methods CML 2016 and ReCiPe 2016. Finally, models for environmental reliability and complex decision-support tools have been developed. This work addresses two main questions: how to characterize the environmental and energy impacts of the systems under study, and what is the optimal scenario for the system? The research results show that the gas boiler system has a greater environmental impact. The most significant differences between the systems relate to the degrada-tion of abiotic fossil fuels when using a gas boiler and the process of acidification when using an electric heat pump. The results can be used to develop sustainable heating systems with reduced environmental impacts and enhanced energy efficiency.

This study, which was supported by a quantitative research paradigm with two experiment and two control groups of 4x4 quasi-experimental design, aimed to find out the impact of a sustainable progressive STEAM (SP-STEAM Model) application model on 5th grade primary school students critical thinking dispositions and mathematic achievements in Northern Cyprus. The treatment model was applied to experimental groups for 14 weeks of time. Split-plot multiple group analysis of variance (Split-plot ANOVA) statistical technique was used to calculate between and within group significances regarding exogenous variable. SPSS24 software package was used for the analysis. Pre-test and post-test results derived from experiment and control groups revealed significant effect of SP-STEAM Model on 5th grade primary school students’ critical thinking dispositions as measured with CCTDI and mathematic achievements as measured with a dedicated ex-am. The results were discussed in detail under the light of related literature and suggestions for further studies were proposed.

COVID-19 pandemic-related pressures on primary care may have driven inappropriate continuation of antibiotic prescriptions. Yet prescribing modality (repeat/non-repeat) has not previously been investigated in a pandemic context. Using the OpenSAFELY-TPP analytics platform, we analysed repeat/non-repeat prescribing frequency in monthly patient cohorts between Jan 2020–2022. In-depth analysis was conducted on Jan 2020 (“pre-pandemic”) and Jan 2021 (“pandemic”) cohorts. Per-patient prescribing and clinical conditions were determined by searching primary care record data using clinical code lists. Repeat prescribing was defined as >=3 prescriptions in a 6 month lookback period. Associations between demographics (e.g. age, sex, geography) and repeat/non-repeat prescribing were explored using unadjusted risk ratios. Antibiotic prescribing declined from May 2020; non-repeat prescribing declined more strongly than repeat prescribing (maximum declines -26% vs -11%, respectively). In the pandemic cohort, older patients were at higher risk of prescribing (especially repeat prescribing). The most common clinical conditions for repeat prescribing were COPD comorbidity and urinary tract infection. Comorbidities were more common among repeat vs non-repeat prescribed patients. In the pandemic cohort, vs pre-pandemic, repeat and non-repeat prescribing for comorbidities generally declined less compared with shorter-term conditions (infections, including COPD exacerbation/lower respiratory tract infection). Our findings inform ongoing development of stewardship interventions in England..

Background: Media coverage of Lyme disease (LD) has led to an increase in consultations for presumed LD in Europe. However, LD is confirmed in only 10-20% of patients, with a significant number remaining in a diagnostic dead-end. Objectives: To reach a deeper understanding of how patients themselves contribute to the diagnostic process. To describe the genesis of the LD hypothesis in care pathways. Methods: In 2019, 30 patients from a prospective cohort consulting in the infectious diseases department at University Hospital in Marseille for presumed LD were recruited for semi-structured interviews. The inclusion criteria were : suffering from subjective symptoms for 6 months, no clinical or paraclinical argument suggesting current LD. The patients’ medical trajectories were collected using a biographical approach. Results: The diagnosis of Lyme disease was primarily triggered by identification with personal testimonies found on the internet. Most of patients were leading their own diagnostic investigation. The majority of participants were convinced they had LD despite the lack of medical evidence and the scepticism of their referring GP. Conclusion: GPs should first systematically explore patients’ etiologic representations in order to improve adherence to the diagnosis especially in the management of medically unexplained symptoms. Long COVID-19 syndrome challenge offers an opportunity to promote active patient involvement in diagnosis.

This article propose a didactic, through games, tool based on information and communication technologies, in order to eliminate possible communication barriers and to promote the inclusion of students with hearing impairment in Physical Education classes. To this end, a dossier of traditional games has been developed. These are structured in turn into objectives, materials, organisation, graphic description and a QR code for each game. These codes are linked to different videos hosted on the YouTube platform, in which the explanation of the games, mentioned above, can be visualised graphically using sign language. The whole creative process is described in the article, as well as possible pedagogical applications of the use of the tools created for this purpose in other educational contexts.

The primary cilium plays a pivotal role during embryonic development of vertebrates. It acts as a somatic signaling hub for specific pathways, such as sonic hedgehog signaling. In humans, mutations in genes that cause dysregulation of ciliogenesis or ciliary function lead to severe developmental disorders called ciliopathies. Beyond its obvious role in early morphogenesis, growing evidence points towards an essential function of the primary cilium in neural circuit formation in the central nervous system. However, very little is known about a potential role in the formation of the peripheral nervous system. Here, we investigated the presence of the primary cilium in neural crest cells and their derivatives in the trunk of the developing chicken embryo in vivo. We found that neural crest cells, sensory neurons, and boundary cap cells all bear a primary cilium during key stages of early peripheral nervous system formation. Moreover, we described differences in the ciliation of neuronal cultures of different populations from the peripheral and central nervous system. Our results offer a framework for further in vivo and in vitro investigations on specific roles that the primary cilium might play during peripheral nervous system formation.

Kaposi’s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the first in vivo model for a virally-induced lymphoma in zebrafish, whereby KSHV-infected PEL tumour cells engraft and proliferate in the yolk sac of zebrafish larvae. Using a PEL cell line engineered to produce the viral lytic switch protein RTA in the presence of doxycycline, we demonstrate drug-inducible reactivation from KSHV latency in vivo, which enabled real-time observation and evaluation of latent and lytic phases of KSHV infection. In addition, we developed a sensitive droplet digital PCR method to monitor latent and lytic viral gene expression and host cell gene expression in xenografts. The zebrafish yolk sac is not well-vascularized and using fluorogenic assays we confirmed that this site provides a hypoxic environment that may mimic the microenvironment of some human tumors. We found that PEL cell proliferation in xenografts was dependent on the host hypoxia-dependent translation initiation factor, eukaryotic initiation factor 4E2 (eIF4E2). This demonstrates that the zebrafish yolk sac is a functionally hypoxic environment and xenografted cells must switch to dedicated hypoxic gene expression machinery to survive and proliferate. The establishment of the PEL xenograft model enables future studies that exploit the innate advantages of the zebrafish as a model for genetic and pharmacologic screens.

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics (GLP-1ra and SGLT2-in). Despite new guidelines, clinical inertia, that can be caused by physicians, patients or healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient's overall situation in decision-making. We looked for the possible reasons of clinical inertia and poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiative in diabetes aims to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.

Background. Ovarian cysts are common in premenopausal women but can present with vague, non-specific symptoms, making discovery more challenging. Most are benign and resolve spontaneously; however, they can present, as in this case, as ovarian torsions, which is a gynecological emergency. Case presentation. A twenty-year-old female had presented over 3–4 times per year for the last 6 years to her primary doctor citing intermittent abdominal pain, irregular menstruation, dyspnea, and an enlarging abdomen circumference. The doctor stated, she was “just fat” and could, benefit from a “special camp to lose weight”, so she stopped mentioning her concerns. Upon presenting to the emergency department with acute onset abdominal pain, a computed tomography scan showed a large cyst lesion filling the abdominal and pelvic cavity. Its origin appeared to be from the left adnexa. Surgery was performed, and an acute ovarian torsion caused by a 36 cm craniocaudal left ovarian cyst was found and removed along with the left fallopian tube and 16 L of fluid. Conclusions. The value of respecting the “third presentation” rule indicates to health care providers that any patient who presents with any /or other symptoms or complaint needs to be thoroughly investigated. In this case the patient presented recurring pelvic/abdominal concerns, irregular menstruation, which warranted further investigation to safeguard fertility and prevent errors of omission. It is important to consider the differentials and be aware of vague symptoms that may lead to early recognition and effective management to prevent adverse consequences, complications, or even death.

The annual demand for fibres continues to rise worldwide. Consequently, more and more fibres must be produced to meet this demand, most of which are melt-spun polymeric man-made fibres. [1] Smooth filaments made of polymers are mainly used for technical applications in industry. For use in clothing or home textiles, for example, a texturing process is used to give the filaments a crimp and thus a feel like that of natural fibres. In this state, they can be processed together with natural fibres and used in textiles. Partially oriented yarns (POY) are of great importance in tex-turing. The yarns are mainly crimped with the help of the so-called false-twist texturing process (FTTP). [2] Since POY accounts for about 60 % of the melt-spun filament yarn produced world-wide, the FTTP is the most important texturing process in the textile industry [3]. In this paper, the main components of false-twist texturing (FTT) machines are explained along with the state of the art and research for each component and its influence on the process. Relevant patents are dis-cussed as well as process optimisation techniques, innovative polymers and yarn types recently used in FTT, followed by a conclusion and an outlook for the process.

Background. Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. Methods: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates. Results: Of 8,602 participants at risk at baseline, 3,580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93−0.99), and CRF (95% CI of 0.94−0.98). Each 1-MET increase was associated with a 4% reduced risk. Conclusion: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

Low-cost miniature hyperspectral and thermal cameras onboard lightweight unmanned aerial vehicles (UAV) bring new opportunities for monitoring land surface variables at unprecedented fine spatial resolution with acceptable accuracy. This research applies hyperspectral and thermal imagery from a drone to quantify upland rice growth and water use efficiency (WUE) after biochar application in a Costa Rican dry region. The field flights were conducted over two experimental groups with bamboo biochar and sugarcane biochar amendments and one control group without biochar application. Rice canopy biophysical variables were estimated by inversion of a canopy radiative transfer model on hyperspectral reflectance. Variations in gross primary production (GPP) and WUE across treatments were estimated from the normalized difference vegetation index (NDVI), canopy chlorophyll content (CCC), and evapotranspiration. We found that GPP was increased by 41.9±3.4 % when using bamboo biochar and 17.5±3.4 % when using sugarcane biochar, which was probably due to higher soil moisture in the biochar-amended plots and led to significantly higher WUE by 40.8±3.5 % in bamboo biochar and 13.4±3.5 % in sugarcane biochar. This study demonstrated the use of hyperspectral and thermal imagery from drone to provide indicators for quantifying biochar effects on tropical dry cropland by integrating with ground point samples and physical models.

In this study, we evaluated chlorophyll fluorescence (CF) under two extreme illumination conditions at plant scale with a passive spectroradiometer. Fluorescence (F) was estimated by reading directly from radiance spectra of a variety of plants illuminated with light-emitting diode (LED) grow lights in the laboratory. Solar-induced fluorescence (SIF) was estimated from spectral measurements of the same plants under sunlight using the Fraunhofer Line Depth (FLD) method. Chlorophyll fluorescence yield (F_yield) and solar-induced fluorescence yield (SIF_yield) were calculated by normalizing F and SIF with absorbed photosynthetically active radiation (APAR). Two approaches to estimating APAR were compared: utilizing white reference spectra and reflected spectra versus white reference spectra combined with the fraction of absorbed photosynthetically active radiation (fPAR) derived from literature. Average F and SIF were different by a factor of approximately twenty-four (F = 0.110 ± 0.038 Wm⁻²μm⁻¹sr⁻¹ versus SIF = 2.60 ± 1.87 Wm⁻²μm⁻¹sr⁻¹). In contrast, the average normalized values F_yield and SIF_yield were within the margin of error of one another (F_yield = 0.022 ± 0.008 μm⁻¹sr⁻¹ and SIF_yield = 0.030 ± 0.020 μm⁻¹sr⁻¹). This study highlights the influence of APAR on CF and the importance of properly accounting for it when estimating yield and demonstrates the ability of two simple and portable experimental setups with a passive instrument to obtain fluorescence metrics.

Cerebral cavernous malformations (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene (CCM1/Krit1, CCM2, CCM3) and its origin (spontaneous or familial), different types of this dis-ease can be found. In this work we have isolated and cultivated primary endothelial cells (ECs) from peripheral blood of a type 1 CCM patient. Differential functional and gene expression pro-file of these cells were analyzed and compared to primary ECs from a healthy donor. The muta-tion of the familial index case consisted of a heterozygous point mutation in the position +1 splicing consensus between exons 15 and 16, causing failure in RNA processing and in the final protein. Furthermore, gene expression analysis by quantitative PCR revealed a decreased ex-pression of genes involved in intercellular junction formation, angiogenesis, and vascular ho-meostasis. Cell biology analysis showed that CCM1 ECs were impaired in angiogenesis and cell migration. Taken together, the results obtained suggest that the alterations found in CCM1 ECs are already present in the heterozygous condition, suffering from vascular impairment and someway predisposed to vascular damage.

One of the most common subgroups of cutaneous T-cell lymphomas is the that of primary cutaneous CD30 positive lymphoproliferative disorders. The group includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), as well as some borderline cases. Recently, significant progress has been made in understanding the genetics and treatment of these disorders. This review article summarizes the clinical evidence supporting the current treatment options in these diseases. Recent years have seen the introduction of novel agents into clinical practice; most of these target CD30, such as anti-CD30 monoclonal antibodies and conjugated antibodies (brentuximab vedotin), bispecific antibodies and cellular therapies, particularly anti-CD30 CAR-T cells. This paper briefly reviews the biology of CD30 that makes it a good therapeutic target, and describes the anti-CD30 therapies that have emerged to date.

Migraine is a primary headache disorder characterized by unilateral throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This review article discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.

This cross-country four-year longitudinal study investigated the development of processing speed throughout primary school education. The analyses were conducted on data collected from 441 schoolchildren in Grades 1, 2, 3 and 4 (aged 6.42 to 11.85 years) in the Kyrgyzstan and Russia. Mixed effects growth modeling was applied to estimate average and individual growth trajectories for processing speed at two cross-country samples. Latent class growth modeling was conducted to identify different types of growth trajectories for processing speed and to compare the distribution of the types within the analyzed samples. According to the results, processing speed significantly increases across primary school years. The trajectory is characterized by nonlinear changes with more intensive growth between Grades 1 and 2, which later slows down until Grade 4. There were no significant cross-country differences in the initial score of processing speed or developmental changes in processing speed across primary school years. The development of processing speed is described by a model with three quadratic growth types but minimally differs. It is concluded that in both samples, the development of processing speed may be characterized by homogeneity, with the most intensive growth from Grade 1 to Grade 2 and subsequent linear improvement until Grade 4.

This study aimed to evaluate whether primary school classroom teachers reported changes in physical education teaching self-efficacy (SE-PE) and work engagement (WE) during the first COVID-19 wave. Six-hundred-twenty-two classroom teachers filled in an online questionnaire on SE-PE and WE, referring to before and during the lockdown, and on perceived digital competence. While controlling for perceived digital competence, a mixed between-within Repeated Measures Multivariate Analysis of Covariance (RM-MANCOVA) was performed, with a two-time (before vs. during the lockdown) and three age-categories (≤40 vs. 41-50 vs. ≥51 years) factorial design. The RM-MANCOVA revealed that perceived digital competence significantly adjusted teachers’ SE-PE and WE values (p&lt;0.001). The analysis yielded a significant multivariate main effect by time (p&lt; 0.001) and by time × age-categories (p=0.001). Follow-up univariate ANCOVA showed significant differences by time in teachers’ SE-PE (p&lt;0.001) and WE (p &lt; 0.001), with a reduction of both values from before to during the lockdown. A Bonferroni post hoc pairwise comparisons showed teachers’ SE-PE significantly decreased in all age categories (p&lt;0.001). The present findings confirm the importance of promoting SE-PE among primary school teachers, regardless of the crisis due to the COVID-19 pandemic. Teachers’ self-efficacy and WE are essential to master the challenges of PE teaching.

Anterior-tooth (ANT) contacts induce short latency reflex inhibition of human jaw-closing muscles. The jaw is a rigid class 1 lever for pinpoint-targeting muscle force into a single bite-point, the pivoting food particle. See-saw reflex movements around the food particle fulcrum multiply the food-crushing force. Unpredictable jolts of reaction force caused by food-crushing are subjected to the rostral ANT and caudally to the two articulate ends of the jaw triangle. Compression/distraction strains of food-crushing must be monitored and inhibited by withdrawal reflexes. The mesencephalic ganglion (Vmes), neural myelin sheath, and muscle stretch receptors evolved subsequently to the advent of jaws to improve the velocity of proprioceptive and withdrawal reflexes. In mammalians, the spindles of the taut motor units, stretched by the food-fulcrum send excitatory monosynaptic feedback for the efferent neurons of the respective ipsilateral muscle units, via Vmes. In the Vmes, the spindle-input-mediating afferent neurons are coupled with another source of afferent feedback, which is also excitatory, from the back-tooth (BAT) mechanoreceptors. The two sources of excitatory pulses are summated and targeted for the efferent neurons to boost the stretched and taut motor units. Likewise, the afferent feedback from ANT mechanoreceptors is also coupled in the Vmes with concomitant feedback from spindles. The ANT output, however, is inhibitory to negate the excitatory feedback from the stretched jaw-muscle units. The inhibitory feed from ANT temporarily blocks the excitatory potential of masticatory motor efferent neurons to protect the ANT and jaw-joints from inadvertent strains. The inhibitory inputs from ANT alternate with the excitatory inputs from BAT to determine which jaw-closing muscle units are activated or inhibited at any given instant of food-crushing. The Vmes exists in all jawed vertebrates, and its’ evolution was probably motivated by demands for the control of bite force. The monosynaptic unilateral food-crushing excitatory and inhibitory reflexes (UFCR) override the coexisting bilaterally executed feed for jaw muscles from the central nervous system. Hypothesis: The Vmes-mediated UFCR combine neural inputs from tooth contacts with concomitant feedback from muscle stretch receptors for the control of mammalian food-crushing bite force.

The streptavidin and biotin interaction is one of the strongest non-covalent interactions in nature. As a result, this non-covalent interaction has been of great interest when it comes to biochemical assays, diagnosis of diseases, and cell-targeted drug delivery. Past research has proven that biotin-streptavidin is useful in biosensor development to improve the detection of a system when conjugated to nanoparticles. This study aims to prove that streptavidin-coated nanoparticles can be conjugated with biotinylated antibodies using the primary-secondary method to non-invasively detect adenocarcinoma in-vitro. While the use of nanoparticles is not uncommon to the diagnostics area of scientific research, the technique this research aims to investigate is a non-invasive one, utilizing the primary-secondary method. Specifically, the increased stability of fluorophores when bound to antibodies as opposed to nanoparticles directly can be indicative of the particles conjugated through the primary-secondary method’s ability to specifically bind to overexpressed transferrin receptors in the A549 cell line. In this paper, streptavidin-coated nanoparticles were conjugated with biotinylated anti-transferrin receptor antibodies and AlexaFluor-488 secondary antibodies were used to enable fluorescence-based detection. The efficiency of these particles were observed quantitatively through a plate reader and qualitatively through a fluorescence microscope. I demonstrated that these nanoparticles are able to specifically bind to the target proteins in this study. These findings contribute to the field of nanoparticle diagnostics and can be extended to different diseases caused by overexpression of proteins in the future. While this was conducted in-vitro, conjugates can be prepared to detect cancer in-vivo and can be tested with magnetic relaxometry in the future.

This paper presents a method of fusion of identification (attribute) information provided by two types of sensors: combined primary and secondary (IFF) surveillance radars and ESM (Electronic Support Measures). In the first section, the basic taxonomy of attribute identification is adopted in accordance with the standards of STANAG 1241 ed. 5 and STANAG 1241 ed. 6 (draft). These standards provide the following basic values of the attribute identifications: FRIEND, HOSTILE, NEUTRAL, UNKNOWN and additional values: ASSUMED FRIEND and SUSPECT. The basis of theoretical considerations is Dezert-Smarandache theory (DSmT) of inference. The paper presents and practically uses for combining identification information from different ESM sensors and radars six information fusion rules proposed by DSmT - the Proportional Conflict Redistribution rules (PCR1, PCR2, PCR3, PCR4, PCR5 and PCR6). In the paper, rules of determining attribute information by ESM sensor equipped with the data base of radar emitters are presented. It was proposed that each signal vector sent by the ESM sensor contained an extension specifying a randomized identification declaration (hypothesis) - basic belief assignment (BBA). The paper also presents a model for determining the basic belief assignment for a combined primary and secondary radar. Results of the PCR rules of sensor information combining for different scenarios of radio-electronic situation (deterministic and Monte Carlo) are presented in the final part of the paper. They confirm the legitimacy of the use of Dezert-Smarandache theory into information fusion for primary radars, secondary radars and ESM sensors.

Our skin epidermis constitutes the most important innate defense barrier against all pathogens. Therefore, even if skin lesions are common due to infections, scarring, genetic disorders, and other diseases, skin integrity is crucial for maintaining body homeostasis. Marine collagen peptides (MCPs) and Glycosaminoglycans (GAGs) have been described as potential wound healing (WH) agents. Recently, through an ex vivo clinical approach, we have demonstrated the nutricosmetic potential of fish cartilage hydrolysate (FCH), which presents a combination of collagen peptides and GAGs. Here, we coupled a clinical approach with in vitro experiments on human dermal fibroblasts (HDFs) and applied a Data Independent Acquisition - Parallel Accumulation Serial Fragmentation (diaPASEF) proteomic analysis, to assess the potential benefit of FCH in WH and its mode of action. Our results show that human serum enriched with circulating metabolites resulting from FCH ingestion, improved wound closure in scratch assays. In support, some proteins with anti-inflammatory and immunomodulatory properties or prone to promote hydration and extracellular matrix (ECM) stability showed increased expression in HDFs, after exposure to FCH-enriched serum. These findings suggest that FCH appears as a promising nutrient for WH and skin regeneration.

The theory of heterogeneous nucleation was initially developed as a part of condensed matter physics and later it was used as an important engineering tool to design metallurgical processes. The success leads to wide applications of the theory in metallurgical practice. For example, engineering heterogeneous nucleation in ductile iron has been used to reduce shrinkage defects, suppress cementite formation, and modify size and shape of micro-structural constituencies. This demonstrates how theoretical knowledge could benefit industry practice. This overview aims to summarize the authors’ published studies in co-authorship with colleagues and students, which covered different aspects of engineering heterogeneous nucleation in multiphase cast alloys. Several approaches for engineering heterogeneous nucleation using thermodynamic simulation and practical methods for improving efficiency of nucleation using co-precipitation technique and a local transient melt supersaturation were suggested. Automated Scanning Electron Microscopy Energy-Dispersive-X-ray (SEM/EDX) analysis and a high-resolution Transmission Electron Microscopy (TEM) were used to verify simulation predictions. Practical examples of controlling micro-porosity shrinkage in cast irons with spheroidal graphite are presented to illustrate the power of engineering heterogenous nucleation. The authors appreciate the great efforts that the co-authors have made on the original, overviewed articles here.

Drug functionalization through formation of hydrophilic groups is the norm in phase I metabolism of drugs for modification of drug action. The reactions involved are mainly oxidative catalyzed mostly by CYP isoenzymes. The benzene ring, as phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e. the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e. the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retaining, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues have been presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design and drug development.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous hu-mour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side ef-fects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGF affects both the structural and functional changes in the outflow pathway and IOP is required to de-velop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study we evaluated the effects of TGF-1 and -2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are pre-sented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in net-works to control cellular pathways and processes, a pathway-centric view of miRNA ac-tion is also reported. Evaluating TGF-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Alkyl moieties—open chain or cyclic—are common in drug molecules and can be internal or terminal. The open-chain alkyls can be linear or branched; the cyclic alkyls may be substituted. Usually, the branches in open-chain alkyls and substituents in cycloalkyls influence both the pharmacokinetics and pharmacodynamics of a drug molecule. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some parent-drug equiactive hydroxy metabolites have been developed into metabolite ester prodrugs, while some of the parent-drug carboxy metabolites have been developed into metabolite drugs. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. Some subtexts found to manifest from the hydroxy and carboxy functionalization of alkyl moieties in drug molecules are presented and discussed. The review provides basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules; and (ii) whether the resulting metabolites will possess pharmacologic activity or be devoid of it.

Cisplatin (CDDP) is a platinum-based drug effective against various cancers, including lung, bladder, prostate, ovarian, esophageal, stomach, and cervical cancer and malignant lymphoma. It plays a central role as the first choice in current anticancer therapy. However, CDDP causes serious side effects, such as neurological disorders, myelosuppression, and renal damage, because it is a small molecule indiscriminately distributed in normal tissues. Therefore, it is very important to prevent or attenuate CDDP toxicity. We hypothesized that liposomalization of CDDP could alleviate serious side effects. Therefore, this study aimed to evaluate the safety and efficacy of CDDP liposomes. A patient with multiple recurrent liver metastases from metastatic nasal carcinoma was administered CDDP liposomes with consent. Magnetic resonance imaging showed that the patient remained stable-diseased; however, no apparent side effects were observed, and blood draw data showed no worsening of renal function. Patients undergoing partial pancreatectomy and jejunoileal biliary anastomosis for biliary tract cancer who consented to receive CDDP liposomes demonstrated a partial response on angiographic computed tomography; however, they showed slight fatigue. To our knowledge, the present study is the first in Japan to suggest that liposomalization of CDDP may have anticancer effects while alleviating renal damage and bone marrow suppression.

To date, the patent foramen ovale (PFO) does not get the deserved medical attention. The PFO poses a serious threat to health and even life of mankind. The first respective case report in the medical literature dates back to the 19th century. It led to death. The fact that a PFO is present in roughly 25% of people underscores its overall potential to do harm. Yet at the same time by the sheer number, it discourages the medical community from screening for it and from treating it. About 5% of the population have particularly dangerous forms of PFOs. Such PFOs portray a high enough risk for clinical events, the likes of death, stroke, myocardial infarction, or ocular, visceral, and peripheral embolism, to justify screening for them. Highly significant health incidents being at stake, it appears obvious that PFO closure should be used for primary prevention. This is supported by the fact that closing a PFO is the simplest intervention in cardiology, with presumably the highest clinical yield. Being mainly a preventive measure, PFO closure represents a mechanical vaccination. When closing PFOs for one of the rarer therapeutic indications (migraine, platypnea orthodeoxia, etc.), patients automatically profit from the collateral benefit of getting at the same time mechanically vaccinated for life against paradoxical embolism. Vice versa, closing a PFO for prevention of paradoxical embolism not infrequently betters or cures migraine or exercise dyspnea, thereby improving quality of life as a collateral benefit.

Despite being a rare disease worldwide, rabies has the highest morbidity and mortality rates, with nearly all symptomatic cases leading to coma and death. Rabies represents an infectious disease caused by the Rabies virus (RABV), which is part of the Lyssavirus group and the Rhabdoviridae family, and it mainly spreads through the bite and scratch of an infected mammal, but particularly of wild animals, such as bats, foxes, wolves and racoons, and of domestic animals, such as dogs and cats, in rabies-prone areas of the world. Airborne transmission has been deemed as extremely rare, and no clinical case as such has been recorded worldwide yet, except in the enclosed environment, such as research laboratories and caves where infected bats are present. Domestic mammals, such as dogs and ferrets, represent other important reservoirs of disease transmission, and the human cases of Asia and Africa amount approximately 95% of all human cases worldwide. Infected animals most commonly start transmitting the virus once the first symptoms have occurred, and if they experience disease aggravation and death within 10 days, a case of rabies is registered, more easily if the incidence occurred in the urban area and then, any person or animal that had been potentially exposed are strongly recommended to receive the inoculation. It is rare for asymptomatic mammals to transmit the illness. Most First-World and several Second-World countries have recently been declared dog rabies-free by the World Health Organization. The disease can only be treated prophylactically, with three doses of a vaccine containing an inactivated form of RABV, or with five doses of the vaccine and two doses of anti-RABV immunoglobulins within 28 days if the patient is believed to have been exposed to the virus beforehand. It has been projected that, once the viral load reaches elements of the central nervous system, prophylactic approaches are no longer effective, even if symptoms have not begun yet, and this highlights the urgent trait of the medical condition, strongly recommending exposed people to receive the prophylactic doses immediately after the potential exposure to the virus. The pathogen first infects the bodily fluids, before reaching the peripheral nervous system, from where it will gradually move toward the spinal cord or the encephalon, at a speed of movement ranging from 1 to 40 cm per day. It was also found, in extremely rare circumstances, to infect the nasopharyngeal cavity and the lungs. The primary cause of a successful, gradual advance of the viral load toward the point of clinical no-return for the patient - the CNS - is a complex mechanism of induced innate immune evasion, with the interferon system being heavily targeted and silenced by RABV proteins. The ‘Milwaukee’ protocol is locally believed to decrease the mortality rate of the clinical illness to approximately 80%, although significantly more research is required in this sense. First-line immune evasion represents the central mechanism developed by viruses during their evolutionary process to gain control over human immunity, so it could be the development and adjustment of a counter-offensive to this evolutionary operating system that could address the core elements of the problem. Human recombinant Type I and Type III Interferons were found to be significant vaccine adjuvants and to considerably delay the clinical onset of the disease. Despite their central role in natural immunity-based prophylaxis, vaccine support and, in often cases, vaccination per se, a local administration of IFNs as such may not be enough to tackle the core problem of the endemic disease, and a specific and systemic treatment of potential host cells with IFN I and III, as well as IFN-stimulating proteins, may constitute a major research requirement in the coming years of disease investigation, as the inoculation efforts with the inactivated virus and immunoglobulin administration continue. The administration of a relatively low dosage of somatic Natural Killer cells, gamma-interferon and perhaps, of somatic helper CD4+ and somatic cytotoxic CD8+ T-lymphocytes treated with alpha-, beta- and lambda-interferon could be merged with the administration of a similar dosage of alpha-, beta- and lambda-interferon during the efforts to develop an effective and less costly prophylactic vaccine against rabies. A combination of a nasal substance containing a low dosage of IFN I and III with a reduced concentration of neutralized RABV copies, and/or with a low dose of anti-RABV IgA antibodies, could also be tested for humans for the purposes of pre- and post-exposure prophylaxis.

The concept of gray-zone lymphoma (GZL) has been progressively refined since its in-troduction in the literature in 1998. For several years, it was applied to a rather broad spectrum of conditions, posing the problem of the differential diagnosis between any type of Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma, with special reference to primary mediasti-nal forms (PMBL). Officially recognized as a provisional entity in the 4th and revised 4th editions of the WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues with the term “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lym-phoma and classical Hodgkin lymphoma”, it was limited to tumours, which showed either morphologic features reminiscent of classical HL (CHL) but carrying a complete B-cell pheno-type or conversely provided with a PMBL morphology but revealing CHL phenotypic charac-teristics. The definition of GZL has been further revised in the recently published International Lymphoma Classification and 5th Edition of the WHO Classification of Haemato-lymphoid Tu-mours, which have limited it to mediastinal neoplasms based on emerging molecular evidences. The aim of this review is to critically discuss the issue of GZL, also in the light of the suboptimal response to current therapies.

Measures in the SARS-CoV-2 pandemic were based on rough ideas regarding transmission routes of pathogens. Quantified models of physical transmission routes are mostly lacking, a gap to be filled. Vaccines and medicines, important, are not studied here. We first survey main routes, from primary production in the alveoli and intestines to emissions, environmental routes, to exposure and alveolar infection. Next, specific routes are modelled, mostly at a preliminary state, open to systematic improvement. Starting from a standardized emitter, modelling results show extreme differences in potential exposure, in a range covering up to 4 orders of magnitude. The outcomes are pathogen-specific, already different between SARS-CoV-2 and influenza. Extreme exposures may result in smaller spaces; with lower ventilation rates; with a high density of emitting persons per m3; who stay there for several hours; and visitors staying more than a few minutes. In spaces where a build-up of concentrations is low, exposures are low, lowest in open air situations. A main conclusion for the next pandemic is that a quantified model can give strong guidance on where measures are primarily due. For SARS-CoV-2, ventilation can be improved short-term. Longer-term, effective ventilation rules and adaptation of buildings may reduce high exposures substantially.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.