Glioblastoma (GBM) is the most common and aggressive adult brain cancer with an average survival rate of around 15 months in patients receiving standard treatment. Oncolytic adenovirus expressing therapeutic transgenes represent a promising alternative treatment for GBM. Of the many human adenoviral serotypes described to date, adenovirus 5 (Ad5) has been most utilized clinically and experimentally. However, the use of Ad5 as an anti-cancer agent may be hampered by naturally high seroprevalence rates to Ad5 coupled with infection of healthy cells via native receptors. To explore whether alternative natural adenoviral tropisms are better suited to GBM therapeutics, we pseudotyped an Ad5 based platform with the fiber knob protein from alternative serotypes. We demonstrate that the adenoviral entry receptors coxsackie and adenovirus receptor (CAR) and CD46 are highly expressed by both GBM and healthy brain tissue, whereas Desmoglein 2 (DSG2) is expressed at low level in GBM. We demonstrate that adenoviral pseudotypes, engaging CAR, CD46 and DSG2, effectively transduce GBM cells. However, the presence of these receptors on non-transformed cells presents the possibility of off-target effects and therapeutic transgene expression in healthy cells. To enhance specificity of transgene expression to GBM, we assessed the potential for tumour specific promoters hTERT and survivin to drive reporter gene expression selectively in GBM cell lines. We demonstrate tightly GBM specific transgene expression using these constructs, indicating that the combination of pseudotyping and tumour specific promoters approaches may enable the development of efficacious therapies better suited to GBM.

Sports traumatic brain injury (TBI) accounts for up to 20% of all sports injuries, and the number of cases is growing year by year due to an increase in the number of people involved in sports, the growing popularity of extreme and contact sports, as well as a high level of motivation to achieve record results. Mild TBI dominates, which can provoke the development of a very wide range of complications and negative consequences. In the programs for the prevention of complications and the rehabilitation of athletes after TBI, TBI features are not sufficiently considered, which significantly differ from household, road or criminal injuries. There are no instrumental methods for diagnosing the severity of the injury. Sports TBI is characterized by repeated frequent TBI, elevated body and brain temperature, peripheral redistribution of blood flow and hypocapnia, which significantly affect cerebral blood flow. Brain injury is an independent cause of the development of cerebral hyperthermia, which significantly worsens the consequences of TBI. To diagnose sports TBI, the method of microwave radiometry of the brain (MWR) can be used. For the prevention of complications, the technology of craniocerebral hypothermia (CCH), which allows for to reduce of physical general and cerebral hyperthermia, and increases the resistance of cerebral cortex neurons to hypoxia and trauma could be used However, these approaches in sports medicine are used sporadically, which, is due to the lack of awareness of coaches and doctors of sports teams. The purpose of the review is to present MWR and CCH in sports TBI.

Background: Cognitive-behavioral alterations can occur after an acquired brain injury. It is a stressful situa-tion for patient and relatives. Objectives: To develop and evaluate a synchronous online training program on emotional intelligence (EI) for caregivers of adult patients with cognitive-behavioral impairment due to acquired brain injury. Methods: A quasi-experimental study was designed, a target population of ten caregivers attended to a one-month virtual synchronous course about EI. The emotional status of caregivers was registered one-month-previous and one-month-post program using comparative measures: The Trait Meta-Mood Scale (TMMS-24) and the Positive and Negative Affect Schedule (PANAS). Results: Median age of the ten caregivers was 48 years, 80% of women with a median care-time of 6 years. 50% of them were spouses of the patients. 60% of the patients were affected by stroke (hemorrhagic or ischemic cause). The main cognitive impairment of the patients reported by relatives was memory deficit. After re-ceiving training, favorable changes were found regarding emotional affect measured with the PANAS, both positive (increase) and negative (decrease), as well as with the TMMS-24-mood-repair area (p < 0.05). Conclusions: Training in EI helps caregivers to make their mood more positive and improve aspects of their emotional intelligence such as emotional regulation.

Background. Traumatic brain injury (TBI) is the main cause of disabilities over the industrialized countries. Cognitive decline appears in the chronic phase of the pathology consecutively to cellular and molecular processes. Here we described the use of KCC2, a neuronal-specific potassium-chloride transporters as potent biomarker to predict cognitive dysfunctions after TBI. Methods. Using neuronal and total exosomes collection from blood serum in control and TBI subjects we were able to anticipate the decline of cognitive performance. Results. After TBI, we observed a significative and persistant loss of KCC2 expression in the blood exosomes that is correlated to changes in network activity and cellular processes such as secondary neurogenesis. Also we correlated this KCC2 loss in expression to the appearance of the cognitive decline observed in mice and more particularly we correlate the KCC2 loss of expression to the appearance of the depressive-like behavior. Conclusion. According to our protocol, we were able to confirm our previous findings in agreement with the potential therapeutic effect of bumetanide in the prevention of the post traumatic depression after TBI, by restoring the KCC2 expression thus preventing the massive neuronal death of interneurons and the secondary neurogenesis effect observed in such model.

Scientific theories on the functioning and dysfunction of the human brain require a good understanding of both its development — before and after birth, and through maturation to adulthood — and its evolution from the ancestral primate brain. Adopting a complex-systems approach, here we propose that the apparent uniqueness of humans’ cognitive capacities might best be understood as emerging from multiple nested “virtuous cycles.” In particular, we propose that the intimate link that exists between oxygen metabolic loops, cortical expansion, and ultimately cognitive and social demands is a key driver of genetic developmental programs for the human brain. Overall, our proposed evolutionary model makes explicit mechanistic links between metabolism, molecular and cellular brain heterogeneity, and behaviour that may in time provide a clearer understanding of brain developmental trajectories and their disorders.

Fluorescence microscopy provides an unparalleled tool for imaging biological samples. However, producing high-quality volumetric images quickly and without excessive complexity remains a challenge. Here, we demonstrate a simple multi-camera structured illumination microscope (SIM) capable of simultaneously imaging multiple focal planes, allowing for the capture of 3D fluorescent images without any axial movement of the sample. This simple setup allows for the acquisition of many different 3D imaging modes, including 3D time lapses, high-axial-resolution 3D images, and large 3D mosaics.

Brain tumors are neoplasms with one of the highest mortality rates. Therefore, the availability of methods that allow the quick and effective diagnosis of brain tumors and selection of appropriate treatments is of critical importance for patient outcomes. In this study, coated blade spray-mass spectrometry (CBS-MS), which combines the features of microextraction and fast ionization methods, is applied for the analysis of brain tumors. In this approach, a sword-shaped probe is coated with a sorptive material to enable the extraction of analytes from biological samples. The analytes are then desorbed using only a few microliters of solvent, followed by the insertion of the CBS device into the interface on the mass spectrometer source. The results of this proof-of-concept experiment confirmed that CBS coupled to high-resolution mass spectrometry (HRMS) enables the rapid differentiation of two histologically different lesions: meningiomas and gliomas. Moreover, quantitative CBS-HRMS/MS analysis of carnitine, the endogenous compound, previously identified as discriminating metabolite showed good reproducibility with the variation below 10% when using a standard addition calibration strategy and deuterated internal standards for correction. The resultant data show that the proposed CBS-MS technique can be useful for on-site qualitative and quantitative assessments of brain tumor metabolite profiles.

In the current pilot study, we attempt to find out how double neurofeedback influences functional hemispheric asymmetry and activity. We examined 30 healthy participants (8 males; 22 females, mean age = 29; SD= 8). To measure functional hemispheric asymmetry and activity, we used computer laterometry in the ‘two-source’ lead-lag dichotic paradigm. Double biofeedback included 8 minutes of EEG oscillation recording with five minutes of basic mode. During the basic mode, the current amplitude of the EEG oscillator gets transformed into feedback sounds while the current amplitude of alpha EEG oscillator is used to modulate the intensity of light signals. Double neurofeedback did not directly influence the asymmetry itself but accelerated individual sound perception characteristics during dichotic listening in the preceding effect paradigm. Further research is needed to investigate the effect of double neurofeedback training on functional brain activity and asymmetry taking into account participants’ age, gender, and motivation.

Parenting has been robustly associated with offspring psychosocial development, and these effects are likely reflected in brain development. However, the claim that parenting influences offspring brain development in humans, as measured by structural and functional Magnetic Resonance Imaging (MRI), is subject to numerous methodological limitations. To interpret the state of the parenting and brain development literature, we review these limitations. Four limitations are common. First, most literature has been cross-sectional. Where longitudinal, studies rarely included multiple assessments of brain structure or function, precluding measurement of actual brain development. Second, parenting has largely been measured via selfor parent-report, as opposed to observational assessment. Third, there has been a focus on extreme forms of developmental adversity which do not necessarily lie on a continuum with normative parenting. Fourth, although not a limitation per se, studies have generally focused on negative as opposed to positive parenting behaviours. While not all studies are subject to all these limitations, the study of parenting in relation to offspring brain development is in its infancy.

Geometry deals both with analogical thinking and physical/biological observables. Naïve, common-sense descriptions of objects’ shapes and systems’ trajectories in geometric phase spaces may help experimental investigation. For example, very different biological dynamics, as the developmental growth patterns of the oldest known animal (the extinct Dickinsonia) and the human brain electric oscillations, display a striking analogy: when encompassed in abstract geometric spaces, their paths describe the same changes in curvature: from convex, to flat, to concave and vice versa. This dynamical behavior, anticipated by Nicholas de Cusa in his analogical account of “coincidentia oppositorum” (1440), helps to describe widespread biological paths in the manageable terms of concave, flat and convex curves on donut-like structures. Every trajectory taking place on such toroidal manifolds can be located, through a topological technique called Hopf fibration, into a four-dimensional space. We discuss how the correlation between Hopf fibration and Navier-Stokes equations allows us to treat the above-mentioned biological and neuroscientific curved paths in terms of flows taking place into a viscous fluid medium that can be experimentally assessed and quantified.

The French-Swiss Professor in inductive philosophy Richard Avenarius (1843-1896), the father of empirio-criticism together with Ernst Mach, is one of the most underrated and misunderstood philosophers ever. It mostly depends upon his terminology, which displays an insurmountable difficulty. However, influenced by the most innovative proposals of his times of transition between the idealistic/rationalist legacies and the new Materialism/scientific interpretation of reality – i.e, by cultural evolutionism, linguistics, biomechanics, entropy/energy and, above all, by the newborn experimental psychology-, he produced a complete system of philosophy and innovative methods of investigation of the laws of knowledge. Hints (chunk, scrap, fragments) of his original ideas can be found not only in philosophers of mind after him - such as Gestalt, phenomenalism, behaviourism, functionalism and cybernetics, autopoiesis, dynamical systems theory, embedded/embodied mind, free-energy principle of the brain – but also in recent neuroscientific theories – nervous transduction, electric spikes, cracking of neural code, multisensory integration -. Our aim is to provide the first chronological English summary of his masterpiece, the “Kritik”, to give the possibility to the (almost) totally unaware English speakers to appreciate such a neglected and innovative thinker.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

A growing area in neurosciences is focused on the modeling and analysis the complex system of connections in neural systems, i.e. the connectome. Here we focus on the representation of connectomes by using graph theory formalisms. The human brain connectomes are usually derived from neuroimages; the analyzed brains are co-registered in the image domain and brought to a common anatomical space. An atlas is then applied in order to define anatomically meaningful regions that will serve as the nodes of the network - this process is referred to as parcellation. Recently, it has been proposed to perform atlas-free random brain parcellation into nodes and align brains in the network space instead of the anatomical image space to define network nodes of individual brain networks. In the network domain, the question of comparison of the structure of networks arises. Such question is tackled by modeling the comparison of brain network as a network alignment (NA) problem. In this paper, we first defined the NA problem formally, then we applied three existing state of the art of multiple alignment algorithms (MNA) on diffusion MRI-derived brain networks and we compared the performances. The results confirm that MNA algorithms may be applied in cases of atlas-free parcellation for a fully network-driven comparison of connectomes.

Deep Learning (DL) has made significant advances in computer vision with the advent of Vision Transformers (ViT). Unlike Convolutional Neural Networks (CNNs), ViTs use self-attention to extract both local and global features from image data, and then use residual connections to feed these features directly into a fully networked multilayer perceptron head. In hospitals, hematologists prepare peripheral blood smears (PBSs) and read them under a medical microscope to detect abnormalities in blood counts such as leukemia. However, this task is time-consuming and prone to human error. This study investigates the transfer learning process of Google ViT and ImageNet CNNs to automate the reading of PBSs. The study used two online PBS datasets, PBC and BCCD, and transferred them into balanced datasets to investigate the influence of data amount and noise immunity on both neural networks. The PBC results show that Google ViT is an excellent DL neural solution for data scarcity. The BCCD results show that Google ViT is superior to ImageNet CNNs in dealing with unclean, noisy image data because it is able to extract both global and local features and use residual connections, despite the additional time and computational overhead.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Background: The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assesses circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. Aim: Evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes. Identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities related to social determinants of health (SDoH). Design: IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon. Survival analyses utilized Kaplan–Meier curves. Setting/Participants: Single-institution study involving patients receiving whole-brain radiotherapy. Collected demographic, disease, and socioeconomic parameters from electronic medical records. Results: Morning treatment (n=158) showed a trend towards improved overall survival vs. afternoon (n=79), median survival 158 vs. 79 days (p=0.20, HR=0.84, CI95% 0.84–0.91). Subgroup benefits for morning treatment in females (p=0.04) and trends in controlled primary disease (p=0.11) and breast cancer metastases (p=0.08). SDoH-based disparities observed, with Black and lower-income patients exhibiting diminished circadian influence. Conclusions: Emphasizes chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlates with improved survival, particularly in specific subgroups. Identifies potential circadian influence disparities based on SDoH, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

This study compared growth performance, serum biochemical indicators, rumen fermentation parameters, rumen bacterial structure, and fecal bacterial structure of cattle and yaks, fed for two months, given a feed containing concentrate to roughage ratio of 7: 3 on dry matter basis. Compared with cattle, yak showed better growth performance. The serum biochemical results showed that the albumin: globulin ratio in yaks serum was significantly higher than that in cattle. Aspartate aminotransferase, indirect bilirubin, creatine kinase, lactate dehydrogenase and total cholesterol were significantly lower in yaks than that in cattle. Rumen pH, acetate to propionate ratio, and acetate were lower in yaks than in cattle while the lactate in yaks was higher than in cattle. There were significant differences in the structure of ruminal as well as fecal bacteria between cattle and yaks. The prediction of rumen bacterial function showed that there was metabolic difference between cattle and yaks. In general, the metabolic pathway of cattle was mainly riched in de novo synthesis of nucleotides, while that of yaks was mainly riched in the metabolic utilization of nutrients. This study provides a basis for understanding the rumen ecology under the condition of high concentrate diet.

Consumption of high amounts of ethanol is a risk factor for development of cardiovascular diseases such as arterial hypertension. The hypertensive state induced by ethanol is a complex multi-factorial event, and oxidative stress is a pathophysiological hallmark of vascular dysfunction associated with ethanol consumption. Increasing levels of reactive oxygen species (ROS) in the vasculature triggers important processes underlying vascular injury, including accumulation of intracellular Ca2+ ions, reduced bioavailability of nitric oxide (NO), activation of mitogen-activated protein kinases (MAPKs), endothelial dysfunction, and loss of the anticontractile effect of perivascular adipose tissue (PVAT). The enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a central role in vascular ROS generation in response to ethanol. Activation of the renin-angiotensin-aldosterone system (RAAS) is an upstream mechanism which contributes to NADPH oxidase stimulation, overproduction of ROS and vascular dysfunction. This review discusses the mechanisms of vascular dysfunction induced by ethanol, detailing the contribution of ROS to these processes. Data examining the association between neuroendocrine changes and vascular oxidative stress induced by ethanol are also reviewed and discussed. These issues are of paramount interest to public health as ethanol contributes to blood pressure elevation in the general population, and it is linked to cardiovascular conditions and diseases.

To learn what mothers know on newborn bloodspot screening (NBS), the procedure, and sources used, a pilot study was performed. An online questionnaire was developed, with a first part fo-cused on characteristics and the NBS procedure, a second on knowledge, information sources, and health care providers (HCP). This questionnaire was accessible until 200 answers were received. Characteristics of respondents were representative for the population. Mothers recalled verbal consent in 69.5%, 12.5% did not, 18% stated that no consent was requested. The ‘knowledge’ part contained 12 closed questions, 5 multiple-choice questions on sources, and assessment (5-point Likert) of the information transfer. The mean knowledge level was 7.2/12. Screening concepts (consequences, likelihood, sensitivity, carrier) and absence of notification of normal findings were well known. The fact that NBS is not compulsory and post-analysis sample handling were poorly known. Key HCPs were midwifes (80.5%) and nurses (38.5%). When the leaflet (44%) was pro-vided, the majority read it. Mean Likert scores were 3.36, 3.38, 3.11 and 3.35 (clarity, timing ap-propriateness, sufficiency, usefulness). The knowledge level and consent practices were reasonable well. Key HCP were midwives and nurses, leaflets were supporting. This should enable a quality improvement program to a sustainable NBS program in Flanders.

Background: Scaffold (SCA) functionalization with aptamers (APT) provides adsorption of specific bioactive molecules on biomaterials surface. The aim of this study was to observe if SCA enriched with anti-fibronectin APT can favor coagulum (PhC) and osteoblasts (OSB) differentiation. Methods: 20 ug of APT was functionalized on SCA by simple adsorption. For PhC formation, SCAs were inserted into rat calvaria defects for 17 hours. Following proper transportation (Buffer solution-PB), OSB (UMR-106 lineage) were seeded over PhC + SCAs with and without APT. Cells and PhC morphology, PhC cell population, protein labelling and gene expression were observed in different time points. Results: The APT induced higher ALP and BSP immunolabeling in OSB. CD90, CD45 and CD44 expression was more detected in APT group than when scaffolds were not functionalized. Additionally, an enriched and dense fibrin network and different cell types were observed, with more OSB and white blood cells in PhC formed on SCA with APT. The gene expression showed higher TGF-β1 detection in SCA with APT. Conclusions: The SCA functionalization with fibronectin aptamers provides a selective expression of proteins related to coagulation pattern and osteo differentiation. Additionally, aptamers increase TGF-β1 gene expression, which is highly associated with improvements in regenerative therapies.

Background and Aim. Recently made analysis for anti-HBcor prevalence within Kazakhstan blood donors population concluded 17.2% rate. Considering these data are among the highest of infectivity results worldwide, an objective of this study was to define an association of positive Hepatitis B serology markers with risk and behavior factors. Methods. The blood donors’ samples were tested for anti-HBcore total (IgG/IgM) and anti-HBs, by CLIA on the Architect i2000SR platform (Abbott). Surrogate alanine transferase (ALT) markers for all blood donors were tested by kinetic method on the Biosystems A25 analyzer. A questionnaire was developed for socio-demographic characteristics, donors’ nutrition habits, cholesterol levels and history of smoking, alcohol consumption. Informed consent was obtained from all study participants. Statistics was calculated using the R software program (version 4.1.1, USA, 2021). Results. A group of 5709 blood donors participated in the study. Participants with positive anti-HBcore scores were on average older (41.8 vs 34.4 years, p<0.001), Kazakh (88.7% vs 83.0%, p<0.001), married (74.0% vs 55.6%, p<0.001), had a secondary education (70.1% vs. 59.4%, p=0.03), smoked (27.9% vs. 24.3%, p=0.05), had a longer smoking history (13.6±9.5 years vs. 9.8±8.5 years, p<0.001), and various hypercholestesterolaemia (6.2% vs 3.9%, p=0.02). Predominantly their main meal was dinner (17.0% vs 14.2%, p=0.03). Analysis for associations of socio-demographics characteristics, risk factors, nutrition with anti-HBs, showed that those who have secondary education level (70.1%) were more likely to be anti-HBs-positive (p=0.03). No other significant correlations for anti-HBs were observed. Conclusions. The risk factors and behavior analysis highlighted the blood donors’ overall health status. Positive Hepatitis B markers associated with statistically significant characteristics from socio-demography, nutrition habits or risk factors could support further pathogenesis studies looking for HBV treatment guides fulfilling the existing gaps.

Aquaculture is growing rapidly as a food-producing sector and in recent years, fishmeal prices have climbed by more than twofold on a global scale. This review of previous studies was performed to contribute to the extant literature on the aquaculture sector to aid cost reduction of aquafeeds by identifying substitute protein that can replace fishmeal. The review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) using the SCOPUS and WOS (Web of Science), DOAJ (Directory of Open Access Journals), Academia, and Pubmed Central databases with the following search terms: “fishmeal,” “alternative protein source” and “aquafeeds.” This resulted in 5,331 articles from the SCOPUS and WOS databases. Finally, the titles and abstracts of the articles were screened, giving a total of 162 articles that were used in the study; another 58 articles came from open databases. Results have shown that 100% replacement of fishmeal with blood meal did not affect the growth of fish as well as 75% to 100% combination of poultry-by-product (PBM), feather meal (FEM), and blood meal (BM). Moreover, a 10% replacement of fishmeal using seaweed (Gracilaria arcuata) has no adverse effect on feed efficiency and growth performance of tilapia, a 50% replacement of fishmeal using black soldier fly (Hermetia illucens), and 25% replacement using soybean (Glycine max) also showed better results for fish growth. With that, this review shows that alternative protein can be a great alternative to the aquaculture sector in reducing the cost of aquafeeds since alternative proteins are much cheaper than the usual fishmeal.

Cryptococcosis is a leading cause of death among people with HIV in sub-Saharan Africa. Limited diagnostic and therapeutic options significantly impair treatment options in Africa. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective cohort at 1) Adama Hospital Medical College and 2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult HIV-infected patients presenting with suspected sepsis and assessed 28-day survival. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years and 61% being female. Overall, 11(13%) had positive CrAg tests, of which 5 had Cryptococcus detected in blood cultures. Despite high-dose fluconazole (1200mg/d) monotherapy in patients with positive CrAg tests, the 28-day mortality was 64%(7/11), being significantly higher than in CrAg-negative patients (9%(6/71); p&lt;0.001). Cryptococcosis is the leading cause of mortality among HIV-infected sepsis patients. CrAg screening in HIV-infected patients attending emergency department can minimize the cryptococcosis missing case irrespective of CD4 count and viral load. These findings warrant the need of a bundle approach for diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

Many assets of clinical medicine, such as clinical chemistry and diagnostic imaging, make clinical diagnosis outstanding compared to postmortem diagnosis. An assessment of functional status certainly has priority over the postmortem, cross-sectional use of diagnostic tests and laboratory equipment. In addition, the cost of these tools is sometimes steep, and their use does not always fit into a reasonable cost–benefit ratio. However, sometimes postmortem observations, such as inflammation, pulmonary edema, or infiltration and cerebral swelling, cannot be explained without implementing immunohistochemical markers for postmortem diagnosis. Introducing blood-based biomarkers in postmortem care could significantly reduce the rates of inconclusive postmortems and discrepancies in autopsy findings and clinical diagnoses. This is particularly relevant in the scope of vascular pathology, considering the great burden of vascular diseases in overall mortality. Expanding traditional autopsy with blood-based (circulating) biomarkers to avoid invasive postmortem examination would have cultural, religious, and potential economic advantages. All of the target molecules are discussed in the context of the process they up-regulate or down-regulate and which turns out to be the final cause of death. Ultimately, it is evident that further studies are needed to provide concrete validation for a combination of markers on a specific case order to reach a postmortem diagnosis with or without clinical records.

Blood flow-restricted training (BFR) is constantly growing in popularity. Despite growing evidence of the significant influence of BFR training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of exercise without restriction of blood flow or other active intervention, influences arterial functions and angiogenesis in adults. Studies comparing the effect of BFR versus non-BFR training on arterial parameters are divided into three categories. Endothelial function, angiogenesis, and other vasculature functions. The search was based on three databases (Cochrane Library, PubMed®, Embase). In this systematic review, 38 studies were included. Meta-analysis revealed a more significant improvement in flow-mediated dilatation (FMD) (p=0.002) and the production of the primary angiogenesis biomarker Vascular Endothelial Growth Factor (VEGF) (p=0.009) after training in BFR compared to nonBFR (p=0.002). Analysis of pulse wave velocity, ankle-brachial index, systolic blood pressure, or heart rate did not show a significant difference in changes between BFR and non-BFR training. Other parameters examined were not sufficiently provided to be included in the meta-analysis. The results obtained, present trends suggesting the significant impact of BFR training on endothelial functions and angiogenesis. Unfortunately, there is still a lack of multicenter randomized clinical trials, including many participants, that are necessary to confirm the advantage of BFR over non-BFR activity.

A novel physiologically based algorithm (PBA) for fast CFD computation of Flow Fractional Reserve (FFR) in Coronary Artery Trees (CATs) is proposed and developed, which, unlike traditional methods, is based on the extension of the Murray’s law for blood vessels at the outlets and extra inlet conditions prescribed alternatively and iteratively. The PBA is then implemented in both SimVascular and Ansys CFD for testing and validation. For validation purpose, 3D models of CATs are built by using their CT images and computational meshes generated for mesh convergence study. Results obtained are then compared with Invasive Coronary Angiographic (ICA) data for validation and evaluation of its accuracy and computational efficiency. It is found that discrepancies between experimental and calculated values of pressure and flow rate at the inlet were less than 0.1% at the end of the 10^th round of iteration or less. Further validation shows that the difference between estimated and experimental FFR agree with each other with a maximum difference of 1.62% after convergence is achieved. The PBA is found to be a robust patient-specific and physiologically sound method that can be a good alternative to the existing Lumped Parameter Model (LPM) which is based on empirical scaling correlations using limited population-averaged data and requires nonlinear iterative computation for convergence.

Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data is for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. It is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, and response to hypoxia via HIF1A targets (↑in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.

After the first weeks of vaccination against the SARS-CoV-2, several cases of acute thrombosis were reported. These news reports began to be shared frequently across social media platforms. The aim of this study was to conduct an analysis of Twitter data related to the overall discussion. Data was retrieved from 14th March to 14th April using the keyword ‘blood clots’. A dataset with n=266,677 tweets was retrieved, and a systematic random sample of 5% of tweets (n=13,334) were entered into NodeXL for further analysis. Social network analysis was used to analyse the data by drawing upon the Clauset-Newman-Moore algorithm. Influential users were identified by drawing upon the betweenness centrality metric. Text analysis was applied to identify the key hashtags and websites used at this time. More than half of the network was comprised of retweets and the largest groups within the network were broadcast clusters where a number of key users were retweeted. The most popular narratives were around highlighting the low risk of obtaining a blood clot from a vaccine and highlighting higher blood clot risks in medicines commonly consumed. A wide-variety of actors drove the discussion on Twitter ranging from writers, physicians, the general public academics, celebrities, and journalists. Twitter was used to highlight the low potential of obtaining a blood clot from a vaccine and encouraged vaccinations among the public.

(1) Background: We reviewed the logistics of the implementation of pathogen inactivation (PI) using the INTERCEPT Blood System™ for platelets and the experience with routine use and clinical outcomes in the patient population at the Sírio-Libanês Hospital of São Paulo, Brazil. (2) Methods: Platelet concentrate (PC), including pathogen reduced (PR-PC) production, inventory management, discard rates, blood utilization, and clinical outcomes were analyzed over the 40 months before and after PI implementation. Age distribution and wastage rates were compared over the 10 months before and after approval for PR-PC to be stored for up to 7 days. (3) Results: A 100% PR-PC inventory was achieved by increasing double apheresis collections and production of double doses using pools of two single apheresis units. Discard rates decreased from 6% to 3% after PI implementation and further decreased to 1.2% after 7-day storage extension for PR-PCs. The blood utilization remained stable, with no increase in component utilization. A significant decrease in adverse transfusion events was observed after the PI implementation. (4) Conclusion: Our experience demonstrates the feasibility for Brazilian blood centers to achieve a 100% PR-PC inventory. All patients at our hospital received PR-PC and showed no increase in blood component utilization and decreased rates of adverse transfusion reactions.

The aim of the work was to update the distribution range of Aedes (Stegomyia) albopictus Skuse in the Americas, review the blood feeding patterns and compare the minimum infection rate (MIR) between studies of vertical and horizontal transmission of arboviruses. The current distribution of Ae. albopictus encompasses 21 countries in the Americas. In eleven published papers on the blood feeding pattern of Ae. albopictus, DNA from 16 species of mammals and five species of avian species was found. The most common host is humans, and dogs. We found 24 published papers on the identification of arboviruses in wild populations of Ae. albopictus with the potential to infect humans and animals. Eight arboviruses have been isolated in different studies carried out in Brazil, USA, Mexico, Colombia, and Costa Rica. Fifty-eight percent (14/24) of the publications reported vertical transmission of arbovirus. Positive pools were higher in vertical (8.45%) compared to horizontal transmission (0.97%). This was supported by the MIR, which was 3 times greater in vertical (MIR=3.21) than horizontal transmission (MIR= 1.08). In conclusion, Ae. albopictus is an invasive mosquito with wide phenotypic plasticity to adapt to broad and new areas, high vectorial competence to transmit several arboviruses mainly by transovarial transmission, it can participate in the endemic transmission, and serve as a bridge vector for emerging arboviruses between sylvan, rural, and urban areas.

Pathogens and adulterants in human feeding consumables can be readily identified according to their electrical properties. Electrical bioimpedance analysis (BIA) has been widely used for body contents characterization, such as blood, urine, lactate and sweat. If the blood glucose concentration alters the electrical properties of the blood medium, then the impedance spectrum obtained by BIA can be used to measure glycemia. In some applications, artificial neural networks allows the correlation of these parameters (impedance and glucose concentration) by means of symbolic and statistical rules. According to our literature review, there is any physical model that allows the interpretation of the relationship between blood’s electrical properties, obtained by BIA, and the concentration of glucose in the blood plasma. This article proposes a simplified physical model for blood electrical conductivity as a function of glucose concentration, based on Bruggeman’s effective medium theory. The equations of this model were obtained considering an insulating phase distribution diffused in a conductive matrix, in which red blood cells are represented by macroscopic insulating nuclei and glucose molecules by microscopic insulating particles. The impedance spectrum for different glucose concentrations (4.0 to 6.8 mmol/L) in a blood sample, published by Kamat Bagul (2014), were compared with the proposed model. The results showed a significant correlation with the experimental data, showing a maximum error of 5.2%. The proposed model might be useful in the design of noninvasive blood glucose monitoring systems.

Aedes aegypti is the primary mosquito vector of several human arboviruses including dengue virus (DENV). Vector control is the principal intervention to decrease the transmission of these viruses. The characterization of molecules involved in the mosquito physiological responses to blood-feeding may help to identify novel targets useful in the design of effective control strategies. In this study, we evaluated the in vivo effect of feeding adult female mosquitoes with human blood containing either heat-inactivated (IB), normal serum (NB), and RNA-seq based transcript expression was compared against sugar-fed (SF) mosquitoes. In the in vitro experiments, we treated Aag2 cells with a recombinant version of the complement proteins (hC3 or hC5a) and compared transcript expression to untreated control cells after 24h. The transcript expression analysis revealed that human complement proteins modulate approximately 2,300 transcripts involved in multiple biological functions, including the immune system. We also found 161 up-regulated and 168 down-regulated transcripts differentially expressed when hC3 and hC5a were compared against the control untreated cells. We conclude that active human complement induces significant changes in the transcriptome of Ae. aegypti mosquitoes, which can influence the infective capacity of pathogens ingested during blood meals.

COVID-19 induces coagulopathy at the base of SIC (sepsis-induced coagulopathy) and it is an important cause of death in the patients. Cytokine storm causes imbalance in coagulation and fibrinolytic system. A combination of hypercoagulability state, decrease or inhibition of fibrinolytic and endothelialopathy causes thromboembolic events. Underlined disease with a high rate of mortality in COVID-19 like diabetes, hypertension and some conditions like aging and obesity are the main disorders with hemostatic disturbance and increase of coagulopathy. Therefore, it seems that the combination of COVID-19 infection and these risk factors increase the risk of thromboembolic all together.

Ixodes scapularis is the major vector of Lyme disease in the eastern United States. Each active life stage (larva, nymph, and adult) takes a blood meal either for developing and molting to the next stage (larvae and nymphs) or for oviposition (adult females). This protein-rich blood meal is the only food taken by Ixodes ticks and therefore blood digestion is very important for tick survival. Most studies on blood digestion in ticks have shown that the initial stages of digestion are carried out by cathepsin proteases within acidic digestive cells. However, most of these studies have focused on partially engorged ticks. In other hematophagous arthropods, the serine proteases play an important role in blood protein degradation. In this study, we determined transcript expression of four I. scapularis serine proteases with previously characterized roles in blood digestion. RNA interference was used for functional analysis and a trypsin-benzoyl-D, L-arginine 4-nitoanilide assay was used to measure active trypsin levels. An in vitro hemoglobinolytic assay was performed with or without serine protease inhibitor. Our data suggest that trypsin levels increase significantly after blood feeding and peaked in larvae, nymphs, and adults at 3, 1, and 1 day post host detachment, respectively. The knockdown of three previously identified serine proteases by RNAi negatively impacted blood intake, survival, fecundity, levels of active trypsin in the gut and resulted in lower hemoglobin degradation in vitro. A trypsin inhibitor, PMSF, blocked the action of trypsin in the gut extract resulting in 65% lower hemoglobin degradation. We provide evidence of the serine proteases as digestive enzymes in fully engorged, replete females. Our data also demonstrated that in addition to blood digestion, these serine proteases might have a role in blood feeding success in I. scapularis.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Different alcoholic beverages can have different effects on blood alcohol concentrations (BAC) and neurotoxicity even if equalized for alcohol content by volume. Anecdotal evidence suggested that natural wine is metabolized differently from conventional wines. This triple-blind study compared the BAC of 55 healthy male subjects after consuming the equivalent of 2 units of alcohol of a natural or conventional wine over 3 mins in two separate sessions one week apart. BAC was measured using a professional breathalyzer every 20 mins after consumption for 2 hrs. The BAC curves in response to the two wines diverged significantly at twenty minutes, at forty minutes and also at their maximum concentrations (peaks), with the natural wine inducing a lower BAC than the conventional wine (T20 0.40 vs. 0.46 [p<0.0002], T40 0.49 vs. 0.53 [p<0.0015], peak 0.52 vs. 0.56 [p<0.0002]). These differences are likely related to the development of different amino acids and antioxidants in the two wines during their production. This in turn may affect the kinetics of alcohol absorption and metabolism. Other contributing factors may also include pesticide residues, differences in dry extract content and the use of indigenous or selected yeasts. Further studies are needed to fully understand why natural wines are metabolized differently from conventional wines.

1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. 2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension undergoing treatment with ACE inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive susbtances, were also quantified before and after the treatment period. 3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. 4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.

This present study was designed to find out whether the acankoreagenin showed the antidiabetic and renoprotective effects in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats. Type I diabetes was induced by a single intraperitoneal injection of STZ (70 mg/kg). At the end of the experiment, rats were euthanized and serum/plasma was separated for the determination of glucose, insulin, glycated hemoglobin A1c (HbA1c), C-peptide, biochemical parameters, and kidney function. One kidney was used for determining glutathione, superoxide dismutas, malondialdehyde, and tumor necrosis factor-alpha levels. The other kidney and pancreas were used for histopathological studies and immunohistochemical measurement of transforming growth factor beta (TGF-β) or NF-κB. Acankoreagenin (2 mg/kg) treatments led to a significant reduction in blood glucose assessed via oral glucose tolerance test (OGTT) in diabetic rats at 2 h. The treatment also resulted in improved body weight, decreased HbA1c, restored lipid profile, and renal oxidative stress. By inhibiting NF-κB, the release of proinflammatory cytokines was suppressed and by inhibiting TGF-β, the renal fibrosis was suppressed in STZ-induced diabetic rat model. Histopathological injury was also observed in pancreatic and renal tissues. These findings support the beneficial effect of acankoreagenin treatment in DN, which could be attributed to its antidiabetic and renoprotective effects.

The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012 Taiwan National Health Insurance Research Database, patients with IDA (case group [n=35,751]) and individuals without IDA (control group [n=178,755]) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to 5 individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p<0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio [HR]=1.74; 95% CI=1.61-1.88) and remained similar after adjustment for covariates (adjusted HR=1.81; 95% CI=1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR=2.21; 95% CI=1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR=1.47; 95% CI=1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis. In contrast to blood transfusion treatment, the use of intravenous ferrum may further increase the risk for future osteoporosis.

Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.

Post-concussion syndrome, recently recognized as a complication of mild traumatic brain injury, is considered a consequence of the summative effect of multiple concussions received over lifetime. In elderlies, the main mild brain trauma mechanism is fall (low impact force). Many falls are often not reported or noticed but may generate serious medical and medico-legal consequences. Our research question was to find if a single, very mild brain trauma can induce neuro-behavioral consequences in elderlies. One database was queried (PubMed – MeSH terminology) looking for histopathological, neuro-cognitive and behavioral changes that can be generated by sub-concussional trauma in senescent rodents, in comparison with young animals. 41 published research articles were selected. 17 of them used very mild brain trauma in young and senescent animals, in the same experiment (6 rats and 11 mice). 24 articles evaluated the effect of sub-threshold brain trauma in adult animals (no control group). Five trauma models were used (blast models were excluded). Neuro-inflammatory changes were detected immediate after very mild primary impact. In young animals, observed pathology disappeared fast (after 3 to 7 days). Increased apoptosis, mild axonal injury in white matter tracts plus maladaptive astrogliosis and microglial activation was stronger in aged animals, persisted over time (8 months) and significantly altered animals’ cognition and behavior. Associated preexisting pathology (hypertension, tau protein deposits, microbleeds, reactive inflammation) was often responsible for amplification of the primary impact results. As translation of observation is the weak spot of pathology and behavior animal research, further investigation is needed before to conclude that even a single, very mild brain trauma may have medical consequences on human senescent brain.

Peptides of hydrolysates of food proteins are an easily digestible source of amino acids necessary for the body to adapt to physical stress. Commercially significant hydrolysates include whey protein, casein, and other animal proteins. Hydrolysates of plant proteins are gaining popularity, but they are less common, then animal ones. Soy protein isolate is promising for obtaining the hydrolysates due to its affordable price and balanced amino acid profile. However, there are no direct studies showing an improvement in the result of physical activity when eating soy protein isolate hydrolysate (SPIH). In this work, for the first time, the study was conducted on the safety and efficacy of SPIH during physical load on model animals (rats). It was shown that the hydrolysate did not lead to pathological changes in the viscera, food intake, and weight of animals did not differ from the control group (animals consumed whey protein). Under physical load rats enteral fed SPIH showed a tendency to adapt more quickly to physical stress than the control group and the group of animals that was fed by free amino acids. The metabolites of animal blood serum were studied by NMR spectroscopy. It was shown that by the 95th minute after feeding in the group of rats receiving SPIH, the difference of proteinogenic amino acids concentrations in blood between individuals was significantly less than in the groups receiving whey protein or a mixture of amino acids. In other words, individual biochemical and physiological characteristics of individuals did not affect the assimilation of amino acids of hydrolysate.

Acute kidney injury (AKI), especially if recurring represents a risk factor for future chronic kidney disease. In intensive care units, increased intraabdominal pressure is well-recognized as a significant contributor of AKI. However, the importance of transiently increased intra-abdominal pressures procedures is less commonly appreciated during laparoscopic surgery, the use of which has rapidly increased over the last few decades. Unlike the well-known autoregulation of the renal cortical circulation, medulla perfusion is modulated via partially independent regulatory mechanisms and strongly impacted by changes in venous and lymphatic pressures. In our review paper, we will provide a comprehensive overview of this evolving topic, covering a broad range from basic pathophysiology up to and including current clinical relevance. Key regulators of oxidative stress such as ischemia-reperfusion injury, the activation of inflammatory response and humoral changes interacting with procedural pneumoperitoneum formation and AKI risk will be recounted. Moreover, we present an in-depth review of the interaction of pneumoperitoneum formation with general anesthetic agents and animal models of congestive heart failure. A better understanding of the relationship between pneumoperitoneum formation and renal perfusion will support basic and clinical research, leading to improved clinical care and collaboration among specialists.

Smart cities are a new approach to facilitating urban development and transformation, driving coordinated development between regions, and achieving sustainable urban development. In the era of smart cities, industrial cloud platforms, as a concrete representation and carrier of “industrial brains”, are gradually becoming one of the core competences of urban manufacturing industries. Case study and qualitative comparative analysis (QCA) of a knitting industrial platform in Yiwu City, China are carried out. The following conclusion can be drawn: the construction mechanism and path of the manufacturing “industrial brain” in the smart city are divided into three stages according to the construction of the industrial platform. These include: functional development (FD), trust-building (TB), and value co-creation (VCC). The research conclusion helps to more deeply understand the effects of industrial platforms on constructing “industrial brains”. It provides effective transformation strategies and guidance for the manufacturing industry in the smart city, and pushes the industry to develop towards an intelligent, efficient, and environmental-friendly one. The research provides useful reference for applying the industrial platform to other industries and fields. Exploring the construction mechanism and path of the manufacturing “industrial brain” in the smart city can also contribute to the establishment of a new industrial ecosystem in the era of smart cities.

The changes in the properties of three biological events, that occur with cerebral aging, are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs. The emphasis of this review is the major role played by mitochondria in such transition of these three important processes toward more deleterious variants as brain aging proceeds. 1. The immune system. The shift away from an efficient immune response to a more unfocused, continuing inflammatory condition. Such a state is both ineffective and harmful. 2. Reactive oxygen species are important intracellular signaling systems. Also, microglial phagocytic activity utilizing short lived reactive oxygen species contribute to the removal of aberrant or dead cells and bacteria. These processes are transformed into an excessive, untargeted and persistent generation of pro-oxidant free radicals (oxidative stress). 3. The normal efficient neural transmission is modified to a state of undirected, chronic low-level excitatory activity. Each of these changes is characterized by the occurrence of continuous activity that is inefficient and diffuse. The signal/noise ratio of several critical biological events is thus reduced as beneficial responses are gradually replaced by their impaired and deleterious variants.

This paper describes a memory model with 2 levels of information. The lower-level stores source data, is Markov-like and unweighted. Then an upper-level ontology is created from a further 3 phases of aggregating source information, by transposing from an ensemble to a hierarchy at each level. The ontology is useful for search processes and the aggregating process transposes the information from horizontal set-based sequences to more vertical typed-based clusters. The base memory is essentially neutral, where any weighted constraints or preferences should be sent by the calling module. This therefore allows different weight sets to be imposed on the same linking structure. The success of the ontology typing is open to interpretation, but the author would suggest that when clustering text, the result was types based more on use and context, for example, 'linking' with 'structure' or 'provide' with 'web,' for a document describing distributed service-based networks. This allows the system to economise over symbol use, where links to related symbols will be clustered together. The author then conjectures that a third level would be more neural in nature and would include functions or operations to be performed on the data, along with related memory information.

Pathological Brain Detection (PBD) is a crucial field aimed at identifying and diagnosing structural or functional abnormalities in the brain related to neurological, neurodegenerative, or psychiatric disorders. This detection process typically employs medical imaging technologies such as MRI, CT, or PET scans, along with neurological evaluations, blood tests, and other diagnostic tools. Early detection is essential for effective treatment, improving prognosis, and enhancing the quality of life for affected individuals. Each common computational method provides unique insights into brain pathologies. Despite significant advancements in technology and methodology, PBD faces challenges such as variability in brain anatomy, the complexity of disorders, data quality, standardization issues, interpretability of models, and ethical concerns. Addressing these challenges necessitates collaboration among researchers, clinicians, and policymakers to develop robust and ethical methods for improving the detection and diagnosis of brain disorders.

Epigenetic changes are changes in gene expression that do not involve alterations to the basic DNA sequence. These changes lead to establishing a so-called epigenetic code that dictates which and when genes are activated, thus orchestrating gene regulation and playing a central role in development, health, and disease. The brain, being for the most formed by cells that do not undergo a renewal process through life, is highly prone to the risk of alterations leading to neuronal death and neurodegenerative disorders, mainly at late age. Here we review the main epigenetic modifications that have been described in the brain, with particular attention to those related to the onset of developmental anomalies or neurodegenerative conditions and/or occurring in old age. DNA methylation and several types of histone modifications (acetylation, methylation, phosphorylation, ubiquitination, sumoylation, lactylation, and crotonylation) are major players in these processes. They are directly or indirectly involved in the onset of neurodegeneration in Alzheimer’s or Parkinson’s disease. Therefore, this review briefly describes the role of these epigenetic changes in the mechanisms of brain development, maturation, and aging and some of the most important factors dynamically regulating or contributing to these changes such as oxidative stress, inflammation, and mitochondrial dysfunction.

During a multi-detector computed tomography (MDCT) examination, it is crucial to efficiently organize, store, and transmit medical images in DICOM standard, which requires significant hardware resources and memory. Our project processed large amounts of DICOM images by classifying them based on cross-section views that may carry important information about a possible diagnosis. We ensured that images were retained and saved in PNG format to optimize hardware resources while preserving patient confidentiality. Furthermore, we have developed a graphical, user-friendly interface that allows physicians to visualize specific regions of interest in a patient's brain where changes may indicate disease. Our proposed method enables quick classification of medical images into predefined classes of confirmed diseases of brain parenchyma, contributing to swift decision-making for further diagnosis for more precisely evaluating and characterizing brain changes, and it can lead to the rapid application of adequate therapy, which may result in better outcomes.

CLIPPERS which stand for Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a chronic inflammatory disorder of the central nervous system. The aetiology of CLIPPERS remains unclear, although its pathogenesis shows immune-mediated processes. The diagnosis of CLIPPERS is challenging without a specific biomarker hence, it is important to consider if both the clinical and radiological features are consistent with the diagnosis, or rather any other disease that mimics CLIPPERS. The Authors present a case of a 40-year-old Female patient diagnosed with CLIPPERS syndrome in India. Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome, and treatment approaches are discussed.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Depression is one of the psychiatric disorders characterized by anxiety, pessimism, and suicidal tendencies, which seriously affect the quality of life of patients and their families. In this paper, we used polynomial-based kernel Granger causality values as network node connectivity indicators to construct brain networks for 5 depressed patients and 11 healthy individuals’ magnetoencephalogram(MEG) under positive, neutral, and negative emotional stimuli, respectively, and found that depressed patients had closer information exchange between frontal and occipital regions compared to healthy individuals and other brain regions, and fewer causal connections in parietal and central regions. Further analysis of the topological properties of the network revealed that depressed patients had higher mean degrees under negative stimuli (p=0.008)and lower mean clustering coefficients than healthy individuals(p=0.034). Comparing the mean degree and mean clustering coefficient of the same sample under different emotional stimuli, we found that depressed patients had the greater mean degree and mean clustering coefficient under negative stimuli than neutral and positive stimuli. We also found that patients’ feature path lengths under negative and neutral stimuli significantly deviated from small-world attributes. The results suggest that analysis of nuclear Granger causality-based brain networks can effectively characterize depression pathology.

Abstract: Accurately predicting a fetus's gestational age (GA) is of utmost importance in prenatal care. This study aimed to develop an artificial intelligence (AI) model that can automatically predict GA using biometric measurements derived from fetal brain mag-netic resonance imaging (MRI). Additionally, we aimed to assess the significance of con-sidering different references when interpreting GA predictions. To achieve this, we obtained measurements such as Biparietal Diameter (BPD), Fron-to-occipital Diameter (FOD), and Head Circumference (HC) from a dataset comprising 52 normal fetal MRI cases with T2 Haste sequences from Rush University. Both manual and AI-based methods were utilized to acquire these measurements. We also employed three reference papers (Garel, Freq, and Bio) for comparison purposes. The results demonstrated a strong correlation between manual and AI measure-ments, indicating consistency between the two methods. The AI-based measurement of HC exhibited a higher correlation with actual values compared to BPD, FOD, and correct-ed BPD (BPDC). When comparing these measurements with GA in the Picture Archiving and Communication System (PACS), the differences varied depending on the reference used. Specifically, the differences ranged from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Furthermore, the Pearson correlation coeffi-cient analysis revealed that all correlation coefficients between PACS records and GA pre-dictions using different references were greater than 0.97. In conclusion, the AI model based on fetal brain MRI accurately predicts GA by uti-lizing BPD, FOD, and HC measurements. The AI approach, which involves combining line segments to calculate fetal head circumference, offers improved accuracy and con-venience compared to manual estimation. This study underscores the potential of AI models in accurately estimating gestational age and highlights their utility in prenatal care. By integrating AI as a valuable tool in prenatal care, we can enhance the accuracy, ef-ficiency, and decision-making involved in assessing fetal development and monitoring pregnancies using MRI measurements.

Hemorrhagic complications arising from ventricular drainage procedures are typically asymptomatic and of low volume. A particular subset of these complications known as Delayed Intracranial Hemorrhage (DICH) is however recognized for its particularly poor prognosis. We primarily aimed to identify epidemiological characteristics associated with DICH, to shed light on its occurrence and potential risk factors. To do so, we performed a retrospective analysis of a series of ten patients who presented with DICH in the context of a ruptured brain Arteriovenous Malformation (bAVM), and a systematic literature review of all DICH cases reported in the literature. Our ten patients showed delayed neurological deterioration after Ventriculoperitoneal Shunt (VPS) procedure, with a computed tomography (CT) scan revealing a DICH surrounding the ventricular catheter, distinct and away from the nidus of their previously ruptured bAVM. Four patients (40%) rapidly declined and passed away, three (30%) required surgical management and the remaining three (30%) demonstrated gradual clinical improvement with conservative management. In the literature, most patients presenting with DICH had hydrocephalus associated with neurovascular disorders (47% of cases), such as bAVM rupture in our present series. These constatations point out the significance of underlying pathologies potentially predisposing to these unusual complications.

The cough assessment is fundamental in the weaning process as it gives information on the possibility to expel food and secretion from the airways. The majority of persons suffering from severe acquired brain injury (ABI) are not able to cough voluntarily due to severe motor deficits. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. 100 Healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve cough strength training reflexive cough modulation in ABI patients.

Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p&lt;0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.

Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer. Even less frequent is the association of lung and brain abscess due to this agent with left heart endocarditis. We describe the case of a 40-year-old man with a brain abscess due to S. intermedius and concomitant lung abscess and aortic native valve endocarditis. He was treated with surgical drainage of the brain abscess and a 4-week course of intravenous ceftriaxone, followed by oral amoxicillin/clavulanate, obtaining healing of the lesions without relapse of the infection.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. The dysfunction of redox system and failures in control the inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. Intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites like the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease and Irritable Bowel Syndrome.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

Abstract: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, signif-icantly prolonged survival when compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemo-therapy and a PD-1 or PD-L1 inhibitor. The confirmed overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published about the activity in brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old male Caucasian patient, who was heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. The first evaluation after three cycles of EV showed a partial remission by RECIST v1.1 with a near complete response in the brain metastasis and disappear-ance of the neurological complaints. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and maintenance avelumab. The patient achieved complete response and remained on therapy for five months. However, therapy was discontinued at the patient’s re-quest. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old male Caucasian patient also received EV, after previous progression on cisplatin-gemcitabine and ate-zolizumab maintenance followed by palliative whole brain radiotherapy and two cycles of vin-flunine. The first evaluation after three cycles of EV showed a significant reduction of the brain metastases. The patient is currently still receiving EV. These are the first reports on efficacy of EV in patients with urothelial carcinoma and active brain metastases.

Tardive dyskinesia (TD) is a phenomenon predominantly observed as a result of the long-term use of dopamine receptor blockers (antipsychotics). TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid muscles, lips, tongue, and cheeks, and less frequently in the limbs, neck, pelvis, and trunk. In some patients, TD takes on an extremely severe form, massively disrupting functioning, moreover, causing stigmatization and suffering. Deep brain stimulation (DBS), a method used, among others, in Parkinson's disease, is also an effective treatment for TD and often becomes a method of last resort, especially in severe, drug-resistant forms. The procedure is relatively new in TD, so the available reliable clinical studies are few and consist mainly of case reports. Unilateral and bilateral stimulation of two sites has proven efficacy in TD treatment. Most authors describe stimulation of the globus pallidus internus (GPi); less frequent descriptions involve the hypothalamic nucleus (STN). In the present paper, we provide up-to-date information on the stimulation of both mentioned brain areas. We also compare the efficacy of the two methods by comparing the two available studies, which included the largest groups of patients. Although GPi stimulation is more frequently used clinically, our initial analysis indicates comparable results (reduction of involuntary movements) with STN DBS.

This concept paper gives a narrative about intelligence from insects to the human brain, showing where evolution may have been influenced by the structures in these simpler organisms. The ideas also come from the author's own cognitive model, where a number of algorithms have been developed over time and the precursor structures should be codable to some level. Through developing and trying to implement the design, ideas like separating the data from the function have become architecturally appropriate and there have been several opportunities to make the system more orthogonal. Similarly for the human brain, neural structures may work in-sync with the neural functions, or may be slightly separate from them. Each section discusses one of the neural assemblies with a potential functional result, that cover ideas such as timing or scheduling, structural intelligence and neural binding. Another aspect of self-representation or expression is interesting and may help the brain to realise higher-level functionality based on these lower-level processes.

If the development of machine learning and artificial intelligence plays a role in many fields of research and technology today, it has a special relationship with neurosciences. Indeed, historically inspired by our knowledge of the brain, deep learning shares some vocabularies with neurosciences and can sometimes be considered a brain’s model. Taking the particular example of epileptic seizure, which can develop in any biological neural tissue, we raise the question if and how the models used for deep learning can capture or model these pathological events. This particular example is a starting point to discuss the nature, limits, and functions of these models, and what we expect from a model of the brain. Finally, we argue that a pluralistic approach leading to the integrated coexistence of different models is necessary to study the brain in all its complexity.

Abstract—Low-frequency Fahræus–Lindqvist-driven (not blood pressure-driven) oscillations in the small vessels are crucial because oscillations in small vessels support nutrient supply. Understanding of this is critical in type 2 diabetes mellitus (T2DM) to develop therapeutic measures to prevent Alzheimer's Disease Related Dementias: vascular factors contribute to cerebrovascular disease as well as mild cognitive impairment and dementia, which are predicted to affect 152 million people by 2050 (Alzheimer's Disease International London, UK, 2019). In this clinical study, we performed functional near-infrared spectroscopy (fNIRS) of the forehead to investigate the effect of the Mini-Cog with three-item recall test on the prefrontal cortex (PFC) activation and the relative oscillatory power in the 0.01–0.02-Hz (Fahræus–Lindqvist effect) and 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency bands in elderly (60 years and older) T2DM and age-matched controls. We found a significant (p<0.01) difference in the PFC activation between elderly subjects with T2DM and age-matched elderly controls. Moreover, power spectral density (PSD) analysis revealed a significantly lower relative power in 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency band in elderly subjects with T2DM during the Mini-Cog three-item recall test. Furthermore, a drop in the oscillatory power in the 0.01–0.02-Hz frequency band during Mini-Cog three-item recall test was found more pronounced in the elderly subjects with T2DM. Therefore, our study highlighted portable brain imaging to capture cerebrovascular reactivity to cognitive load that may provide a biomarker of cerebrovascular dysfunction in T2DM.Clinical Relevance— Our study establishes forehead portable brain imaging for monitoring cerebrovascular function in T2DM under cognitive load.

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.

(1) Background: Extremely low alanine aminotransferase (ALT) levels are be-ing recognized as a risk factor of increasing mortality in the elderly in relation to frailty. In the elderly, both frailty and ischemic stroke are not only common, but also associated with mortality. This study aimed to investigate whether extremely low ALT levels increase the all-cause mortality rate in the elderly after ischemic stroke. (2) Methods: A retrospective review was performed on 901 patients with ischemic stroke admitted to a university-affiliated hospital between February 2014 and April 2019. The multivariate Cox proportional hazard analysis was performed to determine whether extremely low ALT lev-els are an independent risk factor of mortality in elderly patients after ischem-ic stroke. (3) Results: This study enrolled 323 older adults (age ≥65 years) who were first diagnosed with ischemic stroke. The mean age of the participants was 76.5 ± 6.6 years, mean survival time was 37.1 ± 20.4 months, and the num-ber of deaths was 96 (29.7%). The multivariate Cox proportional hazard analy-sis revealed that the risk factors for all-cause mortality in the elderly after is-chemic stroke were age, initial National Institutes of Health Stroke Scale score, serum creatinine, and extremely low ALT level (<10 U/L) at the time of diag-nosis (adjusted hazard ratio: 3.243, 95% confidence interval: 1.945–5.408; P < 0.001) (4) Conclusions: Extremely low ALT level at the time of diagnosis (<10 U/L) is an independent risk factor that increases the mortality rate in the el-derly after ischemic stroke.

We aim to determine the sleep correlates of age-related brain loss in a sample of middle-aged to older males with obstructive sleep apnea. We evaluated consecutive treatment naïve male patients with OSA (AHI≥15 events/hr) without dementia, stroke or heart disease, from January to November of 2019. We collected demographic variables, vascular risk factors, and sleep questionnaires. We also obtained computerized neurocognitive testing with the Go-No-Go Response Inhibition Test, Stroop Interference Test, Catch Game Test, Staged Information Processing Speed Test, Verbal Memory Test and Non-Verbal Memory Test. We derived age and education adjusted domain-specific Z-scores for global cognition, memory, attention, processing speed and executive function. We used brain MRI T1-weighted images to derive total hippocampal and gray matter volumes. Partial correlations evaluated associations between the ISI, AHI, and oxygen level during sleep, with cognitive domains and brain volumes. Sixteen participants, age 40-76 years, 73% Hispanic/Latino, with mean AHI=48.9±25.5 and mean oxygen saturation of 91.4±6.9% during sleep. Hypertension was seen in 66% and diabetes in 27%. We observed that ISI and oxygen level during sleep had strong correlations with brain volumes and cognition. These preliminary findings may aid in developing future strategies to improve age-related brain loss in OSA.

A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

Glioma tumors are one of the most devastating cancer types. Of the different glioma tumors, glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advantages in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OV) in cancer treatment is one of those immune-therapeutic alternatives. OV have a double oncolytic action by both, directly destroying the cancer cells, sparing the patient’s life, and stimulating a tumor specific immune response to revert the ability of tumors to escape the control of the immune system. OV are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility to use some viruses to specifically infect tumors eluding undesired toxic effects in the patient. Here we have revisited the literature in order to describe the main OV proposed so far as therapeutic alternatives to destroy glioma cells in vitro and trigger tumor destruction in vivo. Some clinical trials are exploring the use of this therapy as an alternative were other approaches provide limited hope.

Lewis et al. published an important and timely necessary article about the determination of death by neurological criteria, revising the Uniform Determination of Death.The acceptance of brain death (BD) has been progressively accepted beginning at the late 1950s. Nonetheless, contentious brain-death cases have recently raised new controversies about the diagnosis of BD, such as the Jahi McMath case, extensively covered by the US and international press. Jahi McMath meant a terrible tragedy for her and her family. But further than this gloomy story, the case has also raised confusion and challenging qualms about a fundamental query: how we confirm whether a person is dead or alive? Since 1981, the Uniform Determination of Death Act (UDDA) has served as the legal foundation for the medical practice of determining death. But, although death by neurologic criteria is considered legal death throughout the United States, several recent lawsuits have quizzed the rightfulness the authority of the UDDA to declare death by neurological criteria. This issue explains the importance of Lewis’s et al. paper. In this article I want to present the historical procedure for issuing a law in Cuba for the determination and certification of death. Of course, it is impossible to compare our country with USA. Cuba is a small and developing country, in which a law encompasses a national scenery, in contrast with USA, a multistate nation.

Visual imagery, i.e., the mental experience of an object occurring in the absence of external visual stimulus, might encompass diverse content according to different observers. Further, subjectively experienced time is encoded in the later entorhinal cortex. Starting from these two observations, and considering Einstein’s account of spacetime, we show how, in terms of special relativity, the content of visual imagery is not stationary and fixed, rather depends on the standpoint of the observer. We elucidate how the subjective definition of time (perceived by our mind as static) might give rise to modifications in the length of the imagined object which are experimentally assessable and quantifiable. In particular, based on recent neuroscientific literature, we show how changes in our mental time windows are able to squeeze the visual content of mental imagery.

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.

1) Introduction: Brain parcellation is an important processing step in the analysis of structural brain MRI. Existing software implementations are optimized for fully developed adult brains, and provide inadequate results when applied to neonatal brain imaging. 2) Methods: We developed a semi-automated pipeline, NeBSS, for extracting 50 discrete brain structures from neonatal brain MRI, using an atlas registration method that leverages the existing ALBERT neonatal atlas 3) Results: We demonstrate a simple linear workflow for neonatal brain parcellation. NeBSS is robust to variation in imaging acquisition protocol and magnet field strength. 4) Conclusion: NeBSS is a robust pipeline capable of parcellating neonatal brain MRIs using a simple processing workflow. NeBSS fills a need in clinical translational research in neonatal imaging, where existing automated or semi-automated implementations are too rigid to be successfully applied to multi-center neuroprotection studies and clinically heterogeneous cohorts. The software is open source and freely available.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

A crucial aspect in developing machine learning algorithms (or any type of predictive models) is the comparison of different algorithmic candidates based on evaluation criteria that measure their accuracy and practical value in terms of successfully capturing the complexity of the underlying problem and generalizing in a wide range of real-world scenarios. In the domain of diabetes mellitus machine learning techniques are widely employed in the prediction of future values of glucose concentration in the blood in order to assist the patient in avoiding deviations from the normo-glycemic value range and the consequences of hyper- and hypoglycemia. In the relative literature there is an apparent lack of a uniformly adopted evaluation metric which could combine the clarity and direct comparative nature of statistical mathematical formulas dealing with prediction error residuals (e.g., the RMSE) with the clinical insights and the visual-qualitative approach of clinical evaluation tools (e.g., Clarke's EGA). Mean Adjusted Exponent (MADEX) error metric, proposed in this paper, attempts to address this need by providing a validation tool based on an easy to implement mathematical formula, that incorporates adjustable parameters of clinical significance.

It is unknown whether postprandial plasma glucose measured from blood taken between 4 and 7.9 h (PPG4-7.9h) is associated with mortality from hypertension, diabetes, or cardiovascular disease (CVD). This study aimed to investigate these associations in 4,896 US adults who attended the third National Health and Nutrition Examination Survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PPG4-7.9h for mortality. This cohort was followed up for 106,300 person-years (mean follow-up, 21.7 years). A 1-natural-log-unit increase in PPG4-7.9h was associated with a higher risk of mortality from hypertension (HR, 3.50; 95% CI, 2.34-5.24), diabetes (HR, 11.7; 95% CI, 6.85-20.0), and CVD (HR, 2.76; 95% CI, 2.08-3.68) after adjustment for all the tested confounders except hemoglobin A1c (HbA1c). After further adjustment for HbA1c, PPG4-7.9h remained positively associated with mortality from hypertension (HR, 2.15; 95% CI, 1.13-4.08) and CVD (HR, 1.62; 95% CI, 1.05-2.51), but was no longer associated with diabetes mortality. Subgroup analyses showed that similar results were obtained in the sub-cohort of participants without a prior diagnosis of myocardial infarction or stroke. In conclusion, PPG4-7.9h predicts mortality from hypertension and CVD independent of HbA1c.

Background: Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Its serum concentration increases in cardiovascular disease (CVD). We hypothesized that DCA may affect hemodynamic parameters in rats. Methods: The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3-4-month-old Sprague-Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo. Results: The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/l. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds: prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor) significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly. Conclusions: DCA increases BP by increasing cardiac output. As a bioactive gut bacteria-derived metabolite, DCA may co the interaction between gut microbiota and the host’s circulatory system.

Blood biomarkers represent a promising future for studying cognitive impairment, particularly in Alzheimer's Disease (AD), as they offer a non-invasive alternative to cerebrospinal fluid tests and have potential as population screening tools. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations between Amyloid-β, Total Tau, Phosphorylated Tau (p-tau), Neurofilament Light (Nfl), and Glial Fibrillary Acidic Protein (GFAP) with cognition. The reviewed studies are heterogeneous, varying in design and population (mixed, cognitively impaired, or unimpaired), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-tau measures tend to show stronger associations with cognitive functions than other biomarkers, no single blood marker has emerged as predominantly associated with a specific cognitive domain. These findings add to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical evaluations of cognition.

(1) Background: The incidence of vancomycin-induced neutropenia in hospitalized patients is estimated to be around 2 to 8 percent [1,2]. Data surrounding vancomycin-induced neutropenia is limited as it is based on a small number of observational case reports. Additionally, it is difficult to provide generalized conclusions since patient characteristics and indications for treatment vary between reports. (2) Case Reports: We present two cases of vancomycin-induced neutropenia that occurred at our facility; a 50-year-old male who developed neutropenia after treatment with vancomycin for a gluteal abscess and a 51-year-old female who developed neutropenia after treatment with vancomycin for lumbar osteomyelitis. In both cases, neutropenia resolved within 2 days of discontinuation of vancomycin. (3) Conclusion: The risk of developing neutropenia increases with age, prolonged drug exposure, decreased renal clearance, and in those of female sex. Treatment involves discontinuation of vancomycin with or without administration of granulocyte colony-stimulating factor (G-CSF). Additional studies are needed to better understand the true incidence of this adverse drug reaction and to identify risk factors that may predispose patients to vancomycin-induced neutropenia.

Objective To observe the effect of roxadustat on blood pressure and micro-inflammatory response in patients with hemodialysis anemia, and to provide a viable technique for the treatment of hemodialysis anemia patients. Methods A total of 100 hemodialysis anemia patients admitted to the Nephrology Department of our hospital from July 2020 to July 2021 were enrolled and randomly divided into an observation group (roxadustat) and a control group (human recombinant erythropoietin (rhEPO). The clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure were recorded and compared. Results There was no significant difference in baseline data and serum indicators (P>0.05). The study group demonstrated superior performance to the control group in terms of clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure (all P<0.05). Conclusion Compared with rhEPO treatment, roxadustat exhibits a promising outcome in treating anemia and has slight impact on blood pressure of patients.

Background: The purpose of this study was to ascertain the reliability of two 15-sec sprint cycling tests in men and women to estimate the maximum rate of glycolysis or lactate production (VLa-Max). Methods: Eighteen men and twelve women completed two sprint sessions over 1-week. A 10-min warm-up preceded a 3 µl blood lactate (BLC) sample, after which a 15-sec sprint was completed; cyclists then rested passively while multiple lactate samples were taken until levels peaked. VLaMax was calculated as (Peak BLC – Pre BLC) * (15-sec – Talac)-1. Trial differences and reliability across trials were analyzed using a paired-sample t-test, Pearson correlation, ICC, and Bland-Altman analysis with α=0.05 for all tests; data are reported as mean ± sd. Results: Power (W) was similar across trails (773.0 ±143.5 vs. 758.2 ± 127.4; p = 0.333) and coefficient of varia-tion (CV) of 4.7%. VLaMax was similar (0.673 ± 0.024 vs 0.635 ± 0.237; p = 0.280), but only moder-ately reliably across trials with a CV, ICC, and R value of 18.6%, 0.661, and 0.67, respectively. Conclusions: A 15-sec VLaMax cycling sprint is moderately reliable being affected both by the lac-tate measurement and other variables used in the calculation. More research may offer ways to improve reliability.

While fibrinolytic enzymes and thrombolytic agents offer assistance in treating cardiovascular diseases, the existing options are associated with a range of adverse effects. In our previous research, we successfully identified ficin, a naturally occurring cysteine protease that possesses unique fibrin and fibrinogenolytic enzymes, making it suitable for both preventing and treating cardiovascular disorders linked to thrombosis. Papain is a prominent natural cysteine protease derived from the latex of Carica papaya. The potential role of papain in preventing fibrin(ogen)lytic, anticoagulant, and antithrombotic activities has not yet been investigated. Therefore, we examine how papain influences fibrinogen and the process of blood coagulation. Papain is highly stable at pH 4-11 and 37-60°C by azocasein assay. In addition, SDS gel separation electrophoresis, zymography, and fibrin plate assays were used to determine fibrinogen and fibrinolysis activity. Papain appears to have a molecular weight of around 37 kDa, and is highly effective in degrading fibrin, with a molecular weight of over 75 kDa. Furthermore, papain-based hemostatic performance was confirmed in blood coagulation tests, a blood clot lysis assay, and a κ-carrageenan rat tail thrombosis model, highlighting its strong efficacy in blood coagulation. Papain shows dose-dependent blood clot lysis activity, cleaves fibrinogen chains of Aα, Bβ, and γ-bands and significantly extends prothrombin time (PT) and activated partial thromboplastin time (aPTT). Moreover, the mean length of the infarcted regions in the tails of Sprague-Dawley rats with κ-carrageenan was shorter in rats administered 10 U/kg of papain than in streptokinase-treated rats. Thus, papain, a natural cysteine protease, has distinct fibrin and fibrinogenolytic properties, suggesting its potential for preventing or treating cardiovascular issues and thrombosis-related diseases.

Cadmium (Cd) is a pervasive, toxic environmental pollutant that preferentially accumulates in tubular epithelium of the kidney. Current evidence suggests that the cumulative burden of Cd here leads to progress loss of the glomerular filtration rate (GFR). In this study, we have quantified changes in estimated GFR (eGFR) and albumin excretion (Ealb) in according to levels of blood Cd ([Cd]b) and excretion of Cd (ECd) after adjustment for confounders. ECd and Ealb were normalized to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr. Among 482 residents of Cd-polluted and non-polluted regions of Thailand, 8.1% had low eGFR and 16.9% had albuminuria, (Ealb/Ccr)×100 ≥ 20 mg/L filtrate. In the low Cd burden group, (ECd/Ccr) ×100 &lt; 1.44 µg/L filtrate, eGFR did not correlate with ECd/Ccr (β = 0.007), while an inverse association with ECd/Ccr was found in the medium (β =−0.230) and high-burden groups (β =−0.349). Prevalence odds ratios (POR) for low eGFR were increased in the medium (POR 8.26) and high Cd burden groups (POR 3.64). Also, eGFR explained a significant proportion of Ealb/Ccr variation among those with middle (η2 0.093) and high [Cd]b tertiles (η2 0.132), but did not with low tertile (η2 0.001). With adjustment of eGFR, age and BMI, POR values for albuminuria were increased in the middle (POR 2.36) and high [Cd]b tertiles (POR 2.74) and those with diabetes (POR 6.02) and hypertension (2.05). These data argue that ECd/Ccr of 1.44 µg/L filtrate (0.01−0.02 µg/g creatinine) could determine a Cd threshold level from which protective exposure guidelines should be formulated.

The study aimed to manage and to analyse the results of the laboratory tests, routinallypractice for hepatitis C diagnosis, using blood tests. Statistical analysis of this study results, was performed using the laboratory informatic system. The results of the study are substantial and intricate reffering to comparision between two methods concretlly ELISA method (Enzyme-Linked Immunosorbent Assay) and chemiluminescence methods and their results. Good to know our opinion that RT-PCR technique, it is considered proper for the diagnosis of HCV ( Hepatitis C virus).

Purpose: The study aimed to investigate the efficacy of TXA supplemented with local infiltration analgesia (LIA) in reducing blood loss in patients undergoing total knee replacement. Materials: A retrospective study on 530 individuals with a mean age of 71,44 years after posterior stabilized total knee arthroplasty was evaluated. Patients were divided into three groups, corresponding to the method of bleeding control: I - patients without additional bleeding protocol (control group); II - patients with iV TXA administration (TXA group); III - patients with exact TXA protocol combined with intraoperative local infiltration analgesia (TXA + LIA group). Blood loss was measured as a substitute for blood loss by maximal Hb drop compared to preoperative Hb level. Results: The mean hospitalization for patients from the control group was 7.02 (SD 1.34) days, 6.08 (SD 1.06) days for the TXA group, and 5.56 (SD 0.79) for the TXA + LIA group. The most significant hemoglobin drop was found in the control group, which amounted to an average of 30.08% output value. In the TXA group, the decrease in hemoglobin was, on average, 25.17% (p<0.001), and in the TXA + LIA group, it was 23.67% (p<0.001). A decrease in the rate of allogeneic blood transfusions was observed, which was 24.4% in the control group, 9.9% in the TXA group, and 8% in TXA + LIA group (p<0.01). Conclusions: Compared to the separate administration of tranexamic acid, the combination of perioperative administration with local infiltration analgesia statistically significantly reduces blood loss in patients after total knee replacement.

Carbapenemase resistance in Enterobacterales is a global public health problem and rapid and effective methods to detect resistance mechanisms are needed urgently. Our aim was to evaluate the performance of a MALDI-TOF MS based KPC detection protocol from patients’ positive blood cultures, short-term cultures and colonies at health care settings. Bacterial identification and KPC detection were achieved after protein extraction with organic solvents and target spot loading with suitable organic matrices. Confirmation of KPC production was performed by susceptibility tests, blaKPC amplification by PCR and sequencing. KPC direct detection (KPC-peak at approximately 28.681 Da) from patients’ positive blood cultures, short-term cultures and colonies, once bacterial identification was achieved, showed an overall sensibility and specificity of 100% (CI95: [95%,100%] and CI95: [99%, 100%], respectively). Concordance between hospital routine bacterial identification protocol and identification with this new methodology from the same extract used for KPC detection was ≥92%. This study represents the pioneering effort to directly detect KPC using MALD-TOF MS technology, conducted on patient-derived samples obtained at the hospitals for validation purposes, in a multi-resistance global context that requires concrete actions to preserve available therapeutic options and reduce the spread of antibiotic resistance markers.

Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. This study evaluated the sensitivity and specificity of a commercial kit for the detection of Histoplasma antigen by an EIA (HC-Ag) technique in 50 patients with histoplasmosis associated with AIDS. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. HC-Ag had a sensitivity (S) of 94%, specificity (E) 95.5%, positive predictive value (PPV) 94% and negative predictive value (NPV) 95.5%. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S and NPV: 100%; with similar values in E and PPV. The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be an important therapeutic agent. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to check whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg/dose) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of acute pancreatitis was assessed immediately after the last dose of cerulein, as well as 1, 2, 3, 5, and 10 days after AP induction. Treatment with warfarin dose-dependently increased interna-tional normalized ratio (INR) and attenuated the severity of pancreatitis in histological ex-amination and accelerated pancreatic recovery. Those effects were accompanied with a faster reduction in the pancreatitis-evoked increase in serum activity of amylase and lipase, serum concentration of pro-inflammatory interleukin-1β, and plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg/dose. Conclusion: Administration of warfarin accelerates re-generation of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

INTRODUCTION: Cardiovascular prevention is less effective than expected due to the concern about polymedication of professionals and the lack of adherence of patients. Polypills are presented as a possible solution, increasing therapeutic adherence in the medium or long term and improving therapeutic results compared to the administration of drugs separately: they increase effectiveness and Adherence of patients to primary and secondary cardiovascular prevention programs, without increasing the cost of the intervention. OBJECTIVES: Study #Trigeria: to specify the combined prevalence of Atrial Fibrillation, Dyslipidemia and Hypertension and analyze the pharmacological prescription for these pathologies and the possible indications and advantages that would have the prescription of a polypill for these risk factors.METHODS: Observational analytical study on the pathological history in elderly institutionalized in nursing homes and analysis of prescribed oral medication.RESULTS: 169 people analyzed (79.3% women) from 4 nursing homes; 8.9% had a history of Atrial Fibrillation, Dyslipidemia and Arterial Hypertension; these had a higher prevalence of heart disease (42.9%) and Cerebral Vascular Accident (35.7%). Polymedication was present in 88.5%, with an average of 6.94 oral drugs prescribed; among those with the three pathological antecedents, the average number of oral medications was 8.60. Only 26.7% of those with all three factors were prescribed drugs to control them.DISCUSSION: There are high rates of polymedication in the sample and low rates of prescription of antiplatelet agents in people with Atrial Fibrillation (26.5%); the low prescription of statins and antihypertensives of the ACE inhibitor or ARB-II groups may be due to good control with non-pharmacological measures or by the use of other groups of drugs . A polypill holding the drugs that control the three factors studied could increase the prescription rate while simplifying the administration schedule and reducing polymedication by 23.25% improving prescription, increasing adherence and control of risk factors without increasing pharmaceutical expenditure.CONCLUSIONS: There is a low rate of prescription of antiplatelet agents among people with atrial fibrillation. Combination methods (polypills) can increase the suitability of prescriptions in people with polypathology, improving prescribing, simplifying administration and increasing adherence to pharmacological treatments.

Our understanding of how microbiome signatures are modulated in wild fish populations remains poorly known and has, until now, mostly been inferred from studies in commercial and farmed fish populations. Here, we have studied for the first time changes in the skin and blood microbiomes of the Salmo trutta population of the volcanic Kerguelen archipelago located at the northern limit of the Antarctic Ocean. Kerguelen is a natural framework of population expansion and a likely situation under further climate change in distribution areas. Our results showed that S. trutta of Kerguelen has a microbiome signature distinct from those of salmonids of the Northern Hemisphere. Our study also revealed that the skin and blood microbiomes differ between sedentary and migratory S. trutta. While 18 phyla were shared between both groups of trout, independent of the compartment, six phyla were unique to migratory trout. Further analyses showed that microbiome signatures undergo significant site-specific variations that correlate, in some cases, to the peculiarity of specific ecosystems. Our study also revealed the presence of potential pathogens at particular sites and the impact of abiotic factors on the microbiome, most notably due to the volcanic nature of the environment. This study contributes to a better understanding of the factors that modulate the microbiome signatures of migratory and sedentary fish populations. It will also help better monitor climate change's impacts on the colonization process in the sub-Antarctic region.

There are a number of Anopheles species playing either primary or secondary roles in malaria transmission. Hence, understanding the species composition, their bionomics, and behaviors are all important in designing and implementing vector control intervention tools. Moreover, accurate identification of different species is vital. This study aimed to assess species composition, sporozoite infection rate, and blood meal origins of malaria mosquitoes in two malaria-endemic villages of Boreda district in Gamo zone, southwest Ethiopia. Thirty houses, 20 for Centers for Disease Control and Prevention (CDC) light traps and 10 for Pyrethrum Spray Catches (PSC), were randomly selected for bimonthly mosquito collection from October 2019 to February 2020. Enzyme-linked-immunosorbent assay (ELISA) test was done to detect the blood meal origins and circumsporozoite proteins (CSPs). The entomological inoculation rate (EIR) was calculated by multiplying the sporozoite and human biting rates from PSCs. Anopheles gambiae and An. funestus complexes were further identified into species by polymerase chain reaction (PCR). Anopheles species with some morphological structures confusing with An. gambiae or An. funestus complexes were father confirmed by PCR. A total of 15 Anopheles species were documented, of which An. demeilloni was the dominant one. Only An. arabiensis was positive for P. falciparum CSP. The overall P. falciparum CSP rate of An. arabiensis was 0.54%. The overall estimated P. falciparum EIR of An. arabiensis from PSC was 1.5 infectious bites/person/five months. Of the 145 freshly fed Anopheles mosquitoes tested for blood meal source, 57.9% (84/145) had bovine blood meal, 22 (15.2%) had human blood meal origin alone and 24 (16.5%) had mixed blood meal origins of human and bovine. An. demeilloni mainly fed on bovine blood (102/126 = 80.9%). Among 420 morphologically classified An. demeilloni, 11 (2.6%) were confirmed as An. lessoni (one of the An. funestus complexes) by PCR. A substantial number of morphologically classified An. salbaii, An. maculipalpis and An. fuscivenosus were found to be An. arabiensis by PCR. Regardless of the high diversity of Anopheles mosquitoes, An. arabiensis is playing the primary role in malaria transmission. Morphological misclassification of species could be a challenge in malaria mosquito monitoring and surveillance, and hence it should be supported by more sensitive techniques for confirmation.

Systemic sclerosis is an autoimmune disease characterized by organ fibrosis and vasculopathy. Almost all patients suffer from Raynaud’s phenomenon (RP). Currently, several imaging techniques are available; nailfold video capillaroscopy (NVC) is the most widely available, but flow quantification is not possible with NVC. Novel imaging techniques are of interest in this population. We performed a single-center feasibility study using Micro Vascular Imaging (MVI) as a novel imaging technique for flow quantification of small fingertip vessels. We compared a group of 20 healthy controls (HCs) with 20 Systemic Sclerosis (SSc) patients. In HCs, flow measurements assessed with MVI were statistically significantly higher in individual fingers and combined for all fingers (p&lt;0.0001). As a cut-off value to discriminate HCs from SSc, a peak systolic (PS) flow velocity of &lt;6.9 cm/s and an end-diastolic (ED) flow velocity of &lt;2.68 cm/s was determined. Test characteristics for PS flow velocity showed moderate sensitivity (0.69, 95% CI 0.58-0.78) but high specificity (0.88, 95% CI 0.79-0.93). Similar test characteristics for ED flow velocity were obtained. The optimal cut-off point was estimated at &lt;2.68 cm/s, sensitivity was moderate (0.65, 95% CI 0.53-0.75), specificity was 0.80 (95% CI 0.70-0.87). Here, we present the first study on the use of MVI to assess blood flow in the fingertips with high specificity in SSc patients. Future studies need to investigate correlations with the risk for organ complications, such as digital ulcers or pulmonary arterial hypertension.

Surgeries that take place in medicine and dentistry or during any form of childbirth results in a significant amount of blood loss. The prevalent measurement methods that surgeons and anesthesiologists utilize as the “gold - standard” has several drawbacks. There are numerous other methods to measure blood loss, which, however, due to their impracticality and limitations, are not ideal either. This paper focuses on minimally invasive neurosurgery in particular, by taking into account a surgical technique known as Endoscopic Endonasal Transphenoidal surgery (EETS), which is used to treat pituitary tumors and adenomas. Along with the review of the existing literature pertaining to blood loss management, this paper proposes a modified electrode probe method along with the concept of usage, computer interface, and the system of integration. The probe is intended to measure the hematocrit count from the collected blood under all circumstances, such that the medical practitioner is assisted to improve the blood loss management technique for better patient recovery.

Accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated its effect on the number of macrophages and endothelial cells (ECs) within the CM. Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and Transglutaminase II, respectively. Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and 4-fold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p<0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals.

Plasma and serum are the most widely used blood-derived biofluids for metabolomics and lipidomics assays, but the isolation of these products from blood may introduce additional bias as indicated by the fact that many analytes that are present at high concentrations in blood cells cannot be measured and evaluated in those samples. Of particular concern, variable hemolysis during the pre-processing of blood products could compromise accurate and reproducible quantification. Compared with plasma or serum, whole blood may be a better alternative due to simplicity of processing. In this study, we provide a comprehensive method for quantification of the whole blood sphingolipidome and the concentrations were compared with those from plasma. Combining a single-phase extraction method with liquid-chromatography high resolution mass spectrometry (R=120, 000), assisted by alkaline hydrolysis, we were able to identify and simultaneously quantify more than 150 sphingolipids. Furthermore, most of sphingolipids remained stable after a freeze/thaw cycle. Whole blood contained a higher concentration of most sphingolipids than corresponding plasma. Moreover, individual variations in the levels of sphingolipids were lower for whole blood than plasma. These findings demonstrate that whole blood could be a better alternative to plasma, and potentially guide the evaluation of sphinglipidome for biomarker discovery.

It has been demonstrated that brief cycles of ischemia followed by reperfusion (IR) applied before exercise can improve performance and, IR intervention, applied immediately after exercise (post-exercise ischemic conditioning – PEIC) exerts a potential ergogenic effect to accelerate recovery. Thus, the purpose of this systematic review with meta-analysis was to identify the effects of PEIC on exercise performance, recovery and the responses of associated physiological parameters, such as creatine kinase, perceived recovery and muscle soreness, over 24 h after its application. From 3281 studies, six involving 106 subjects fulfilled the inclusion criteria. Compared to sham (cuff administration with low pressure) and control interventions (no cuff administration), PEIC led to faster performance recovery (p=0.004; ES=-0.49) and lower increase in creatine kinase (p&lt;0.001; ES=-0.71) and muscle soreness (p&lt;0.001; ES=-0.89) over 24 h. The effectiveness of this intervention is more pronounced in subjects with low/moderate fitness level and at least a total time of 10 min of ischemia (e.g. 2 cycles of 5 min) is necessary to promote positive effects.

Clinically, knowing the number of red blood cells (RBCs) and white blood cells (WBCs) helps doctors to make the better decision on accurate diagnosis of numerous diseases. The manual cell counting is a very time-consuming and expensive process, and it depends on the experience of specialists. Therefore, a completely automatic method supporting cell counting is a viable solution for clinical laboratories. This paper proposes a novel blood cell counting procedure to address this challenge. The proposed method adopts SegNet - a deep learning semantic segmentation to simultaneously segment RBCs and WBCs. The global accuracy of the segmentation of WBCs, RBCs, and the background of peripheral blood smear images obtains 89% when segment WBCs and RBCs from the background of blood smear images. Moreover, an effective solution to separate grouped or overlapping cells and cell count is presented using Euclidean distance transform, local maxima, and connected component labeling. The counting result of the proposed procedure achieves an accuracy of 93.3% for red blood cell count using dataset 1 and 97.38% for white blood cell count using dataset 2.

Lead pollutants mainly from urban agricultural practices, Leaded paints, Leaded fuels spillages, Lead-contaminated air, soils, and water sources pause a health threat to urban children in Uganda. Prolonged Lead exposure affects iron metabolism, by competitively blocking iron absorption leading to anemia. Blood Lead (BL) inhibits key enzymes ferrochelatase and aminolevulinic acid dehydrogenase (ALAD) involved in hemoglobin (Hb) biosynthesis even at very low levels. Lead poisoning and malaria infection geographically overlap, and both produce similar hematological outcome especially in children. Malaria parasites cause anemia by destroying parasitized red blood cells, therefore, co-existence of BL and malaria parasites infection worsens the anemia status of the host. This study aimed at expounding the extent of heme synthesis inhibition by BL levels among a study group of malaria positive children by measuring levels of free erythrocyte protoporphyrin (FEP) in blood samples. Briefly venous blood samples from 198 children were analyzed for malaria parasite densities by the thick smear method, hemoglobin (Hb) concentrations determined by the standard cyan methemoglobin method, BLL were analyzed on an atomic absorption spectrophotometer and FEP levels were fluorometrically measured. The results showed means of BLL (9.3 µg/dL), Hb (7.5 g/dL), FEP/Hb (8.3 µg/g) and parasite density (PD) (3.21×10³ parasites / µL) among the study group. A majority of 151/198 (76.3%) of the children were moderately anemic while 8/198 (4%) were severely anemic. There was weak correlation between PD and Hb (R²= -0.15, P-value < 0.001), as compared to one between FEP/Hb and Hb (R²= -0.6, P-value=0.001). The study concludes that BL is a significant contributor to malaria anemia and should be considered in the management of anemia in malaria-endemic areas.