Addressing the sources of inter-subject variability in E-field parameters in anodal tDCS stimulation over motor cortical network.

BACKGROUND: Although tDCS constitutes a non-invasive neuromodulation technique with promising results in a great variety of applications, its clinical implementation is compromised by the high inter-subject variability reported. This study aims to analyze the inter-subject variability in electric fields (E-fields) over regions of the cortical motor network under two electrode montages: the classical C3Fp2 and an alternative P3F3, which confines more the Efield over this region. Methods: Computational models of the head of 98 healthy subjects were developed to simulate the E-field under both montages. E-field parameters such as magnitude, focality and orientation were calculated over three regions of interest (ROI): M1S1, SMA and preSMA. The role of anatomical characteristics as a source of inter-subject variability on E-field parameters was addressed using linear mixed-effect models. Results: P3F3 showed a more confined E-field distribution over M1S1 than C3Fp2; the latter elicited higher E-fields over supplementary motor areas. Both montages showed high inter-subject variability, especially for the normal component over C3Fp2. Skin, bone and CSF ROI volumes showed a negative association with E-field magnitude irrespective of montage. Grey matter volume and montage were the main sources of variability for focality. The curvature of gyri was found to be significantly associated with the variability of normal E-fields. Conclusions: Computational modelling proves useful in the assessment of E-field variability. Our simulations predict significant differences in E-field magnitude and focality for C3Fp2 and P3F3. However, anatomical characteristics were also found to be significant sources of E-field variability irrespective of electrode montage. .

Treatment with fostamatinib in patients with immune thrombocytopenia: Experience from the Andalusian region in Spain-The Fostasur Study.

Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.

Antibacterial Activity Assessment of Chitosan/Alginate Lavender Essential Oil Membranes for Biomedical Applications.

The demand for natural products in the treatment of dermatological pathologies has boosted the use of bioactive substances such as lavender essential oil (LEO), which stands out for its anti-inflammatory and antioxidant properties and its antimicrobial potential. Biopolymers such as chitosan (CHT) and alginate (ALG) are biodegradable and biocompatible and have proven their viability in biomedical applications such as skin regeneration. The inhibitory effect of LEO on the growth of skin-related bacterial species Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and the fungus Candida albicans was studied by incorporating 1% v/v LEO encapsulated in CHT, ALG, and CHT/ALG membranes. Despite the verification of the antimicrobial effect of all type of membranes, no synergistic effect was observed following the addition of LEO. S. aureus and P. aeruginosa showed the most growth on the different substrates and C. albicans demonstrated the highest inhibition. This is a first approach using microorganisms isolated from clinical samples or skin microbiota. Further investigation would be advisable using more clinical strains for each microorganism to validate their biomedical applicability.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

Standalone middle meningeal artery embolization versus middle meningeal artery embolization with concurrent surgical evacuation for chronic subdural hematomas: a multicenter propensity score matched analysis of clinical and radiographic outcomes.

BACKGROUND: Middle meningeal artery embolization (MMAE) has emerged as a promising therapy for chronic subdural hematomas (cSDHs). The efficacy of standalone MMAE compared with MMAE with concurrent surgery is largely unknown. METHODS: cSDH patients who underwent successful MMAE from 14 high volume centers with at least 30 days of follow-up were included. Clinical and radiographic variables were recorded and used to perform propensity score matching (PSM) of patients treated with standalone MMAE or MMAE with concurrent surgery. Multivariable logistic regression models were used for additional covariate adjustments. The primary outcome was recurrence requiring surgical rescue, and the secondary outcome was radiographic failure defined as <50% reduction of cSDH thickness. RESULTS: 722 MMAE procedures in 588 cSDH patients were identified. After PSM, 230 MMAE procedures remained (115 in each group). Median age was 73 years, 22.6% of patients were receiving anticoagulation medication, and 47.9% had no preoperative functional disability. Median midline shift was 4 mm and cSDH thickness was 16 mm, representing modestly sized cSDHs. Standalone MMAE and MMAE with surgery resulted in similar rates of surgical rescue (7.8% vs 13.0%, respectively, P=0.28; adjusted OR (aOR 0.73 (95% CI 0.20 to 2.40), P=0.60) and radiographic failure (15.5% vs 13.7%, respectively, P=0.84; aOR 1.08 (95% CI 0.37 to 2.19), P=0.88) with a median follow-up duration of 105 days. These results were similar across subgroup analyses and follow-up durations. CONCLUSIONS: Standalone MMAE led to similar and durable clinical and radiographic outcomes as MMAE combined with surgery in select patients with moderately sized cSDHs and mild clinical disease.

Presence of Myeloid Mutations in Patients with Chronic Myeloid Leukemia Increases Risk of Cardiovascular Event on Tyrosine Kinase Inhibitor Treatment.

For chronic myeloid leukemia (CML) patients with a known risk of cardiovascular events (CVE), imatinib is often recommended for first-line tyrosine kinase inhibitor (TKI) treatment rather than a second-generation TKI (2G-TKI) such as nilotinib or dasatinib. To date, very few studies have evaluated the genetic predisposition associated with CVE development on TKI treatment. In this retrospective study of 102 CML patients, 26 CVEs were reported during an average follow-up of over 10 years. Next-generation sequencing identified pathogenic/likely pathogenic mutations in genes associated with myeloid malignancies in 24.5% of the diagnostic samples analyzed. Patients with a recorded CVE had more myeloid mutations (0.48 vs. 0.14, p = 0.019) and were older (65.1 vs. 55.7 years, p = 0.016). Age ≥ 60 years and receiving a 2G-TKI in first-line were CVE risk factors. The presence of a pathogenic somatic myeloid mutation was an independent risk factor for CVE on any TKI (HR 2.79, p = 0.01), and significantly shortened the CV event-free survival of patients who received first-line imatinib (by 70 months, p = 0.011). Indeed, 62% of patients on imatinib with mutations had a CVE vs. the 19% on imatinib with a mutation and no CVE. In conclusion, myeloid mutations detectable at diagnosis increase CVE risk, particularly for patients on imatinib, and might be considered for first-line TKI choice.

Corticospinal adaptations following resistance training and its relationship with strength: A systematic review and multivariate meta-analysis.

Neural adaptations to resistance training (RT) and their correlation with muscle strength remain partially understood. We conducted a systematic review and multivariate meta-analysis to examine the effects of metronome-paced (MP), self-paced (SP), and isometric (IM) training on M1 and corticospinal pathway activity. Following MP RT, a significant increase in corticospinal excitability was observed, correlating with increased strength. Conversely, no significant relationship was found after SP or IM training. RT also reduced the duration of the cortical silent period, but this change did not predict strength changes and was not specific to any training modality. No significant effects were found for short-interval intracortical inhibition. Our findings suggest that changes in corticospinal excitability may contribute to strength gains after RT. Furthermore, the relationship between these adaptations and strength appears dependent on the type of training performed.

Crosslinked Bifunctional Particles for the Removal of Bilirubin in Hyperbilirubinemia Cases.

This work describes the development of styrene-divinylbenzene (St-DVB) particles with polyethylene glycol methacrylate (PEGMA) and/or glycidyl methacrylate (GMA) brushes for the removal of bilirubin from blood in haemodialyzed patients. Bovine serum albumin (BSA) was immobilized onto the particles using ethyl lactate as a biocompatible solvent, which allowed the immobilization of up to 2 mg BSA/g of particles. The presence of albumin on the particles increased their capacity for bilirubin removal from phosphate-buffered saline (PBS) by 43% compared to particles without albumin. The particles were tested in plasma, finding that St-DVB-GMA-PEGMA particles that had been wetted in ethyl lactate with BSA reduced the concentration of bilirubin in plasma by 53% in less than 30 min. This effect was not observed in particles without BSA. Therefore, the presence of albumin on the particles enabled quick and selective removal of bilirubin from plasma. Overall, the study highlights the potential use of St-DVB particles with PEGMA and/or GMA brushes for bilirubin removal in haemodialyzed patients. The immobilization of albumin onto the particles using ethyl lactate increased their capacity for bilirubin removal and enabled quick and selective removal from plasma.

Thiosulfinate-Enriched Allium sativum Extract Exhibits Differential Effects between Healthy and Sepsis Patients: The Implication of HIF-1α.

Garlic (Allium sativum) has historically been associated with antioxidant, immunomodulatory, and microbiocidal properties, mainly due to its richness in thiosulfates and sulfur-containing phytoconstituents. Sepsis patients could benefit from these properties because it involves both inflammatory and refractory processes. We evaluated the effects of thiosulfinate-enriched Allium sativum extract (TASE) on the immune response to bacterial lipopolysaccharide (LPS) by monocytes from healthy volunteers (HVs) and patients with sepsis. We also explored the TASE effects in HIF-1α, described as the key transcription factor leading to endotoxin tolerance in sepsis monocytes through IRAK-M expression. Our results showed TASE reduced the LPS-triggered reactive oxygen species (ROS) production in monocytes from both patients with sepsis and HVs. Moreover, this extract significantly reduced tumor necrosis factor (TNF)-α, interleukin-1ß, and interleukin-6 production in LPS-stimulated monocytes from HVs. However, TASE enhanced the inflammatory response in monocytes from patients with sepsis along with increased expression of human leukocyte antigen-DR. Curiously, these dual effects of TASE on immune response were also found when the HV cohort was divided into low- and high-LPS responders. Although TASE enhanced TNFα production in the LPS-low responders, it decreased the inflammatory response in the LPS-high responders. Furthermore, TASE decreased the HIF-1α pathway-associated genes IRAK-M, VEGFA and PD-L1 in sepsis cells, suggesting HIF-1α inhibition by TASE leads to higher cytokine production in these cells as a consequence of IRAK-M downregulation. The suppression of this pathway by TASE was confirmed in vitro with the prolyl hydroxylase inhibitor dimethyloxalylglycine. Our data revealed TASE's dual effect on monocyte response according to status/phenotype and suggested the HIF-1α suppression as the possible underlying mechanism.

Tailor-Made Bio-Based Non-Isocyanate Polyurethanes (NIPUs).

Non-isocyanate polyurethanes (NIPUs) based on biobased polyamines and polycarbonates are a sustainable alternative to conventional polyurethanes (PU). This article discloses a novel method to control the crosslinking density of fully biobased isocyanate-free polyurethanes, synthesized from triglycerides carbonated previously in scCO2 and different diamines, such as ethylenediamine (EDA), hexamethylenediamine (HMDA) and PriamineTM-1075 (derived from a dimerized fatty acid). As capping substances, water or bioalcohols are used in such a way that the crosslinking density can be adjusted to suit the requirements of the intended application. An optimization of the NIPU synthesis procedure is firstly carried out, establishing the polymerization kinetics and proposing optimal conditions set for the synthesis of the NIPUs. Then, the influence of the partial blocking of the active polymerization sites of the carbonated soybean oil (CSBO), using monofunctional amines, on the physical properties of the NIPUS is explored. Finally, the synthesis of fully biobased NIPUs with a targeted crosslinking density is achieved using hybrid NIPUs, employing partially carbonated oil and H2O or ethanol as blockers to achieve the desired physical properties in a very precise manner.

Homocysteine levels, genetic background, and cognitive impairment in Parkinson's disease.

BACKGROUND: Hyperhomocysteinemia is considered an independent risk factor for cognitive impairment. OBJECTIVE: To study the correlation between homocysteine levels and cognitive impairment in patients with PD. METHODS: We conducted a case-control study that included 246 patients with PD, of whom 32 were cognitively impaired. The levels of homocysteine, folate, and vitamin B12 were measured in peripheral blood. Multivariate logistic regression analysis was applied to determine differences in homocysteine levels between PD patients with and without cognitive impairment. A meta-analysis was performed to clarify the role of Hcy levels in PD with cognitive decline. Five polymorphisms in genes involved in Hcy metabolism, including MTHFR rs1801133 and rs1801131, COMT rs4680, MTRR rs1801394, and TCN2 rs1801198, were genotyped. RESULTS: Our case-control study showed that homocysteine levels were associated with cognitive impairment in PD after adjusting for possible confounding factors such as levodopa equivalent daily dose. The results of our meta-analysis further supported the positive association between homocysteine levels and cognition in PD. We found that the MTHFR rs1801133 TT genotype led to higher homocysteine levels in PD patients, whereas the MTHFR rs1801131 CC genotype resulted in higher folate levels. However, the polymorphisms studied were not associated with cognitive impairment in PD. CONCLUSIONS: Increased homocysteine levels were a risk factor for cognitive decline in PD. However, no association was found between polymorphisms in genes involved in homocysteine metabolism and cognitive impairment in PD. Large-scale studies of ethnically diverse populations are required to definitively assess the relationship between MTHFR and cognitive impairment in PD.

Black Garlic and Thiosulfinate-Enriched Extracts as Adjuvants to Ceftriaxone Treatment in a Rat Peritonitis Model of Sepsis.

To date, there have been no new drugs or adjuvants able to decrease both morbidity and mortality in the context of sepsis and septic shock. Our objective was to evaluate the use of thiosulfinate-enriched Allium sativum and black garlic extracts as adjuvants in the management of sepsis. An experimental in vivo study was carried out with male Sprague-Dawley® rats. Animals were randomized in four treatment groups: antibiotic (ceftriaxone) treatment (group I), ceftriaxone plus thiosulfinate-enriched extract (TASE, group II), ceftriaxone plus thiosulfinate-enriched extract and black garlic extracts (TASE + BGE, group III), and ceftriaxone plus black garlic extract (BGE, group IV). All animals were housed and inoculated with 1 × 1010 CFU/15 mL of intraperitoneal Escherichia coli ATCC 25922. Subsequently, they received a daily treatment according to each group for 7 days. Clinical, analytical, microbiological, and histopathological parameters were evaluated. Statistically significant clinical improvement was observed in rats receiving garlic extracts in weight (groups II and III), ocular secretions, and piloerection (group IV). Moreover, less liver edema, vacuolization, and inflammation were observed in groups receiving adjuvant support (groups II, III, and IV). When comparing interleukins 24 h after bacteria inoculum, we found statistically significant differences in TNF-alpha levels in groups receiving BGE (groups III and IV, p ≤ 0.05). Blood and peritoneal liquid cultures were also analyzed, and we detected a certain level of Enterococcus faecalis in peritoneal cultures from all treatment groups and less bacteria presence in blood cultures in rats receiving garlic extracts (groups II, III, and IV). In conclusion, TASE and BGE could be promising nutraceutical or medicinal agents as coadjuvants in the treatment of sepsis because of its effects in modulating the inflammatory response.

Intervención temprana educativa sobre hábitos alimentarios como estrategia de prevención en amas de casa / Educational intervention on eating habits as a prevention strategy in housemakers

Resumen Objetivo: Realizar una intervención temprana educativa, para fortalecer el conocimiento sobre hábitos alimentarios saludables en amas de casa de la Zona Centro de Nuevo Padilla, Tamaulipas, México. Materiales y Métodos: Para poder llegar a la intervención se requirió previamente de un diagnóstico de salud, en el cual se identificaron los factores determinantes, daños, servicios y recursos para la salud. Posteriormente, se propuso realizar una intervención temprana educativa mediante un programa dirigido a amas de casa, impartiendo 3 exposiciones con tópicos selectos de alimentación y nutrición, y 2 talleres prácticos donde participaron 50 amas de casa dentro de la zona de intervención, cuya duración fue de abril a junio 2021. El nivel de conocimiento adquirido previo y posterior de la intervención fue analizado a través una prueba no paramétrica Man-Whitney (P˂0.01), para el análisis de las variables de los conocimientos de hábitos alimentarios saludables del cuestionario, se utilizó un análisis de varianza (ANOVA) (P˂0.0318). Resultados: En el diagnóstico de salud, se identificaron 14 problemas de salud, siendo la dieta inadecuada uno de los principales problemas detectados. Durante la intervención temprana educativa se observó que en el total de las participantes el conocimiento adquirido sobre hábitos alimentarios saludables se incrementó en un 14%. Por su parte, en la aplicación del cuestionario sobre el conocimiento de hábitos alimentarios saludables aumentó principalmente sobre los siguientes puntos: la definición de dieta (72%), grupos de alimentos (14%), propiedades organolépticas (78%), ingesta correcta de agua (30%), la combinación de leguminosas con cereales (6%), consumo moderado de grasas (12%) y alimentos industrializados (26%). Conclusiones: Con la intervención temprana educativa aplicada a las amas de casa se logró aumentar el grado de conocimientos sobre hábitos alimentarios saludables, lo cual contribuirá a llevar un estilo de vida más saludable.

Abstract Objective: To carry out an early educational intervention to strengthen the knowledge about healthy eating habits in homemakers of the Central Zone of Nuevo Padilla, Tamaulipas, Mexico. Materials and Methods: A health diagnosis was required previously applied early educational intervention, in which the determining factors, damages, services and resources for health were identified. Subsequently, it was proposed to carry out an educational intervention through a program aimed at homemakers, giving three presentations with selected topics of food and nutrition and two practical workshops where 50 housewives participated within the intervention area, whose duration was from April to June 2021. The level of knowledge acquired before and after the intervention was analyzed using a Man-Whitney non-parametric test (P˂0.01) for the analysis of the variables of the healthy eating habits knowledge of the questionnaire, an analysis of variance (ANOVA) (P˂0.0318). Results: In the health diagnosis, 14 health problems were identified, being the inadequate diet one of the main problems detected. During the early educational intervention, it was observed that the knowledge acquired about healthy eating habits increased by 14% in all the participants. For its part, in the application of the questionnaire on the knowledge of healthy eating habits, it increased mainly on the following points: the definition of diet (72%), food groups (14%), organoleptic properties (78%), correct intake of water (30%), the combination of legumes with cereals (6%), moderate fat consumption (12%) and industrialized foods (26%). Conclusions: With the early educational intervention applied to homemakers, it was possible to increase the degree of knowledge about healthy eating habits, contributing to leading a healthier lifestyle.

In Vitro Antioxidant and Pancreatic Anticancer Activity of Novel 5-Fluorouracil-Coumarin Conjugates.

Molecular hybridization consists of the combination of two or more non-identical pharmacophores in a single molecule. It has emerged as a promising strategy that allows the design of molecular frameworks with enhanced activity and affinity compared to their parent drugs. In this work, two novel hybrids that combine the well-known anticancer chemotherapeutic agent 5-fluorouracil with antioxidant coumarin derivatives have been synthesized and characterized by means of a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The conjugates showed good antioxidant properties and a high tendency to aggregate and form stable nanoparticles in aqueous media, with regular shape and uniform size. These materials have proven to be preferential cytotoxic agents in vitro against human pancreatic cancer cells PANC-1, with an activity superior to free 5-fluorouracil. These results open up the possibility of exploiting the synergistic combination between 5-fluorouracil and coumarin derivatives and warrant further investigation of these hybrids as promising pancreatic anticancer agents.

Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration.

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.

Functionalization of Poly(styrene-co-methyl methacrylate) Particles for Selective Removal of Bilirubin.

Hyperbilirubinemia is one of the main causes of death in patients with severe hepatic problems, which justifies the research for bilirubin removal solutions. In this study, St-MMA particles with PEGMA and/or GMA brushes were synthesized. First, the recipe for St-MMA was optimized and then adapted for PEGMA and GMA incorporation. Different solvents were then assayed to improve the BSA immobilization capacity of the particles. Ethyl lactate proved to be the best solvent, reaching a BSA immobilization capacity improvement of up to 60% for St-MMA-GMA-PEGMA particles. These particles also presented the best results for BR removal from PBS. No significant differences in the final capacity for BR removal from PBS media were observed when BSA was attached to the particles; however, the kinetics were greatly improved, requiring half the time. Finally, St-MMA-GMA-PEGMA particles that were wetted in EL with BSA reduced the bilirubin concentration in plasma from levels that threaten the survival of critical patients to levels close to those of healthy individuals in less than 30 min. On the contrary, particles without BSA were unable to remove bilirubin from plasma. Thus, the attachment of albumin to the particles plays a key role in selectively reducing bilirubin levels.

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission.

PURPOSE OF REVIEW: Clinical factors alone do not enable us to differentiate which patients will maintain treatment-free remission (TFR) from those who are likely to relapse. Thus, patient-specific factors must also play a role. This review will update the reader on the most recent studies presenting biological factors that can help predict tyrosine kinase inhibitor (TKI) discontinuation success. RECENT FINDINGS: Cellular and molecular factors with a suggested role in TFR include immune factors and leukemic stem cell (LSC) persistence; the BCR::ABL1 transcript type, halving time, and BCR::ABL1 DNA and RNA positivity; as well as other molecular factors such as somatic mutations, RNA expression, and telomere length. Our review presents several biomarkers with predictive value for TFR but also highlights areas of unmet need. Future discontinuation guidelines will likely include biological factors for the personalization of TFR prediction. However, it will be important that such advances do not prevent more patients from making a TKI discontinuation attempt.

Delaying sexual onset: outcome of a comprehensive sexuality education initiative for adolescents in public schools.

BACKGROUND: A common risk behavior in adolescence is the early initiation of unprotected sex that exposes adolescents to an unplanned pregnancy or sexually transmitted infections. Schools are an ideal place to strengthen adolescents' sexual knowledge and modify their behavior, guiding them to exercise responsible sexuality. The purpose of this article was to evaluate the knowledge of public secondary school teachers who received training in comprehensive education in sexuality (CES) and estimate the counseling's effect on students' sexual behavior. METHODS: Seventy-five public school teachers were trained in participatory and innovative techniques for CES. The change in teacher knowledge (n = 75) was assessed before and after the training using t-tests, Wilcoxon ranks tests and a Generalized Estimate Equation model. The students' sexual and reproductive behavior was evaluated in intervention (n = 650) and comparison schools (n = 555). We fit a logistic regression model using the students' sexual debut as a dependent variable. RESULTS: Teachers increased their knowledge of sexuality after training from 5.3 to 6.1 (p < 0.01). 83.3% of students in the intervention school reported using a contraceptive method in their last sexual relation, while 58.3% did so in the comparison schools. The students in comparison schools were 4.7 (p < 0.01) times more likely to start sexual initiation than students in the intervention schools. CONCLUSION: Training in CES improved teachers' knowledge about sexual and reproductive health. Students who received counseling from teachers who were trained in participatory and innovative techniques for CES used more contraceptive protection and delayed sexual debut.

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study.

INTRODUCTION: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia. METHODS: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models. RESULTS: Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02). CONCLUSIONS: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.

Peripheral Immune Profile and Neutrophil-to-Lymphocyte Ratio in Parkinson's Disease.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) in peripheral blood is a well-established inflammatory marker, but its role in Parkinson's disease (PD) remains unclear. OBJECTIVES: To determine whether a different peripheral immune profile and NLR were present in PD patients. METHODS: We conducted a case-control study that included 377 PD patients and 355 healthy controls (HCs). Leukocytes, subpopulations, and the NLR were measured. Multivariate linear regression analyses were applied to determine the differences between groups and the association between NLR and clinical characteristics in PD. A meta-analysis was performed to clarify the association between NLR and PD. RESULTS: In our case-control study, the NLR was significantly higher in PD patients compared with HCs (2.47 ± 1.1 vs. 1.98 ± 0.91, P < 0.001). No association between NLR and age at onset, disease severity, or disease duration was found. The meta-analysis showed that the NLR was likely to be higher in PD patients. CONCLUSIONS: PD patients had an altered peripheral immune profile and a higher NLR compared with HCs. © 2021 International Parkinson and Movement Disorder Society.