LOLA

The intensive cultivation under plastic in southern Spain has made the agricultural model highly productive. Although strict regulations on pesticide usage exist, exposure to pesticides in the environment has been associated with an increased appearance of neurodegenerative diseases including Alzheimer's disease (AD). A cross-sectional study was performed to examine the prevalence and risk of AD related to pesticide exposure in Andalusia (Spain). We utilized the Odds Ratio statistical test to compare the prevalence rate of AD in the exposed and unexposed areas...

Ensuring the safety of patient medication management is a public health priority. In hospitals, the medication circuit involves risks, especially in terms of storage. As part of an institutional project, the deployment of computerized medicine cabinets in our hospital's care units was initiated in 2015. By 2022, almost all care departments were equipped. Each drug picking is carried out by the registered nurse according to the patient's name, in accordance with the administration plan. In addition, local recommendations are to collect medication for a maximum of 24 hours...

Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic β-cell function (Pβf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes...

l-Ornithine- l-aspartate (LOLA) reduces toxic ammonium (NH3 ) plasma levels in hepatic encephalopathy. NH3 detoxification/excretion is achieved by its incorporation into urea and glutamine via activation of carbamoyl phosphate synthetase 1 (CSP1) by l-ornithine and stimulation of arginase by l-aspartate. We aimed at identifying additional molecular targets of LOLA as a potential treatment option for non-alcoholic fatty liver disease (NAFLD). In primary hepatocytes from NAFLD patients, urea cycle enzymes CSP1 and ornithine transcarbamylase (OTC) increase, while the catabolism of branched-chain amino acids (BCAAs) decreases with disease severity...

Understanding gene evolution across genomes and organisms, including ctenophores, can provide unexpected biological insights. It enables powerful integrative approaches that leverage sequence diversity to advance biomedicine. Sequencing and bioinformatic tools can be inexpensive and user-friendly, but numerous options and coding can intimidate new users. Distinct challenges exist in working with data from diverse species but may go unrecognized by researchers accustomed to gold-standard genomes. Here, we provide a high-level workflow and detailed pipeline to enable animal collection, single-molecule sequencing, and phylogenomic analysis of gene and species evolution...

This open-label, two-part, phase Ib drug-drug interaction study investigated whether the pharmacokinetic (PK) and safety profiles of lurbinectedin (LRB), a marine-derived drug, are affected by co-administration of itraconazole (ITZ), a strong CYP3A4 inhibitor, in adult patients with advanced solid tumors. In Part A, three patients were sequentially assigned to Sequence 1 (LRB 0.8 mg/m2 , 1-h intravenous [IV] + ITZ 200 mg/day oral in Cycle 1 [C1] and LRB alone 3.2 mg/m2 , 1 h, IV in Cycle 2 [C2]). In Part B, 11 patients were randomized (1:1) to receive either Sequence 1 (LRB at 0...

Neutrophils, major regulators of innate immunity, have recently emerged as key components of the tumor microenvironment. The role of neutrophils in cancer has been linked to their ability to form neutrophil extracellular traps (NETs), structures composed of decondensed DNA decorated with enzymes that are released into the extracellular space. Here, we discuss the pivotal roles of NETs in influencing responses to anticancer therapies such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Highlighting recent insights, we delve into the dual nature of NETs in the context of anticancer treatments, examining their potential to either counteract or enhance treatment outcomes...

Abstract The Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne bunyavirus that causes high mortality in humans with a wide geographic range. This enveloped virus has a tri-segmented negative or ambisense RNA genome that harbors two surface glycoproteins (GP), Gn and Gc. The maturation of the Gn/Gc glycoprotein precursor complex takes place in the ER and is completed through the secretion pathway. Here, we aimed at characterizing the trafficking network exploited by CCHFV GPs during the stages of virus assembly, envelopment, and/or egress...

The use of silicone breast implants has a history of over 60 years. In recent years, specific health issues among implant wearers have repeatedly come into focus. The term "breast implant illness" has been circulating in scientific literature and on social media for several years. It describes a cluster of up to 60 different symptoms. The present results of an online survey conducted within a clinic's patient population of the last 8 years show, among other things, the evolution of 8 reported symptoms before and after breast implant removal...

While dysfunction and death of light-detecting photoreceptor cells underlie most inherited retinal dystrophies, knowledge of the species-specific details of human rod and cone photoreceptor cell development remains limited. Here, we generate retinal organoids carrying retinal disease-causing variants in NR2E3, as well as isogenic and unrelated controls. Organoids were sampled using single-cell RNA sequencing across the developmental window encompassing photoreceptor specification, emergence, and maturation...

Ecological nutrition aims to unravel the extensive web of nutritional links that drives animals in their interactions with their ecological environments. Nutrition plays a key role in the success of European wild rabbit (Oryctolagus cuniculus) and could be affected by the breeding status of the animals and reflected in the metabolome of this species. As nutritional needs are considerably increased during pregnancy and lactation, the main objective of this work was to determine how the breeding status (pregnant and lactating) of European wild rabbit does affects nutritional requirements and their metabolome (using targeted and untargeted metabolomics), aiming to find a useful biomarker of breeding status and for monitoring nutritional requirements...

The emergence of compulsive drug-seeking habits, a hallmark feature of substance use disorder, has been shown to be predicated on the engagement of dorsolateral striatal control over behaviour. This process involves the dopamine-dependent functional coupling of the anterior dorsolateral striatum (aDLS) with the nucleus accumbens core, but the mechanisms by which this coupling occurs have not been fully elucidated. The striatum is tiled by a syncytium of astrocytes that express the dopamine transporter (DAT), the level of which is altered in individuals with heroin use disorder...

Adult skeletal muscle stem cells (MuSC) are the regenerative precursors of myofibers and also have an important role in myofiber growth, adaptation, and maintenance by fusing to the myofibers-a process referred to as "myonuclear accretion." Due to a focus on MuSC function during regeneration, myofibers remain a largely overlooked component of the MuSC niche influencing MuSC fate. Here, we describe a method to directly measure the rate of myonuclear accretion in vitro and in vivo using ethynyl-2'-deoxyuridine (EdU)-based tracing of MuSC progeny...

OBJECTIVES: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. METHODS: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients...

BACKGROUND: In West Africa, healers greatly outnumber trained mental health professionals. People with serious mental illness (SMI) are often seen by healers in "prayer camps" where they may also experience human rights abuses. We developed "M&M," an 8-week-long dual-pronged intervention involving (1) a smartphone-delivered toolkit designed to expose healers to brief psychosocial interventions and encourage them to preserve human rights (M-Healer app), and (2) a visiting nurse who provides medications to their patients (Mobile Nurse)...

IMPORTANCE: Less than 5% of patients with cancer enroll in a clinical trial, partly due to financial and logistic burdens, especially among underserved populations. The COVID-19 pandemic marked a substantial shift in the adoption of decentralized trial operations by pharmaceutical companies. OBJECTIVE: To assess the current global state of adoption of decentralized trial technologies, understand factors that may be driving or preventing adoption, and highlight aspirations and direction for industry to enable more patient-centric trials...

To evaluate the predictive value of the sFlt-1/PlGF ratio for the prediction of preeclampsia in women with preexisting diabetes mellitus. This is a monocentric retrospective observational study conducted between January 2018 and December 2020. All singleton pregnancies with preexisting diabetes mellitus, who had a dosage of the sFlt-1/PlGF ratio between 30 and 34 + 6 weeks of gestation were included. The principal outcome was preeclampsia. The secondary outcomes were preterm preeclampsia, gestational hypertension, placental abruption, intrauterine fetal death, IUGR, small for gestational age and a composite outcome named "hypertensive disorder of pregnancy" including gestational hypertension, preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count)...

BACKGROUND: Ten percent of the female population suffers from congenital abnormalities of the vagina, uterus, or oviducts, with severe consequences for reproductive and psychological health. Yet, the underlying causes of most of these malformations remain largely unknown. ADGRA3 (GPR125) is involved in WNT signaling and planar cell polarity, mechanisms vital to female reproductive tract development. Although ADGRA3 is a well-established spermatogonial stem cell marker, its role within the female urogenital system remains unclear...

The human gut microbiome establishes and matures during infancy, and dysregulation at this stage may lead to pathologies later in life. We conducted a multi-omics study comprising three generations of family members to investigate the early development of the gut microbiota. Fecal samples from 200 individuals, including infants (0-12 months old; 55% females, 45% males) and their respective mothers and grandmothers, were analyzed using two independent metabolomics platforms and metagenomics. For metabolomics, gas chromatography and capillary electrophoresis coupled to mass spectrometry were applied...

BACKGROUND: Persons with Parkinson's disease (PD) who have received genetic test results are faced with the decision of whether, and how, to share that information with family. Studies in other specialties have shown high rates of disclosure motivated by a sense of responsibility. Rates of, and attitudes surrounding, disclosure have yet to be reported in this population. OBJECTIVES: To explore the disclosure practices and motivations of patients with PD regarding genetic test results, allowing insight to guide genetic counseling and navigation of test result discussions...