Prevalence, Risk Factors and Residential Variation among HIV/TB co-infected Mortality in Amhara Region, Fenote Selam Hospital: Application of Multilevel Logistic Regression

The purpose of this study was to identify the factors that affect the mortality among adult HIV/TB co-infected patients and to see the nutritional difference among mortality in residence level. Retrospective cohort studies of 417 patients which fulfill our criteria were included. Multilevel logistic regression models were used. MLwiN and SPSS software are used to estimate the parameter. The variance of the random factor in the empty model was significant which indicates that there were residential differences in TB-HIV co-infected mortality and it shows multilevel analysis was an appropriate approach for further analysis. The prevalence of HIV/TB co-infected patients' death was 12.9% in study time. Functional status, age of patients, WHO clinical stages, nutritional status, CD4 counts, regimen, and BMI were found to be significant determinants of HIV/TB co-infected mortality. In our study, patients with the bedridden category of functional status, the fourth stages of WHO clinical stages (stage IV), patients with higher age, patients whose treatments were second-line regimen and low CD4 cell counts were more at risk of death. The study also revealed that; poor nutritional status increased the risk of mortality among HIV/TB co-infected patients and it varies among the residence of the patients (rural area were more at risk).

Discriminative Analysis of Schizophrenia Patients Using Topological Properties of Structural and Functional Brain Networks: A Multimodal Magnetic Resonance Imaging Study

Interest in the application of machine learning (ML) techniques to multimodal magnetic resonance imaging (MRI) data for the diagnosis of schizophrenia (SZ) at the individual level is growing. However, a few studies have applied the features of structural and functional brain networks derived from multimodal MRI data to the discriminative analysis of SZ patients at different clinical stages. In this study, 205 normal controls (NCs), 61 first-episode drug-naive SZ (FESZ) patients, and 79 chronic SZ (CSZ) patients were recruited. We acquired their structural MRI, diffusion tensor imaging, and resting-state functional MRI data and constructed brain networks for each participant, including the gray matter network (GMN), white matter network (WMN), and functional brain network (FBN). We then calculated 3 nodal properties for each brain network, including degree centrality, nodal efficiency, and betweenness centrality. Two classifications (SZ vs. NC and FESZ vs. CSZ) were performed using five ML algorithms. We found that the SVM classifier with the input features of the combination of nodal properties of both the GMN and FBN achieved the best performance to discriminate SZ patients from NCs [accuracy, 81.2%; area under the receiver operating characteristic curve (AUC), 85.2%; p < 0.05]. Moreover, the SVM classifier with the input features of the combination of the nodal properties of both the GMN and WMN achieved the best performance to discriminate FESZ from CSZ patients (accuracy, 86.2%; AUC, 92.3%; p < 0.05). Furthermore, the brain areas in the subcortical/cerebellum network and the frontoparietal network showed significant importance in both classifications. Together, our findings provide new insights to understand the neuropathology of SZ and further highlight the potential advantages of multimodal network properties for identifying SZ patients at different clinical stages.

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

SARS-CoV2 infection in symptomatic patients: interest of serological tests and predictors of mortality: experience of DR Congo

Background In symptomatic patients, the diagnostic approach of COVID-19 should be holistic. We aimed to evaluate the concordance between RT-PCR and serological tests (IgM/IgG), and identify the factors that best predict mortality (clinical stages or viral load). Methods The study included 242 patients referred to the University hospital of Kinshasa for suspected COVID-19, dyspnea or ARDS between June 1st, 2020 and August 02, 2020. Both antibody-SARS-CoV2 IgM/IgG and RT-PCR method were performed on the day of admission to hospital. The clinical stages were established according to the COVID-19 WHO classification. The viral load was expressed by the CtN2 (cycle threshold value of the nucleoproteins) and the CtE (envelope) genes of SARS- CoV-2 detected using GeneXpert. Kappa test and Cox regression were used as appropriate. Results The GeneXpert was positive in 74 patients (30.6%). Seventy two patients (29.8%) had positive IgM and 34 patients (14.0%) had positive IgG. The combination of RT-PCR and serological tests made it possible to treat 104 patients as having COVID-19, which represented an increase in cases of around 41% compared to the result based on GeneXpert alone. The comparison between the two tests has shown that 57 patients (23.5%) had discordant results. The Kappa coefficient was 0.451 (p < 0.001). We recorded 23 deaths (22.1%) among the COVID-19 patients vs 8 deaths (5.8%) among other patients. The severe-critical clinical stage increased the risk of mortality vs. mild-moderate stage (aHR: 26.8, p < 0.001). The values of CtE and CtN2 did not influence mortality significantly. Conclusion In symptomatic patients, serological tests are a support which makes it possible to refer patients to the dedicated COVID-19 units and treat a greater number of COVID-19 patients. WHO Clinical classification seems to predict mortality better than SARS-Cov2 viral load.

BASICS OF A PERSONALIZED APPROACH TO MEDICAL AND PSYCHOLOGICAL SUPPORT OF CARDIAC SURGERY PATIENTS

The concept of a personalized approach is becoming more and more popular in modern medicine. Today it is often understood as a multidisciplinary approach designed to improve therapeutic options, as well as help diagnose diseases at an early stage. In a cardiac surgery clinic, such an approach can take into account not only biological, but also psychological risk factors for the disease, especially its history, clinical condition, mental and psychological status to create an individual route within the framework of medical and psychological support for the patient at the stages of treatment and rehabilitation. The aim of the work was to develop, based on the analysis of the literature and the authors' own work experience, the organizational and psychological foundations for the implementation of a personalized approach in medical and psychological support of cardiac patients. The fundamental principles of support in the work include the following: the principle of accessibility, the principle of openness, the principle of continuity, the principle of complexity, the principle of integrativity, the principle of differentiation, the principle of variability, the principle of participativeness, the principle of awareness, the principle of prevention. In the process of medical and psychological support of cardiac surgical patients within the framework of a personalized approach, the most optimal was the identification of the following clinical stages, different in duration and content, corresponding to the periods of outpatient and inpatient treatment and rehabilitation of patients: preoperative outpatient, preoperative inpatient, early postoperative, postoperative inpatient, postoperative rehabilitation and rehabilitation outpatient stages. For each of the clinical stages of medical and psychological support, a differentiation of goals, objectives, duration and expected results of the impact was carried out, which makes it possible to personalize the programs for accompanying a cardiac patient and individualize the route for each patient, taking into account the specificity and relevance of the influence of biologi cal, psychological and social factors.

Advances in Antifungal Drug Development: An Up-To-Date Mini Review

The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets for antifungals. Novel antifungals in clinical development include first-in-class agents, new structures for an established target, and formulation modifications to marketed antifungals, in addition to repurposed agents. Membrane interacting peptides and aromatherapy are gaining increased attention in the field. Immunotherapy is another promising treatment option, with antifungal antibodies advancing into clinical trials. Novel targets for antifungal therapy are also being discovered, allowing the design of new promising agents that may overcome the resistance issue. In this mini review, we will summarize the current status of antifungal drug pipelines in clinical stages, and the most recent advancements in preclinical antifungal drug development, with special focus on their chemistry.

Identification of Stage-related and Severity-Related Biomarkers and Exploration of Immune Landscape for Dengue by Comprehensive Analyses

At present, there are still no specific therapeutic drugs and appropriate vaccines for Dengue. Therefore, it is very important to explore distinct clinical diagnostic indicators. In this study, we combined differentially expressed genes (DEGs) analysis and weighted co-expression network analysis (WGCNA) to screen a stable and robust biomarker which can be used to distinguish three clinical stages of Dengue and severity of Dengue. CD38 can distinguish excellently Early Acute, Late Acute, Convalescent stages for Dengue patients, and ZNF595 can discriminate DHF from DF in whole acute stages. We also found that three clinical stages can be discriminated based on the fractions of Plasma cells, activated memory CD4+ T cells, and Monocytes. In different clinical stages different immune cells function positively. Negative inhibition of viral replication based on Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA), up-regulated autophagy genes and impairing immune system are potential reasons resulting in dengue hemorrhagic fever (DHF).

Clinical Radiological and Pathological considerations of Epiphysitis and Apophysitis

A prospective longitudinal study of 157 patients between the ages of five and 16 years, high-performance athletes, who were treated with epiphyseal and / or apophyseal injuries due to chronic stress in our service, was carried out in the period between January 1, 2000 and December 31, 2020, at the Mártires del 9 de Abril University Hospital in Sagua La Grande, Villa Clara province, Cuba. Of these patients, 102 are male, the most frequent ages of the affected children are between 13 and 14 years, pain and poor sports performance were the predominant symptoms, 67.7% (n = 106) were in radiological stage II and 70.9% (n = 7) in pathological anatomical stage II, which is closely related, but not the clinical stages.