P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Blood cell analysis is a crucial diagnostic process in medical practice. In particular, detecting white blood cells (WBCs) is essential for diagnosing of many diseases. The manual screening of blood films is a time-consuming and subjective process, which can lead to inconsistencies and errors. Therefore, automated detection of blood cells can improve the accuracy and efficiency of the screening process. In this study, an explainable Vision Transformer (ViT) model was proposed for the automatic detection of WBCs from blood films. The proposed model utilizes the self-attention mechanism to extract relevant features from the input images and leverages transfer learning by incorporating pre-trained model weights to improve its performance. The proposed model achieved a classification accuracy of 99.40% for five distinct types of WBCs and exhibited potential in reducing the time required for manual screening of blood films by pathologists. Upon examination of the misclassified test samples, it was observed that incorrect predictions were correlated with the presence or absence of granules in the cell samples. To validate this observation, the dataset was divided into two classes, namely Granulocytes and Agranulocytes, and a secondary training process was conducted. The resulting ViT model trained for binary classification achieved an accuracy of 99.70%, recall of 99.54%, precision of 99.32%, and F-1 score of 99.43% during the test phase. To ensure the reliability of the ViT model's multi-class classification of WBCs, the pixel areas that the model focuses on in its predictions are visualized through the Score-CAM algorithm.

Rotaviruses are highly infectious and typically transmitted by fecal-oral route via in the tropics and leading the cause of diarrheal deaths in children of developing countries, besides causing significant economic impacts like neonatal disease agents of domestic animals. This present report aims to present the clinical and diagnostic findings of two confirmed cases of rotavirus (RV) infection in orphaned Leopardus tigrinus (Schreber, 1775) and Leopardus pardalis (Linnaeus, 1758), the first register of the infection by group A rotavirus in these species. Both felids were rescued in the Pará State Amazon Brazil by the IBAMA (the Brazilian Institute of Environment and Renewable Natural Resources), and treated by veterinarians into intensive care ward in a public Environmental Park of Belém city. After the adaptation period to the quarantine, these animals showed non-specific symptoms of acute fulminant gastroenteritis. Rotavirus group A antigen was identified in blood and faecal samples of L. tigrinus analyzed by immunochromatography (ICG) and immunoassay methods (ELISA) at the Virology Laboratory of the Institute Evandro Chagas. The animals died within few days during the clinical exacerbation unresponsive to current treatment, its necropsies and histopathological analysis were performed in the Laboratory of Veterinary Pathology of the Federal Rural University of Amazonia (UFRA). Despite the compatible pathologic findings of rotavirus infection in both animals, the atypical hemorrhagic character was a curious finding, considering the presumed etiology.

The aim of this study was to find a correlation between in vivo NIR scan patterns, oxidative status, and blood serum metabolites in rabbits fed diets protected or unprotected against oxidation. Rabbits does in groups of eight were fed for 9 weeks with diets containing linseed, rich in polyunsaturated fatty acids (LS), or linseed plus hazelnut skins, with antioxidant function (LS+HS), and palm oil, rich in saturated fatty acids (PO). The animals were examined at days 1, 31, and 63 using a smart SCÏO molecular sensor, a new miniaturized web-based wireless device, applied to the internal ear flap (NIR range 740-1070 nm). The hazelnut peels integrated diet protected the rabbits from the oxidative stress induced by the addition of unprotected polyunsaturated fats. NIR tomoscopy was variously correlated with serum parameters, lysozyme (R2=0.71), ROMs (0.47), cholesterol (0.49), triglycerides (0.40), and a multivariate Index of Oxidative Risk (0.67 [IOR]). The correlations suggested a close connection between the clustering of the diets according to the laboratory variables and the NIRS scan pattern clustering at the ending trial day, as shown by the highly significant odds ratios. Advantageous use of this simple, painless technique was evident in the planning phase, with no difference among the groups at the beginning of the study, but an effect size that evolved differently over time until the end of the study. In a practical validation of the SCÏO model in 92 commercial rabbit does, the average spread of the predicted IOR was 33% in lactating does (2.54±0.05) vs. dry does (1.91±0.07).

Background: High blood pressure (BP) has been implicated as a major risk factor for cardiovascular diseases in several global populations, including in individuals of African ancestry. Despite the elevated burden of high BP-induced cardiovascular diseases in Africa and other global populations with African ancestry, limited genetic studies have been carried out to explore the genetic machinery driving this phenomenon. Methods: We performed univariate and multivariate analyses using Genome-wide association studies (GWAS) and summary statistics data of 77,850 individuals of African ancestry for systolic (SBP) and diastolic blood pressure (DBP) traits. The six independent cohorts used included individuals derived from the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). Subsequently, we annotated, prioritized, visualized, and interpreted our meta-analyses results using FUMA, to gain further insight into the molecular mechanism(s) that contribute to the genetics of BP traits. Finally, loci attaining genome-wide significance, GWS (p<5x10-8) were also followed up with Bayesian fine-mapping to identify potential causal variants. Results: Our meta-analyses altogether identified 350 GWAS SNPs for SBP (166 SNPs) and DBP (184 SNPs, including two novel loci) whilst our multivariate GWAS method identified 166 SNPs (including three novel loci). Interestingly, in FUMA there was significant tissue enrichment of up-regulated differentially expressed genes (DEGs) in the sigmoid and transverse colon for SBP, as well as 10 significant gene sets from MAGMA gene set analyses, However, for DBP, no significant DEGs nor gene sets in MAGMA were found; instead, in DBP for gene property analysis for tissue specificity nine candidates were found to be significant and all nine were in different brain regions. Finally, Bayesian fine-mapping revealed that only 11 variants from the lead SNPs had >50% posterior probability (PP) of being causal and they included novel variant rs562545 (MOBP, PP = 77%) and 10 other previously published variants. Conclusion: Our results demonstrate the importance of performing GWAS in large sample sizes of global populations of African ancestry, including continental Africans; which yield novel insights, from novel loci to novel pathways/tissue expression candidates. Large-scale genomic datasets are required to enhance further discovery and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits. Our study highlights the need for diversity in genetic research and the importance of expanding large GWASs to include ancestrally diverse populations.

Several common and functional genes are known to contribute to responsiveness to blood pressure (BP) therapy. BP therapy is typically guided by algorithms that do not include a patient’s genetic information. This study aimed to determine the impact of a multi-organ genetic panel on BP response to pharmacotherapy. Eighty-six patients completed one study visit consisting of a buccal swab collection, measurement of office BP, and a medical chart review for BP history. Genes analyzed included those that encode for one drug metabolizing enzyme, renal Na+ handling, vascular, and cardiac function. Relationships between genotype and control of BP (<140/<90), ∆ systolic BP, ∆ diastolic BP, and ∆ mean arterial BP were assessed. SLC12A3 resulted in a significant association between the target drug and the functional genotype for BP control (<140/<90 cut off) (p<0.05). Conversely, three of five renal genotypes were associated with BP control using 120/80 as a cut-off (p<0.05). Three of four cardiac genotypes were associated with the BP control at <140/<90, with one being statistically significant (position 49 of ADRB1). Only one vascular genotype was predictive of blood pressure control at <140/<90. We found a significant drop in mean BP from baseline in six genes, three important in the diuretic response and three in β-blockade (p<0.05 on target drug vs. not). These results demonstrate that a multi-gene panel for renal Na+ handling, vascular function, and cardiac output may influence the BP response to therapy, but larger studies with more statistical power are needed.

The aim of our study was to describe our experience using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated red blood cell exchange (RCE) to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter (CVC). We recommend the use of heparin locking, with 500 units in each lumen of a CVC. This method was well tolerated, with few complications during the procedures. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30% since this is a mandatory condition imposed by the anaesthesiologist. With a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RCE procedure of ≤30 days, it was able to maintain the residual HbS level below 30%. Despite a target pre‐exchange HbS level of 47%, we did not encounter a single stroke recurrence. Erythrocytapheresis is useful and safe for children with SCD.

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant to treat partial seizures and neuropathic pain. While a majority of the side effects are associated with the nervous system, emerging evidence suggests a high risk for heart diseases in the patients taking GBP. In the present study, we used a preclinical model of rats to investigate (1) the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and (2) the effects of chronic GBP treatment (i.p. 100 mg/kg/day x 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane-anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In experiment (1), we found that i.v. GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (*p < 0.05 and **p < 0.01 vs baseline; n = 4/group). In experiment (2), we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Particularly, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.

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.

A variable annuity is a popular life insurance product that comes with financial guarantees. Using Monte Carlo simulation to value a large variable annuity portfolio is extremely time-consuming. Metamodeling approaches have been proposed in the literature to speed up the valuation process. In metamodeling, a metamodel is first fitted to a small number of variable annuity contracts and then used to predict the values of all other contracts. However, metamodels that have been investigated in the literature are sophisticated predictive models. In this paper, we investigate the use of linear regression models with interaction effects for the valuation of large variable annuity portfolios. Our numerical results show that linear regression models with interactions are able to produce accurate predictions and can be useful additions to the toolbox of metamodels that insurance companies can use to speed up the valuation of large VA portfolios.

The growing interest related to the proposal of formal definition of a new geological period that has being called “Anthropocene” has introduced a buzzing dynamics in the scientific community, but its conduct is perhaps due to various interests involved in a discussion that has long surpassed the contours of the so-called “Geosciences”. Themes such as “Climate Change or Drift”, “Global Warming”, “Massive Extinction of Species” and “Loss of bio and geodiversity”, among others, are the wheel of a geomorphogenetic dynamics of anthropocentric origin, which leads the debate. But are the conditions for the formal establishment of a new morphosedimentary cycle following the Meghalayanian (Upper Holocene) Age? This work pursues a line of thought that seeks to answer these and other questions, based on the official position of the institutes that have the scientific competence for the formalization under consideration, and the formal criteria that should be considered for this purpose.

Any quantization maps linearly functions on a phase space to symmetric operators in a Hilbert space. Covariant integral quantization combines operator-valued measure with symmetry group of the phase space. Covariant means that the quantization map intertwines classical (geometric operation) and quantum (unitary transformations) symmetries. Integral means that we use all ressources of integral calculus, in order to implement the method when we apply it to singular functions, or distributions, for which the integral calculus is an essential ingredient. In this paper we emphasize the deep connection between Fourier transform and covariant integral quantization when the Weyl-Heisenberg and affine groups are involved. We show with our generalisations of the Wigner-Weyl transform that many properties of the Weyl integral quantization, commonly viewed as optimal, are actually shared by a large family of integral quantizations.

Public goods are produced at all levels of the biological hierarchy, from the secretion of diffusible molecules by cells to social interactions in humans. However, the cooperation needed to produce public goods is vulnerable to exploitation by free-riders — the Tragedy of the Commons. The dominant solutions to this problem of collective action are that some form of positive assortment (due to kinship or spatial structure) or enforcement (reward and punishment) is necessary for public-goods cooperation to evolve and be maintained. However, these solutions are only needed when individual contributions to the public good accrue linearly, and the assumption of linearity is never true in biology. We explain how cooperation for nonlinear public goods is maintained endogenously and does not require positive-assortment or enforcement mechanisms, and we review the considerable empirical evidence for the existence and maintenance of nonlinear public goods in microbiology, cancer biology, and behavioral ecology. We argue that it is time to move beyond discussions about assortment and enforcement in the study of cooperation in biology.

Late January 2020, COVID-19 unexpectedly imposed world-wide limitations on daily life. Deemed a pandemic mid-March 2020, lockdowns were imposed for an indefinite period, including at academic institutions. Consequently, interest in digital literacy—an on-going and increasing concern of academic institutions in the 21^st century—exponentially heightened. Continuing meetings of academic groups now necessitated online communication. In the almost overnight closure of all non-essential services, academic units at one post-secondary institution expeditiously selected Zoom—a popular video conferencing application—as the preferred platform for meetings until social distancing was lifted. In contrast to this widely accepted use of Zoom for scheduled meetings, one unique health-related group at the institution, tailored to the 4Cs of 21^st century learning of critical thought, communication, cooperation and creativity, found social networking through a private Facebook group a more appropriate and satisfying group experience than likely possible with the Zoom app. Pros and cons of both online platforms are presented along with when each choice is warranted. In promoting digital literacy as the primary goal in online communication for academic meetings, private Facebook groups hold promise for collaborative online academic meetings with similar features to this health-related group.

Abstract: The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered blood grafts (TEBGs) have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEBG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEBG with a focus on the biomaterials and deposition methods.

This study reports results of focus groups with school nurses and teachers from elementary, middle, and high schools to explore their perceptions of child and adolescent oral health. Participants included 14 school nurses and 15 teachers (83% Female; 31% Hispanic, 21% White, 21% Asian, 14% African American, and 13% Others). Respondents were recruited from Los Angeles County schools and scheduled by school level for six one-hour focus groups, using Zoom. Audio recordings were transcribed, reviewed, and saved with anonymization of speaker identities. NVivo software was used to facilitate content analysis and identify key themes. The nurses’ rate of “Oral Health Education” comments statistically exceeded that of teachers, while teachers had higher rates for “Parental Involvement” and “Mutual Perception” “Need for Care” was perceived to be more prevalent in immigrants to the United States based on student behaviors and complaints. “Access to Care” was seen as primarily the nurse’s role. Strong relationships between community clinics and schools were viewed by some as integral to students achieving good oral health. The results suggest dimensions and questions important to item development for oral health surveys of children and parents to address screening, management, program assessment, and policy planning.

Background: Strong indicators of inflammation, such as C-reactive protein (CRP), hypersensitive CRP (hs-CRP), and a series of hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and red blood cell distribution width (RDW), are regarded related with the incidence of contrast induced nephropathy (CIN) closely. Whereas, it remains unclear whether they can function as predictors of CIN onset. The objective of this meta-analysis was to determine the relationship between above indicators and CIN incidence among patients receiving coronary intervention. Methods: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to June 3rd, 2020. Meta-analysis was performed on pool eligible studies. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 26 studies involving 29,454 patients were included in the meta-analysis. Pooled analysis results revealed that patients with higher CRP (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.01–1.12, P=0.02), hs-CRP (OR=1.03, 95% CI: 1.01–1.06, P=0.004), NLR (OR=1.11, 95% CI: 1.01–1.20, P=0.02), RDW (OR=1.35, 95% CI: 1.19–1.53, P<0.00001), and lower HCT (OR=0.94, 95% CI: 0.92–0.97, P=0.0003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR=1.12, 95% CI: 0.99–1.26, P=0.07). Conclusion: The meta-analysis reported here demonstrates that pre-angiography CRP/hs-CRP and some hematological indices are associated with CIN.

Background: Transit-time flow measurement (TTFM) is frequently used to evaluate intraoperative quality control during coronary artery bypass grafting (CABG). Although TTFM has the ability to assess graft failure intraoperatively, the perioperative factors affecting TTFM during CABG surgery remain poorly understood. Methods: Patients who underwent CABG surgery at a single institution between July 2016 and May 2018 were prospectively evaluated. Patients’ demographic characteristics, previous medical history, Euroscore, the results of preoperative blood tests, and intraoperative data were recorded. TTFM and blood viscosity were measured hemodynamically, and mean flow (mL/min) and pulsatility index (PI) were recorded. Arterial blood gas was analyzed immediately after anastomosis of the left internal mammary artery (LIMA) to the left descending artery (LAD) and before sternal closure. Factors associated with TTFM were assessed by multiple linear regression analysis. Results: Of the 62 patients who underwent CABG surgery during the study period, 57 were evaluated, including 49 who underwent off-pump and eight who underwent on-pump surgery. Blood viscosity was not significantly associated with TTFM (p > 0.05). However, TTFM was significantly associated with body mass index (BMI), systolic blood pressure, and cardiac index (p < 0.05 each). Conclusions: Blood viscosity was not significantly associated with intraoperative graft flow. Blood flow of graft vessels, however, was significantly associated with BMI, systolic blood pressure, and cardiac index.

Bioconvective flows have attracted attention in recent years due to actual and potential applications. In this paper, we consider a steady and laminar convective MHD flow of a nanofluid with heat, mass and microorganism transfer with a heat source/sink present. In addition, we assume there exists a first order chemical reaction. The governing partial differential equations (PDEs) are reduced to ordinary differential equations (ODEs) using the scaling group transformation and the associated boundary value problem is then solved. The influences of selected governing parameters on the dimensionless velocity, temperature, nanoparticle concentration, density of motile microorganisms, skin friction, heat transfer, mass transfer, and motile microorganism density rates are computed and discussed

Gonorrhea is a major global public health problem with emergence of multiple drug-resistant strains with no effective vaccine. This retrospective cohort study aimed to estimate the effectiveness of the New Zealand meningococcal B vaccine against gonorrhea associated hospitalization. The cohort consisted of individuals born 1984-1999 residing in New Zealand, therefore eligible for meningococcal B vaccination during 2004-2008. Administrative datasets of demographics, customs, hospitalization, education, income tax and immunization, were linked using the national Integrated Data Infrastructure. The primary outcome was hospitalization with a primary diagnosis of gonorrhea. Cox’s proportional hazards models were applied with a Firth correction for rare outcomes to generate estimates of hazard ratios. Vaccine effectiveness estimates were calculated as 1-Hazard Ratio expressed as percent. There were 1,143,897 eligible cohort members, with 135 missing information on gender, 16,245 missing ethnicity and/or 197,502 missing deprivation hence 935,496 were included in the analysis. After adjustment for gender, ethnicity and deprivation, vaccine effectiveness (MeNZB™) against hospitalization caused by gonorrhea was estimated to be 24% (95% CI 1-42%). In conclusion, vaccination with MeNZB™ significantly reduced the rate of hospitalization from gonorrhea. This supports prior research indicating possible cross protection of this vaccine against gonorrhea acquisition and disease in the outpatient setting.

Methylmercury is a neurotoxin present in fish tissues that permeates the blood-brain barrier after consumption. Previous research has shown that methylmercury is harmful to neurons, causing pH alterations, oxidative stress, excitotoxicity, and parenchymal damage. Methylmercury is a known factor of neurological disorders including Alzheimer's and Parkinson's. The method by which methylmercury passes through the blood-brain barrier is largely unknown. According to preliminary studies, one way methylmercury crosses the blood-brain barrier is by creating a complex with L-Cysteine, which facilitates its passage by the LATs system through mimicking another amino acid existing in the body. The human blood-brain barrier was studied using C. elegans as a model organism. It was hypothesized that if methylmercury passes through the blood-brain barrier of C. elegans faster with L-Cysteine present than without L-Cysteine present, the methylmercury's adverse effects (death and locomotive difficulty) will occur sooner. Each of the four experimental groups contained one C. elegans: the control, the L-Cysteine group, the methylmercury group, and the methylmercury and L-Cysteine combination group. The effects of L-Cysteine and methylmercury on C. elegans were studied using three metrics: viability, locomotive disability, and time for locomotive effects to occur. The group that received both methylmercury and L-Cysteine had reduced viability rates and a decreased time for locomotive difficulty to develop, supporting the hypothesis. These findings suggest that L-Cysteine aids methylmercury permeation through the blood-brain barrier. Because the experiment indicates how methylmercury penetrates the blood-brain barrier, these results aid in finding a therapeutic solution to reverse methylmercury neurotoxicity in the brain. Additionally, this study further opens channels into potential therapeutic and preventative measures for dementia, improving morbidity and mortality in neurodegenerative diseases.

Background: Sex differences in blood pressure (BP) exist during all reproductive life between women and men whereas a sharper increase in BP occurs after menopause which is associated with increased prevalence of cardiovascular diseases. This study examined cardiovascular and biochemical parameters in perimenopausal women (PW) aiming to investigate the influence of sex on a) office BP and for 24 hours; b) cardiac autonomic modulation; c) redox state by measuring MDA, SOD, and catalase; d) NO_x^- concentration. In addition, aerobic exercise training (AET) was applied for detecting changes in cardiovascular responsiveness during the menopausal transition. Methods: Thirty-one participants were enrolled, healthy PW and age-matched men. Cardiovascular and biochemical biomarkers were evaluated at baseline and after AET (8 weeks of exercise on a treadmill, three sessions/week, duration of 30-40 minutes). Results: At rest, PW presented: a) a lower diastolic BP during daytime; b) a lower absolute and normalized LF component as well as a higher HF normalized component; d) no sex differences for redox biomarkers and NO_x^- concentration. After AET, only PW was responsive in lowering systolic BP that was accompanied by an increase in NO_x^- concentration and SOD activity. Regarding HRV, both groups were responsive to the AET. Conclusions: During the menopausal transition, systolic BP was similar to men whereas cardiac autonomic modulation remained unaltered showing the influence of sex steroids on BP. In Addition, AET was fundamental during the menopause transition by preventing an elevation in BP, minimizing the effects of aging associated with estrogen deficiency on women's cardiovascular health.

COVID-19 appeared as an infectious disease of global health emergency and the highest public health concern of 21st century for this world due to its high-speed of spread across the globe. The disease started as one single case to a cluster of cases in Wuhan, China (Dec 2019) and within few months with its continuous upsurge of cases spreading globally which has created enormous threat and tension across the global Public health care field. Most significantly to share the fact that, this disease caused high level of Risk Group mortality, high morbidity, health care services burden, panic anxiety, mental trauma and tension, social and economic insecurity, which also collectively surfaced by diverse range of social reaction and political pressure across the world. Also with the appearance of new and unknown pathogenesis of the disease has created the most and significant attention and concern for the scientific community and political leaders as well. The disease also varies much with its pattern of virus, sign, symptoms, characteristics including its epidemiological and public health response (like prevention strategy, diagnoses, case management, treatment pattern) across the countries. However, this variance is comparatively less rather even more in commonality while it comes to basic public health prevention interventions like frequent hand washing, wearing face mask, maintaining social/physical distancing (2 - 6 meter in between), individual isolation and community quarantine for suspected exposure and lockdown in community areas where cases are identified. These are with the most commonly practiced public health interventions to deal with this disease in majority of the epicenters across countries. Also with the progress of the disease with its diverse categorical appearance of sign symptoms which are uniquely portraying this disease is more of a kind of COVID-19 syndrome than as COVID-19. Moreover, various factors including socio economic status, health status, population dynamics, health system and infrastructure, health behavioral pattern, nutrition and food habit and access to information and knowledge made this viral disease one of the historically counted on expensive disease of the modern world to fight for. Specially to mention here, the case fatality rate distinctively vary with the population dynamics and the health system infrastructure and ability factors which have already created clear evidence as explained in this paper how these factors are uniquely distinguished and different from country to country. Apart from the contextual differences, the various kind of ongoing preventive measures (like prevention, diagnosis and treatment) learnt every day from the emerging characteristics and pattern of this viral disease which are most commonly practiced across countries with a variance. According to the Public health prevention practice and interventions, the total world is connected and learning from each other’s public health experiences to fight for the virus. However, the world communities are eagerly waiting to see the result and outcome of the ongoing therapeutics and vaccine trial initiated in several countries, the people of the world are quite optimistic and hopeful that, global scientific community will be able to invent some miraculous and magic solution in upcoming months which ultimately will free the world from this most terrifying COVID-19 pandemic of 21st century.

Introduction: multiple sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS), affecting young people. Due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on the patients’ health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: in this review, we summarise the most up to date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Author commentary: the current diagnostic criteria of MS rely on three pillars; MRI imaging, clinical events and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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.

The present study was conducted the status of sea bass from Kokko and Kyuntone of The Gulf of Motttama Wetland (GoMW) area in Thanatpin Township in Bago Region Myanmar from September 2019 to August 2020. Fifty specimens were monthly collected, measured and weighed. Invoices of sea bass were collected for the depot and fish sellers by monthly. In Kokko, mean value of standard length and body weight were highest in March (32.70±1.58, 660.7±112.23). The mean value of standard length was peak in January (31.39±7.16) but peak of body weight was in March (963.24±280.86) in Kyuntone villages. The lowest mean value of standard length and body weight were found in June at both study areas. According to the invoice data revealed that monthly catch weight of sea bass is most abundance in October (829.92) kg in Kokko, (339.12) kg in Kyuntone. Based on price of relations to size group, small size C &lt; 300g (41%) was mostly abundance in Kokko and in Kyuntone small size C &lt; 300g (35%) was second abundance. Specimens were not landed in April and May. In June, young specimens were very rarely seen in both study sites. The important roles of wetland fishes, the economic valuation of GOMW in Myanmar and samples of fishing gear and value chain of sea bass in Myanmar was expressed in this study.

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.

In the coming years, the Anthropocene Working Group (AWG) will submit its proposal on the ‘Anthropocene’ as a new geological epoch to the International Commission on Stratigraphy (ICS) for approval. If approved, the proposal will be send to the International Union of Geological Sciences (IUGS) for ratification. If the proposal is approved and ratified, the ‘Anthropocene’ will be formalised and the Holocene Series/Epoch will be officially terminated. Currently, the ‘Anthropocene’ is a broadly used term and concept in a wide range of scientific and non-scientific situations and, for many, the official acceptance of this term is only a matter of time. However, the AWG proposal, in its present state, seems to not fully meet the ICS requirements for a new geological epoch. This paper asks what could happen if the current ‘Anthropocene’ proposal is not formalised by the ICS/IUGS. The possible stratigraphic alternatives are evaluated on the basis of the more recent literature and the personal opinions of distinguished AWG and ICS members. The eventual impact on environmental sciences and on non-scientific sectors, where the ‘Anthropocene’ seems already firmly rooted and de facto accepted as a new geological epoch, are also discussed.

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.

The deterioration and destruction of the environment is becoming more and more considerable and greater efforts are needed to stop it. To accomplish this feat, all members of society must identify with environmental problems, with collective environmental action being one of the most relevant means of doing so. From this perspective, the analysis of the psychosocial factors that lead to participation in environmental collective action emerges as a priority objective in the research agenda. Thus, the aim of this study is to examine the role of "environmental identity" as conceptualized by Clayton, as a central axis for explaining environmental collective action. The inclusion of the latter in the theoretical framework of the SIMCA model gives rise to the model that we have called EIMECA. Two studies were conducted, and the results reveal that environmental identity, a variety of negative affects, as well as group efficacy accompanied by hope for a simultaneous additive effect, are critical when it comes to predicting environmental collective action.

The idea of using the lytic power of viruses against the malignant cells has been entertained for many decades. However, oncolytic viruses (OV) gained broad attention as an emerging anti-cancer therapy only recently with the successful implementation of the oncolytic herpesvirus to treat advanced melanoma. OVs offer an attractive therapeutic combination of tumor-specific cell lysis together with immune stimulation, yet the latter effect is less well studied. Nevertheless, OVs can be envisaged as potential in situ tumor vaccines. The therapeutic potential of OVs can be instigated further by using the molecular biological and biotechnological tools to modify the existing viruses for their optimal tumor selectivity and enhanced immune stimulation. Furthermore, OVs can be readily combined with other therapeutic agents to increase the efficacy of the existing therapeutic schemes. In this review, we discuss biotechnological advances in the development of therapeutic applications of OVs in Russia. Particular emphasis is made on the OV-mediated treatment of glioblastoma. In addition, we highlight the challenges of oncolytic virotherapy, and describe the strategies to optimize current approaches to improve clinical outcomes.

The entropy of Boltzmann-Gibbs, as proved by Shannon and Khinchin, is based on four axioms, where the fourth one concerns additivity. The group theoretic entropies make use of formal group theory to replace this axiom with a more general composability axiom. As has been pointed out before, generalized entropies crucially depend on the number of allowed number degrees of freedom $N$. The functional form of group entropies is restricted (though not uniquely determined) by assuming extensivity on the equal probability ensemble, which leads to classes of functionals corresponding to sub-exponential, exponential or super-exponential dependence of the phase space volume $W$ on $N$. We review the ensuing entropies, discuss the composability axiom, relate to the Gibbs' paradox discussion and explain why group entropies may be particularly relevant from an information theoretic perspective.

Marine invertebrates are model organisms in several areas of biological sciences, being a source of massive biological information. Although, the scientific relevance of marine invertebrates, the research with them can be limited for their tissue characteristics and troubles for the replication of physical and chemical properties of seawater. Thence, the main goal of this laboratory workflow is to provide a useful methodological approach to reduce the experimental limitations during the study of marine invertebrates. The present study describes experimental methodologies for the collection, transport, and maintenance of sessile tunicates. Also, an approach to observe and characterize, a diverse population of blood cells in marine invertebrates, by several cytological stains and electron microscopy. Lastly, suggestions and protocols to extract quality RNA from samples with high concentrations of salts, pigments, secondary metabolites, and polysaccharides. This methodological approach can be easily adapted to other marine invertebrates, moreover uses low-cost reagents and widely available laboratory equipment. Making possible the study of different types of marine animals in diverse locations.

Patient group engagement is increasingly used to inform the design, conduct, and dissemination of clinical trials and other medical research activities. However, the priorities of industry sponsors and patient groups differ, and there is currently no framework to help these groups identify mutually beneficial engagement activities. Methods: We conducted 28 qualitative, semi-structured interviews with representatives from research sponsor organizations (n=14) and patient groups (n=14) to determine: 1) how representatives define benefits and investments of patient group engagement in medical product development and, 2) to refine a list of 31 predefined patient group engagement activities. Results: Patient group and sponsor representatives described similar benefits: engagement activities can enhance the quality and efficiency of clinical trials by improving patient recruitment and retention, reduce costs, and help trials meet expectations of regulators and payers. All representatives indicated that investments include both dedicated staff time and expertise, and financial resources. Factors to consider when evaluating benefits and investments were also identified as were suggestions for clarifying the list of engagement activities. Discussion: Using these findings, we refined the 31 engagement activities to 24 unique activities across the medical product development lifecycle. We also developed a web-based prioritization tool (https://prioritizationtool.ctti-clinicaltrials.org/) to help clinical research sponsors and patient groups identify high priority engagement activities. Use of this tools can help sponsors and patient groups identify the engagement activities that they believe will provide the most benefit for the least investment and may lead to more meaningful and mutually beneficial partnerships in medical product development.

This study aims to develop a performance evaluation system that can facilitate performance evaluation at region, hospital, and department levels to enable better cost management for sustainable development. A multi-level system of performance evaluation informs a hierarchical assessment of cost management from regions to hospitals to departments using diagnosis-related group (DRGs). Various metrics are developed employing the variances between targets and actuals where targets are determined from two perspectives: benchmarking using external regional prices and change management using internal data. Targets for the latter are statistically based and specifically incorporate variability. The model is applied to two hospitals, twenty departments, nine DRGs and 1071 inpatients. The analyses indicate that the approach can provide a practical evaluation tool that allows for particular characteristics at multiple levels. The system provides macro-micro and external-internal perspectives in performance, enabling high-level variances to be decomposed thereby identifying sources of performance variability and financial impact.

We hypothesized possibility that inline registered reticulorumen pH can be as biomarker of cows reproduction and health status. Aim of this study was to evaluate the relationship of reticulorumen pH with biomarkers from automatic milking system (AMS) and some blood parameters and determinate reticulorumen pH as biomarker of cows reproduction and health status. According to cows reproductive status the cows were classified as belonging to the following four groups: 15-30 d. postpartum; 1-34 d. after insemination; 35 d. after insemination (non-pregnant); 35 d. after insemination (pregnant). According reticulorumen pH assay experimental animals were divided into four classes: 1) pH<6.22 (5.3% of cows), 2) pH - 6.22-6.42 (42.1% of cows), 3) pH - 6.42-6.62 (21.1% of cows), 4) pH >6.62 (10.5% of cows). Rumination time, body weight, milk yield, milk fat – protein ratio, milk lactose, milk somatic cell count (SCC), milk electrical conductivity of all quarters of udder were registered with the help of Lely Astronaut® A3 milking robots. The pH, temperature of the contents of cow reticulorumens and cow activity were measured using specific smaX-tec boluses. Blood gas parameters were analyzed using a blood gas analyzer (EPOC, Canada). We found that pregnant cows has higher reticulorumen pH during insemination time, comparing with non-pregnant. Cows with lower reticulorumen pH has lowest milk fat – protein ratio, and lactose concentration, and highest SCC. Cows with lowest reticulorumen pH has lowest blood pH. With increase reticulorumen pH, increases blood potasium and hematocrit, decreases CO2, saturation and sodium.

Inherited platelet disorders (IPDs) are rare diseases featured by low platelet count and/or defective platelet function. Patients have variable bleeding diathesis and sometimes additional features that can be congenital or acquired. Identification of an IPD is desirable to avoid misdiagnosis of immune thrombocytopenia and use of improper treatments. Diagnostic tools include platelet function studies and genetic testing. The latter can be challenging as the correlation of its outcomes with phenotype is not easy. The immune-morphological evaluation of blood smear (by light- and immunofluorescence microscopy) represents a reliable method to phenotype subjects with suspected IPD. It is relatively cheap, not excessively time-consuming, and applicable to shipped samples. In some forms, it can provide diagnosis by itself, as for MYH9-RD, or in addition to other first-line tests as aggregometry or flow cytometry. In regard to genetic testing, it can guide specific sequencing. Since only minimal amounts of blood are needed for preparation of blood smears, it can be used to further characterize thrombocytopenia in pediatric patients and even newborns. In principle it is based on visualizing alterations in the distribution of proteins, which result from specific genetic mutations, by using monoclonal antibodies. It can be applied to identify deficiencies in membrane proteins, disturbed distribution of cytoskeletal proteins, and alpha as well as delta granules. On the other hand mutations associated with impaired signal transduction are difficult to identify by immunofluorescence of blood smears. This review summarizes technical aspects and the main diagnostic patterns achievable by this method.

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.

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Also, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including N=229 African American and N=381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, N = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (N = 27,955) and Hispanic/Latino (N = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p < 1×10^(-4)) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (N=802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

In the implementation of thermal enhanced oil recovery (TEOR) techniques, the temperature impact on relative permeability in oil - water systems is of special concern. Hence, developing a fast and reliable tool to model the temperature effect on two-phase oil - water relative permeability is still a major challenge for precise studying and evaluation of TEOR processes. To reach the goal of this work, two promising soft-computing algorithms, namely Group Method of Data Handling (GMDH) and Gene Expression Programming (GEP) were employed to develop reliable, accurate, simple and quick to use paradigms to predict the temperature dependency of relative permeability in oil - water systems (K_rw and K_ro). To do so, a large database encompassing wide-ranging temperatures and fluids/rock parameters, including oil and water viscosities, absolute permeability and water saturation, was considered to establish these correlations. Statistical results and graphical analyses disclosed the high degree of accuracy for the proposed correlations in emulating the experimental results. In addition, GEP based correlations were found to be the most consistent with root mean square error (RMSE) values of 0.0284 and 0.0636 for K_rw and K_ro, respectively. Lastly, the comparison of the performances of our correlations against those of the preexisting ones indicated the large superiority of the introduced correlations compared to previously published methods. The findings of this study can help for better understanding and studying the temperature dependency of oil - water relative permeability in thermal enhanced oil recovery processes.

Discriminatory attitudes towards people living with HIV/AIDS are prevalent. A Joint United Nations Program on HIV/AIDS report (2019) indicated that more than 50% of the people surveyed in one of the studies spanning 26 countries expressed unfavorable attitudes towards HIV-positive people. The objective of this study was to assess the attitudes of senior Education Studies students at a university in Spain towards people with HIV/AIDS so as to propose specific educational interventions. The study employed a quantitative methodological approach; a questionnaire with a 14-item attitude score served as the analytical instrument. The study sample comprised 613 students from the School of Education at the University of Huelva, Spain. The results showed that more than 50% of the School’s senior students had discriminatory attitudes towards HIV-positive people, some of whom were fellow classmates. This study proposes several formative approaches to reducing the stigma suffered by HIV-positive people, while also improving senior students’ skills and capabilities in the field of health promotion.

Current lines of research into mood disorders indicate that immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain functions, even when these mediators are produced in peripheral tissues. Elevated levels of circulating immune molecules have been consistently associated with depressive symptoms in a number of clinical populations and experimental models, to the extent that major depressive disorder (MDD) is now seen, at least in part, as a disorder of immunity. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy with the hope to improve treatment efficacy, particularly in those cohorts that do not respond well to standard medication. Such new practice requires the availability of biomarkers to tailor these new therapies to those most likely to benefit but also clear mechanisms of action describing the interaction between peripheral immunity and brain function. These mechanisms are generally studied in preclinical models that try to recapitulate the human disease through peripherally induced sickness behaviour as the model for immune-induced MDD. After an appraisal of the data in rodent models and their adherence to the data in clinical cohorts, we propose a modified model of periphery-brain interaction that goes beyond the currently established view of interaction between peripheral cytokines and microglia cells as the driver of depression. Instead, we suggest that brain barriers are primary actors in the communication between body and brain and, as a consequence, in the pathophysiology of the disease. This model suggests novel biomarkers, novel targets for therapies as well as a novel mechanism for resistance to standard treatments.

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

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.

Approximately 300 different types of blood groups are identified so far, the ABO and Rh antigens are still the clinically most significant and genetically most polymorphic of all human blood group systems to date. A total of 200 unrelated individuals from Uttar Pradesh were studied for the phenotype and allele frequency distribution of ABO and Rh (D) blood groups. In total 200 samples analyzed, phenotype B blood type has the highest frequency 36.5% (n=73), followed by O (34.5%; n=69), A (20.5%; n=41) and AB (8.5%; n=17). The O, A and B frequencies were 0.5849, 0.1571 and 0.2580 respectively. The overall phenotypic frequencies of ABO blood groups were B>O>A>AB. The variation in phenotypic frequencies between male and female might be due to small sample size of male sample. The allelic frequency of Rh-negative was 0.2.

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.

Introduction: Blood transfusion involves the transfer of blood from donors to patients. A blood transfusion is carried out every 2 seconds in the US. It is made up of about 29000 units of red blood cells and is transfused every day in the US. When blood transfusion is done correctly, it can result in the saving of lives and the improvement of healthcare. However, it may also lead to immediate, late, delayed, and chronic complications. No previous studies have been conducted in Qatar to address this issue. Methods: This is a cross-sectional study intended to determine the knowledge, attitude, and practice toward blood transfusion among healthcare providers at Hamad Medical Corporation (HMC), which is the principal healthcare provider in Qatar. Participants between 18 and 25 years of age were selected for the research study. A 10-item online questionnaire that people can fill out on their own will be used to get the data needed for the analysis and meet the study's goals. Results: the analysis has indicated that facing negative reactions after blood transfusion and being worried about getting affected by any infection have a small positive association, with the specific values coming in at r = 0.317, p = 0.000. Fever after blood transfusion and feeling like refusing blood transfusion have a significant and moderate positive correlation, with the specific values coming in at r = 0.630 and p = 0.000. Conclusion: The findings of this study have helped us figure out how healthcare providers feel, what they know, and what they do during a blood transfusion.

Deep learning has achieved lots of successes in many fields, but when trainable sample are extremely limited, deep learning often under or overfitting to few samples. Meta-learning was proposed to solve difficulties in few-shot learning and fast adaptive areas. Meta-learner learns to remember some common knowledge by training on large scale tasks sampled from a certain data distribution to equip generalization when facing unseen new tasks. Due to the limitation of samples, most approaches only use shallow neural network to avoid overfitting and reduce the difficulty of training process, that causes the waste of many extra information when adapting to unseen tasks. Euclidean space-based gradient descent also make meta-learner's update inaccurate. These issues cause many meta-learning model hard to extract feature from samples and update network parameters. In this paper, we propose a novel method by using multi-stage joint training approach to post the bottleneck during adapting process. To accelerate adapt procedure, we also constraint network to Stiefel manifold, thus meta-learner could perform more stable gradient descent in limited steps. Experiment on mini-ImageNet shows that our method reaches better accuracy under 5-way 1-shot and 5-way 5-shot conditions.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

An explanation of the origin of dark matter is suggested in this work. The argument is based on symmetry considerations about the concept of mass. In the Wigner's view, the rest mass and the spin of a free elementary particle in flat space-time are the two invariants that characterize the associated unitary irreducible representation of the Poincar\'e group. The Poincar\'e group has two and only two deformations with maximal symmetry. They describe respectively the de Sitter (dS) and Anti de Sitter (AdS) kinematic symmetries. Analogously to their shared flat space-time limit, two invariants, spin and energy scale for de Sitter and rest energy for Anti de Sitter, characterize the unitary irreducible representation associated with dS and AdS elementary systems. While the dS energy scale is a simple deformation of the Poincaré rest energy and so has a purely mass nature, AdS rest energy is the sum of a purely mass component and a kind of zero-point energy derived from the curvature. An analysis based on recent estimates on the chemical freeze-out temperature marking in Early Universe the phase transition quark-gluon plasma epoch to the hadron epoch supports the guess that dark matter energy might originate from an effective AdS curvature energy.

Every protein consists of a linear sequence over an alphabet of $20$ letters/amino acids. The sequence unfolds in the $3$-dimensional space through secondary (local foldings), tertiary (bonds) and quaternary (disjoint multiple) structures. The mere existence of the genetic code for the $20$ letters of the linear chain could be predicted with the (informationally complete) irreducible characters of the finite group $G_n:=\mathbb{Z}_n \rtimes 2O$ (with $n=5$ or $7$ and $2O$ the binary octahedral group) in our previous two papers. It turns out that some quaternary structures of protein complexes display $n$-fold symmetries. We propose an approach of secondary structures based on free group theory. Our results are compared to other approaches of predicting secondary structures of proteins in terms of $\alpha$ helices, $\beta$ sheets and coils, or more refined techniques. It is shown that the secondary structure of proteins shows similarities to the structure of some hyperbolic $3$-manifolds. The hyperbolic $3$-manifold of smallest volume --Gieseking manifold--, some other $3$ manifolds and the oriented hypercartographic group are singled out as tentative models of such secondary structures. For the quaternary structure, there are links to the Kummer surface.

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.

CXCR4 is a chemokine receptor crucial in tumor progression, although the angiogenic role of CXCR4 in oral squamous cell carcinoma (OSCC) has not been investigated. Here we show that CXCR4 is crucial for tumor angiogenesis thereby supports tumor survival in OSCC. Immunohistochemistry on human clinical specimens revealed that CXCR4 and a tumor vasculature marker CD34 were co-distributed in tumor vessels in human OSCC specimens. To ask the effects of CXCR4 inhibition, we treated the OSCC-xenografted mice with AMD3100, so-called plerixafor, an antagonist of CXCR4. Notably, we found a unique pathophysiological structure defined as Tumor Angiogenic Inhibition Triggered Necrosis (TAITN) induced by the CXCR4 antagonism. Treatment with AMD3100 increased necrotic area with the induction of hypoxia-inducible factor-1α in the xenografted tumors, suggesting that AMD3100-induced TAITN was involved in hypoxia and ischemia. Taken together, we demonstrated that CXCR4 plays a crucial role in tumor angiogenesis required for OSCC progression, whereas TAITN induced by CXCR4 antagonism could be an effective anti-angiogenic therapeutic strategy in OSCC treatment.

In emergency scenarios service vehicles must identify potential route(s) and use the best available route. However, route identification requires intelligent decision-support systems which generally use non-traditional approaches with tools characterised by flexible non-hierarchical structures. Conventional models using group decision-support systems have been applied; however, when used in smart urban environments, emergency response services have limitations in their ability to identify unobstructed paths (routes) in dynamic operating environments. In this paper we introduce a novel path planning method for autonomous vehicle control in emergency situations. The proposed model uses self-organizing maps in an integrated Spiral STC algorithm termed the: Hybrid SOM-Spiral STC model which uses hedge algebras and \emph{Kansei} evaluation in group decision-support. The proposed model has been designed to quantify qualitative factors using sensor derived data processed with human sensibilities and preferences in emergency decision support. The experimental results show that the proposed model achieves significant improvements in group decision-support under dynamic uncertainty. We posit that our novel approach holds the prospect of improvements in the provision of emergency services.

AbstractBackground: the development of nursing, especially related to the nursing intervention approach, is running so fast. This can be seen from the use of peer group support in nursing interventions in individual humans. The purpose of this literature is to find the impact of implementing nursing interventions using a peer group support approach.Method: this literature review method uses JBI and Prisma on 120 articles taken from journal databases, namely Scopus, PubMed and Sciendirect.Result: From the articles analyzed, it was found that the application of peer groups can improve individual abilities both in psychological and behavioral aspects.Conclusion: the application of the peer group approach is able to be one of the approaches in the world of nursing in carrying out nursing actions today.

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.

Introduction: Leprosy, caused by Mycobacterium leprae is one of the oldest infectious diseases in human history and its eradication is linked to poverty control, lack of basic sanitation, the fragility of health, and education services. Objective: To evaluate the frequency of blood groups (ABO/Rh) and the sociodemographic and clinical profile of Angolan patients with Leprosy treated at the Anti-Tuberculosis and Leprosy Dispensary in Luanda, the capital city of Angola. Methodology: A descriptive, introspective, cross-sectional study with a quantitative approach was carried out with 102 patients of Luanda, in the second half of 2021. Results: Of the 102 patients included in the study, the majority belonged to the ORh+ group (51.9%), followed by the BRh+ group (27.4%) and ARh+ (18.6%), most were under 51 years of age ( 87.3%), with low education (54.9%), coming from urban areas (44.1%). As for clinical conditions, most had a multibacillary infection (93.1%), diagnosed mainly by smear microscopy (75.5%) without other infection (79.4%), some of them with complications (28.4%) and individuals with non-O blood group showed changes in the blood count. Conclusion: Leprosy seems to be common in ORh+ individuals, it continues to affect especially those residing in areas of population agglomerations and with low education, presenting itself as a multibacillary infection, where changes in the blood count are greater in non-O individuals.

We consider a four-dimensional Riemannian manifold M with an additional structure S, whose fourth power is minus identity. In a local coordinate system the components of the metric g and the structure S form skew-circulant matrices. Both structures S and g are compatible, such that an isometry is induced in every tangent space of M. By a special identity for the curvature tensor, generated by the Riemannian connection of g, we determine classes of Einstein and almost Einstein manifolds. For such manifolds we obtain propositions for the sectional curvatures of some characteristic 2-planes in a tangent space of M. We consider a Hermitian manifold associated with the studied manifold and find conditions for g, under which it is a K\"{a}hler manifold. We construct some examples of the considered manifolds on Lie groups.

The textbook analysis of vacuum energy density (VED) in flat spacetime follows from Pauli’s lectures of 1951, in which quantum vacuum is modeled as a reservoir of free harmonic oscillators. In his lectures, Pauli shows that deriving a nearly vanishing VED is contingent upon fulfilling three corollary conditions called polynomial-in-mass-constraints. The goal of this work is to evaluate Pauli’s constraints against the Standard Model parameters and the Higgs mechanism of spontaneous symmetry breaking.

As the world endures the coronavirus disease 2019 (COVID-19) pandemic, conditions of 35 million vulnerable individuals struggling with substance use disorders (SUDs) worldwide have not received sufficient attention for their special health and medical needs. Many of these individuals are complicated by underlying health conditions, such as cardiovascular and lung diseases and undermined immune systems. During the pandemic, access to the healthcare systems and support groups is greatly diminished. Current research on COVID-19 has not addressed the unique challenges facing individuals with SUDs, including the heightened vulnerability and susceptibility to the disease. In this systematic review, we will discuss the pathogenesis and pathology of COVID-19, and highlight potential risk factors and complications to these individuals. We will also provide insights and considerations for COVID-19 treatment and prevention in patients with SUDs.

Background: A malfunction of the innate immune response in COVID-19 is associated with eosinopenia particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils.. Methods: Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16 and CD62L) in the absence or presence of a formyl peptide (fNLF). 45 SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n=20) or other viral (n=10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSom algorithm. Results: Low blood eosinophil numbers (<100 cells/microL; p<0.005) were found both in patients with COVID-19 and with other infectious diseases albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11bbright population consisted of 5.4% (CI95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11bbright cells comprised nearly half the population (42.21%, CI95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11bbright cells before activation (7.6%, CI95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11bbright fraction after activation (23.7%, CI95% = 18.5, 27.6; p<0.001). Conclusion: Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF, which is likely caused by migration of fully functional cells to the tissue. Such homing might be beneficial as eosinophils have been implicated in viral killing.

(1) Background: High blood pressure is one of the symptoms of stroke, the Self Care Deficit theory by Dorothea Orem focuses on a person's ability to care for himself independently so that the ability to maintain his health and well-being is achieved. There are currently 600 million hypertensive patients worldwide, of which 3 million die every year. Uncontrolled high blood pressure can lead to a 7-fold increase in the chances of stroke. The existence of this condition can be minimized in patients through several innovative interventions, one of which is foot massage. This study aims to determine the effectiveness of stretching and foot massage with lavender oil in stabilizing high blood pressure in stroke patients.(2) Methods: The method used in this research is descriptive. The subjects of this case study were selected according to the inclusion and exclusion criteria of the journal Evidence-Based. Subjects included intervention patients and control patients. Foot massage therapy with lavender oil is done 2 times a day for 10-15 minutes using the effleurage technique after showering in the morning and evening. Stretching is done 2 times a day every 10-15 minutes.(3) Results: The results of the analysis showed that there was a change in blood pressure after the application of stretching and foot massage with lavender oil. From the initial examination, the results showed that the blood pressure of 170/100 mmHg decreased to 140/90 mmHg and the pain scale decreased from 4 to 0.

Ecklonia cava (E.cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. Alzheimer's disturbs the life of at least five million persons in the USA. CD4+ T cells could both exacerbate and reduce AD symptoms. Regulating CD4+ T cells homing to the leaky blood-brain barrier (BBB) constitutes a new hope for enhancing AD prognosis. Alzheimer's drugs such as Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) and memantine are known to play an important part in regulating the neurotransmitters mechanisms. However, little is known about the effect of these drugs on CD4+ T cells homing. In this review, we focus on current and new drugs that could modulate CD4+ T cells interactions with the BBB in AD.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) are environmental pollutants with a great persistence, capacity of bioaccumulation, and well known important toxic effects in humans and animals. Incinerators of hazardous, municipal and medical waste, chlorine bleaching of paper pulp, cement plants, and the traffic of motor vehicles are the most frequent emission sources of these compounds. The diet, followed at a great distance by inhalation, is generally the main way of human exposure to PCDD/Fs. Human biomonitoring is of a great importance to prevent potential adverse effects derived from exposure to chemicals such as PCDD/Fs. In relation to this, blood is among the most used biological monitors. In the current review, we have summarized the recent information (2000-2009) published in the scientific literature (databases: Scopus and PubMed) on the concentrations of PCDD/Fs in blood samples of non-occupationally exposed populations, as well as in some groups of occupationally exposed individuals. We have revised a number of studies conducted in various African American, Asian and European countries, and Australia. Unfortunately, the information is quite limited. No data are available for most countries over the world. Based on the results here reviewed –where available- the current health risks for the general populations do not seem to be of concern. Moreover, taking into account the important reductions observed in the levels of PCDD/Fs in foodstuffs, new decreases in the concentrations of PCDD/Fs in blood -and other biological tissues- are very probable in the immediate years.

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.

Associations between blood cancer and genetic predisposition, including both inherited variants and acquired mutations and epimutations, have been well characterized. However, the majority of these variants affect noncoding regions, making their mechanisms difficult to hypothesize and hindering the translation of these insights into patient benefits. Fueled by unprecedented progress in next-generation sequencing and computational integrative analysis, studies have started applying combinations of epigenetic, genome architecture and functional assays to bridge the gap between noncoding variants and blood cancer. These complementary tools have not only allowed us to understand the potential malignant role of these variants but also to differentiate key variants, cell types and conditions from misleading ones. Here, we briefly review recent studies that have provided fundamental insights into our understanding of how noncoding mutations at enhancers predispose and promote blood malignancies in the context of spatial genome architecture.

The objective of this experiment was to study the effect of feeding pellet containing high sulfur (PELFUR) diet and fresh cassava root (FCR) to Thai native beef cattle on feed use efficiency, ruminal characteristics, and blood metabolites. Four male Thai native beef cattle (150 ± 15.0 kg of body weight (BW)) were allocated with a 2 × 2 factorial arrangement in a 4 × 4 Latin square design. Factor A was FCR supplementation at 15 and 20 g/kg of BW. Factor B was the sulfur level in the PELFUR ration at 15 and 30 g/kg of dry matter (DM). No interaction effect was found among FCR supplementation and PELFUR in terms of feed intake and nutrient intake (p > 0.05). Cyanide intake was significantly increased based on FCR supplementation (p < 0.05), whereas sulfur intake was increased by level addition of PELFUR levels (p < 0.05). There were interaction effects among FCR supplementation and PELFUR on digestibility coefficients of DM and organic matter (OM) (p < 0.05). FCR supplementation at 20 g/kg BW with PELFUR 30 g/kg demonstrated the highest digestibility of DM and OM. Moreover, interactions were observed between FCR and PELFUR for bacterial populations (p < 0.01). The populations of bacteria were highest in FCR supplementation at 20 g/kg BW with PELFUR 30 g/kg at various feeding times. An interaction effects from among feeding FCR with PELFUR was found on blood thiocyanate concentrations at various feeding times (p < 0.01). The highest mean values of blood thiocyanate were observed when feeding FCR at 20 g/kg BW with PELFUR at 30 g/kg. No interaction effect was found between FCR and PELFUR on total volatile fatty acids (VFA) and their profiles (p >0.05). However, the proportions of the total VFA at 0 and 4 h post-feeding were increased when FCR at 20 g/kg BW was supplemented (p < 0.01). FCR at 20 g/kg BW could enhance propionate (C3) at 4 h post-feeding when compared with FCR at 15 g/kg BW (p < 0.01). Moreover, supplementation of PELFUR at 30 g/kg increased the total VFA at 0 and 4 h post-feeding, whereas the concentration of C3 at 4 h post-feeding was enhanced (p < 0.05). However, no significant changes were found for any parameters among treatments and between the main effect of FCR and PELFUR supplementation (p > 0.05). In conclusion, feeding of two combinations (FCR 20 g/kg BW with PELFUR 30 g/kg) could promote the nutrient digestibility, the bacterial populations, and the rate of disappearance of cyanide without having any adverse effect on rumen fermentation.

Animal models of Alzheimer’s disease amyloidosis that recapitulate cerebral amyloid-beta pathology have been widely used in preclinical research, and have greatly enabled the mechanistic understanding of Alzheimer’s disease and the development of therapeutics. Comprehensive deep phenotyping of the pathophysiological and biochemical features in these animal models are essential. Recent advances in positron emission tomography have allowed the non-invasive visualization of the alterations in the brain of animal models as well as in patients with Alzheimer’s disease, These tools have facilitated our understanding of disease mechanisms, and provided longitudinal monitoring of treatment effect in animal models of Alzheimer’s disease amyloidosis. In this review, we focus on recent positron emission tomography studies of cerebral amyloid-beta accumulation, hypoglucose metabolism, synaptic and neurotransmitter receptor deficits (cholinergic and glutamatergic system), blood-brain barrier impairment and neuroinflammation (microgliosis and astrocytosis) in animal models of Alzheimer’s disease amyloidosis. We further propose the emerging targets and tracers for reflecting the pathophysiological changes, and discuss outstanding challenges in disease animal models and future outlook in on-chip characterization of imaging biomarkers towards clinical translation.

Focal cerebral ischemia can lead to blood-brain barrier (BBB) breakdown, which is implicated in neuroinflammation and elevation of matrix metalloproteinases (MMPs). The role of the anti-inflammatory protein, monocyte chemotactic protein–induced protein 1 (MCPIP1) plays in the injury of BBB in stroke has not yet been reported. This study was conducted to identify and characterize the role MCPIP1 plays in BBB breakdown. Transient middle cerebral artery occlusion (MCAO) is induced in both wild-type and Mcpip1^-/- mice for 2 hours of occlusion periods followed by reperfusion for 24 or 48 hours. BBB permeability was measured by FITC-dextran extravasation, MMP-9/3 expression was analyzed by western blot, and claudin-5 and zonula occludens-1 (ZO-1) were analyzed by immunohistochemistry and western blot. After MCAO in wild type mouse is induced, there is significantly increase in MCPIP1 mRNA and protein levels. Absence of MCPIP1 leaded to significant increase in FITC-dextran leakage in peri-infarct brain, significant upregulation of MMP-9, MMP-3 and reduced levels of tight junction components, claudin-5 and ZO-1 in the brain after MCAO. Our data demonstrate that absence of MCPIP1 exacerbates ischemia-induced blood-brain barrier disruption by enhancing the expression of matrix metalloproteinases and degradation of tight junction proteins. Overall data indicate that MCPIP1 is important protective role against BBB disruption in cerebral ischemia.

In this study, the decision-making process management of forest tending in the forestry business is decentralized, and forest tending decision-making activities at different points in time are integrated by decision makers at different geographical locations. The decision-making process was analyzed and optimized from a system perspective. Based on the optimized decision-making process, a forest tending business group decision support system (FTGDSS) was established. We first reviewed and discussed the characteristics and development of the forest tending business and forestry decision support system. Business Process Modeling Notation was used to draw a current state flow chart of the forest tending business, to identify and discover important decision points in the process of tending decision-making. We also analyzed the content and attributes of each decision point, and described the system structure, functional framework, knowledge base structure, and reasoning algorithm of FTGDSS in detail. Finally, FTGDSS was evaluated from the two dimensions of the technology adoption model. FTGDSS integrates different levels of time-space decision-making activities, historical tending data, business plans, decision-makers' management tendencies into the decision-making process and automatically extracts decision-making data from the forest business process management enterprise resource planning system (Smartforest) that improves the ease of use of the decision support system (DSS). It also improves the quality of forest tending decisions, and enables the DSS to better support multi-target management strategies.

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.

Background and Aim: Multiple sclerosis (MS) is known as an autoimmune disease and a chronic inflammatory condition, inducing a wide variety of mood affective disorders, including depression and feelings of hopelessness in many aspects of patients’ quality of life (QoL). In view of the positive side effects of spirituality and spiritual care on finding appropriate strategies for further adaptation, this study aimed to determine the impact of group spiritual care (GSC) on levels of hope in patients suffering from MS. Materials and Methods: This clinical trial was conducted on a total number of 96 patients with MS, referring to the National Multiple Sclerosis Society (NMSS) in the city of Zahedan, Iran. Following sample selection via the convenience sampling technique, the patients meeting the inclusion criteria were randomized into two groups, i.e., intervention and control. The data collection tools for this purpose included a demographic information form and the Adult Hope Scale (AHS, Snyder et al. 1991), completed by the subjects at the pre- and post-intervention stages. As well, the intervention group received five sessions of GSC during three weeks but the control group members only talked over daily issues along with their mental health problems. The data were also analyzed using the SPSS Statistics software (ver. 14). Results: The Kruskal-Wallis test results revealed that the GSC intervention could have a significant positive effect on raising hope in the patients with MS (p<0.001). Moreover, a significant growth was observed in the scores of hope dimensions including agency and pathway (p<0.001). Conclusion: GSC can effectively boost levels of hope in patients suffering from MS in all dimensions. Therefore, it is recommended to utilize this type of care in order to nurture hope in such individuals.

The Seljuks, who came from the Central Asian prairies, invaded Asia Minor towards the end of the 11th century. The land had been settled by then mainly by the Christian Eastern Romans and Armenian peoples. Seljuks were Moslems; they built monumental structures, some of which have survived the natural disasters of several centuries to the present day. Most of these architectural marvels contain extraordinary decorations in the form of ornaments, friezes and rosettes. I have studied periodic ornaments and classified them into 17 mathematical wallpaper groups according to their symmetry properties that reveal their global structure. On the other hand, the local details of the ornaments, the motifs, show a clear variation from simple geometric patterns to complicated and refined forms. Seljuk art was originally influenced by Persian styles, later influenced by the Christian population in Asia Minor, and finally represents the impact of Islamic culture.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized mainly by the gradual decay in neuronal function as a consequence of diverse degenerating events primarily including mitochondria dysfunction and cascades of neuro-immune reactions. Besides the acquired harmful reactive oxygen species (ROS), neurotoxins, and amyloid-beta (Aβ) and TAU pathologies in neurons, accumulating evidence with time underlined the roles of cytokines and growth factors in the AD pathogenesis. It may help us in evaluating the propensities and specific mechanism(s) of cytokines and factors impacting neuron upon apoptotic decline. Proinflammatory cytokines often induce inflammation in AD and AD-like pathogenesis in response to the apoptotic scenarios where some growth factors are involved in cytokinetic reactions to activate microglia and causing inflammation in AD. In this report, we comprehensively reviewed role of cytokines and chemokines in immune response to AD and neuropsychiatry. We provided insights into the neuroinflammation and the role of diverse factors including the pro-/anti-inflammatory cytokines, APP, TAU phosphorylation, glycation end products, complement system, and the role of glial cells. Also, we discussed the pathogenic and protective role of macrophage migration inhibitory factors, choroid plexus-, neurotrophic- and hematopoietic -related growth factors in AD. We further shed light on the availability and accessibility of the cytokines across the blood-brain barrier in AD pathophysiology. Taken together, the emerging role of these factors in AD pathology emphasized the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

Malaria remains a life-threatening disease in many tropical countries. Honduras has successfully reduced malaria transmission as different control methods have been applied focusing mainly on indoor mosquitoes. The selective pressure exerted by the use of insecticides inside the households could modify the feeding behavior of the mosquitoes forcing them to search for available animal hosts outside the houses. These animal hosts in the peridomicile could consequently become an important factor in maintaining vector populations in endemic areas. Herein, we investigated the blood meal sources and Plasmodium spp. infection on anophelines collected outdoors in endemic areas of Honduras. Individual PCR reactions with species-specific primers were used to detect five feeding sources on 181 visibly engorged mosquitoes. In addition, a subset of these mosquitoes where chosen for pathogen analysis by a nested PCR approach. Most mosquitoes fed on multiple hosts (2 to 4), and 24.9% of mosquitoes were fed on a single host, animal or human. Chicken and bovine were the most frequent blood meal sources (29.5% and 27.5% respectively). The average human blood index (HBI) was 22.1%. None of the mosquitoes was found to be infected with Plasmodium spp. Our results show the opportunistic and zoophilic behavior of Anopheles mosquitoes in Honduras.

The dynamical processes of living systems are characterized by the cooperative interaction of many units. This claim enables us to portray the embryo-fetal development of the central and peripheral nervous systems in terms of assemblies of building blocks. We describe how the structure and arrangement of nervous fibers is - at least partially - dictated by biophysical and topological constraints. The far-flung field of soft-matter polymers/nematic colloids sheds new light on the neurulation in mammalian embryos, suggesting an intriguing testable hypothesis: the development of the central and peripheral nervous systems might be correlated with the occurrence of local thermal changes in embryo-fetal tissues. Further, we show a correlation between the fullerene-like arrangement of the cortical microcolumns and the Frank-Kasper phases of artificial quasicrystals assemblies. The last, but not the least, we explain how and why the multisynaptic ascending nervous fibers connecting the peripheral receptors to the neocortical areas can be viewed as the real counterpart of mathematical tools such as knot theory and braid groups. Their group structure and generator operations point towards a novel approach to long-standing questions concerning human sensation and perception, leading to the suggestion that the very arrangement and intermingling of the peripheral nervous fibers contributes to the cortical brain activity. In touch with the old claims of D’Arcy Thompson, we conclude that the arrangement and the pattern make the function in a variety of biological instances, leading to countless testable hypotheses.

We review past and present results on the non-local form-factors of the effective action of semiclassical gravity in two and four dimensions computed by means of a covariant expansion of the heat kernel up to the second order in the curvatures. We discuss the importance of these form-factors in the construction of mass-dependent beta functions for the Newton's constant and the other gravitational couplings.

In the existing group decision-making fuzzy analytic hierarchy process (FAHP) methods, the consensus among experts has rarely been fully reached. To fill this gap, in this study, a pre-aggregation fuzzy collaborative intelligence (FCI)-based FAHP approach is proposed. In the proposed pre-aggregation FCI-based FAHP approach, fuzzy intersection is applied to aggregate experts’ pairwise comparison results if these pairwise comparison results overlap. The aggregation result is a matrix of polygonal fuzzy numbers. Subsequently, alpha-cut operations are applied to derive the fuzzy priorities of criteria from the aggregation result. The pre-aggregation FCI-based FAHP approach has been applied to select suitable alternative suppliers for a wafer foundry in Taiwan amid the COVID-19 pandemic. The experimental results revealed that the pre-aggregation FCI-based FAHP approach significantly reduced the uncertainty inherent in the decision-making process by deriving fuzzy priorities with very narrow ranges.

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

Androgens are key for pubertal development of the mammalian testis, a phenomenon tightly linked to Sertoli cell maturation. In this review, we discuss how androgen signalling affects Sertoli cell function and morphology by concomitantly inhibiting some processes and promoting others that contribute jointly to the completion of spermatogenesis. We focus on the molecular mechanisms that underlie AMH inhibition by androgens at puberty, as well as on the role androgens have on Sertoli cell tight junction formation and maintenance and, consequently, on its effect on proper germ cell differentiation and meiotic onset during spermatogenesis.

We provide an axiomatic base for the set of natural numbers, that has been proposed as a canonical construction, and use this definition of $\mathbb N$ to find several results on finite group theory. Every finite group $G$, is well represented with a natural number $N_G$; if $N_G=N_H$ then $H,G$ are in the same isomorphism class. We have a linear order, on the quotient space of isomorphism classes of finite groups, that is well behaved with respect to cardinality. If $H,G$ are two finite groups such that $|H|=m<n=|G|$, then $H<\mathbb Z_n\leq G\leq\mathbb Z_{p_1}^{n_1}\oplus\mathbb Z_{p_2}^{n_2}\oplus\cdots\oplus\mathbb Z_{p_k}^{n_k}$ where $n=p_1^{n_1}p_2^{n_2}\cdots p_{k}^{n_k}$ is the prime factorization of $n$. We find a canonical order for the objects of $G$ and define equivalent objects of $G$, thus finding the automorphisms of $G$. The Cayley table of $G$ takes canonical block form, and we are provided with a minimal set of independent equations that define the group. We show how to find all groups of order $n$, and order them. We give examples using all groups with order smaller than $10$, and we find the canonical block form of the symmetry group $\Delta_4$. In the next section, we extend our results to the infinite case, which defines a real number as an infinite set of natural numbers. A real function is a set of real numbers, and a sequence of real functions $f_1,f_2,\ldots$ is well represented by a set of real numbers, as well. In general, we represent mathematical objects using the smallest possible data-type. In the last section, mathematical objects are well assigned to tree structures. We conclude with brief comments on type theory and future work on computational aspects of these representations.

In a completely randomized design (CRD), 400 day-old Ross 308 broilers were randomly allotted to 5 diets with 0, 5, 10, 15 and 20% MSC, each with 8 replicates of 10. Weekly feed intake (FI), body weight gain (BWG) and feed conversion efficiency (FCE) were calculated whilst haemato-biochemistry was measured at d42. Overall, FI was linearly (P &lt; 0.05) and quadratically (P &lt; 0.01) decreased by MSC, of which the optimum inclusion was 15%, as BWG was linearly (P &lt; 0.001) and quadratically (P &lt; 0.05) decreased and FCE linearly decreased (P &lt; 0.01) by MSC, of which the optimum dietary inclusion was 10%. Also, MSC linearly and quadratically decreased slaughter weight (P &lt; 0.001 and P &lt; 0.05, respectively), hot carcass weight (P &lt; 0.001 and P &lt; 0.05, respectively) and cold carcass weight (P &lt; 0.001 and P &lt; 0.05, respectively). Similarly, it linearly decreased white blood cells (P &lt; 0.01) and lymphocytes (P &lt; 0.05) as it linearly (P &lt; 0.001) and quadratically (P &lt; 0.01) decreased symmetric dimethylarginine (SDMA) and linearly (P &lt; 0.001) increased serum cholesterol. In conclusion, up to 10% MSC can be incorporated into broiler diets in replacement of SBM without adverse effects.

The general theory of relativity (GR) is known to be invariant under smooth coordinate transformations (diffeomorphism). This group has a subgroup known as the Lorentz group of symmetry which is manifested in the weak field approximation to GR. The dominant operator in the weak field equation of GR is thus the d'Alembert (wave) operator which has a retarded potential solution. Galaxies are huge physical systems having dimensions of many tens of thousands of light years. Thus any change at the galactic center will be noticed at the rim only tens of thousands of years later. Those retardation effects are neglected in present day galactic modelling used to calculate rotational velocities of matter in the rims of the galaxy and surrounding gas. The significant differences between the predictions of Newtonian instantaneous action at a distance and observed velocities are usually explained by either assuming dark matter or by modifying the laws of gravity (MOND). In this paper we will show that taking general relativity seriously without neglecting retardation effects one can explain the radial velocities of galactic matter in the M33 galaxy without postulating dark matter.

Hemorrhage is a detrimental event present in traumatic injury, surgery, and disorders of bleeding, that can become life-threatening if not properly managed. Moreover, uncontrolled bleeding can complicate surgical interventions, altering the outcome of surgical procedures. Therefore, to reduce the risk of complications and decrease the risk of morbidity and mortality associated with hemorrhage, it is necessary to use an effective hemostatic agent that ensures immediate control of bleeding. In recent years, there have been increasingly rapid advances in developing novel generation of biomaterials with hemostatic properties. Nowadays, a wide array of topical hemostatic agents is available, including chitosan-based biomaterials that have shown outstanding properties such as: antibacterial, antifungal, hemostatic, analgesic activity, in addition to their biocompatibility, biodegradability, and wound-healing effects. This review provides an analysis of chitosan-based hemostatic and discusses the progress made in their performance, mechanism of action, efficacy, cost, and safety in recent years.

Background: Little is known about potential confounding factors influencing the humoral response in individuals having received the BNT162b2 vaccine. Methods: Blood samples from 231 subjects were collected before and 14, 28 and 42 days following COVID-19 vaccination with BNT162b2. Anti-Spike Receptor-Binding-Domain protein (anti-Spike/RBD) immunoglobulin G (IgG) antibodies were measured at each time-point. Impact of age, sex, childbearing age status, hormonal therapy, blood group, body mass index and past-history of SARS-CoV-2 infection were assessed by multivariable analyses. Results and Conclusions: In naïve subjects, the level of anti-Spike/RBD antibodies gradually increased following administration of the first dose to reach the maximal response at day 28 and then plateauing at day 42. In vaccinated subjects with previous SARS-CoV-2 infection, the plateau was reached sooner (i.e. at day 14). In the naïve population, age had a significant negative impact on anti-Spike/RBD titers at day 14 and 28 while lower levels were observed for males at day 42, when corrected for other confounding factors. BMI as well as B and AB blood groups had a significant impact in various subgroups on the early response at day 14 but no longer after. No significant confounding factors were highlighted in the previously infected group.

As the name implies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another most common but debilitating complication caused by the SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized covid patients and ranging from shortness of concentration, overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and “brain fog” are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully; and the underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.

The study reports about a case of a lung cancer patient with increasing difficulties in falling asleep and frequent periods of wakefulness. Severe dyspnea related to pneumonitis caused as a side effect of immunotherapy worsened the situation. Eventually, fear of falling asleep developed, including panic attacks and anxiety of choking, which was shown to lead to nights of complete wakefulness. The patient did not only sleep poorly; he did not sleep at all at night for several days, as evidenced by the notes he made during the night. Polygraphy showed no evidence of sleep-disordered breathing, but frequent periods of wakefulness and reduced basal saturation around 90% during sleep due to lung changes such as extensive functional failure of the left upper lobe with position-dependent shunts. The authors hypothesized that the symptoms described were causally related to a drop in oxygen saturation in the patient's blood. Therefore, they pursued the goal of finding a measurement technique that is as inexpensive as possible and that the patient can operate without outside assistance and great effort. So the patient started using a low-cost wearable device that allows simultaneous measurements of blood oxygen content, pulse rate and movement intensity. It consists of a finger ring with pulse oximetry sensor and a wristband with the control unit containing a vibration motor. The described device reliably warned of disturbances in oxygen concentration in the blood during the night with its vibration alarm. By use of that device during the whole night at home, the events of reduced oxygen saturation and the anxiety symptoms were reduced. Sleep disturbances with sudden awakenings did not occur when using the device. The patient benefited from the security gained in this way and slept much more peacefully, and he could spend nights without waking up again. In conclusion, wearable oximeters with vibration alarm can be recommended for patients’ home care in lung cancer patients.

Microsamples (collections usually less than 50 µL) have been introduced in pre-clinical, clinical, and research settings to overcome obstacles in sampling via traditional venipuncture. However, venipuncture remains the sampling gold standard for metabolic phenotyping of blood. This pre-sents several challenges in metabolic phenotyping workflows: accessibility for individuals in ru-ral and remote underserved areas (due to the need for trained personnel), the unamenable nature to frequent sampling protocols in longitudinal research (for its invasive nature), and sample col-lection difficulty in the young and elderly. Furthermore, venous sample stability may be compro-mised when temperate conditions necessary for cold-chain transport are beyond control. Alter-natively, research utilising microsamples extends phenotyping possibilities to inborn errors of metabolism, therapeutic drug monitoring, nutrition, as well as sport and anti-doping. Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome. In this review, we provide an overview of the common uses and workflows for mi-crosampling in metabolic phenotyping research. We discuss the advancements in technologies, highlighting key considerations and remaining knowledge gaps for employment of microsamples in metabolic phenotyping research. Supporting the translation of research from the ‘bench to the community’.

Pyrochlore group minerals are the main raw phases in granitic rocks of the Katugin complex-ore deposit that stores Nb, Ta, Y, REE, U, Th, Zr, and cryolite. They are of three main generations: primary magmatic (I), early postmagmatic (II), and supergene (III) pyrochlores. The primary magmatic phase (generation I) is fluornatropyrochlore with high concentrations of Na2O (to 10.5 wt.%), F (to 5.4 wt.%) and REE2O3 (to 17.1 wt.%) but low CaO (0.6-4.3 wt.%), UO2 (to 2.6 wt.%), ThO2 (to 1.8 wt.%), and PbO (to 1.4 wt.%). Pyrochlore of this type is very rare in nature and limited to a few occurrences, such as rare-metal deposits of Nechalacho in syenite and nepheline syenite (Canada) and Mariupol in nepheline syenite (Ukraine). It may have crystallized synchronously with or slightly later than melanocratic minerals (aegirine, biotite, and arfvedsonite) at the late magmatic stage when Fe from the melt became bound making impossible the formation of columbite. Second generation pyrochlore formed at the early postmagmatic stage of the Katugin deposit. It differs from that of first generation in lower Na2O concentrations (2.8 wt.%), relatively low F (4 wt.%), and les occupancy of the A and Y sites at similar contents of other components. Generation III pyrochlore is a product of supergene alteration processes. It is compositionally heterogeneous and contains K, Ba, Pb, Fe, and significant Si concentrations but low Na and F. Its compositions mostly fall within the filed of hydro- and kenopyrochlore.

A construction for the systems of natural and real numbers is presented in Zermelo-Fraenkel Set Thoery, that allows for simple proofs of the properties of these systems, and practical and mathematical applications. A practical application is discussed, in the form of a Simple and Linear Fast Adder (Patent Pending). Applications to finite group theory and analysis are also presented. A method is illustrated for finding the automorphisms of any finite group $G$, which consists of defining a canonical block form for finite groups. Examples are given, to illustrate the procedure for finding all groups of $n$ elements along with their automorphisms. The canonical block form of the symmetry group $\Delta_4$ is provided along with its automorphisms. The construction of natural numbers is naturally generalized to provide a simple and sound construction of the continuum with order and addition properties, and where a real number is an infinite set of natural numbers. A basic outline of analysis is proposed with a fast derivative algorithm. Under this representation, a countable sequence of real numbers is represented by a single real number. Furthermore, an infinite $\infty\times\infty$ real-valued matrix is represented with a single real number. A real function is represented by a set of real numbers, and a countable sequence of real functions is also represented by a set of real numbers. In general, mathematical objects can be represented using the smallest possible data type and these representations are calculable. In the last section, mathematical objects of all types are well assigned to tree structures in a proposed type hierarchy.

Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (> 100 mg/L) and signs of respiratory failure were treated with CRP apheresis. 2-12 CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest x-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. All patients had comorbidities. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation require-ments. Our clinical observations regarding the here presented seven patients support the hypoth-esis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.

The lymphatic system of the brain meninges and head plays a crucial role in the clearance of amyloid-β protein (Aβ), a peptide thought to be pathogenic in Alzheimer’s disease (AD), from the brain. The development of methods to modulate lymphatic clearance of Aβ from the brain coild be a revolutionary step in the therapy of AD. The opening of the blood-brain barrier (OBBB) by focused ultrasound is considered as a possible tool for stimulation of clearance of Aβ from the brain of humans and animals. Here, we propose an alternative method of non-invasive music-induced OBBB that is accompanied by the activation of clearance of fluorescent Aβ (Fαβ) from the mouse brain. Using confocal imaging, fluorescence microscopy and magnetic resonance tomography, we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in the cerebrospinal fluid and lymphatic clearance of Fαβ from the brain. We propose the extended detrended fluctuation analysis (EDFA) as a promising method for the identification of OBBB markers in the electroencephalographic (EEG) patterns. These pilot results suggest that music-induced OBBB and the EDFA analysis of EEG can be a non-invasive, low cost, labelling free, clinical perspective and completely new approach for the treatment and monitoring of AD.

Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.

Peptide-based drugs are promising anticancer candidates due to their biocompatibility, and low toxicity. Particularly, tumor homing peptides (THPs) have the ability to bind specifically to can-cer cells receptors and tumor vasculature. Despite their potential to develop antitumor drugs, there are few available prediction tools to assist the discovery of new THPs. Two webservers based on machine learning models are currently active, the TumorHPD (https://webs.iiitd.edu.in/raghava/tumorhpd) and the THPep (http://codes.bio/thpep), and more recently the SCMTHP (SCMTHP (pmlabstack.pythonanywhere.com), based on scoring card method. Herein, a novel method based on network science and similarity searching implemented in the starPep toolbox (http://mobiosd-hub.com/starpep/) is presented for THPs discovery. The approach leverages from exploring the structural space of THPs with Chemical Space Networks (CSNs) and from applying centrality measures to identify the most relevant and non-redundant THPs sequences within the CSN. Such THPs were considered as queries (Qs) for multi-query similarity searches that applies a group fusion (MAX-SIM rule) model. The resulting multi-query similarity searching models (SSMs) were validated with three benchmarking datasets of THPs/non-THPs. Predictions achieved accuracies ranged from 92.64 to 99.18% and Matthews Correlation Coefficients between 0.894-0.98, outperforming state-of-the-art predictors. The best model was applied to repurpose AMPs from the starPep database as THPs, which were subse-quently optimized for the TH activity. Finally, 54 promising THP leads were discovered, and their sequences were analyzed to encounter novel motifs. These results demonstrate the potential of CSNs and multi-query similarity searching for a rapid and accurate identification of THPs.

In open, sustainable policymaking, we are expecting to develop the valuable results that will bring us closer to a fairer and more balanced society. One way to involve the public in these processes is to engage them in online e-participation projects. Despite the hopes, empirical analyses show that many e-participation initiatives have failed to deliver expected benefits. Revealing what actually works in examined projects and what requires improvement would allow for better policy planning in the future. In this article, I made an attempt to identify and assess the cognitive processes enabling emergence of collective intelligence (CI) in a singular e-participation project. For this reason, I worked out and tested an evaluation technique, combining the MILCS framework for group cognition and the results of empirical research on CI. A case study method based on semi-structured interviews was selected to evaluate a sample participatory budgeting initiative, Civic Budget of the City of Kraków. Results reveal that most cognitive processes are working satisfactorily, but the real problem is using collective memory, which works only to a very limited extent. A guideline for future policymakers should be to develop a shared memory system, to which all community members should have access.

This is the fourth part of [6] on the existence of K¨ahler Einstein metrics of the general type I almost homogeneous manifolds of cohomogeneity one. We actually carry out all the results in [8] to the type I cases. In part II [14], we obtained a lot of new K¨ahler-Einstein manifolds as well as Fano manifolds without K¨ahler-Einstein metrics. In particular, by applying Theorem 15 therein, we have complete results in the Theorems 3 and 4 in that paper. However, we only have some partial results in Theorem 5 there. In this note, we shall give a report of recent progress on the Fano manifolds Nn,m when n > 15 and N′n,m when n > 4. We actually give two nice pictures for these two classes of manifolds. See our Theorems 1 and 2 in the last section. Moreover, we post two conjectures. Once we could solve these two conjectures, the question for these two classes of manifolds would be completely solved. With applying our results to the canonical circle bundles we also obtain Sasakian manifolds with or without Sasakian-Einstein metrics. That also give some open Calabi-Yau manifolds.

Green innovation has become the mainstream of the era, and New Urbanization is an inevitable choice in the process of urbanization in China. Focusing on the topics of green innovation and new urbanization, much work has been done to find their factors respectively while the relationship between the two remains to be explored. Hence, in this article, representative indicators of new urbanization and green innovation are selected to study the Yangtze River Delta City Group from the perspective of both the entire urban agglomeration and a single city, in terms of time and space, using the entropy method and the coupling model. The results show that (1). Green innovation promotes the new urbanization development and there is a synergistic effect between the two systems. (2). The level of economic development is an important factor that affects the degree of coupling degree and coordination degree between the two interactions, and its influence is better than the spatial effect. (3). Green innovation and new urbanization have positive spatial autocorrelation and regional agglomeration (there are High-High, Low-Low, and High-Low collections).

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.

The emergence of multi-drug resistant E. coli is an important matter of increasing considerable concern to global public health. The aim of this study was to investigate the incidence, antibiotic resistance pattern, phylogroups and genetic variation of E. coli isolates from raw milk, vegetable salad and ground meat samples. Methods: Culture-based techniques, Kirby-Bauer disk diffusion susceptibility testing, PCR and RAPD assays were used to determine the incidence rate, antimicrobial resistance pattern, phylogenetic groups and genetic diversity of the E. coli isolates. Results: E. coli isolates were highly resistant to amoxicillin (79.16%), trime-thoprim-sulfamethoxazole (70.83%), amoxicillin-clavulanic acid (62.50%), tetracycline (54.16%), chloramphenicol (54.16%), nitrofurantoin (54.16%), ampicillin (45.83%), streptomycin (45.83%), and kanamycin (33.33%); and completely susceptible to norfloxacin and azithromycin. 70.83% of the isolates were multi-drug resistant. Most E. coli isolates (46%) belonged to phylogroup A. RAPD with UBC245 primer categorized the isolates into 11 clusters. A high level of genetic di-versity was found among the isolates; however, 33.3% of the isolates were grouped in a major cluster (R5). Conclusions: Antibiotic resistance patterns are randomly distributed among the ge-netic clusters. Novel, practical, efficient food safety control and surveillance systems of multi-drug resistant foodborne pathogens are required to control the foodborne pathogen contamina-tion.