A novel nonparametric computational strategy for identifying differential methylation regions

Background DNA methylation has long been known as an epigenetic gene silencing mechanism. For a motivating example, the methylomes of cancer and non-cancer cells show a number of methylation differences, indicating that certain features characteristics of cancer cells may be related to methylation characteristics. Robust methods for detecting differentially methylated regions (DMRs) could help scientists narrow down genome regions and even find biologically important regions. Although some statistical methods were developed for detecting DMR, there is no default or strongest method. Fisher’s exact test is direct, but not suitable for data with multiple replications, while regression-based methods usually come with a large number of assumptions. More complicated methods have been proposed, but those methods are often difficult to interpret. Results In this paper, we propose a three-step nonparametric kernel smoothing method that is both flexible and straightforward to implement and interpret. The proposed method relies on local quadratic fitting to find the set of equilibrium points (points at which the first derivative is 0) and the corresponding set of confidence windows. Potential regions are further refined using biological criteria, and finally selected based on a Bonferroni adjusted t-test cutoff. Using a comparison of three senescent and three proliferating cell lines to illustrate our method, we were able to identify a total of 1077 DMRs on chromosome 21. Conclusions We proposed a completely nonparametric, statistically straightforward, and interpretable method for detecting differentially methylated regions. Compared with existing methods, the non-reliance on model assumptions and the straightforward nature of our method makes it one competitive alternative to the existing statistical methods for defining DMRs.

COVID-19 and Digestive Surgical Emergencies: Experience of the General Surgery Department of Tangier University Hospital.

On March 11, 2020, the WHO declared that the epidemic of COVID-19 had become a pandemic, and this disrupted all the regulated operative programs. On the other hand and by its urgent nature, the emergency surgery was maintained with particularity in some situations, an association with infection by COVID-19. The circumstances of diagnosis of the association of infection by COVID-19 and surgical emergency are based on clinical, radiological, and biological criteria. In this work we report the experience of the University Hospital of Tangier concerning the management of three patients with the particularity of associating a covid infection and a digestive surgical emergency, we will discuss through these cases, the necessary protective measures in intraoperative and the impact of the covid infection on the morbi-mortality Concerning the impact of covid infection on postoperative morbidity and mortality, there are generally two situations: When the covid infection is benign, the prognosis depends on the severity of the surgical emergency and in this situation the prognosis is the same as for patients not infected by covid, this is the case of the first and third cases. The second situation; when the covid infection is severe, it has a great impact on the prognosis and the postoperative care in intensive care. With this publication, we are trying to provide information to help surgeons better manage this category of patients, especially in view of the panic caused by the pandemic, and the difficulty of adapting to the new patient circuit, but more studies recruiting more cases are needed to confirm our findings.

A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library

Three marketed anti-PD-L1 antibodies almost have severe immune-mediated side effects. The therapeutic effects of anti-PD-L1 chemical inhibitors are not satisfied in the clinical trials. Here we constructed human-derived protein scaffolds library and screened scaffolds with a shape complementary to the PD-1 binding domain of PD-L1. The RNA binding domain of U1 snRNPA was selected as one of potential binders because it had the most favorable binding energies with PD-L1 and conformed to pre-established biological criteria for the screening of candidates. The recombinant U1 snRNPA (rU1 snRNPA) in Escherichia coli exhibits anti-cancer activity in melanoma and breast cancer by reactivating tumor-suppressed T cells in vitro and anti-melanoma activity in vivo. Considering hydrophobic and electrostatic interactions, three residues were mutated on the interface of U1 snRNPA and PD-L1 complex, and the ranked variants by PatchDock and A32D showed an increased active phenotype. The screening of human-derived protein scaffolds may become the potential development of therapeutic agents.

The Contribution of Lumbar Puncture in Neonatal Infections - About 206 cases

Background: Neonatal meningitis is a serious infection, no clinico-biological score has been established to accurately identify neonates at high risk of developing neonatal meningitis.Objective: The aim of this work is to clarify the place of lumbar puncture in neonatal infections and to identify the predictive factors of meningeal localization in case of neonatal infection.Materials and methods: This is a prospective study of 861 observations of newborns hospitalized in the pediatric department of Mohammed V Hospital, CHU of Tangier, during a 14-month period from 1January 2019 to 29 February 2020. Among these patients the diagnosis of neonatal infection (NNI) was retained in 473 cases. Initial lumbar puncture was performed in 206 cases (43%). We included neonates aged 0 to 28 days, suspected of NNI, who had a lumbar puncture. Neonates treated as carriers of neonatal infection without sufficient anamnestic and clinical evidence and with an inconclusive or unperformed biological workup were excluded from the study.Results: During the study period, 861 newborns were hospitalized and the diagnosis of neonatal infection was retained in 473 cases, a rate of 55%, and the initial lumbar puncture was performed in 206 cases (43%). 61 newborns were diagnosed with neonatal meningitis, with fever in 76% of cases, 85% with convulsions, hypotonia and/or refusal to suckle in 63% of cases, and CRP >25mg/l in 67% of newborns.Conclusion: Lumbar puncture is the only diagnostic means of meningitis. Indeed, the indication of this procedure should not be systematic, but it should be dictated by the careful and simultaneous analysis of the anamnestic, clinical and biological criteria evocative of the infection and its meningeal localization in order to diagnose meningitis early and treat it correctly. The need to establish scores combining these different parameters, in order to accurately identify newborns at high risk of developing neonatal meningitis

ENVENIMATIONS VIPERINES

Rational:The viper envenomations are a real public health problem in Morocco more deaths are reported each year. It is a medical-surgical emergency which can be daunting and life-threatening, as well as the patients functional prognosis. Patients and Methods or Material and Methods:We present 24 cases of serious viper envenomation, on a retrospective study extended over a period of 9 years from 2010 to 2019, and through a literature review we clarify the following aspects: epidemiological, pathophysiological, clinical and therapeutic. Inclusion criteria: The presence of traces of hooks with at least one locoregional and / or general sign of envenomation. The actual presence of the snake in question and / or its description by a witness or the victim. Results:This is a retrospective study that interested 12 men and 13 women, mean age 41 years. The bites were due to vipers, the species was known cerastescerastes type in two cases, MacroviperaMauritanica in one case. 13 patients had a consumptive coagulopathy table with two cases of ischemic stroke, one case of hypovolemic shock and 4 cases of hemorrhagic shock, ten patients had compartment syndrome treated by emergency fasciotomy discharge.11 patients received anti venom serum with clinical improvement and reduction of complications. Discussion:The poison of vipers is a chemical proteinaceous with two essential components: the toxins and enzymes. These proteins are responsible for the observed symptoms. The severity of envenomation is related to the plasma concentration of the venom. The definition of early clinical and biological criteria of gravity has envenomation better assess and clarify the therapeutic indications. Processing viper envenomation considerably simplified over the past decade. The medical care is based on a symptomatic therapy component associated with a specific serum therapy. On early treatment with these specific immunoglobulins from the onset of signs of grades II or III envenomation reduces morbidity, sequelae and the total cost of care. Conclusion:Improving the prognosis of envenomation involves information education and good care that can only be achieved through close collaboration between.

Establishment of Reference Values of Gamma-Glutamyl-Transferase and Plasma Aminotransferases in Young Congolese

Objectives: Our goal was to contribute to the production of reference values ​​of plasma or serum biochemical markers by determining the reference values ​​of gamma-glutamyltransferase (GGT), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in young Congolese presumed to be healthy. Methods: 250 young Congolese presumed to be healthy (125 boys and 125 girls) aged 15 to 25 participated in the study. They were selected according to anamnestic and clinico-biological criteria. Samples were taken on a tube containing EDTA and the resulting plasma was stored at -20 ° C. The KENZA MAX spectrophotometer was used to analyze GGT, ASAT and ALAT. The median and the 2.5-97.5 percentiles were used to set the reference limits for each enzyme. The benchmarks determined were compared with those reported by other Africans, Europeans, Indians and Americans. Results: The established reference values ​​were: GGT 12.15-61.85 IU/L for boys and 7-51.95 IU / l for girls (p˂0.0001); ASAT 21.60-94.85 IU/L for boys and 17-84.85 IU/L for girls (p = 0.0003); ALAT 8.30-74.40 IU/L for boys and 8-53.85 IU/L for girls (p˂0.0001). In addition, the comparison between our values ​​and those of other populations showed significant differences. Conclusion: Our results underline the importance of establishing reference values ​​for plasma enzymes specific to the Congolese population. The use of the values ​​established in the ’other populations could induce errors of judgment by excess or by default. Key words: Gamma-glutamyltransferase, Aspartate aminotransferase, Alanine aminotransferase, Reference values, Congo.

Treatment of Human Babesiosis: Then and Now

Babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia. With its increasing incidence worldwide and the risk of human-to-human transmission through blood transfusion, babesiosis is becoming a rising public health concern. The current arsenal for the treatment of human babesiosis is limited and consists of combinations of atovaquone and azithromycin or clindamycin and quinine. These combination therapies were not designed based on biological criteria unique to Babesia parasites, but were rather repurposed based on their well-established efficacy against other apicomplexan parasites. However, these compounds are associated with mild or severe adverse events and a rapid emergence of drug resistance, thus highlighting the need for new therapeutic strategies that are specifically tailored to Babesia parasites. Herein, we review ongoing babesiosis therapeutic and management strategies and their limitations, and further review current efforts to develop new, effective, and safer therapies for the treatment of this disease.

Inflammatory Biomarkers Aid in Diagnosis of Dementia

Dual pathology of Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) commonly are found together at autopsy, but mixed dementia (MX) is difficult to diagnose during life. Biological criteria to diagnose AD have been defined, but are not available for vascular disease. We used the biological criteria for AD and white matter injury based on MRI to diagnose MX. Then we measured multiple biomarkers in CSF and blood with multiplex biomarker kits for proteases, angiogenic factors, and cytokines to explore pathophysiology in each group. Finally, we used machine learning with the Random forest algorithm to select the biomarkers of maximal importance; that analysis identified three proteases, matrix metalloproteinase-10 (MMP-10), MMP-3 and MMP-1; three angiogenic factors, VEGF-C, Tie-2 and PLGF, and three cytokines interleukin-2 (IL-2), IL-6, IL-13. To confirm the clinical importance of the variables, we showed that they correlated with results of neuropsychological testing.

Optic neuritis classification in 2021

Optic neuritis (ON) can be associated with inflammatory disease of the central nervous system or can be isolated, with or without relapse. It can also be associated with infectious or systemic disease. These multiple associations based on a variety of clinical, radiological, and biological criteria that have changed over time have led to overlapping phenotypes: a single ON case can be classified in several ways simultaneously or over time. As early, intensive treatment is often required, its diagnosis should be rapid and precise. In this review, we present the current state of knowledge about diagnostic criteria for ON aetiologies in adults and children, we discuss overlapping phenotypes, and we propose a homogeneous classification scheme. Even if distinctions between typical and atypical ON are relevant, their phenotypes are largely overlapping, and clinical criteria are neither sensitive enough, nor specific enough, to assure a diagnosis. For initial cases of ON, clinicians should perform contrast enhanced MRI of the brain and orbits, cerebral spinal fluid analysis, and biological analyses to exclude secondary infectious or inflammatory ON. Systematic screening for MOG-IgG and AQP4-IgG IgG is recommended in children but is still a matter of debate in adults. Early recognition of neuromyelitis optica spectrum disorder, MOG-IgG-associated disorder, and chronic relapsing idiopathic optic neuritis is required, as these diagnoses require therapies for relapse prevention that are different from those used to treat multiple sclerosis.

Hypercoagulability Evaluation in Antiphospholipid Syndrome without Anticoagulation Treatment with Thrombin Generation Assay: A Preliminary Study

Antiphospholipid syndrome (APS) is associated with thrombotic events (tAPS) and/or obstetrical morbidity (oAPS), with persisting antiphospholipid antibodies (aPL). Despite an update of aPL in 2006, several patients had typical clinical events without the classical biological criteria. The aim of our study was to evaluate the hypercoagulability state with both thrombin generation (TG) profiles and activated protein C resistance (aPCR) in different types of APS. Methods: We retrospectively included 41 patients with Sydney criteria classification (tAPS, oAPS) and no clinical manifestation of APS with persistent aPL (biological APS). A thrombin generation assay was performed with a Fluoroskan Ascent fluorometer in platelet-poor plasma (PPP). Activated protein C resistance was measured as a ratio: ETP+aPC/ETP-aPC × 100. Results: Thrombotic APS and oAPS had an increase of global thrombin generation (ETPcontrol = 808 nM.min (756–853) vs. 1265 nM.min (956–1741) and 1863 nM.min (1434–2080), respectively) (Peakcontrol = 78 nM (74–86) vs. 153 nM (109–215) and 254 nM.min (232–289), respectively). Biological APS had only a lag time increase (Tcontrol = 4.89 ± 1.65 min vs. 13.6 ± 3.9 min). An increased aPCR was observed in tAPS (52.7 ± 16.4%), oAPS (64.1 ± 14.6%) as compared to the control group (27.2 ± 13.8%). Conclusion: Our data suggest an increase of thrombin generation in thrombotic and obstetrical APS and no hypercoagulable states in patients with biological APS. The study of a prospective and a larger controlled cohort could determine the TGA useful for APS monitoring and could confirm an aPCR evaluation in PPP.