Understanding paralogous epilepsy-associated GABA receptor variants: Clinical implications, mechanisms, and potential pitfalls.

Recent discoveries have revealed that genetic variants in γ-aminobutyric acid type A (GABA) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABA receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in , , and Seven mutations (α1, α1, β2, β3, β3, γ2, and γ2) in α1β2/3γ2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations.

TWEAK and TNFɑ Pro-inflammatory Soluble Cytokines and their Specific Autoantibodies Secretion in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a complex, chronic inflammatory disease of the central nervous system, where immune dysregulation plays a critical role. We sought to explore the modulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFɑ) and TNF-like weak inducer of apoptosis (TWEAK), along with their respective autoantibodies, TNAb and TWAb, and to decipher potential associations between these and clinical characteristics which could assist personalized therapy in MS. We also assessed the complementarity to leading candidate biomarkers in MS patient monitoring, namely, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL).

Altered plasma levels of the SARS-CoV-2-related proteins ACE2 and TMPRSS2 in patients with Crohn's disease.

The SARS-CoV-2 coronavirus infects cells through the cellular receptor angiotensin-converting enzyme 2 (ACE2), and the protease TMPRSS2 for the priming of viral spike protein. Thus, changes in these key proteins due to chronic conditions can increase risk for SARS-CoV2 infection; but significance of changes may differ is these changes correspond to full-length species or proteolytic fragments. Here, we determined that full-length ACE2 decreased in the plasma of uninfected Crohn's disease (CD) patients before treatment onset compared to controls.

Sportsman's Hernia repair using Nesovic procedure, a 13-year single-center experience.

Sportsman's hernia is very frequent in some sports, particularly in football. This painful syndrome is reported by high-level athletes as well as amateurs. There is no consensus about the management of sportsman's hernia, because of the heterogeneity in anatomoclinic forms.

Communicative health literacy and associated variables in nine European countries: results from the HLS survey.

Our study aimed to report on variables associated with communicative health literacy (COM-HL) in European adults. The HLS survey was conducted in 2019-2021 including nine countries which measured COM-HL by using a validated questionnaire (HLS-COM-P-Q6 with a score ranging from 0 to 100). Linear regression models were used to study variables associated with COM-HL globally (multilevel model with random intercepts and slopes and at country level) and in each country.

Patients' psychosocial attributes and aggressiveness of cancer treatments near the end of life.

Background: While the use of chemotherapy near the end of life (EOL) has been identified as a relevant criterion for assessing quality of cancer care and has been estimated as non-beneficial, a trend of aggressiveness in cancer care during the last period of life remains. Both patients' sociodemographic characteristics and physicians' practice setting are associated with this use. The role of patients' psychosocial characteristics has however been understudied.

The efficacy and safety of first-line metastatic melanoma treatment with ipilimumab + nivolumab versus nivolumab in a real-world setting.

Background: The Checkmate 067 randomized controlled trial, published in 2015, demonstrated improved progression-free survival and numerically, although not statistically, superior overall survival for ipilimumab + nivolumab. The objective of this study was to compare the efficacy and safety of nivolumab to ipilimumab + nivolumab as first-line treatment for metastatic melanoma in a real-world setting.

Methods: Patients were prospectively included in the French Melbase cohort from 2013 to 2022.

Tailoring glioblastoma treatment based on longitudinal analysis of post-surgical tumor microenvironment.

Glioblastoma (GBM), an incurable primary brain tumor, typically requires surgical intervention followed by chemoradiation; however, recurrences remain fatal. Our previous work demonstrated that a nanomedicine hydrogel (GemC-LNC) delays recurrence when administered post-surgery. However, tumor debulking also triggers time-dependent immune reactions that promote recurrence at the resection cavity borders.

Impact of Sanitation on Rodent Pullulation and Plague Status in an Informal Settlement on the Outskirts of Mahajanga (Madagascar).

Plague is a zoonotic disease caused by , and it is endemic in Madagascar. The plague cycle involves wild and commensal rodents and their fleas; humans are an accidental host. Madagascar is the country where plague burden is the highest.

Dihydroartemisinin-Piperaquine Combination in the Treatment of Uncomplicated Malaria: Update on Clinical Failures in Africa and Tools for Surveillance.

Dihydroartemisinin (or artenimol)-piperaquine is one of the six artemisinin-based combination therapies recommended in uncomplicated malaria treatment. However, artemisinin partial resistance has been reported in Cambodia, Laos, Vietnam, India, and, recently, in Africa. Polymorphisms in the gene have been described as molecular markers of artemisinin resistance and the amplification of the plasmepsine II/III (/) gene has been associated with piperaquine resistance.

Setting Up an NGS Sequencing Platform and Monitoring Molecular Markers of Anti-Malarial Drug Resistance in Djibouti.

Djibouti is confronted with malaria resurgence, with malaria having been occurring in epidemic proportions since a decade ago. The current epidemiology of drug-resistant is not well known. Molecular markers were analyzed by targeted sequencing in 79 clinical isolates collected in Djibouti city in 2023 using the Miseq Illumina platform newly installed in the country.

Identification of 2,4-Di--Butylphenol as an Antimicrobial Agent Against Bacteria from Rwandan Propolis.

Background/objectives: Acne is the most prevalent dermatological condition among humans, affecting approximately 80% of adolescents during puberty. To date, numerous compounds have been used for acne treatment, including erythromycin ointments and antiseptics, with varying degrees of success. The emergence of erythromycin-resistant strains has spurred the search for new antimicrobial agents, particularly from natural sources.

Different sustained and induced alpha oscillations emerge in the human auditory cortex during sound processing.

Alpha oscillations in the auditory cortex have been associated with attention and the suppression of irrelevant information. However, their anatomical organization and interaction with other neural processes remain unclear. Do alpha oscillations function as a local mechanism within most neural sources to regulate their internal excitation/inhibition balance, or do they belong to separated inhibitory sources gating information across the auditory network? To address this question, we acquired intracerebral electrophysiological recordings from epilepsy patients during rest and tones listening.

Quorum Quenching Lactonase Alters Virulence of and Reduces Maceration in Potatoes.

is a soft rot phytopathogenic bacterium mainly infecting potatoes. The virulence of is controlled by quorum sensing (QS), a communication mechanism which enables bacteria to coordinate their behavior in a population density-dependent manner. Inhibiting QS has gained interest as a sustainable alternative to conventional treatments to control pathogens in agriculture.

Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping.

Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate.

Nationwide analysis of one-year mortality following pancreatectomy in 17,183 patients with pancreatic cancer.

Background: The use of 1-year mortality following pancreatectomy for PDAC as a measure of surgical quality has not been evaluated. We aim to i) assess the 1-year mortality rate following pancreatectomy for PDAC, and ii) identify patient and hospital characteristics associated with 1-year mortality.

Methods: Data was extracted retrospectively from the French national medico-administrative database.

Curative-intent surgery for solitary bone metastasis from extremity and trunk wall sarcoma: What are the outcomes and complications?

Introduction: Approximately 40-50 % of sarcoma patients will develop lung metastasis, but only 10 % will develop bone metastasis. The survival benefit of surgery for solitary bone metastasis remains unclear.

Methods: From 1987 to 2019, 47 patients who underwent curative-intent treatment for localized bone or soft tissue sarcoma in the extremities or trunk wall developed solitary bone metastases as the first distant recurrence.

Coinfections and iterative detection of respiratory viruses among 17,689 patients between March 2021 and December 2022 in Southern France.

Objectives: We aimed to describe coinfections and iterative infections with respiratory viruses diagnosed over a 22-month period in 2021-2022 in public university hospitals of the second largest French city.

Material And Methods: Respiratory virus infections were diagnosed by qPCR with the Fast Track Diagnostics Respiratory Pathogens 21 on nasopharyngeal swabs collected between 01/03/2021-31/10/2022 and sent for routine diagnosis purpose to our clinical microbiology-virology laboratory at public university hospitals of Marseille, Southern France.

Results: Nasopharyngeal swabs from 17,689 patients were tested, of which 8,133 (46 %) were positive for ≥1 respiratory virus and 1,255 (15%) were co-infected with ≥2 viruses including 213 (2.

Therapeutic Contribution of Tau-Binding Thiazoloflavonoid Hybrid Derivatives Against Glioblastoma Using Pharmacological Approach in 3D Spheroids.

Growing evidence has unveiled the pathological significance of Tau in many cancers, including the most aggressive and lethal brain tumor glioblastoma multiform (GBM). In this regard, we have recently examined the structure-activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau-overexpressing GBM cells. Here, we evaluated the anticancer activities of the two lead compounds and using multi-cellular spheroids (MCSs) which represent an easy 3D human cell model to mimic GBM organization, physical constraints and drug penetration.

Inputs of pharmacoepidemiology in addictovigilance: How do they fit together?

The French Addictovigilance Network has been using data from the French Heath insurance since the late 1990s to assess prescription drug abuse. In this narrative review, we illustrate the inputs of pharmacoepidemiology in addictovigilance based on the experience of the French Addictovigilance Network. The review focuses on pharmacoepidemiology using the French National Health Data System.