Predictive risk score for isolated brain metastasis in non-small cell lung cancer.

Background: Brain metastasis is common with non-small cell lung cancer (NSCLC). Patients with some early-stage cancers don't benefit from routine brain imaging. Currently clinical stage alone is used to justify additional brain imaging. Other clinical and demographic characteristics may be associated with isolated brain metastasis (IBM). We aimed to define the most salient clinical features associated with synchronous IBM, hypothesizing that clinical and demographic factors could be used to determine the risk of brain metastasis. Methods: The National Cancer Database was used to identify patients with NSCLC from 2016-2020. Primary outcome was the presence of IBM relative to patients without evidence of any metastasis. Cohorts were divided into test and validation. The test cohort was used to identify risk factors for IBM using multivariable logistic regression. Using the regression, a scoring system was created to estimate the rate of synchronous IBM. The accuracy of the scoring system was evaluated with receiver operating characteristic (ROC) analysis using the validation cohort. Results: Study population consisted of 396,113 patients: 25,907 IBM and 370,206 without metastatic disease. IBM was associated with age, clinical T stage, clinical N stage, Charlson/Deyo comorbidity score, histology, and grade. A scoring system using these factors showed excellent accuracy in the test and validation cohort in ROC analysis (0.806 and 0.805, respectively). Conclusions: Clinical and demographic characteristics can be used to stratify the risk of IBM among patients with NSCLC and provide an evidence-based method to identify patients who require dedicated brain imaging in the absence of other metastatic disease.

The Telehealth chain: a framework for secure and transparent telemedicine transactions on the blockchain.

BACKGROUND: Blockchain technology provides a secure and decentralized platform for storing and transferring sensitive medical data, which can be utilized to enable remote medical consultations. AIM: A theoretical framework for creating a blockchain-based digital system created to facilitate telemedicine system. RESULTS: This paper proposes a theoretical framework based on Hyperledger fabric for creating a blockchain-based digital entity to facilitate telemedicine services. The proposed framework utilizes blockchain technology to provide a secure and reliable platform for medical practitioners to interact remotely with patient transactions. CONCLUSION: The blockchain will serve as a one-stop digital service to secure patient data, ensure privacy, and facilitate payments. The proposed framework leverages the existing Hyperledger fabric platform to build a secure blockchain-assisted telemedicine platform.

Simulating implications of fish behavioral response for managing hypoxia in estuaries with spatial dissolved oxygen variability.

Hypoxia, or low dissolved oxygen (DO), is a widespread water quality problem affecting estuaries and coastal waters around the world. Water quality criteria for DO have been established for every estuary in the US and are an important part of the regulatory response to nutrient pollution and associated anthropogenic eutrophication. Experimental studies examining effects of low DO exposure have been to quantify outcomes based on hypoxia effects observed in individuals, such as increased mortality or growth impairment. Although laboratory exposure tests provide useful benchmarks for policy development, most of those considered in policy development did not consider behavioral responses to low DO. However, experimental research has shown that behavioral responses occur, and that behavior modifies exposure to low DO conditions. Here we begin development of a spatially explicit individual based model (SEIBM) intended to project behavioral outcomes of exposure to spatially variable hypoxia in estuaries. Our goal is to consider the responsiveness of an SEIBM to both different behavioral hypotheses, as well as realistic spatial patterns in hypoxia. A sensitivity analysis was used to explore responsiveness based on two movement strategies: avoidance and behavioral switching. We tested the sensitivity of a suite of movement parameters to changes in spatial patterns representative of an index estuary. The sensitivity analysis demonstrated that model responses to changes in movement strategies include biologically meaningful changes in site occupancy and movement distance centered on individual behavior near a normoxic-hypoxic boundary. Further, the model demonstrated important sensitivity to realistic changes in movement parameters, including the size and shape of the individual neighborhood describing knowledge useful for movement decisions. These results support the utility of the developed SEIBM for exploring behavioral responses of fish to hypoxia in estuaries. The sensitivity analysis also demonstrates parameter values that must be set based on empirical data and are sensitive to data quality. These results will be used to further develop the model and to plan field and laboratory studies to support model parametrization. The end goal is a model framework that can inform policy decisions regarding hypoxia resulting from anthropogenic nutrient loading in estuaries.

Effect of telemedicine use on medical spending and health care utilization among patients with gastrointestinal cancer.

BACKGROUND: We sought to assess the impact of telemedicine on healthcare utilization and medical expenditures among patients with a diagnosis of gastrointestinal (GI) cancer. METHODS: Patients with newly diagnosed GI cancer from 2013 to 2020 were identified from the IBM MarketScan database (IBM Watson Health) . Healthcare utilization, total medical outpatient insurance payments within 1 year post-diagnosis, and out-of-pocket (OOP) expenses among telemedicine users and non-users were assessed after propensity score matching (PSM). RESULTS: Among the 32,677 patients with GI cancer (esophageal, n = 1862, 5.7%; gastric, n = 2009, 6.1%; liver, n = 2929, 9.0%; bile duct, n = 597, 1.8%; pancreas, n = 3083, 9.4%; colorectal, n = 22,197, 67.9%), a total of 3063 (9.7%) utilized telemedicine. After PSM (telemedicine users, n = 3064; non-users, n = 3064), telemedicine users demonstrated a higher frequency of clinic visits (median: 5.0 days, IQR 4.0-7.0 vs non-users: 2.0 days, IQR 2.0-3.0, P < .001) and fewer potential days missed from daily activities (median: 7.5 days, IQR 4.5-12.5 vs non-users: 8.5 days, IQR 5.5-13.5, P < .001). Total medical spending per month and utilization of emergency room (ER) visits for telemedicine users were higher vs non-users (median: $10,658, IQR $5112-$18,528 vs non-users: $10,103, IQR $4628-$16,750; 46.8% vs 42.6%, both P < .01), whereas monthly OOP costs were comparable (median: $273, IQR $137-$449 for telemedicine users vs non-users: $268, IQR $142-$434, P = .625). CONCLUSION: Telemedicine utilization was associated with increased outpatient clinic visits yet reduced potential days missed from daily activities among patients with GI cancer. Telemedicine users tended to have more ER visits and total medical spending per month, although monthly OOP costs were comparable with non-users.

Modeling Full Life-Cycle Effects of Copper on Brook Trout (Salvelinus fontinalis) Populations.

Population models are increasingly used to predict population-level effects of chemicals. For trout, most toxicity data are available on early-life stages, but this may cause population models to miss true population-level effects. We predicted population-level effects of copper (Cu) on a brook trout (Salvelinus fontinalis) population based on individual-level effects observed in either a life-cycle study or an early-life stage study. We assessed the effect of Cu on predicted trout densities (both total and different age classes) and the importance of accounting for effects on the full life cycle compared with only early-life stage effects. Additionally, uncertainty about the death mechanism and growth effects was evaluated by comparing the effect of different implementation methods: individual tolerance (IT) versus stochastic death (SD) and continuous versus temporary growth effects. For the life-cycle study, the same population-level no-observed-effect concentration (NOECpop) was predicted as the lowest reported individual-level NOEC (NOECind; 9.5 µg/L) using IT. For SD, the NOECpop was predicted to be lower than the NOECind for young-of-the-year and 1-year-old trout (3.4 µg/L), but similar for older trout (9.5 µg/L). The implementation method for growth effects did not affect the NOECpop of the life-cycle study. Simulations based solely on the early-life stage effects within the life-cycle study predicted unbounded NOECpop values (≥32.5 µg/L), that is, >3.4 times higher than the NOECpop based on all life-cycle effects. For the early-life stage study, the NOECpop for both IT and SD were predicted to be >2.6 times higher than the lowest reported NOECind. Overall, we demonstrate that effects on trout populations can be underestimated if predictions are solely based on toxicity data with early-life stages. Environ Toxicol Chem 2024;43:1662-1676. © 2024 SETAC.

Epigenetic regulation of high light-induced anthocyanin biosynthesis by histone demethylase IBM1 in Arabidopsis.

In plant species, anthocyanin accumulation is specifically regulated by light signaling. Although the CONSTITUTIVELY PHOTOMORPHOGENIC1/SUPPRESSOR OF PHYA-105 (COP1/SPA) complex is known to control anthocyanin biosynthesis in response to light, the precise mechanism underlying this process remains largely unknown. Here, we report that Increase in BONSAI Methylation 1 (IBM1), a JmjC domain-containing histone demethylase, participates in the regulation of light-induced anthocyanin biosynthesis in Arabidopsis. The expression of IBM1 was induced by high light (HL) stress, and loss-of-function mutations in IBM1 led to accelerated anthocyanin accumulation under HL conditions. We further identified that IBM1 is directly associated with SPA1/3/4 chromatin in vivo to establish a hypomethylation status on H3K9 and DNA non-CG at these loci under HL, thereby releasing their expression. Genetic analysis showed that quadruple mutants of IBM1 and SPA1/3/4 resemble spa134 mutants. Overexpression of SPA1 in ibm1 mutants complements the mutant phenotype. Our results elucidate the significance and mechanism of IBM1 histone demethylase in the epigenetic regulation of anthocyanin biosynthesis in Arabidopsis under HL conditions.

Identification of distinct immune signatures in inclusion body myositis by peripheral blood immunophenotyping using machine learning models.

Objective: Inclusion body myositis (IBM) is a progressive late-onset muscle disease characterised by preferential weakness of quadriceps femoris and finger flexors, with elusive causes involving immune, degenerative, genetic and age-related factors. Overlapping with normal muscle ageing makes diagnosis and prognosis problematic. Methods: We characterised peripheral blood leucocytes in 81 IBM patients and 45 healthy controls using flow cytometry. Using a random forest classifier, we identified immune changes in IBM compared to HC. K-means clustering and the random forest one-versus-rest model classified patients into three immunophenotypic clusters. Functional outcome measures including mTUG, 2MWT, IBM-FRS, EAT-10, knee extension and grip strength were assessed across clusters. Results: The random forest model achieved a 94% AUC ROC with 82.76% specificity and 100% sensitivity. Significant differences were found in IBM patients, including increased CD8+ T-bet+ cells, CD4+ T cells skewed towards a Th1 phenotype and altered γδ T cell repertoire with a reduced proportion of Vγ9+Vδ2+ cells. IBM patients formed three clusters: (i) activated and inflammatory CD8+ and CD4+ T-cell profile and the highest proportion of anti-cN1A-positive patients in cluster 1; (ii) limited inflammation in cluster 2; (iii) highly differentiated, pro-inflammatory T-cell profile in cluster 3. Additionally, no significant differences in patients' age and gender were detected between immunophenotype clusters; however, worsening trends were detected with several functional outcomes. Conclusion: These findings unveil distinct immune profiles in IBM, shedding light on underlying pathological mechanisms for potential immunoregulatory therapeutic development.

Quantitative whole-body muscle MRI in idiopathic inflammatory myopathies including polymyositis with mitochondrial pathology: indications for a disease spectrum.

OBJECTIVE: Inflammatory myopathies (IIM) include dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and overlap myositis (OLM)/antisynthetase syndrome (ASyS). There is also a rare variant termed polymyositis with mitochondrial pathology (PM-Mito), which is considered a sIBM precursor. There is no information regarding muscle MRI for this rare entity. The aim of this study was to compare MRI findings in IIM, including PM-Mito. METHODS: This retrospective analysis included 41 patients (7 PM-Mito, 11 sIBM, 11 PM/ASyS/OLM, 12 IMNM) and 20 healthy controls. Pattern of muscle involvement was assessed by semiquantitative evaluation, while Dixon method was used to quantify muscular fat fraction. RESULTS: The sIBM typical pattern affecting the lower extremities was not found in the majority of PM-Mito-patients. Intramuscular edema in sIBM and PM-Mito was limited to the lower extremities, whereas IMNM and PM/ASyS/OLM showed additional edema in the trunk. Quantitative assessment showed increased fat content in sIBM, with an intramuscular proximo-distal gradient. Similar changes were also found in a few PM-Mito- and PM/ASyS/OLM patients. In sIBM and PM-Mito, mean fat fraction of several muscles correlated with clinical involvement. INTERPRETATION: As MRI findings in patients with PM-Mito relevantly differed from sIBM, the attribution of PM-Mito as sIBM precursor should be critically discussed. Some patients in PM/ASyS/OLM and PM-Mito group showed MR-morphologic features predominantly observed in sIBM, indicative of a spectrum from PM/ASyS/OLM toward sIBM. In some IIM subtypes, MRI may serve as a biomarker of disease severity.

One-pot synthesis of alginate-antimicrobial peptide nanogel.

Nanosized alginate-based particles (NAPs) were obtained in a one-pot solvent-free synthesis procedure, achieving the design of a biocompatible nanocarrier for the encapsulation of IbM6 antimicrobial peptide (IbM6). IbM6 is integrated in the nascent nanosized hydrogel self-assembly guided by electrostatic interactions and by weak interactions, typical of soft matter. The formation of the nanogel is a dynamic and complex process, which presents an interesting temporal evolution. In this work, we optimized the synthesis conditions of IbM6-NAPs based on small-angle X-ray scattering (SAXS) measurements and evaluated its time evolution over several weeks by sensing the IbM6 environment in IbM6-NAPs from photochemical experiments. Fluorescence deactivation experiments revealed that the accessibility of different quenchers to the IbM6 peptide embedded in NAPs is dependent on the aging time of the alginate network. Lifetimes measurements indicate that the deactivation paths of the excited state of the IbM6 in the nanoaggregates are reduced when compared with those exhibited by the peptide in aqueous solution, and are also dependent on the aging time of the nanosized alginate network. Finally, the entrapment of IbM6 in NAPs hinders the degradation of the peptide by trypsin, increasing its antimicrobial activity against Escherichia coli K-12 in simulated operation conditions.

Plaque heterogeneity and the spatial distributions of its components dictate drug-coated balloon therapy.

Drug-coated balloon (DCB) angioplasty is one of the potential approaches to alleviating in-stent restenosis and treating peripheral artery disease. An in-silico model has been developed for sirolimus drug eluted from an inflated balloon in a patient-specific arterial cross-section consisting of fibrous tissue, fibrofatty tissue, dense calcium, necrotic core, and healthy tissue. The convection-diffusion-reaction equation represents the transport of drug, while drug binding, both specific and non-specific, can be modelled as a reaction process. The Brinkman equations describe the interstitial flow in porous tissue. An image processing technique is leveraged for reconstructing the computational domain. The Marker and Cell, and Immersed Boundary Methods are used to solve the set of governing equations. The no-flux interface condition and convection do amplify the tissue content, and the regions of dense calcium and necrotic core limited to or extremely close to the interface pose a clinical threat to DCB therapy. Simulations predict the effects of the positioning and clustering of plaque components in the domain. This study demands extensive intravascular ultrasound-derived virtual histology (VH-IVUS) imaging to understand the plaque morphology and determine the relative positions of different plaque compositions about the lumen-tissue interface, which have a significant impact on arterial pharmacokinetics.

The reduced mortality of malignant melanoma at the population level is mainly attributable to treatment advances for the past decade.

BACKGROUND: Cutaneous malignant melanoma (CMM) causes most skin cancer deaths in the United States (US). The mortality has been decreasing in the US population. We hypothesize that this population-level reduction is mainly attributable to the treatment advances, rather than the successful primary and secondary prevention. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) databases, we collected the incidence, incidence-based mortality (IBM), and 5-year survival (5-YS) rates of CMM from 1994 to 2019. Trends by stage and sex were examined by joinpoint regression analyses and age-period-cohort analyses. RESULTS: The overall incidence of CMM rose by 1.6% yearly from 1994 to 2006 (95% confidence interval [CI]: 0.9% to 2.2%) and then increased with a numerical trend. And we projected the incidence will continue to increase until 2029. In contrast, the IBM for all CMM has decreased yearly by 2.8% (95% CI: -3.9% to -1.8%) since 2010 after continuously increasing by 3.8% annually (95% CI: 3.2% to 4.4%) from 1996 to 2010. For early-stage (localized and regional) CMM, we found the incidence since 2005 plateaued without further increase, while the incidence for CMM at distant stage continuously increased by 1.4% per year (95% CI: 0.9% to 2.0%). Improvements in 5-YS were observed over the study period for all CMM and were most obvious in distant stage. And significant period effects were noted around the year 2010. CONCLUSION: This study demonstrated improved survival and reduced mortality of CMM at the US population level since 2010, which were consistent with the introduction of novel therapies. Encouraging effects of primary prevention among adolescents in the most recent cohorts were found. However, the plateaued overall incidence and early diagnosis rates indicated that advances in primary and secondary prevention are very much needed to further control the burden of CMM.

Simulating long-term wildfire impacts on boreal forest structure in Central Yakutia, Siberia, since the Last Glacial Maximum.

Background: Wildfires are recognized as an important ecological component of larch-dominated boreal forests in eastern Siberia. However, long-term fire-vegetation dynamics in this unique environment are poorly understood. Recent paleoecological research suggests that intensifying fire regimes may induce millennial-scale shifts in forest structure and composition. This may, in turn, result in positive feedback on intensifying wildfires and permafrost degradation, apart from threatening human livelihoods. Most common fire-vegetation models do not explicitly include detailed individual-based tree population dynamics, but a focus on patterns of forest structure emerging from interactions among individual trees may provide a beneficial perspective on the impacts of changing fire regimes in eastern Siberia. To simulate these impacts on forest structure at millennial timescales, we apply the individual-based, spatially explicit vegetation model LAVESI-FIRE, expanded with a new fire module. Satellite-based fire observations along with fieldwork data were used to inform the implementation of wildfire occurrence and adjust model parameters. Results: Simulations of annual forest development and wildfire activity at a study site in the Republic of Sakha (Yakutia) since the Last Glacial Maximum (c. 20,000 years BP) highlight the variable impacts of fire regimes on forest structure throughout time. Modeled annual fire probability and subsequent burned area in the Holocene compare well with a local reconstruction of charcoal influx in lake sediments. Wildfires can be followed by different forest regeneration pathways, depending on fire frequency and intensity and the pre-fire forest conditions. We find that medium-intensity wildfires at fire return intervals of 50 years or more benefit the dominance of fire-resisting Dahurian larch (Larix gmelinii (Rupr.) Rupr.), while stand-replacing fires tend to enable the establishment of evergreen conifers. Apart from post-fire mortality, wildfires modulate forest development mainly through competition effects and a reduction of the model's litter layer. Conclusion: With its fine-scale population dynamics, LAVESI-FIRE can serve as a highly localized, spatially explicit tool to understand the long-term impacts of boreal wildfires on forest structure and to better constrain interpretations of paleoecological reconstructions of fire activity. Supplementary Information: The online version contains supplementary material available at 10.1186/s42408-023-00238-8.

Antecedentes: Los incendios de vegetación son reconocidos como un componente importante de los bosques boreales dominados por alerces en el este de Siberia. Sin embargo, la dinámica a largo plazo entre fuegos y vegetación en este ambiente único es pobremente entendido. Estudios paleo-ecológicos recientes sugieren que la intensificación de regímenes de fuego puede inducir cambios, a escala de milenos, en la estructura y composición de estos bosques. Estos pueden, a su vez, resultar en una retroalimentación positiva en la intensificación de los incendios y en la degradación del permafrost, aparte de amenazar la vida humana. Los modelos de fuego-vegetación más comunes, no incluyen específicamente detalles basados en la dinámica poblacional de árboles individuales, aunque el enfocarnos en los patrones de la estructura forestal que emerge de interacciones entre árboles individuales puede proveer de una perspectiva beneficiosa sobre los impactos de los cambios en los regímenes del fuego en el este de Siberia. Para simular estos impactos en la estructura forestal a escalas de milenios, aplicamos el modelo espacialmente explícito, individualmente basado, LAVESI-FIRE, expandido en un nuevo módulo de fuego. Observaciones de fuego basadas en imágenes satelitales junto con datos de campo fueron usados para informar la implementación de la ocurrencia de fuegos de vegetación y ajustar los parámetros del modelo. Resultados: Las simulaciones del desarrollo anual de los bosques y de la actividad de los incendios en un sitio de estudio de la República de Sakha (Yakutia) desde el Último Máximo Glacial (c. 20.000 años atrás), resaltan los impactos variables de los regímenes de fuegos en la estructura forestal a través del tiempo. La probabilidad modelada de forma anual en la ocurrencia de incendios y subsecuentemente del área quemada durante el Holoceno se compara muy bien con la reconstrucción del flujo de carbón en los sedimentos lacustres. Los incendios de vegetación pueden verse mediante diferentes patrones de regeneración del bosque, dependiendo de la frecuencia e intensidad de los fuegos y de las condiciones del bosque en el pre-fuego. Encontramos que fuegos de mediana intensidad a intervalos de retorno de unos 50 años o más, benefician la persistencia del alerce dahurian (Larix gmelinii (Rupr.) Rupr.), especie resistente al fuego, mientras que los fuegos de reemplazo tienden a permitir el establecimiento de coníferas siempreverdes. Aparte de la mortalidad post-fuego, los fuegos de vegetación modulan el desarrollo del bosque, fundamentalmente a través de efectos de competencia y una reducción de la capa de mantillo predicho por el modelo. Conclusiones: Con sus características de detectar la dinámica de la población a una escala fina, el modelo LAVESI-FIRE puede servir como una herramienta altamente localizada y espacialmente explícita, para entender los impactos a largo plazo de los bosques boreales sobre la estructura forestal y para mejorar los condicionamientos de las interpretaciones de las reconstrucciones paleo ecológicas en la reconstrucción de la actividad de los incendios.

Pneumococcal Vaccination Lowers the Risk of Alzheimer's Disease: A Study Utilizing Data from the IBM® MarketScan® Database.

Previous studies demonstrated an association between influenza vaccination and the likelihood of developing Alzheimer's disease. This study was aimed at assessing whether pneumococcal vaccinations are associated with a lower risk of Alzheimer's disease based on analysis of data from the IBM® MarketScan® Database. Vaccinated and unvaccinated matched cohorts were generated using propensity-score matching with the greedy nearest-neighbor matching algorithm. The conditional logistic regression method was used to estimate the relationship between pneumococcal vaccination and the onset of Alzheimer's disease. There were 142,874 subjects who received the pneumococcal vaccine and 14,392 subjects who did not. The conditional logistic regression indicated that the people who received the pneumococcal vaccine had a significantly lower risk of developing Alzheimer's disease as compared to the people who did not receive any pneumococcal vaccine (OR=0.37; 95%CI: 0.33-0.42; P-value < .0001). Our findings demonstrated that the pneumococcal vaccine was associated with a 63% reduction in the risk of Alzheimer's disease among US adults aged 65 and older.

Face to Face: deciphering facial involvement in inclusion body myositis.

OBJECTIVE: The objective of this study is to evaluate the frequency and characteristics of facial involvement in inclusion body myositis (IBM) patients and to compare it to the one previously described in facioscapulohumeral dystrophy (FSHD) patients. METHODS: Thirty-two IBM patients were included and compared to 29 controls and 39 FSHD patients. All participants were recorded in a video as they performed a series of seven facial tasks. Five raters independently assessed facial weakness using both a qualitative evaluation and a semi-quantitative facial weakness score (FWS). RESULTS: IBM patients had higher FWS than controls (7.89 ± 7.56 vs 1.06 ± 0.88, p < 0.001). Twenty IBM patients (63%) had a facial weakness with a FWS above the maximum value for controls. All facial tasks were significantly more impaired in IBM patients compared to controls (p < 0.001), task 2 evaluating orbiculari oculi muscle weakness being the most affected. IBM patients with facial weakness reported more swallowing troubles than IBM patients without facial weakness (p = 0.03). FSHD patients displayed higher FWS than IBM patients (12.16 ± 8.37 vs 7.89 ± 7.56, p = 0.01) with more pronounced facial asymmetry (p = 0.01). FWS inter-rater ICC was 0.775. CONCLUSION: This study enabled us to estimate the frequency of facial impairment in IBM in more than half of patients, to detail its characteristics and to compare them with those of FSHD patients. The standardized, semi-quantitative FWS is an interesting diagnostic help in IBM as it appeared more sensitive than qualitative evaluation to detect mild facial weakness.

Healthcare resource utilization, costs and treatment associated with myasthenia gravis exacerbations among patients with myasthenia gravis in the USA: a retrospective analysis of claims data.

Aim: There are limited data on the clinical and economic burden of exacerbations in patients with myasthenia gravis (MG). We assessed patient clinical characteristics, treatments and healthcare resource utilization (HCRU) associated with MG exacerbation. Patients & methods: This was a retrospective analysis of adult patients with MG identified by commercial, Medicare or Medicaid insurance claims from the IBM® MarketScan® database. Eligible patients had two or more MG diagnosis codes, without evidence of exacerbation or crisis in the baseline period (12 months prior to index [first eligible MG diagnosis]). Clinical characteristics were evaluated at baseline and 12 weeks before each exacerbation. Number of exacerbations, MG treatments and HCRU costs associated with exacerbation were described during a 2-year follow-up period. Results: Among 9352 prevalent MG patients, 34.4% (n = 3218) experienced ≥1 exacerbation after index: commercial, 53.0% (n = 1706); Medicare, 39.4% (n = 1269); and Medicaid, 7.6% (n = 243). During follow-up, the mean (standard deviation) number of exacerbations per commercial and Medicare patient was 3.7 (7.0) and 2.7 (4.1), respectively. At least two exacerbations were experienced by approximately half of commercial and Medicare patients with ≥1 exacerbation. Mean total MG-related healthcare costs per exacerbation ranged from $26,078 to $51,120, and from $19,903 to $49,967 for commercial and Medicare patients, respectively. AChEI use decreased in patients with multiple exacerbations, while intravenous immunoglobulin use increased with multiple exacerbations. Conclusion: Despite utilization of current treatments for MG, MG exacerbations are associated with a high clinical and economic burden in both commercial and Medicare patients. Additional treatment options and improved disease management may help to reduce exacerbations and disease burden.

The effect of TRX, combined with vibration training, on BMI, the body fat percentage, myostatin and follistatin, the strength endurance and layup shot skills of female basketball players.

Introduction: Trx Vibration Training (TVT) focuses on using the entire body weight in combination with vibration. While research has separately examined TRX training and vibration training, there is limited literature on the combined effects of these two methods specifically for female individuals. Therefore, the objective of this study was to examine the impact of combining TRX and vibration training (TVT) on various factors including body mass index (BMI), body fat percentage (BFP), myostatin (MSTN), follistatin (FLST), endurance, and Lay up shooting skills of female basketball players. By addressing this research gap, we aim to shed light on the potential benefits of incorporating TRX and vibration exercises into the training regimen of female basketball players. Method: The study sample comprised 24 female players who were divided into two groups of equal size, with each group consisting of 12 female players: the experimental group (n = 12, age = 19.17 ± 0.68 years, height = 168.33 ± 0.89 cm, weight = 67.00 ± 2.17 kg, training age = 4.54 ± 0.45 years) and the control group (n = 12, age = 19.33 ± 0.78 years, height = 168.08 ± 2.02 cm, weight = 67.33 ± 1.50 kg, training age = 4.58 ± 0.52 years). The experimental method was employed in the study. For eight weeks, the program was used (TVT), with the experimental group participants completing three training sessions each week. The TVT training lasted between 30 and 45 min, out of the overall training session time, which ranged from 90 to 120 min. The control group used a conventional program without Trx Vibration training. Study variables were evaluated before and after the intervention, and a two-way ANOVA was used for repeated measures. Results: The results of the study showed the superiority of the experimental group over the control group in BMI (p = 0.037, [d] = 0.64), BFP (p = 0.001, [d] = 2.97), FLST levels (p = 0.029, [d] = 0.68), MSTN (p = 0.001, [d] = 2.04), endurance (CMS) (p = 0.001, [d] = 4.56), and Lay up skill Y (s) (p = 0.001, [d] = 4.27), Y (sc) (p = 0.012, [d] = 4.27). Conclusion: The results showed that, when comparing the two groups, the TVT program significantly improved the study's variables. Basketball players' motor abilities and skill performance improved after eight weeks of training, and coaches are advised to take this into account when developing seasonal training plans.

Exploring the responses of smallscale poultry keepers to avian influenza regulations and guidance in the United Kingdom, with recommendations for improved biosecurity messaging.

Understanding how smallscale ('backyard') poultry keepers interpret and respond to governmental directives designed to reduce the transmission of highly pathogenic avian influenza (HPAI) is of paramount importance in preparing for future HPAI outbreaks. Qualitative insights from open questions in an online survey conducted during the 2021-22 HPAI season (1,559 responses) shed light on smallscale poultry keepers' understanding of, and responses to, governmental directives to control HPAI exposure and onwards transmission. A follow-up participatory workshop (21 participants) explored the HPAI-related information sources used by smallscale poultry keepers, their trust in these sources, perceptions of HPAI-related risk, and interpretation of, opinions on and adherence to government regulations and communications regarding biosecurity and housing measures. This paper draws on a multi-scale behaviour change model to explore barriers to compliance with HPAI-related regulations. Insights from behaviour settings theory reveal how poultry-keeping settings and routines might be 'disrupted' and 're-configured' to improve long-term biosecurity and reduce the risk of HPAI exposure. The findings highlight the need for HPAI-related guidance that is tailored to smallscale poultry keepers. This guidance should include clear action points and simple, practical, affordable and sustainable suggestions for improving compliance with biosecurity measures.

Integrated Multi-Omics Analysis for Inferring Molecular Players in Inclusion Body Myositis.

Inclusion body myositis (IBM) is an acquired inflammatory myopathy affecting proximal and distal muscles that leads to weakness in patients over 50. It is diagnosed based on clinical and histological findings in muscle related to inflammation, degeneration, and mitochondria. In relation to IBM, a shortage of validated disease models and a lack of biomarkers and effective treatments constitute an unmet medical need. To overcome these hurdles, we performed an omics analysis of multiple samples from IBM patients (saliva, fibroblasts, urine, plasma, and muscle) to gain insight into the pathophysiology of IBM. Degeneration was evident due to the presence of amyloid ß peptide 1-42 (Aß1-42) in the saliva of the analyzed IBM patients. The presence of metabolic disarrangements in IBM was indicated by an imbalanced organic acid profile in fibroblasts and urine. Specifically, abnormal levels of L-pyroglutamic and orotic acid were supported by the abnormal expression of related metabolites in plasma and urine (glutathione and pyrimidines) and the aberrant expression of upstream gene regulators (L2HGDH, IDH2, OPLAH, and ASL) in muscle. Combined levels of L-pyroglutamic and orotic acid displayed an outstanding biomarker signature in urine with 100% sensitivity and specificity. The confirmation of systemic metabolic disarrangements in IBM and the identification of novel biomarkers reported herein unveil novel insights that require validation in larger cohorts.

Sex influences clinical phenotype in valosin-containing protein mutations: A case family report and systematic literature review.

OBJECTIVE: Mutations in the valosin-containing protein (VCP) gene cause autosomal dominant multisystem proteinopathy 1 (MSP1), characterized by a variable combination of inclusion body myopathy (IBM), Paget's disease of bone (PDB), and frontotemporal dementia (FTD). Here we report a novel VCP missense mutations in an Italian family with FTD as the prevalent manifestation and compare our results with those described in the literature. METHODS: We described the clinical, molecular, and imaging data of the studied family. We also conducted a systematic literature search with the aim of comparing our findings with previously reported VCP-related phenotypes. RESULTS: A novel heterozygous VCP missense mutation (c 0.473 T > C/p.Met158Thr) was found in all the affected family members. The proband is a 69-year-old man affected by progressive muscle weakness since the age of 49. Muscle MRI showed patchy fatty infiltration in most muscles, and STIR sequences revealed an unusual signal increase in distal leg muscles. At age 65, he presented a cognitive disorder suggestive of behavioral variant FTD. A bone scintigraphy also revealed PDB. The patient's mother, his maternal aunt and her daughter had died following a history of cognitive deterioration consistent with FTD; the mother also had PDB. No relatives had any muscular impairments. Reviewing the literature data, we observed a different sex distribution of VCP-related phenotypes, being FTD prevalence higher among women as compared to men (51.2 % vs 31.2 %) and IBM prevalence higher among men as compared to women (92.1 % vs 72.8 %). DISCUSSION: This study broadened our clinical, genetic, and imaging knowledge of VCP-related disorders.

Real-World Persistence and Treatment Interval in Patients with Diabetic Macular Edema Treated with Anti-Vascular Endothelial Growth Factors in the USA.

INTRODUCTION: There is little understanding of long-term treatment persistence in patients receiving anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), particularly relating to treatment intervals. The aim of this study was to investigate the association between treatment interval and discontinuation rate after 24 months of unilateral anti-VEGF treatment in patients with DME under routine clinical care in the USA. METHODS: This was a non-interventional, retrospective cohort study to review the health insurance claims of adults with DME linked with the IBM MarketScan® Commercial and Medicare Supplemental databases, who were continuously enrolled in a health plan for at least 6 months prior to their first anti-VEGF treatment and for a duration of at least 24 months between July 2011 and June 2017. Patients were grouped on the basis of the injection interval they achieved at 24 months of treatment. Discontinuation rate beyond 24 months and its association with treatment intervals at 24 months was estimated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The overall discontinuation rate among the 1702 eligible patients from 24 to 60 months after treatment initiation was 30%. At 60 months, patients were more likely to remain on treatment in shorter (75.3% [4-week interval group]) versus longer treatment interval groups (62.1% [> 12-week interval group], difference = 13.2%, [95% confidence interval (CI) 1.06, 2.06], p = 0.01). Patients on a > 12-week interval were twice as likely to discontinue treatment compared with those on an 8-week interval (hazard ratio = 2.01 [95% CI 1.43, 2.82], p < 0.001). CONCLUSION: Patients with DME on longer anti-VEGF treatment intervals at 24 months consistently had higher discontinuation rates in the following years than those on shorter treatment intervals.