Miracle-dz/UniFAR-FTUs huggingface dataset:
ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population

Background Epilepsy is one of the most common neurological disorders with about 30% treatment failure rate. An interindividual variations in efficacy of antiepileptic drugs (AEDs) make the treatment of epilepsy challenging, which can be attributed to genetic factors such as ATP-Binding Cassette sub-family B, member1 (ABCB1) gene polymorphisms. Objective The main objective of the present study is to evaluate the association of ABCB1 C1236T, G2677T, and C3435T polymorphisms with treatment response among Tunisian epileptic patients. Materials and Methods One hundred epileptic patients, originated from north of Tunisia, were recruited and categorized into 50 drug-resistant and 50 drug-responsive patients treated with antiepileptic drugs (AEDs) as per the International League Against Epilepsy. DNA of patients was extracted and ABCB1 gene polymorphisms studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The C1236T, G2677T, and C3435T polymorphisms were involved into AED resistance. Significant genotypic (C1236T TT (p ≤ 0.001); G2677T TT (p = 0.001); C3435T TT (p ≤ 0.001)) and allelic associations (C1236T T (3.650, p ≤ 0.001); G2677TT (1.801, p = 0.044); C3435T T (4.730, p ≤ 0.001)) with drug resistance epilepsy (DRE) were observed. A significant level of linkage disequilibrium (LD) was also noted between ABCB1 polymorphisms. Patients with the haplotypes CT and TT (C1236T-G2677T); GT, TC, and TT (G2677T-C3435T); CT and TT (C1236T-C3435T); CTT, TTC, TGT, and TTT (C1236T-G2677T-C3435T) were also significantly associated to AED resistance. Conclusions The response to antiepileptics seems to be modulated by TT genotypes, T alleles, and the predicted haplotypes for the tested SNPs in our population. Genetic analysis is a valuable tool for predicting treatment response and thus will contribute to personalized medicine for Tunisian epileptic patients.
Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status

We investigated the effect of the mammalian target of rapamycin (mTOR) inhibitor everolimus on tuberous sclerosis complex- (TSC-) associated autistic symptoms and focal seizures with impaired awareness in a female child with TSC. We further evaluated the relationship between improved autistic symptoms and seizures and increased the serum levels of the antioxidant proteins, ceruloplasmin (Cp) and transferrin (Tf), and oxidant-antioxidant status indicated by the oxidant marker oxidized low-density lipoprotein (ox-LDL) and the antioxidant marker total antioxidant power (TAP). Everolimus treatment improved impaired social cognition and autistic behaviors; however, seizure and epileptic activity persisted. Serum Cp and Tf levels gradually increased in response to improved autistic symptoms. Serum TAP levels gradually decreased from baseline to the lowest value at 16 weeks and then increased at 24 weeks, showing a trend toward decreased total score of the Aberrant Behavior Checklist. This study revealed that everolimus treatment improved impaired social cognition with increased serum levels of the copper mediator (Cp) and iron mediator (Tf) via homeostatic control of mTOR activity accompanied by overlap of the oxidant-antioxidant system. Everolimus had no effect on TSC-related epileptiform discharges, and thus, the autistic symptoms and epileptic activity may be two independent end results of a common central nervous system disorder including mTOR hyperactivity. This trial is registered with JMAS-IIA00258.
Depression comorbidity in patients with chronic hepatitis C and its possible relation to treatment outcome

BackgroundThe highest number of hepatits C virus all over the world is in Egypt. Depression, which occurs during the course of illness, can affect the treatment response, compliance to therapy and hence, disease outcome. ObjectivesThe objective of this study was to evaluate the presence of depression in patients with chronic hepatitis C (CHC) either using interferon therapy or not. MethodA case–control study was carried out on 200 patients with CHC and 200 healthy controls. The patients were subdivided into two groups. Group 1 included patients who were treated with pegylated interferon and ribaverin, whereas group 2 included patients with CHC and not receiving interferon. The patients and controls were subjected to careful clinical assessment, laboratory investigation and assessment of depression through Mini-International Neuropsychiatric Interview schedule for psychiatric interview and Beck Depression Inventory. ResultsDepression was more prevalent in patients with CHC. The prevalence of depression in the interferon-receiving group (G1) was 42% (42 patients ) and 30% (30 patients ) in the noninterferon-receiving group (G2). Depression was correlated with decreased number ofred blood cells, decreased haemoglobin percentage, less sustained viral remission and treatment discontinuation. ConclusionDepression is prevalent in a considerable way in patients with CHC, and in a much greater and severe form in those on interferon therapy (G1). The presence of depression might be related to poor treatment outcome. Psychiatric assessment and early intervention is mandatory in this population.
Metformin Ameliorates Testicular Damage in Male Mice with Streptozotocin-Induced Type 1 Diabetes through the PK2/PKR Pathway

Approximately 90% of male diabetes mellitus patients have varying degrees of testicular dysfunction. The molecular mechanism underlying diabetes-induced testicular damage has not been thoroughly elucidated. In this research, we sought to determine the influence of metformin (Met) on diabetes-induced testicular injury and the mechanism involved with a focus on testicular dysfunction, apoptosis, autophagy, and prokineticin 2 (PK2) signalling. In our study, C57BL/6J mice were randomly divided into the normal control group, the diabetes group, and the Met-treated group. Streptozotocin (50 mg·kg−1·d−1) was injected intraperitoneally into the mice for 5 days in a row to induce type 1 diabetes, which was diagnosed by a blood glucose level ≥ 16.7 mmol/L after 7 days. The experimental animals were orally administered Met (250 mg·kg−1·d−1) for 16 weeks. Properties of testicular function, including sperm motility and the total concentration of epididymal sperm, were assessed. Changes in testicular structure, such as the blood-testis barrier, histological pathology, and organelles, were observed. The levels of apoptosis and expression of related proteins, such as Bax and Bcl-2, were measured. Moreover, autophagy-related proteins, including Beclin-1, p62, and LC3B, as well as the PK2/PKR pathway, which consists of PK2, PKR1, PKR2, AKT, and GSK3β, were analysed. Upon the induction of diabetes, reproductive capacity was significantly impaired and a disordered arrangement of testicular seminiferous tubules and destroyed organelles in spermatogenic cells was observed. Met administration preserved testicular function and structure. In addition, in mice with diabetes, the levels of PK2, PKR2, p-Akt, and p-GSK3β were significantly decreased at different times, while that of PKR1 was markedly increased, and these changes were normalized by Met. Furthermore, diabetic mice showed increased apoptosis and decreased autophagy in the testes, the effects of which were nullified by Met. These results suggest that Met rescues diabetes-induced testicular damage by attenuating apoptosis and inducing autophagy. This effect is likely mediated by the PK2/PKR/AKT/GSK3β signalling pathway.
RNA-seq Reveals Dysregulation of Novel Melanocyte Genes upon Oxidative Stress: Implications in Vitiligo Pathogenesis

Oxidative stress is known to induce melanocyte death, but the underlying mechanisms are incompletely understood. To identify oxidative stress-induced global gene expression changes in melanocytes, we treated PIG1 melanocytes with H2O2 in a dose- and time-dependent manner and performed RNA-seq. This approach allowed us to capture the events occurring early as well as late phase after treatment with H2O2. Our bioinformatics analysis identified differentially expressed genes involved in various biological processes of melanocytes which are known to contribute to the vitiligo development, such as apoptosis, autophagy, cell cycle regulation, cell adhesion, immune and inflammatory responses, melanocyte pluripotency, and developmental signaling such as WNT and NOTCH pathways. We uncovered several novel genes that are not previously described to be involved in melanocytic response to stress nor in vitiligo pathogenesis. Quantitative PCR and western blot analysis of selected proteins, performed on PIG1 and primary human epidermal melanocytes, confirmed the RNA-seq data. Interestingly, we discovered an aberrant regulation of several transcription factors that are involved in diabetes, neurological, and psychiatric diseases, all of which are comorbid conditions in patients with vitiligo. Our results may lead to a better understanding of the molecular mechanisms underlying vitiligo pathogenesis and help developing new drug targets for effective treatment.
Weekend-Based Parent-Group Intervention to Reduce Stress in Parents of Children and Adolescents with Type 1 Diabetes: A Pilot Study

Diagnosis of type 1 diabetes (T1D) in a child is often associated with anger, denial, fear, and depression from the parents. The aim of the study was to improve parents' adaptation to the diagnosis of diabetes of their child. Sixty-two parents (29 mothers, 33 fathers) of 36 children with type 1 diabetes (mean age = 11.3‐3.3 years; diabetes duration > 1 year; HbA1c = 57 ± 11 mmol/mol) participated in a three-day educational working group pilot intervention study. Intervention was based on the reexamination of the traumatic event of diagnosis of T1D through spatial and time-line anchorage, retracing of the future, emotional awareness, and interactive discussion. Relaxing technique, diaphragmatic breathing, and guided visualization were used by 2 psychologists and 1 pediatric endocrinologist. The study was approved by EC and participants filled a consent form. At baseline and after intervention, parents filled in a questionnaire including Diabetes-Related Distress (DRD), Parent Health Locus of Control Scale (PHLOC), Parent Stress Index Short Form (PSI-SF), Hypoglycemia Fear Survey-Parents (HFS-P) and Hypoglycemia Fear Survey-Parents of Young Children (HFS-P-YC), and Health Survey Short Form-36 (SF-36). Three months after the intervention, both parents reported a reduction in the “difficult child” subscale of the PSI-SF (p < 0.05) and increased scores of social functioning of the SF-36 (p < 0.05). DRD score was significantly reduced in mothers (p = 0.03), while the “parental distress” subscale of the PSI-SF was significantly improved in fathers (p = 0.03). This weekend-based parent group intervention seems to reduce stress and improve social functioning of parents of children and adolescents with type 1 diabetes.
Evaluation of the Safety of Percutaneous Dilational Tracheostomy Compared with Surgical Tracheostomy in the Intensive Care Unit

Background Tracheostomy is a necessary procedure for patients who require long-term mechanical ventilation support. There are two methods for tracheostomy in current use: surgical tracheostomy (ST) and percutaneous dilational tracheostomy (PDT). In the current study, we retrospectively compared the safety of both procedures performed in our intensive care unit (ICU). Methods In this study, we enrolled subjects who underwent tracheostomy in our ICU between January 2012 and March 2016. We excluded subjects who were <20 years old and underwent tracheostomy in the operating room. As a primary outcome, we evaluated the rate of complications between ST and PDT groups. The length of ICU stay, time to tracheostomy from intubation, and the rate of mechanical ventilation and mortality at 28 postoperative days were also examined as secondary outcomes. Results Compared with the ST group, the rate of all complications was lower in the PDT group (13.4% vs. 38.8%, p=0.007). Although the rate of intraoperative complications did not differ between the two groups (3.8% vs. 8.1%, p=0.62), relative to the ST procedure, the PDT procedure was associated with fewer postoperative complications (34.6% vs. 9.6%, p=0.003). Among postoperative complications, accidental removal of the tracheostomy tube and an air leak from the tracheostomy fistula were less frequent in the PDT group than the ST group. Between the two groups, there were no significant differences in their secondary outcomes. Conclusion This retrospective study indicates that relative to ST, PDT is a safer procedure to be performed in the ICU. Fewer postoperative complications following PDT might be attributed to the small skin incision made during this procedure.
Increased Neuronal Differentiation Efficiency in High Cell Density-Derived Induced Pluripotent Stem Cells

Human pluripotent stem cells (hPSCs), including induced pluripotent stem cells (iPSCs), provide access to hard-to-obtain cells for studies under physiological and disease conditions. For the study of neurodegenerative diseases, especially sporadic cases where the “disease condition” might be restricted towards the neuroectodermal lineage, obtaining the affected neurons is important to help unravel the underlying molecular mechanism leading to the diseases. Although differentiation of iPSCs to neural lineage allows acquisition of cell types of interest, the technology suffers from low efficiency leading to low yield of neurons. Here, we investigated the potential of adult neuroprogenitor cells (aNPCs) for iPSC derivation and possible confounders such as cell density of infected NPCs on their subsequent neuronal differentiation potential from reprogrammed cells under isogenic conditions. Characterized hiPSCs of defined cell densities generated from aNPCs were subjected to neuronal differentiation on PA6 stromal cells. The results showed that hiPSC clones obtained from low seeding density (iPSC-aNPCLow) differentiated less efficiently compared to those from higher density (iPSC-aNPCHigh). Our findings might help to further improve the yield and quality of neurons for in vitro modelling of neurodegenerative diseases.
Increased Choroidal Thickness in Keratoconus Patients: Perspectives in the Disease Pathophysiology

Purpose To analyze and compare choroidal thickness between keratoconus (KC) patients and age-matched non-KC subjects. Methods A cross-sectional, case-control study. One hundred and thirty-four keratoconic eyes and 78 control eyes, from individuals aged from 12 to 30 years old, were studied. Patients with KC followed in Corneal Department of Centro Hospitalar São João, Porto, Portugal, were identified and consecutively included between December 2017 and February 2018. A spectral-domain optical coherence tomography (OCT) using depth enhanced imaging was performed, and choroidal thickness in the center of the fovea and at 500 μm intervals along a horizontal section was measured and compared. Results The statistical analysis showed that keratoconic eyes present a thicker choroid in every measured location (p < 0.05). Mean subfoveal choroidal thickness (SFCT) values obtained were 375.86 ± 89.29 and 322.91 ± 85.14 in keratoconus and control groups, respectively (p < 0.001). In a multivariate analysis, SFCT was significantly associated with spherical equivalent (p=0.004) and the presence of keratoconus (p < 0.001), but not with age (p=0.167), gender (p=0.579), or best-corrected visual acuity (p=0.178). In a “fixed model,” keratoconus patients were found to have a 67.55 μm (95% CI 36.61–98.49) thicker subfoveal choroid compared to controls. Conclusion Keratoconus patients seem to have a thicker choroid than healthy individuals. The exact pathophysiological mechanism resulting in a thicker choroid in KC patients is not known, but it could possibly be associated with inflammatory choroidal mechanisms.
Genome-Wide Identification and Analysis of the Cytochrome B5 Protein Family in Chinese Cabbage (Brassica rapa L. ssp. Pekinensis)

Cytochrome B5 (CB5) family proteins play an important role in various oxidation/reduction reactions in cells as the electron donor and are involved in a variety of biotic and abiotic stress processes. However, the function of the CB5s in Brassica rapa is still unclear. In this study, we carried out genome-wide identification, characterization, and expression analysis of BrCB5s in different tissues under adversities and stresses. It was identified that fifteen BrCB5s were distributed on different chromosomes, which were classified into seven groups (A-G) according to its phylogenetic relationship. Phylogenetic analysis of the CB5 protein sequences from six species showed that the BrCB5s conduct a close evolutionary process with the CB5s of Arabidopsis thaliana and far from those of Oryza sativa. Protein interaction analysis showed that 40 interaction patterns were predicted including two Sucrose Transporter 4 subfamily proteins (SUT 4) and Fatty Acid Hydroxylase 2 protein (FAH 2) can interact with most members of BrCB5s. The expression profile analysis indicated that BrCB5s were differentially expressed in different tissues, and the transcript abundances were significantly different under various abiotic stresses and plant hormone treatments. Our study provides a basis for a better understanding of the characteristics and biological functions of the CB5 family genes in Chinese cabbage during plant development, especially in plant responses to multiple stresses.
Contamination of the Surfaces of a Health Care Environment by Multidrug-Resistant (MDR) Bacteria

Nosocomial infections (NIs) are known worldwide and remain a major problem despite scientific and technical advances in the field of health. The severity of the infection depends on the characteristics of the microorganisms involved and the high frequency of resistant pathogens in the hospital environment. The aim of this study is to determine the distribution of pathogenic bacteria (and their resistance to antibiotics) that spread on hospital surfaces, more specifically, on those of various departments in the Provincial Hospital Center (PHC) of Mohammedia, Morocco. A cross-sectional study was conducted from March 2017 to April 2018. Samples were collected by swabbing the hospital surfaces, and the isolated bacteria were checked for their susceptibility to antibiotics by the Kirby–Bauer disk diffusion method following the standards of the Clinical and Laboratory Standards Institute (CLSI). Among 200 swab samples, 176 (88%) showed bacterial growth. Gram-negative isolates were predominant at 51.5% (101/196), while the Gram-positives were at 48.5% (95/196). The main isolates are Enterobacteria weighted at 31.6% (62/196), Staphylococcus aureus reaching 24% (47/196), Pseudomonas aeruginosa at 9.2% (18/196), and Acinetobacter spp. with 3.3% (6/196). Moreover, the antimicrobial susceptibility profile of the isolates showed that about 31.7% (32/101) of the Gram-negative isolates were found to be MDR. This resistance is also high among isolates of S. aureus of which 44.7% (20/47) were methicillin-resistant Staphylococcus aureus (MRSA). Contamination of hospital surfaces by MDR bacteria is a real danger to public health. The concept of environmental bacterial reservoir is a reality that requires strict compliance with current guidelines and recommendations for hand hygiene, cleaning, and disinfection of surfaces in hospitals.
The Choice of Local Treatment Modalities for Patients with Brain Metastases from Digestive Cancers

Background Brain metastases (BMs) from digestive cancers are rare; therefore, no optimal treatment modality has been defined. Methods We retrospectively reviewed the clinical data of 68257 patients with digestive cancers. Propensity score matching (PSM) was used to balance patient backgrounds between groups. Survival differences between different treatment modalities were compared. Univariate and multivariate Cox proportional hazards models were performed to identify prognostic factors on overall survival (OS). Results 270 patients with BM entered the study. In the entire group, the median survival time after diagnosis of brain metastases was 10.25 months (95% CI: 8.41–12.09 months); local treatment could significantly prolong OS (respectively, P < 0.01; even after PSM, P < 0.01); combination treatment was more effective than single treatment modality (respectively, P < 0.01; even after PSM, P < 0.01). However, each combination modality was identically effective (P > 0.05). When patients were divided into three groups based on 1, 2-3, or more than 3 metastatic lesion(s), same results were identified between local treatment and without local treatment (1 lesion, P < 0.01; 2-3 lesions, P < 0.01; more than 3 lesions, P < 0.01, respectively) and combination and single treatment (P < 0.01, P=0.02, P=0.03, respectively). However, there was no difference between different combined treatments (P > 0.05). Multivariate analysis revealed that performance status (P < 0.01), presence of extracranial metastasis (P=0.04), number of BM (P < 0.01), and local treatment for BM (P < 0.01) were independent prognostic factors. Conclusions Regardless of the number of brain lesions, local treatment achieved higher overall survival times than no local treatment, and combination therapy could offer survival benefit to patients as compared with single therapy.
Lack of Associations between Elevated Serum Uric Acid and Components of Metabolic Syndrome Such as Hypertension, Dyslipidemia, and T2DM in Overweight and Obese Chinese Adults

The overweight and obese population experiences a higher occurrence of both hyperuricemia and metabolic syndrome. The present study was to explore the relationship between serum uric acid and metabolic syndrome-related risk factors among 409 obese Chinese adults (254 women and 155 men) with >24 kg/m2 BMI. Based on sex-specific reference ranges, 233 (57%) patients showed elevated serum uric acid. A total of 15 attributes were selected to assess the associations between elevated serum uric acid and components of metabolic syndrome, including serum uric acid, total cholesterol, HDL-C, LDL-C, triglyceride, systolic blood pressure, fasting blood glucose, glycosylated hemoglobin, HOMA-IR, alanine aminotransferase, creatinine, urine microalbumin, muscle mass amount, BMI, and age. Among the participants stratified into three groups of grade I, grade II, and grade III obesity, as well as among the participants stratified into male and female groups, univariate correlation analysis identified a negative association (P < 0.01) for age, positive associations (P < 0.01) for BMI, muscle mass, alanine aminotransferase, and creatinine. The stepwise multivariate logistic regression proved similar associations for age, BMI, creatinine, and alanine aminotransferase. No significant associations were testified between serum uric acid levels and cholesterol, HDL-C, LDL-C, triglyceride, fasting blood glucose, glycosylated hemoglobin, HOMA-IR, and urine microalbumin. Factor analysis illustrated that 15 attributes could be grouped into two common factors and five individual factors. A common underlying factor was identified among uric acid, muscle mass, creatinine, alanine aminotransferase, and BMI. The results indicate that serum uric acid has no apparent association with metabolic syndromes that are commonly characterized by hypertension, dyslipidemia, and T2DM.