Cerebral collaterals are associated with pre-treatment brain-blood barrier permeability in acute ischemic stroke patients.

INTRODUCTION: To investigate the relationship between collaterals and blood-brain barrier (BBB) permeability on pre-treatment MRI in a cohort of acute ischemic stroke (AIS) patients treated with thrombectomy. METHODS: We conducted a retrospective analysis of the HIBISCUS-STROKE cohort, a single-center observational study that enrolled patients treated with thrombectomy from 2016 to 2022. Dynamic-susceptibility MRIs were post-processed to generate K2 maps with arrival-time correction, which were co-registered with apparent diffusion coefficient (ADC) maps. The 90th percentile of K2 was extracted from the infarct core-defined by an ADC ≤ 620 × 10-6 mm2/s with manual adjustments-and expressed as a percentage change compared to the contralateral white matter. Collaterals were assessed using pre-thrombectomy digital subtraction arteriography with an ASITN/SIR score < 3 defining poor collaterals. RESULTS: Out of 249 enrolled, 101 (40.6%) were included (median age: 72.0 years, 52.5% of males, median NIHSS score at admission: 15.0). Patients with poor collaterals (n = 44) had worse NIHSS scores (median: 16.0 vs 13.0, p = 0.04), larger infarct core volumes (median: 43.7 mL vs 9.5 mL, p < 0.0001), and higher increases in K2 (median: 346.3% vs 152.7%, p = 0.003). They were less likely to achieve successful recanalization (21/44 vs 51/57, p < 0.0001) and experienced more frequent hemorrhagic transformation (16/44 vs 9/57, p = 0.03). On multiple variable analysis, poor collaterals were associated with larger infarct cores (odds ratio (OR) = 1.12, 95% confidence interval (CI): [1.07, 1.17], p < 0.0001) and higher increases in K2 (OR = 6.63, 95% CI: [2.19, 20.08], p = 0.001). CONCLUSION: Poor collaterals are associated with larger infarct cores and increased BBB permeability at admission MRI. CLINICAL RELEVANCE STATEMENT: Poor collaterals are associated with a larger infarct core and increased BBB permeability at admission MRI of AIS patients treated with thrombectomy. These findings may have translational interests for extending thrombolytic treatment eligibility and developing neuroprotective strategies. KEY POINTS: In AIS, collaterals and BBB disruption have been both linked to hemorrhagic transformation. Poor collaterals were associated with larger ischemic cores and increased BBB permeability on pre-treatment MRI. These findings could contribute to hemorrhagic transformation risk stratification, thereby refining clinical decision-making for reperfusion therapies.

Expert Views on Evidence-Based Classification for Goalball: A Delphi Study.

Para sport classification aims to minimize the impact of impairments on the outcome of competition. The International Paralympic Committee requires classification systems to be evidence based and sport specific, yet the sport of goalball uses a structure that is not supported by evidence demonstrating its legitimacy for competition. This study aimed to establish expert opinions on how a sport-specific system of classification should be structured in the sport of goalball. Using a three-round Delphi survey, 30 international experts expressed their views across topics linked to goalball classification. Participants were divided as to whether the current system fulfills the aim to minimize the impact of impairment on competition. Most felt that less impairment should be required to compete but that the one-class structure should remain. Experts identified measures of visual function that should be considered and 15 core components of individual goalball performance. Findings constitute a crucial first step toward evidence-based classification in goalball.

The fecal mycobiome in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Studies investigating the gut-liver axis have largely focused on bacteria, whereas little is known about commensal fungi. We characterized fecal fungi in patients with non-alcoholic fatty liver disease (NAFLD) and investigated their role in a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis. METHODS: We performed fungal internal transcribed spacer 2 sequencing using fecal samples from 78 patients with NAFLD, 16 controls and 73 patients with alcohol use disorder. Anti-Candida albicans (C. albicans) IgG was measured in blood samples from 17 controls and 79 patients with NAFLD. Songbird, a novel multinominal regression tool, was used to investigate mycobiome changes. Germ-free mice were colonized with feces from patients with non-alcoholic steatohepatitis (NASH), fed a Western diet for 20 weeks and treated with the antifungal amphotericin B. RESULTS: The presence of non-obese NASH or F2-F4 fibrosis was associated with a distinct fecal mycobiome signature. Changes were characterized by an increased log-ratio for Mucor sp./Saccharomyces cerevisiae (S. cerevisiae) in patients with NASH and F2-F4 fibrosis. The C. albicans/S. cerevisiae log-ratio was significantly higher in non-obese patients with NASH when compared with non-obese patients with NAFL or controls. We observed a different fecal mycobiome composition in patients with NAFLD and advanced fibrosis compared to those with alcohol use disorder and advanced fibrosis. Plasma anti-C. albicans IgG was increased in patients with NAFLD and advanced fibrosis. Gnotobiotic mice, colonized with human NASH feces and treated with amphotericin B were protected from Western diet-induced steatohepatitis. CONCLUSIONS: Non-obese patients with NAFLD and more advanced disease have a different fecal mycobiome composition to those with mild disease. Antifungal treatment ameliorates diet-induced steatohepatitis in mice. Intestinal fungi could be an attractive target to attenuate NASH. LAY SUMMARY: Non-alcoholic fatty liver disease is one of the most common chronic liver diseases and is associated with changes in the fecal bacterial microbiome. We show that patients with non-alcoholic fatty liver disease and more severe disease stages have a specific composition of fecal fungi and an increased systemic immune response to Candida albicans. In a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis, we show that treatment with antifungals reduces liver damage.

Management of Dyslipidemia in Patients with Non-Alcoholic Fatty Liver Disease.

PURPOSE OF REVIEW: Patients with non-alcoholic fatty liver disease (NAFLD), often considered as the hepatic manifestation of the metabolic syndrome, represent a population at high cardiovascular risk and frequently suffer from atherogenic dyslipidemia. This article reviews the pathogenic interrelationship between NAFLD and dyslipidemia, elucidates underlying pathophysiological mechanisms and focuses on management approaches for dyslipidemic patients with NAFLD. RECENT FINDINGS: Atherogenic dyslipidemia in patients with NAFLD results from hepatic and peripheral insulin resistance along with associated alterations of hepatic glucose and lipoprotein metabolism, gut dysbiosis, and genetic factors. Since atherogenic dyslipidemia and NAFLD share a bi-directional relationship and are both major driving forces of atherosclerotic cardiovascular disease (ASCVD) development, early detection and adequate treatment are warranted. Thus, integrative screening and management programs are urgently needed. A stepwise approach for dyslipidemic patients with NAFLD includes (i) characterization of dyslipidemia phenotype, (ii) individual risk stratification, (iii) definition of treatment targets, (iv) lifestyle modification, and (v) pharmacotherapy if indicated.

Limited implementation of California's Healthy Default Beverage law for children's meals sold online.

OBJECTIVE: To reduce children's sugar-sweetened beverage intake, California's Healthy-By-Default Beverage law (SB1192) mandates only unflavoured dairy/non-dairy milk or water be the default drinks with restaurant children's meals. The objective of this study is to examine consistency with this law for meals sold through online platforms from restaurants in low-income California neighbourhoods. DESIGN: This observational, cross-sectional study examines beverage availability, upcharges (additional cost) and presentation of beverage options consistent with SB1192 (using four increasingly restrictive criteria) within a random sample of quick-service restaurants (QSR) in Supplemental Nutrition Assistance Program Education eligible census tracts selling children's meals online from November 2020 to April 2021. SETTING: Low-income California neighbourhoods (n 226 census tracts). PARTICIPANTS: QSR that sold children's meals online via a restaurant-specific platform, DoorDash, GrubHub and/or UberEats (n 631 observations from 254 QSR). RESULTS: Seventy percent of observations offered water; 63 % offered unflavoured milk. Among all beverages, water was most likely to have an upcharge; among observations offering water (n 445), 41 % had an upcharge (average $0·51). Among observations offering unflavoured milk (n 396), 11 % had an upcharge (average $0·38). No observations upcharged for soda (regular or diet). Implementation consistency with SB1192 ranged from 40·5 % (using the least restrictive criteria) to 5·6 % (most restrictive) of observations. CONCLUSIONS: Based on observations from restaurant websites and three of the most popular online ordering platforms, most California QSR located in low-income neighbourhoods are not offering children's meal beverages consistent with the state's Healthy-By-Default Beverage law. As the popularity of online ordering increases, further work to ensure restaurants offering healthy default beverages with children's meals sold online is necessary.

Comparative analysis of lateral maxillary sinus augmentation with a xenogeneic bone substitute material in combination with piezosurgical preparation and bony wall repositioning or rotary instrumentation and membrane coverage: a prospective randomized clinical and histological study.

OBJECTIVES: The present randomized controlled clinical study aimed to investigate if, in lateral maxillary sinus augmentation, the repositioned bony wall or the application of a collagen membrane results in more preferable new hard tissue formation. MATERIALS AND METHODS: Forty patients were divided into two study groups. Both groups received a xenogeneic bone substitute material (BSM) during lateral sinus augmentation. In the bony wall group (BW), following piezosurgery, the retrieved bony wall was repositioned. In the collagen membrane group (CM), following rotary instrument preparation, collagen membrane coverage was applied. After 6 months, biopsies were taken to histologically analyze the percentage of BSM, connective tissue (CT), and newly formed bone (NFB) following both approaches. RESULTS: Forty implants were placed and 29 harvested biopsies could be evaluated. Duration of surgery, membrane perforations, and VAS were detected. Histomorphometrical analysis revealed comparable amounts of all analyzed parameters in both groups in descending order: CT (BW: 39.2 ± 9%, CM: 37,9 ± 8.5%) > BSM (BW: 32.9 ± 6.3%, CM: 31.8 ± 8.8%) > NB (BW: 27.8 ± 11.2%, CM: 30.3 ± 4.5%). CONCLUSIONS: The results of the present study show that the closure of the access window by means of the retrieved bony wall or a native collagen membrane led to comparable bone augmentation results. CLINICAL TRIAL: clinicaltrials.gov NCT04811768. CLINICAL RELEVANCE: Lateral maxillary sinus augmentation with the application of a xenogeneic BSM in combination with a native collagen membrane for bony window coverage represents a reliable method for surgical reconstruction of the posterior maxilla. Piezosurgery with bony window repositioning delivers comparable outcomes without membrane coverage.

Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response, Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice.

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.

Texture, sensory properties and functionality of extruded snacks from pulses and pseudocereal proteins.

BACKGROUND: The protein-rich fractions of pulses and pseudocereals exhibit a well-balanced amino acid profile, particularly when combined in different portions, and are therefore high-value ingredients for the production of extruded snacks. However, the impact of a combination of pulses and pseudocereals on the physical and sensory qualities of extruded snacks has not been investigated up to now. Native or preconditioned protein isolates and concentrates from pulses - as single ingredients or in combination with protein-rich flours of pseudocereals - were analyzed regarding their thermal and functional properties in relation to extrusion characteristics. Low moisture extrusion cooking was used to investigate the impact of protein source (lentil, lupin, faba bean), pseudocereal source (quinoa, amaranth, buckwheat) and protein content (30%, 50%, 70%) on sectional expansion, specific hardness, density and sensory properties of the snacks. RESULTS: With increasing protein content from 30% to 50%, the sectional expansion decreased and the density and specific hardness of the extrudates increased, which could be counteracted by preconditioning of the protein-rich ingredients. Lupin protein-based extrudates exhibited satisfactory texture and sensory properties. Extruded mixtures of pulses and pseudocereals (70% protein) exhibited a smaller sectional expansion compared to pulses as single ingredients (30%, 50%), regardless of pseudocereal type. However, the texture and sensory properties of the extruded blends were satisfactory. CONCLUSIONS: We show for the first time that protein-rich fractions of pulses and pseudocereals can be processed into expanded snacks with favorable texture and nutritional properties such as increased protein contents (70%) and balanced amino acid profiles. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Alterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD. METHODS: In a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles. RESULTS: Patients with NAFLD and NAS 5-8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0-4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5-8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91-0.99) and F2-F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80-0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity. CONCLUSIONS: In a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies patients with severe NAFLD and fibrosis more accurately than models based only on clinical or bacterial data.

Control of the expiratory flow in a lung model and in healthy volunteers with an adjustable flow regulator: a combined bench and randomized crossover study.

BACKGROUND: Pursed-lips breathing (PLB) is a technique to attenuate small airway collapse by regulating the expiratory flow. During mandatory ventilation, flow-controlled expiration (FLEX), which mimics the expiratory flow course of PLB utilizing a digital system for measurement and control, was shown to exert lung protective effects. However, PLB requires a patient's participation and coordinated muscular effort and FLEX requires a complex technical setup. Here, we present an adjustable flow regulator to mimic PLB and FLEX, respectively, without the need of a patient's participation, or a complex technical device. METHODS: Our study consisted of two parts: First, in a lung model which was ventilated with standard settings (tidal volume 500 ml, respiratory rate 12 min-1, positive end-expiratory pressure (PEEP) 5 cmH2O), the possible reduction of the maximal expiratory flow by utilizing the flow regulator was assessed. Second, with spontaneously breathing healthy volunteers, the short-term effects of medium and strong expiratory flow reduction on airway pressure, the change of end-expiratory lung volume (EELV), and breathing discomfort was investigated. RESULTS: In the lung model experiments, expiratory flow could be reduced from - 899 ± 9 ml·s-1 down to - 328 ± 25 ml·s-1. Thereby, inspiratory variables and PEEP were unaffected. In the volunteers, the maximal expiratory flow of - 574 ± 131 ml·s-1 under baseline conditions was reduced to - 395 ± 71 ml·s-1 for medium flow regulation and to - 266 ± 58 ml·s-1 for strong flow regulation, respectively (p < 0.001). Accordingly, mean airway pressure increased from 0.6 ± 0.1 cmH2O to 2.9 ± 0.4 cmH2O with medium flow regulation and to 5.4 ± 2.4 cmH2O with strong flow regulation, respectively (p < 0.001). The EELV increased from baseline by 31 ± 458 ml for medium flow regulation and 320 ± 681 ml for strong flow regulation (p = 0.033). The participants rated breathing with the flow regulator as moderately uncomfortable, but none rated breathing with the flow regulator as intolerable. CONCLUSIONS: The flow regulator represents an adjustable device for application of a self-regulated expiratory resistive load, representing an alternative for PLB and FLEX. Future applications in spontaneously breathing patients and patients with mandatory ventilation alike may reveal potential benefits. TRIAL REGISTRATION: DRKS00015296, registered on 20th August, 2018; URL: https://www.drks.de/drks_web/setLocale_EN.do .

Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy-proven non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown. METHODS: In this cross-sectional study, we performed 16S gene sequencing using fecal samples, collected dietary intake, PNPLA3 gene variants and clinical and liver histology parameters in a well-described cohort of 180 NAFLD patients. Principal component analyses were used for dimensionality reduction of dietary and microbiota data. Simple and multiple stepwise ordinal regression analyses were performed. RESULTS: Complete data were available for 57 NAFLD patients. In the simple regression analysis, features associated with the metabolic syndrome had the highest importance regarding liver disease severity. In the multiple regression analysis, BMI was the most important factor associated with the fibrosis stage (OR per kg/m2 : 1.23, 95% CI 1.10-1.37, P < .001). The PNPLA3 risk allele had the strongest association with the histological grade of steatosis (OR 5.32, 95% CI 1.56-18.11, P = .007), followed by specific dietary patterns. Low abundances of Faecalibacterium, Bacteroides and Prevotella and high abundances of Gemmiger were associated with the degree of inflammation, ballooning and stages of fibrosis, even after taking other cofactors into account. CONCLUSIONS: BMI had the strongest association with histological fibrosis, but PNPLA3 gene variants, gut bacterial features and dietary factors were all associated with different histology features, which underscore the multifactorial pathogenesis of NAFLD.

Travel distance reduces follow-up compliance but has no effect on long-term weight loss success in bariatric patients.

BACKGROUND: Patients seeking bariatric surgery are traveling longer distances to reach Bariatric Centers. The purpose of this study was to evaluate the impact of travel distance on adherence to follow-up and outcomes after bariatric surgery. METHODS: A retrospective review of all consecutive patients who had undergone bariatric surgery from June 2013 to May 2014 was performed, and the patients were divided into two groups: those who traveled 50 miles or less and those who traveled more than 50 miles. Primary outcome assessed was the influence of distance on post-operative follow-up attrition over 4-year period. Secondary outcomes assessed were excess weight loss, length of stay (LOS), complications and readmission rates. RESULTS: A total of 228 patients underwent bariatric surgery with 4 years of follow-up available. Of these, 145 patients traveled 50 miles or less and 83 patients traveled greater than 50 miles. Patient demographics were similar between the two groups. Those who traveled more had statistically higher probability of attrition up to 3-year follow-up mark. There was no difference in percent excess weight loss at each follow-up visit between the two cohorts. Furthermore, there was no difference in readmission rates (2% vs 5%), minor complications (14% vs 10%), major complications (3% vs 2%) and LOS (2.6 days vs 2.6). CONCLUSION: The distance patients traveled for bariatric surgery did not affect their weight loss success, length of stay, postsurgical complications or readmission rate. Despite the lack of influence on postoperative outcomes, follow-up compliance was statistically affected by distance.

Factors associated with weight regain post-bariatric surgery: a systematic review.

INTRODUCTION: To systematically review the literature to assess the incidence and risk factors of weight regain (WR) after bariatric surgery. Bariatric surgery is the most effective intervention for sustained weight loss of morbidly obese patients, but WR remains a concern. MATERIALS AND METHODS: A PRISMA compliant systematic literature review was performed using the PubMed database, Embase and the Cochrane Library in July of 2019. Studies that reported ≥ 10% WR after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were included. The Newcastle-Ottawa scale (NOS) was used for assessing study quality. RESULTS: Out of 2915 retrieved abstracts, 272 full papers were reviewed, and 32 studies included (25 of high and 7 of fair quality) reporting weight outcomes on 7391 RYGB and 5872 SG patients. 17.6% (95% CI 16.9-18.3) had a WR ≥ 10%. Risk factors related with WR fell into 5 categories, namely anatomical, genetic, dietary, psychiatric, and temporal. Specifically, gastrojejunal stoma diameter, gastric volume following sleeve, anxiety, time after surgery, sweet consumption, emotional eating, portion size, food urges, binge eating, loss of control/disinhibition when eating, and genetics have been positively associated with WR while postprandial GLP-1, eagerness to change physical activity habits, self-esteem, social support, fruit and zinc consumption, HDL, quality of life have been negatively associated. CONCLUSION: At least 1 in 6 patients after bariatric surgery had ≥ 10% WR. This review identified several factors related to WR that can be used to counsel patients preoperatively and direct postoperative strategies that minimize WR risk.

Above cuff vocalisation (ACV): A scoping review.

INTRODUCTION: Patients in intensive care frequently suffer from not being able to communicate verbally. The aim of this scoping review was to study the safety and effectiveness of the above cuff vocalisation (ACV) on speech and quality of life (QOL) in patients dependent on a cuffed tracheostomy. METHODS: A scoping review was conducted. The databases Ovid Medline, Cochrane Library, and Embase were systematically searched in May 2020. We included clinical studies with patients exposed to ACV where speech, QOL or safety issues were assessed. RESULTS: Overall, 17 studies were included, of which 15 were observational and 2 were randomised controlled trials. Totally, 231 patients were included. ACV enabled most of the included patients (115/131; 88%) to speak with an audible voice or whisper (moderate quality of evidence). Voice related QOL (V-RQOL) and QOL in mechanically ventilated patients (QOL-MV) improved from pre- to post- ACV compared to a control group not tolerating a one-way speaking valve (P = .01 and P = .04, respectively) (very low quality of evidence). Several minor complications or problems were reported in 20/75 (27%) cases in addition to two serious adverse events: subcutaneous emphysema in one patient where the tracheostomy was dislodged and a distended trachea in another due to the misconnection of continuous gas to the cuff (low/ very low quality of evidence). CONCLUSION: ACV facilitated communication in patients dependent on a cuffed tracheostomy and attempting to communicate. Quality of evidence in improved V-RQOL and QOL-MV was very low. Several minor complications and two serious adverse events were reported.

COVID-19: Assessing the impact of lockdown on recreational athletes.

BACKGROUND AND AIMS: The COVID-19 pandemic has resulted in associated lockdown restrictions for individuals across England, including the postponement of all recreational sporting provisions. The beneficial effects of regular physical activity are well established yet to the authors' knowledge, no research addresses the cancellation of all recreational provisions. Using quantitative and qualitative methods, this study assessed the impact of COVID-19 restrictions on recreational sports players, what alternative exercise methods have been sought and how players feel about returning to their sport. METHOD: An online survey was distributed across England for six-weeks commencing in May 2020. A questionnaire explored differences in the impact of COVID-19 restrictions between sex, winter/summer/year-round sports, team/individual sports, age, and resilience groups. The use of alternative exercise methods, coping strategies and feelings about returning to sport were also investigated. Responses were gathered from 2023 adults whose recreational sport had been cancelled by COVID-19. All completed questionnaires (n = 1213) were taken for analysis (mean age = 49.41 years, SD = 17.165, 55.2% female). RESULTS: Quantitative findings showed the negative impact of COVID-19 restrictions was greater for females, those involved in winter and team sports, those aged 18-39 and low-resilient copers (p < .05). No significant differences were found between individuals that had had COVID-19 or were considered vulnerable by government guidelines. Acceptance was the most common coping strategy. The average number of days per week that participants exercised significantly increased during lockdown, with significant increases also seen in the use of online workouts, fitness apps and home-gym exercise. Qualitative findings suggested that participants are looking forward to the social and physical benefits of recreational activity restarting yet are concerned about the logistics of returning under social distancing restrictions. Other worries included loss of fitness, spreading (younger age groups) and catching (older age groups) COVID-19 and being in a crowd. CONCLUSIONS: Results highlight what is currently accessible to home-based exercisers and inform the reintroduction of recreational sports clubs. As COVID-19 restrictions look to persist, club representatives should provide accessible home-exercise options and be cautious of participant concerns when considering the return of recreational sport.

Pharmacokinetics of oral and compounded intravenous gabapentin in Duroc swine (Sus Scrofa).

The objective of this study was to determine the pharmacokinetics (PK) of oral (OS; 20 mg/kg) and compounded intravenous (IV; 5.5 mg/kg) gabapentin in 6 healthy, adult, Duroc pigs. Subjects were randomized to receive IV and OS gabapentin in a cross-over design, with at least 14 days of wash-out period between the two rounds of drug administrations. Blood samples were obtained before gabapentin administration and at various times up to 24 h, and harvested plasma was stored at -80°C until analysis. Concentration of gabapentin was quantified using a previously validated liquid chromatography/tandem mass spectrometry method, and compartment models were fitted to time-concentration data using non-linear mixed effect (population) analysis. A two-compartment model best fitted the data following IV administration. Typical values for volume of the central compartment and clearance and calculated volume of distribution at steady-state and terminal half-life were 170 ml/kg, 1.2 ml/(kg*min), and 594 ml/kg and 360 min, respectively. For the oral route, absorption half-life, estimated maximal plasma concentration and time to reach maximal plasma concentration were 58 min, 9155 ng/ml, and 194 min, respectively. Estimated oral bioavailability was 47%. Short-lived sedation (approximately 15 min) with sternal or lateral recumbency after IV administration was observed in all subjects without adverse clinical effects. Simulation based on the results of this study suggests that a first oral gabapentin dose of 15 mg/kg and subsequent doses of 8.5 mg/kg every 8 h would achieve and maintain plasma concentrations between 5 and 8 µg/ml in pigs.

Photoregulation of PRMT-1 Using a Photolabile Non-Canonical Amino Acid.

Protein methyltransferases are vital to the epigenetic modification of gene expression. Thus, obtaining a better understanding of and control over the regulation of these crucial proteins has significant implications for the study and treatment of numerous diseases. One ideal mechanism of protein regulation is the specific installation of a photolabile-protecting group through the use of photocaged non-canonical amino acids. Consequently, PRMT1 was caged at a key tyrosine residue with a nitrobenzyl-protected Schultz amino acid to modulate protein function. Subsequent irradiation with UV light removes the caging group and restores normal methyltransferase activity, facilitating the spatial and temporal control of PRMT1 activity. Ultimately, this caged PRMT1 affords the ability to better understand the protein's mechanism of action and potentially regulate the epigenetic impacts of this vital protein.

Cytolysin-positive Enterococcus faecalis is not increased in patients with non-alcoholic steatohepatitis.

Several studies show associations between gut bacterial dysbiosis and chronic liver diseases, but causative mechanisms are largely unclear. We recently identified cytolysin, a bacterial exotoxin expressed and secreted by Enterococcus faecalis to cause liver damage in the setting of alcohol-related liver disease. Cytolysin was increased and highly correlated with liver disease severity and mortality in alcoholic hepatitis patients. In this study, we investigated if faecal cytolysin-positivity can be linked to non-alcoholic fatty liver disease, a highly prevalent disease where new biomarkers and treatment targets are urgently needed. In contrast to what we observed in alcoholic hepatitis, only seven out of 96 non-alcoholic fatty liver disease patients were cytolysin-positive, and these patients did not have increased liver disease activity compared with cytolysin-negative patients. These results indicate that the association of cytolysin carriage with worse clinical outcome might be specific for alcoholic hepatitis.

Hepatocellular carcinoma surveillance with liver imaging is not associated with improved survival.

Objective: International guidelines recommend hepatocellular carcinoma (HCC) surveillance with ultrasound in high-risk patients with chronic liver diseases. However, there is low-strength evidence about the effects on mortality. The aim of our study was to assess the impact of surveillance on the clinical course and survival of HCC patients seen at a tertiary referral center in Germany.Material and methods: We retrospectively evaluated the data of 401 HCC patients, who presented to our clinic between 1997 and 2015. Two groups were compared regarding patient and disease outcomes: one group included patients who received at least two ultrasound examinations for surveillance purposes prior to first diagnosis (n = 111). The other group consisted of patients with HCC at first presentation without foregoing HCC surveillance (n = 290).Results: Median follow-up in the surveillance group was 76 months (range 4-310 months). Patients in the surveillance group had smaller median tumor sizes (3.5 cm vs. 4.5 cm; p < .001), fulfilled more often Milan criteria (64% vs. 42%; p < .001) and received more often liver transplantation (27% vs. 9%, p < .001) when compared with the non-surveillance group. However, HCC surveillance was not associated with an improved survival (14 months in the surveillance group vs. 12 months in the non-surveillance group, p = .375), hazard ratio regarding overall mortality for the surveillance group: 0.80 (95% CI: 0.62-1.04, p = .09).Conclusions: HCC surveillance with ultrasound led to the detection of earlier disease stages but was not significantly associated with improved survival. Further prospective and long-term studies are needed to clarify benefits and harms of HCC surveillance programs on mortality.

Phenotyping non-alcoholic fatty liver disease by the gut microbiota: Ready for prime time?

BACKGROUND AND AIM: Several studies observed alterations in the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods. METHODS: The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort. RESULTS: Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies. CONCLUSION: Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.