ABSTRACT
BACKGROUND: Respiratory tract infections are readily transmitted in care homes. Airborne transmission of pathogens causing respiratory tract illness is largely unmitigated. Portable high-efficiency-particulate-air (HEPA) filtration units capture microbial particles from the air, but it is unclear whether this is sufficient to reduce infections in care home residents. The Air Filtration to prevent symptomatic winter Respiratory Infections (including COVID-19) in care homes (AFRI-c) randomized controlled trial will determine whether using HEPA filtration units reduces respiratory infection episodes in care home residents. METHODS: AFRI-c is a cluster randomized controlled trial that will be delivered in residential care homes for older people in England. Ninety-one care homes will be randomised to take part for one winter period. The intervention care homes will receive HEPA filtration units for use in communal areas and private bedrooms. Normal infection control measures will continue in all care homes. Anonymised daily data on symptoms will be collected for up to 30 residents. Ten to 12 of these residents will be invited to consent to a primary care medical notes review and (in intervention homes) to having an air filter switched on in their private room. The primary outcome will be number of symptomatic winter respiratory infection episodes. Secondary outcomes include specific clinical measures of infection, number of falls / near falls, number of laboratory confirmed infections, hospitalisations, staff sickness and cost-effectiveness. A mixed methods process evaluation will assess intervention acceptability and implementation. DISCUSSION: The results of AFRI-c will provide vital information about whether portable HEPA filtration units reduce symptomatic winter respiratory infections in older care home residents. Findings about effectiveness, fidelity, acceptability and cost-effectiveness will support stakeholders to determine the use of HEPA filtration units as part of infection control policies.
Subject(s)
Air Filters , COVID-19 , Respiratory Tract Infections , Seasons , Humans , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/transmission , England/epidemiology , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/epidemiology , Aged , SARS-CoV-2/isolation & purification , Nursing HomesABSTRACT
Engram labelling and manipulation methodologies are now a staple of contemporary neuroscientific practice, giving the impression that the physical basis of engrams has been discovered. Despite enormous progress, engrams have not been clearly identified, and it is unclear what they should look like. There is an epistemic bias in engram neuroscience toward characterizing biological changes while neglecting the development of theory. However, the tools of engram biology are exciting precisely because they are not just an incremental step forward in understanding the mechanisms of plasticity and learning but because they can be leveraged to inform theory on one of the fundamental mysteries in neuroscience-how and in what format the brain stores information. We do not propose such a theory here, as we first require an appreciation for what is lacking. We outline a selection of issues in four sections from theoretical biology and philosophy that engram biology and systems neuroscience generally should engage with in order to construct useful future theoretical frameworks. Specifically, what is it that engrams are supposed to explain? How do the different building blocks of the brain-wide engram come together? What exactly are these component parts? And what information do they carry, if they carry anything at all? Asking these questions is not purely the privilege of philosophy but a key to informing scientific hypotheses that make the most of the experimental tools at our disposal. The risk for not engaging with these issues is high. Without a theory of what engrams are, what they do, and the wider computational processes they fit into, we may never know when they have been found.
Subject(s)
Brain , Animals , Humans , Learning/physiology , Memory/physiology , Neuronal Plasticity/physiology , NeurosciencesABSTRACT
Background Immune thrombocytopenia (ITP) is characterised by low platelet counts and often leads to bleeding, fatigue, and reduced health-related quality of life. Methods This observational, retrospective, population-based study using BIG-PAC® database included Spanish paediatric and adult patients with primary ITP diagnosed in primary care and hospitals between 2014 and 2020 (median follow-up: 4 years). Epidemiology, baseline/clinical characteristics, treatment trends, healthcare resources and costs were analysed. Results The BIG-PAC® database contains records of 1,818,588 patients; 170 adults and 27 children with ITP were included in our analysis. ITP prevalence and annual incidence per 100,000 were estimated in 10.8 (2.8 in chronic ITP [cITP] patients) and 1.5 (0.3 in cITP patients), respectively. Epistaxis was the most common bleeding event, followed by genitourinary and gastrointestinal bleeding; >50%/> 75% of ITP/cITP patients reported fatigue. Chronic patients had lower platelet counts at baseline and required more transfusions. Corticosteroids, immunosuppressants, and thrombopoietin receptor agonists were the most used agents in first-, second- and third-line treatment, respectively. Thirty-five patients, all of them in chronic phase, underwent splenectomy. Patients had on average 13.9, 6.6, and 1.2 visits/year to primary care, haematology/internal medicine, and emergency departments, respectively. More than one-fourth of adult patients took on average 16.3 days of sick leave annually. Mean annual total health care costs were 10,741 (ITP patients) and 19,809 (cITP patients). Conclusion This is the first study to provide an overall perspective on the situation of the Spanish ITP population in terms of epidemiology, treatment trends, health care resources and costs, highlighting unmet patient needs, and direct and indirect costs/resource use between 2014 and 2020.
ABSTRACT
Persistent bacterial infections are the leading risk factor that complicates the healing of chronic wounds. In this work, we formulate mixtures of polyvinyl alcohol (P), chitosan (CH), collagen (C), and honey (H) to produce nanofibrous membranes with healing properties. The honey effect at concentrations of 0 % (PCH and PCHC), 5 % (PCHC-5H), 10 % (PCHC-10H), and 15 % (PCHC-15H) on the physicochemical, antibacterial, and biological properties of the developed nanofibers was investigated. Morphological analysis by SEM demonstrated that PCH and PCHC nanofibers had a uniform and homogeneous distribution on their surfaces. However, the increase in honey content increased the fiber diameter (118.11-420.10) and drastically reduced the porosity of the membranes (15.79-92.62 nm). The addition of honey reduces the water vapor transmission rate (WVTR) and the adsorption properties of the membranes. Mechanical tests revealed that nanofibers were more flexible and elastic when honey was added, specifically the PCHC-15H nanofibers with the lowest modulus of elasticity (15 MPa) and the highest elongation at break (220 %). Also, honey significantly improved the antibacterial efficiency of the nanofibers, mainly PCHC-15H nanofibers, which presented the best bacterial reduction rates against Staphylococcus aureus (59.84 %), Pseudomonas aeruginosa (47.27 %), Escherichia coli (65.07 %), and Listeria monocytogenes (49.58 %). In vitro tests with cell cultures suggest that nanofibers were not cytotoxic and exhibited excellent biocompatibility with human fibroblasts (HFb) and keratinocytes (HaCaT), since all treatments showed higher or similar cell viability as opposed to the cell control. Based on the findings, PVA-chitosan-collagen-honey nanofibrous membranes have promise as an antibacterial dressing substitute.
Subject(s)
Anti-Bacterial Agents , Bandages , Chitosan , Collagen , Honey , Membranes, Artificial , Nanofibers , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Nanofibers/chemistry , Bandages/microbiology , Collagen/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Wound Healing/drug effects , Staphylococcus aureus/drug effects , Porosity , Polyvinyl Alcohol/chemistry , Fibroblasts/drug effectsABSTRACT
The public health workforce continues to experience staff shortages, which hampered the ability of US state, tribal, local, and territorial health departments to respond to the COVID-19 pandemic. In April 2020, the US Centers for Disease Control and Prevention (CDC) awarded $45 million to the CDC Foundation to provide field assignees to support these health departments. To expand these efforts, the CDC provided an additional $20 million in May 2021 for vaccination efforts and $200 million in June 2021 to support COVID-19 response and general infrastructure support. The CDC Foundation worked with jurisdictions across the United States to develop job descriptions based on need and recruit nationally for positions. This expanded project, called the Workforce/Vaccine Initiative, hired 3,014 staff in 91 jurisdictions, with 2,310 (77%) hired by January 2022. Most assignments were fully remote (55%) or hybrid (28%). The largest number of staff (n=720) supported COVID-19 response work in schools. Other common functions included contact tracing/case investigation (n=456), program coordination (n=330), epidemiology (n=297), data and surveillance (n=283), and administrative support (n=220). To advance health equity and improve response efforts, 79 health equity staff were assigned to 30 jurisdictions. To support the needs of tribes, 76 field staff supported 22 tribal entities. This project demonstrated the important role of a flexible, centralized approach to rapid placement of staff in public health departments during an emergency response. While the goal of the Workforce/Vaccine Initiative was to meet short-term staffing needs, lessons learned could provide insights for building a sustainable and scalable public health workforce.
Subject(s)
COVID-19 , Public Health , COVID-19/epidemiology , COVID-19/prevention & control , Humans , United States , Health Workforce/organization & administration , Centers for Disease Control and Prevention, U.S. , Emergencies , SARS-CoV-2 , Workforce , Pandemics , Personnel Staffing and Scheduling/organization & administrationABSTRACT
ABSTRACT: Lockie, RG, Dulla, JM, Higuera, D, Ross, K, Orr, RM, Dawes, JJ, and Ruvalcaba, TJ. Age-related differences in body fat and fitness of firefighters participating in a health and wellness program. J Strength Cond Res 38(6): 1127-1135, 2024-Fitness tends to decline, whereas body fat increases, with age, which could impact firefighter occupational performance later in their careers. Health and wellness program participation could reduce these age-related changes. Archival data from 270 firefighters (258 men and 12 women) from a health and wellness program were analyzed. Data included body mass index; body fat percentage (BF%); waist circumference (WC); waist-to-hip ratio (WHR); sit and reach; grip strength; absolute and relative predicted 1 repetition maximum (1RM) leg press; crunches; push-ups; and estimated maximal aerobic capacity (VÌo2max). Firefighters were grouped by age ≤29 (n = 29); 30-34 (n = 44); 35-39 (n = 38); 40-44 (n = 39); 45-49 (n = 48); 50-54 (n = 42); and 55+ (n = 30) years. A univariate analysis of covariance, with sex as a covariate and Bonferroni's post hoc adjustment, determined between-group differences. Effect sizes (d) were calculated. Key results included that the 55+ group had higher BF% and WC compared with the 3 youngest groups (p ≤ 0.002; d = 0.86-1.08). The 50-54 group had higher BF% than the 30-34 group (p = 0.010; d = 0.77). The 55+ group had a greater WHR, lower grip strength, and completed fewer crunches and push-ups than most younger groups (p ≤ 0.05; d = 0.60-1.32). The 50-54 and 55+ groups had a lower 1RM leg press and VÌo2max compared with the younger groups (p ≤ 0.009; d = 0.77-1.79). The program appeared generally effective, with limited differences in groups below 49 years of age. Greater disparities in fat mass and fitness tended to occur in the older groups (50-54, 55+ groups). The data highlighted that older firefighters were participating in the optional program, which could lead to better health outcomes.
Subject(s)
Firefighters , Health Promotion , Physical Fitness , Humans , Male , Female , Adult , Middle Aged , Physical Fitness/physiology , Age Factors , Health Promotion/methods , Waist Circumference/physiology , Body Mass Index , Waist-Hip Ratio , Hand Strength/physiology , Adipose Tissue/physiology , Oxygen Consumption/physiology , Muscle Strength/physiologyABSTRACT
The salty taste is usually associated with the positively charged ion sodium present in sodium chloride. Due to its relevance in the food industry, there have been several studies to determine how this ion behaves in various food matrices, or the use of techniques to improve saltiness perception to reduce the amount necessary for savoury food. Several databases were searched, and it was discovered that sodium can interact with the protein, modifying its mobility, as well as, other components of the food matrix, such as fat, that seem to interfere with saltiness perception, increasing or reducing it. Several techniques were used to identify the interaction between sodium and the food matrix, as well as sensory testing to determine the influence of different modification strategies to enhance the saltiness perception. Due to the multiple factors involved in the salty taste, understanding the effect of the technique to modify saltiness perception, the interaction of the matrix components of the food, and the sodium interaction with those components, can be of use in the developing process of foods with a reduction in the sodium content. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05861-6.
ABSTRACT
The cAMP-dependent protein kinase (PKA) is one of the most extensively distributed kinases among intracellular signal cascades, with a pivotal role in the regulation of various processes, including the capacitation of sperm cells. Traditional assessments of PKA activity relies on the utilization of [γ-32P] ATP and the Kemptide substrate. This methodology presents several major drawbacks, including high-costs and health risks derived from the manipulation of radioactive isotopes. In this work we introduce an enhanced non-radioactive assay for quantifying PKA activity, termed KiMSA which relies on the use of a fluorescent-labeled Kemptide (Kemptide-FITC). Once the kinase reaction is terminated, the products can be easily resolved through electrophoresis on an agarose gel and quantified by fluorescence densitometry. We show that the KiMSA assay is suitable for purified PKA, and also to address both basal and capacitation induced PKA activity in mouse sperm cells. Furthermore, the assay enables monitoring the inhibition of PKA with inhibitors such as sPKI and H-89 in live cells. Therefore, the experimental and optimal assay conditions are set so that the KiMSA assay can be used to either assess in vitro as well as in vivo PKA activity in sperm cells. Finally, this method allows for measurement of cAMP concentrations, rendering a versatile technique for the study of cAMP/PKA pathways.
ABSTRACT
The periodicity of parasite egg excretion refers to variations in the number of eggs produced across time, with significant implications in optimizing diagnostic procedures and conducting the Fecal Egg Count Reduction Test (FECRT). Here, we explore whether Ascaridia galli egg excretion varies across time under Philippine conditions, thus informing the best time to collect fecal samples during flock health examination. A time-course analysis was performed in chickens (N = 12) experimentally infected with A. galli, isolated from a naturally infected Philippine native chicken. We examined the fecal egg per gram (EPG) count at 3-h intervals for 3 days, starting from 5:00-6:00 h AM to the following day at 1:00-2:00 h AM. Our results showed a consistent daily egg excretion pattern with a peak EPG count in the morning that abruptly declined in the afternoon and lowest in the evening. The EPG counts correlated with the amount of excreta produced, suggesting that A. galli fecundity corresponds to the timing of host defecation. Our results imply that the best time to collect fecal samples for A. galli diagnosis and FECRT in Philippine conditions should be from sunrise until late morning when parasite EPG count and host excreta production are at their highest.
ABSTRACT
Different stakeholders, such as authors, research institutions, and healthcare professionals (HCPs) may determine the impact of peer-reviewed publications in different ways. Commonly-used measures of research impact, such as the Journal Impact Factor or the H-index, are not designed to evaluate the impact of individual articles. They are heavily dependent on citations, and therefore only measure impact of the overall journal or researcher respectively, taking months or years to accrue. The past decade has seen the development of article-level metrics (ALMs), that measure the online attention received by an individual publication in contexts including social media platforms, news media, citation activity, and policy and patent citations. These new tools can complement traditional bibliometric data and provide a more holistic evaluation of the impact of a publication. This commentary discusses the need for ALMs, and summarizes several examples - PlumX Metrics, Altmetric, the Better Article Metrics score, the EMPIRE Index, and scite. We also discuss how metrics may be used to evaluate the value of "publication extenders" - educational microcontent such as animations, videos and plain-language summaries that are often hosted on HCP education platforms. Publication extenders adapt a publication's key data to audience needs and thereby extend a publication's reach. These new approaches have the potential to address the limitations of traditional metrics, but the diversity of new metrics requires that users have a keen understanding of which forms of impact are relevant to a specific publication and select and monitor ALMs accordingly.
Different readers have different ways of deciding how important scientific articles are. The usual methods used to measure the impact of research, like the Journal Impact Factor or the H-index, are not meant to measure this for individual articles. These methods mainly look at how many times the articles are mentioned by others, and it can take a long time to see the impact.But in the past ten years, new tools called article-level metrics (ALMs) have been created. These tools measure how much attention an article gets online, like on social media, in the news, or when other researchers talk about it. ALMs are better at explaining how important a specific article is. They can work together with the usual methods to measure impact.This paper talks about why ALMs are important and gives examples of these tools, like PlumX Metrics, Altmetric, the Better Article Metrics score, the EMPIRE Index, and scite. It also explains how these tools can help us see the value of animations, videos, or summaries in simple language. These make it easier for more people to understand and learn from the articles.These new ways of measuring impact can help us see how important articles are in a more complete way. But because there are many different ways to measure this, it's important for users to understand which methods are relevant for a specific article and keep track of them.
Subject(s)
Journal Impact Factor , Social Media , HumansABSTRACT
OBJECTIVE: Acrobatics and Tumbling (A&T), an emerging National Collegiate Athletics Association (NCAA) sport, involves athletes with rigorous training backgrounds, usually extending from youth through early adulthood. This study examines the sleep health, diet quality, and lipid profile of A&T athletes clustered by their performance position. METHODS: Forty-two A&T athletes, clustered as tops (n = 19; age = 19.6 ± 1.0 years; body mass index [BMI] = 22.3 ± 1.7 kg/m2) and bases (n = 23; age = 19.6 ± 1.3 years; BMI = 25.7 ± 2.5 kg/m2), completed preseason sleep and diet quality (Rapid Eating Assessment for Participants-Shortened [REAP-S]) surveys. Fasting blood samples were collected for lipid analysis. Body composition was assessed via dual-energy X-ray absorptiometry. RESULTS: Most athletes (71.4%; base n = 14, top n = 16) reported insufficient sleep (≤7 hours) and "good" sleep quality (90.4%, n = 38; base n = 18, top n = 20). Average REAP-S score was 29.24 ± 3.74. Approximately 31% (n = 13) displayed at least one undesirable lipid concentration according to medical guidelines for normal levels (total cholesterol [TC] < 200 mg/dL, triglycerides [TG] < 150 mg/dL, high-density lipoprotein cholesterol [HDL-C] > 40 mg/dL, low-density lipoprotein cholesterol [LDL-C] < 130 mg/dL). Approximately 20% exhibited elevated TC (top n = 4, base n = 4), 12.5% had elevated TG (base n = 5), 2.5% showed low HDL-C (base n = 1), and 10% presented elevated LDL-C (top n = 2, base n = 2). CONCLUSIONS: Most athletes experienced suboptimal sleep (≤7 hours/night) and 31% displayed at least one undesirable lipid concentration (elevated TC, TG, or LDL-C or reduced HDL-C). Tailoring interventions with sports dietitians is recommended, focused on increasing monounsaturated and polyunsaturated fat intake while reducing saturated fat consumption. These interventions could mitigate cardiovascular risks, improve recovery, and possibly enhance athletic performance.
Subject(s)
Athletes , Diet , Lipids , Sleep , Humans , Cross-Sectional Studies , Male , Young Adult , Athletes/statistics & numerical data , Female , Sleep/physiology , Lipids/blood , Students/statistics & numerical data , Body Composition/physiology , Universities , Adolescent , Sports , Body Mass IndexABSTRACT
Introducción y objetivos: Los vástagos primarios con cuellos modulares fueron introducidos con la ventaja teórica de restaurar la anatomía de la cadera de forma más precisa. Sin embargo, la presencia de un segundo encaje se ha asociado a una mayor corrosión y liberación de detritos metálicos. El objetivo de nuestro estudio es cuantificar los valores séricos de cromo y de cobalto, y analizar su evolución temporal durante cinco años. Material y métodos: Se presenta una serie prospectiva de 61 pacientes intervenidos de artroplastia total de cadera primaria mediante la implantación del vástago HMAX-M® (Limacorporate, San Daniele, Italia) en los que se realizó una determinación sérica de cromo y cobalto a los seis meses, a los dos años y a los cinco años. Resultados: Nuestra serie presenta una elevación progresiva de los niveles de cromo, con una diferencia significativa entre los valores de cromo a los seis meses (0,35±0,18) y los cinco años (0,52±0,36), p=0,01. Respecto al cobalto, se observa una elevación estadísticamente significativa entre los seis meses y los dos años y una posterior estabilización hasta los cinco años, siendo la media de cobalto a los seis meses (1,17±0,8) significativamente menor que a los dos años (2,63±1,76) y a los cinco años (2,84±2,1), p=0,001. Conclusión: Se ha observado una elevación de los niveles séricos de cobalto en aquellos pacientes a los que se les implantó un vástago con cuello modular. Los resultados obtenidos en este estudio han limitado el uso de vástagos con cuello modular en nuestra práctica habitual.(AU)
Introduction and objectives: Modular neck primary stems were introduced with the theoretical advantage of restoring the hip anatomy more precisely. However, the presence of a second junction has been associated with increased corrosion and release of metal debris. The objective of our study is to quantify of chromium and cobalt serum values, and to analyze their temporal evolution during five years. Material and methods: We present a prospective series of 61 patients who underwent primary total hip arthroplasty by implantation of the HMAX-M® stem (Limacorporate, San Daniele, Italy). Serum chromium and cobalt determinations were performed at six months, two years and five years. Results: Our series shows a progressive elevation in chromium levels with a significant difference between chromium values at six months (0.35±0.18) and five years (0.52±0.36), P=.01. Regarding cobalt, a statistically significant elevation is observed between six months and two years and a subsequent stabilization of values between two and five years, with a cobalt mean at six months (1.17±0.8) significantly lower than at two (2.63±1.76) and five years (2.84±2.1), P=.001. Conclusion: Elevated serum cobalt levels have been observed in patients who underwent modular neck stem implantation. The results obtained in this study have limited the use of stems with a modular neck in our clinical practice.(AU)
Subject(s)
Humans , Male , Female , Chromium/administration & dosage , Cobalt/administration & dosage , Arthroplasty, Replacement, Hip , Hip/surgery , Ions , Iron/blood , Prospective Studies , Traumatology , Orthopedics , Orthopedic Procedures , Hip Injuries , ItalyABSTRACT
Introducción y objetivos: Los vástagos primarios con cuellos modulares fueron introducidos con la ventaja teórica de restaurar la anatomía de la cadera de forma más precisa. Sin embargo, la presencia de un segundo encaje se ha asociado a una mayor corrosión y liberación de detritos metálicos. El objetivo de nuestro estudio es cuantificar los valores séricos de cromo y de cobalto, y analizar su evolución temporal durante cinco años. Material y métodos: Se presenta una serie prospectiva de 61 pacientes intervenidos de artroplastia total de cadera primaria mediante la implantación del vástago HMAX-M® (Limacorporate, San Daniele, Italia) en los que se realizó una determinación sérica de cromo y cobalto a los seis meses, a los dos años y a los cinco años. Resultados: Nuestra serie presenta una elevación progresiva de los niveles de cromo, con una diferencia significativa entre los valores de cromo a los seis meses (0,35±0,18) y los cinco años (0,52±0,36), p=0,01. Respecto al cobalto, se observa una elevación estadísticamente significativa entre los seis meses y los dos años y una posterior estabilización hasta los cinco años, siendo la media de cobalto a los seis meses (1,17±0,8) significativamente menor que a los dos años (2,63±1,76) y a los cinco años (2,84±2,1), p=0,001. Conclusión: Se ha observado una elevación de los niveles séricos de cobalto en aquellos pacientes a los que se les implantó un vástago con cuello modular. Los resultados obtenidos en este estudio han limitado el uso de vástagos con cuello modular en nuestra práctica habitual.(AU)
Introduction and objectives: Modular neck primary stems were introduced with the theoretical advantage of restoring the hip anatomy more precisely. However, the presence of a second junction has been associated with increased corrosion and release of metal debris. The objective of our study is to quantify of chromium and cobalt serum values, and to analyze their temporal evolution during five years. Material and methods: We present a prospective series of 61 patients who underwent primary total hip arthroplasty by implantation of the HMAX-M® stem (Limacorporate, San Daniele, Italy). Serum chromium and cobalt determinations were performed at six months, two years and five years. Results: Our series shows a progressive elevation in chromium levels with a significant difference between chromium values at six months (0.35±0.18) and five years (0.52±0.36), P=.01. Regarding cobalt, a statistically significant elevation is observed between six months and two years and a subsequent stabilization of values between two and five years, with a cobalt mean at six months (1.17±0.8) significantly lower than at two (2.63±1.76) and five years (2.84±2.1), P=.001. Conclusion: Elevated serum cobalt levels have been observed in patients who underwent modular neck stem implantation. The results obtained in this study have limited the use of stems with a modular neck in our clinical practice.(AU)
Subject(s)
Humans , Male , Female , Chromium/administration & dosage , Cobalt/administration & dosage , Arthroplasty, Replacement, Hip , Hip/surgery , Ions , Iron/blood , Prospective Studies , Traumatology , Orthopedics , Orthopedic Procedures , Hip Injuries , ItalySubject(s)
Humans , Male , Female , Traumatology , Orthopedics , Orthopedic Procedures , Tibia/surgery , Tibial Fractures/surgerySubject(s)
Humans , Male , Female , Traumatology , Orthopedics , Orthopedic Procedures , Tibia/surgery , Tibial Fractures/surgeryABSTRACT
BACKGROUND: Alcohol use disorders are prevalent mental disorders with significant health implications. Epigenetic alterations may play a role in their pathogenesis, as DNA methylation at several genes has been associated with these disorders. We have previously shown that methylation in the DLGAP2 gene, coding for a synaptic density protein, is associated with alcohol dependence. In this study, we aimed to examine the association between DLGAP2 methylation and treatment response among patients undergoing acamprosate treatment. METHODS: 102 patients under acamprosate treatment were included. DNA methylation analysis at DLGAP2 was performed by bisulfite pyrosequencing at the start and after 3-month treatment. Treatment outcomes were having a relapse during the treatment and severity of craving at the end of three months. Cox proportional hazard and linear regression models were performed. RESULTS: Patients whose methylation levels were decreased during the treatment showed an increased risk for relapse within three months in comparison to the ones without methylation change (hazard ratio [HR]=2.44; 95% confidence interval [CI]=1.04, 5.73; p=0.04). For the same group, a positive association for the severity of craving was observed, yet statistical significance was not reached (ß=2.97; 95% CI=-0.41, 6.34; p=0.08). CONCLUSION: We demonstrate that patients whose DLGAP2 methylation levels decrease during acamprosate treatment are more likely to relapse compared to the ones without changes. This is in line with our previous findings showing that DLGAP2 methylation is lower in alcohol dependent subjects compared to controls, and might suggest a role for changes in DLGAP2 methylation in treatment response.
Subject(s)
Alcoholism , Humans , Alcoholism/drug therapy , Alcoholism/genetics , Acamprosate , DNA Methylation , Chronic Disease , Recurrence , Nerve Tissue ProteinsABSTRACT
Immune thrombocytopenia refractory to multiple thrombopoietin receptor agonists remains a challenging clinical problem. This commentary discusses and contextualizes the recent report on this entity from Moulis and colleagues, and how to move forward with these patients. Commentary on: Moulis et al. Difficult-to-treat primary immune thrombocytopenia in adults: Prevalence and burden. Results from the CARMEN-France Registry. Br J Haematol 2024;204:1476-1482.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Pyrazoles , Thrombocytopenia , Adult , Humans , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Receptors, Thrombopoietin/agonists , Thrombocytopenia/drug therapy , Thrombopoietin/therapeutic use , Benzoates/therapeutic use , Hydrazines/therapeutic use , Receptors, Fc/therapeutic use , Recombinant Fusion Proteins/therapeutic useABSTRACT
Regiodivergent reactions are a fascinating tool to rapidly access molecular diversity while using identical coupling partners. We have developed a new approach for regiodivergent synthesis using the dual character of hypervalent bromines. In addition to the recently reported reactivity of hypervalent bromines as aryne precursors, the first transition metal-catalyzed reaction is reported. Accordingly, the development of these two complementary transformations allows for the alteration of regioselectivity to furnish both ortho- and meta-substituted alkynylation products. Mechanistic and computational studies show how these selectivities are controlled.