Post-transcriptional Regulation of De Novo Lipogenesis by mTORC1-S6K1-SRPK2 Signaling.

mTORC1 is a signal integrator and master regulator of cellular anabolic processes linked to cell growth and survival. Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. Genome-wide transcriptome analysis reveals that lipid biosynthetic enzymes are among the downstream targets of mTORC1-SRPK2 signaling. Mechanistically, SRPK2 promotes SR protein binding to U1-70K to induce splicing of lipogenic pre-mRNAs. Inhibition of this signaling pathway leads to intron retention of lipogenic genes, which triggers nonsense-mediated mRNA decay. Genetic or pharmacological inhibition of SRPK2 blunts de novo lipid synthesis, thereby suppressing cell growth. These results thus reveal a novel role of mTORC1-SRPK2 signaling in post-transcriptional regulation of lipid metabolism and demonstrate that SRPK2 is a potential therapeutic target for mTORC1-driven metabolic disorders.

Wildlife Immune Responses to Mycobacterium bovis and to Bacille of Calmette-Guerin.

Bovine tuberculosis (bTB) is a zoonotic bacterial disease presenting public health, veterinary, and economic threats around the globe. Although cattle producers rely on regular testing and management practices to minimize domestic herd exposure, wildlife species around the world continue to be the main reservoirs for disease. Wildlife reservoirs for bTB include the Eurasian badger (Meles meles) in Great Britain and Ireland, the brushtail possum (Trichosurus vulpecula) in New Zealand, wild boar (Sus scrofa) in Spain, as well as white-tailed deer (Odocoileus virginianus) in the United States and red deer (Cervus elaphus) in Spain. Although all reservoir species share the ability to infect cattle, they differ in transmission capability, disease pathogenesis, diagnostic detection, and vaccination strategies. In this review, bTB interactions with these wildlife reservoirs are discussed, illustrating the need to address bTB disease in wildlife hosts to achieve eradication in domestic livestock.

From Deer-to-Deer: SARS-CoV-2 is efficiently transmitted and presents broad tissue tropism and replication sites in white-tailed deer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in humans, has a broad host range, and is able to infect domestic and wild animal species. Notably, white-tailed deer (WTD, Odocoileus virginianus), the most widely distributed cervid species in the Americas, were shown to be highly susceptible to SARS-CoV-2 in challenge studies and reported natural infection/exposure rates approaching 30-40% in free-ranging WTD in the U.S. Thus, understanding the infection and transmission dynamics of SARS-CoV-2 in WTD is critical to prevent future zoonotic transmission to humans, at the human-WTD interface during hunting or venison farming, and for implementation of effective disease control measures. Here, we demonstrated that following intranasal inoculation with SARS-CoV-2 B.1 lineage, WTD fawns (~8-month-old) shed infectious virus up to day 5 post-inoculation (pi), with high viral loads shed in nasal and oral secretions. This resulted in efficient deer-to-deer transmission on day 3 pi. Consistent a with lack of infectious SARS-CoV-2 shedding after day 5 pi, no transmission was observed to contact animals added on days 6 and 9 pi. We have also investigated the tropism and sites of SARS-CoV-2 replication in adult WTD (3-4 years of age). Infectious virus was detected up to day 6 pi in nasal secretions, and from various respiratory-, lymphoid-, and central nervous system tissues, indicating broad tissue tropism and multiple sites of virus replication. The study provides important insights on the infection and transmission dynamics of SARS-CoV-2 in WTD, a wild animal species that is highly susceptible to infection and with the potential to become a reservoir for the virus in the field.

Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.

PURPOSE: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). METHODS: We coupled phenotyping with exome or genome sequencing of 467 probands (550 affected and 1108 total individuals) with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and de novo variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations. RESULTS: Analyses elucidated phenotypic subgroups, identified pathogenic/likely pathogenic variant(s) in 43/467 probands (9.2%), and prioritized variants of uncertain significance in 70/467 additional probands (15.0%). These included known and novel variants in established oCCDD genes, genes associated with syndromes that sometimes include oCCDDs (e.g., MYH10, KIF21B, TGFBR2, TUBB6), genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2), genes with no reported association with oCCDDs or the syndromic phenotypes (e.g., TUBA4A, KIF5C, CTNNA1, KLB, FGF21), and genes associated with oCCDD phenocopies that had resulted in misdiagnoses. CONCLUSION: This study suggests that unsolved oCCDDs are clinically and genetically heterogeneous disorders often overlapping other Mendelian conditions and nominates many candidates for future replication and functional studies.

The multidisciplinary pancreatic cyst clinic: A collaborative approach to streamlined management.

BACKGROUND: Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different management strategies, and implementation in patient care is inconsistent in the absence of dedicated infrastructure. METHODS: To address the challenges of pancreatic cyst diagnosis and management, we established a multidisciplinary pancreas cyst clinic (PCC) within our health system. This clinic encompasses both tertiary care academic centers and community hospitals, with leadership from surgical oncology, gastroenterology, and radiology. Our PCC's primary goal is to provide accurate diagnosis and tailored management recommendations for all patients with pancreatic cysts. Additionally, we maintain a prospective database to study the disease's natural history and the outcomes of various treatment strategies. CLINIC INFRASTRUCTURE: The clinic meets once per week for 45 min virtually via Zoom in the mornings. Patients are referred via electronic medical record (EMR) order, telephone call, or email from patient or referring provider. A dedicated advanced practice provider reviews referrals several times per day, calls patients to gather clinical data, ensures imaging is uploaded, and coordinates logistical aspects of the meeting during the dedicated time. Conferences are attended by representatives from surgery, radiology, medical pancreatology, and interventional gastroenterology. Each patient case is reviewed in detail and recommendations are submitted to referring providers and patients via an EMR message and letter. For patients requiring imaging surveillance, patients are followed longitudinally by the referring provider, gastroenterology team, or surgical team. For patients requiring endoscopic ultrasound (EUS) or surgical consultation, expedited referral to these services is made with prompt subsequent evaluation. RESULTS: A total of 1052 patients from our health system were evaluated between 2020 and 2021. Of these, 196 (18.6 %) underwent EUS, 41 (3.9 %) underwent upfront surgical resection, and the remainder were referred to gastroenterology (141-13.4 %), surgery (314-29.8 %), or back to their referring provider (597-56.7 %) for ongoing surveillance in collaboration with their primary care provider (PCP). Of cysts under surveillance, 61.3 % remained stable, 13.2 % increased in size, and 2 % decreased in size. A total of 2.3 % of patients were recommended to discontinue surveillance. CONCLUSIONS: The PCC provides infrastructure that has served to provide multidisciplinary review and consensus recommendations to patients with pancreatic cysts. This has served to improve the application of guidelines while providing individualized recommendations to each patient, while aiding non-expert referring providers throughout the region.

Corticosterone and glucose are correlated and show similar response patterns to temperature and stress in a free-living bird.

Glucocorticoid (GC) hormones have traditionally been interpreted as indicators of stress, but the extent to which they provide information on physiological state remains debated. GCs are metabolic hormones that amongst other functions ensure increasing fuel (i.e. glucose) supply on the face of fluctuating energetic demands, a role often overlooked by ecological studies investigating the consequences of GC variation. Furthermore, because energy budget is limited, in natural contexts where multiple stimuli coexist, the organisms' ability to respond physiologically may be constrained when multiple triggers of metabolic responses overlap in time. Using free-living spotless starling (Sturnus unicolor) chicks, we experimentally tested whether two stimuli of different nature known to trigger a metabolic or GC response, respectively, cause a comparable increase in plasma GCs and glucose. We further tested whether response patterns differed when both stimuli occurred consecutively. We found that both experimental treatments caused increases in GCs and glucose of similar magnitude, suggesting that both variables fluctuate along with variation in energy expenditure, independently of the trigger. Exposure to the two stimuli occurring subsequently did not cause a difference in GC or glucose responses compared with exposure to a single stimulus, suggesting a limited capacity to respond to an additional stimulus during an ongoing acute response. Lastly, we found a positive and significant correlation between plasma GCs and glucose after the experimental treatments. Our results add to the increasing research on the role of energy expenditure on GC variation, by providing experimental evidence on the association between plasma GCs and energy metabolism.

Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice.

Cystic fibrosis (CF) is an inherited life-threatening disease accompanied by repeated lung infections and multiorgan inflammation that affects tens of thousands of people worldwide. The causative gene, cystic fibrosis transmembrane conductance regulator (CFTR), is mutated in CF patients. CFTR functions in epithelial cells have traditionally been thought to cause the disease symptoms. Recent work has shown an additional defect: monocytes from CF patients show a deficiency in integrin activation and adhesion. Because monocytes play critical roles in controlling infections, defective monocyte function may contribute to CF progression. In this study, we demonstrate that monocytes from CFTRΔF508 mice (CF mice) show defective adhesion under flow. Transplanting CF mice with wild-type (WT) bone marrow after sublethal irradiation replaced most (60-80%) CF monocytes with WT monocytes, significantly improved survival, and reduced inflammation. WT/CF mixed bone marrow chimeras directly demonstrated defective CF monocyte recruitment to the bronchoalveolar lavage and the intestinal lamina propria in vivo. WT mice reconstituted with CF bone marrow also show lethality, suggesting that the CF defect in monocytes is not only necessary but also sufficient to cause disease. We also show that monocyte-specific knockout of CFTR retards weight gains and exacerbates dextran sulfate sodium-induced colitis. Our findings show that providing WT monocytes by bone marrow transfer rescues mortality in CF mice, suggesting that similar approaches may mitigate disease in CF patients.

Acute Effects of Sprint Interval Training and Blood Flow Restriction on Neuromuscular and Muscle Function.

BFR) applied during sprint interval training (SIT) on performance and neuromuscular function. METHODS: Fifteen men completed a randomized bout of SIT with CBFR, IBFR, and without BFR (No-BFR), consisting of 2, 30-s maximal sprints on a cycle ergometer with a resistance of 7.5% of body mass. Concentric peak torque (CPT), maximal voluntary isometric contraction (MVIC) torque, and muscle thickness (MT) were measured before and after SIT, including surface electromyography (sEMG) recorded during the strength assessments. Peak and mean revolutions per minute (RPM) were measured during SIT and power output was examined relative to physical working capacity at the fatigue threshold (PWCFT). RESULTS: CPT and MVIC torque decreased from pre-SIT (220.3±47.6 Nm and 355.1±72.5 Nm, respectively) to post-SIT (147.9±27.7 Nm and 252.2±45.5 Nm, respectively, all P<0.05), while MT increased (1.77±0.31 cm to 1.96±0.30 cm). sEMG mean power frequency decreased during CPT (-12.8±10.5%) and MVIC (-8.7±10.2%) muscle actions. %PWCFT was greater during No-BFR (414.2±121.9%) than CBFR (375.9±121.9%). CONCLUSION: SIT with or without BFR induced comparable alterations in neuromuscular fatigue and sprint performance across all conditions, without affecting neuromuscular function.

Quantification of Brucella abortus population structure in a natural host.

Cattle are natural hosts of the intracellular pathogen Brucella abortus, which inflicts a significant burden on the health and reproduction of these important livestock. The primary routes of infection in field settings have been described, but it is not known how the bovine host shapes the structure of B. abortus populations during infection. We utilized a library of uniquely barcoded B. abortus strains to temporally and spatially quantify population structure during colonization of cattle through a natural route of infection. Introducing 108 bacteria from this barcoded library to the conjunctival mucosa resulted in expected levels of local lymph node colonization at a 1-wk time point. We leveraged variance in strain abundance in the library to demonstrate that only 1 in 10,000 brucellae introduced at the site of infection reached a parotid lymph node. Thus, cattle restrict the overwhelming majority of B. abortus introduced via the ocular conjunctiva at this dose. Individual strains were spatially restricted within the host tissue, and the total B. abortus census was dominated by a small number of distinct strains in each lymph node. These results define a bottleneck that B. abortus must traverse to colonize local lymph nodes from the conjunctival mucosa. The data further support a model in which a small number of spatially isolated granulomas founded by unique strains are present at 1 wk postinfection. These experiments demonstrate the power of barcoded transposon tools to quantify infection bottlenecks and to define pathogen population structure in host tissues.

Assessment of potentially hazardous elements in soils of the Boyacá industrial corridor (Colombia) using GIS, multivariate statistical analysis, and geochemical indexes.

In the industrial corridor of Boyacá, Colombia, population growth is accompanied by anthropogenic activities such as industrial operations, vehicle exhaust fumes, mining, smelting, atmospheric deposition, and excessive use of chemical products to promote crop growth. These activities are known to have a significant impact on urban and rural soils, contributing significantly to elevated concentrations of potentially hazardous elements in the environment. This industrial corridor is an area of economic and social development that needs to provide reference information that will allow us to know the state of soil quality to preserve and manage the public and geoenvironmental health of this region. Anthropogenic activities have contributed to the accumulation of potentially hazardous elements in the environment, affecting various levels of life and creating risks with economic and social implications. However, igneous activity or detrital deposition also enriches soils and creates geochemical anomalies in specific locations. In these cases, the identification of potentially hazardous elements involves the determination of likely sources of contamination and their relationship to the geological setting. In this study, the concentrations of As, Cd, Pb, Mn, Fe, Zn, Hg, Cu and Ni were determined in eighty-one soil samples from the Boyacá industrial corridor (Colombia). The sequential trend of the concentrations of potentially hazardous elements was as follows: Fe > Mn > Zn > Ni > Cu> Pb > As > Cd > Hg. Furthermore, the application of spatial analysis criteria in GIS software with multivariate statistical tools and geochemical indices allowed the identification of anthropogenic and geogenic sources. Most of the potentially hazardous elements were found in soils exposed to industrial and agricultural activities, except for iron. This element showed low variability in all samples, regardless of the geological formations. Due to the lack of reference values for potentially hazardous elements in Colombia, the concentrations were compared with the environmental standards of the Environmental Protection Agency (EPA) and the Ecuadorian Ministry of Environment, Water and Ecological Transition (MAE). The results demonstrate the complexity of the soil and represent the first exploratory study of potentially hazardous elements in this industrial corridor. These results are the starting point for the establishment of geochemical background lines in Colombia and for inspection policies for areas where productive activities converge.

Rod-like nanostructures through amphiphilic OPE-porphyrin self-organization.

A new amphiphilic monosubstituted porphyrin functionalized by a ß-D-glucoside terminated oligophenylenethylene (OPE) able to self-arrange into nano-aggregates in polar solvents has been synthesized and fully characterized in its monomeric and aggregated forms.

Amino-OPE glycosides and blue light: a powerful synergy in photodynamic therapy.

Herein we report the synthesis and biological properties of sugar-conjugated oligophenylene ethynylene (OPE) dyes, used as novel photosensitizers (PSs) for photodynamic treatment (PDT) under blue light. The OPE-bearing glycosides at both ends are successfully prepared by a Pd-catalyzed Sonogashira cross-coupling reaction. The live-cell imaging studies have shown that these OPE glycosides (including glucose, mannose and maltose derivatives) efficiently penetrate the cytoplasm of cultured HeLa cancer cells. No dark toxicity was observed, but upon irradiating the cells under blue light an extraordinary photodynamic effect was observed at low concentrations (10-6-10-8 M). The localization studies indicate that OPE-glucose 1 and OPE-mannose 2 have Golgi patterns, whereas OPE-maltose 3 could be in lysosomes. The PDT and morphological studies in HeLa cells treated with sublethal doses of PS 1-3 revealed that cell death occurs by necrosis.

Acute effects of low load blood flow restricted and non restricted exercise on muscle excitation, neuromuscular efficiency, and average torque.

OBJECTIVES: The purpose of this investigation was to examine the acute effects of low-load blood flow restriction (LLBFR) and low-load (LL) resistance exercise on muscle excitation, neuromuscular efficiency, and average torque. METHODS: Eleven men (age±SD=22±3yrs) randomly performed LLBFR and LL that consisted of 30 unilateral leg extensions at 30% of one-repetition maximum while surface electromyography (sEMG) and torque were simultaneously assessed. Polynomial regression analyses and slope comparisons were performed to examine patterns of responses and rates of change. RESULTS: sEMG amplitude increased for LLBFR (9 of 11) and LL (8 of 11) and between composite responses (R2=0.939-0.981). For LLBFR, sEMG amplitude increased to a greater extent for 5 of the 11 individual and for the composite responses. Similarly, neuromuscular efficiency decreased for LLBFR (8 of 11) and LL (5 of 11) as well as the composite responses r2=0.902-0.929, but the decrease was larger for LLBFR than LL for the individual (4 of 11) responses. For average submaximal concentric torque, there were individual increases, decreases, and no changes for the composite responses (R2=0.198-0.325). CONCLUSION: LLBFR elicited greater fatigue-induced increases in muscle excitation and decreases in neuromuscular efficiency than LL, but neither LLBFR nor LL affected average submaximal concentric torque.

Seroprevalence and risk factors associated with hepatitis C: a cross-sectional study of persons who inject drugs in Puerto Rico, 2018.

BACKGROUND: People Who Inject Drugs (PWID) are at a higher risk of acquiring bloodborne infections. We aimed to estimate the seroprevalence of the Hepatitis C Virus (HCV) in PWID and identify correlates and risk factors using data from the Puerto Rico National HIV Behavioral Surveillance System, PWID cycle 5, conducted in 2018. METHODS: A total of 502 San Juan Metropolitan Statistical Area participants were recruited through the Respondent Driven Sampling method. Sociodemographic, health-related, and behavioral characteristics were assessed. Testing for HCV antibodies was completed after the face-to-face survey. Descriptive and logistic regression analyses were performed. RESULTS: Overall seroprevalence of HCV was 76.5% (95% CI: 70.8-81.4%). A significantly (p < 0.05) higher HCV seroprevalence was observed among PWID with the following characteristics: heterosexuals (78.5%), high school graduates (81.3%), tested for sexually transmitted infections (STI) in the past 12 months (86.1%), frequent speedball injection (79.4%), and knowing the HCV serostatus of the last sharing partner (95.4%). Adjusted logistic regression models showed that having completed high school and reported STI testing in the past 12 months were significantly associated with HCV infection (ORa = 2.23; 95% CI: 1.06-4.69; ORa = 2.14; 95% CI: 1.06-4.30, respectively). CONCLUSIONS: We report a high seroprevalence of HCV infection in PWID. Social health disparities and potential missed opportunities validate the continuing call for local action for public health and prevention strategies.

Gait speed according to cognitive status in older adults: a cross-sectional study in a resource-limited country.

OBJECTIVE: We aimed to investigate the association between gait speed and cognitive status in outpatient older adults from a resource-limited setting in Peru. METHODS: We performed a cross-sectional study including older adults aged ≥60 years attending a geriatrics outpatient clinic between July 2017 and February 2020. Gait speed was measured over a 10-meters distance without considering the first and last meter traveled. Cognitive status was assessed through the Short Portable Mental Status Questionnaire (SPMSQ) and the Mini-Mental State Examination (MMSE). We used a multivariate binomial logistic regression to conduct both an epidemiological and fully adjusted models. RESULTS: We included 519 older adults (mean age: 75 years; IQR = 10), of whom 95 (18.3%) and 151 (31.5%) were cognitively impaired according to the SPMSQ and MMSE, respectively. Gait speed was slower among patients with poorer cognitive status as assessed by both tools (p < 0.001). Malnutrition (PR: 1.74; CI: 1.45-2.08) and functional dependency (PR: 4.35; CI: 2.68-7.08) were associated with a greater prevalence of cognitive impairment according to the SPMSQ, whereas a faster gait speed (PR: 0.27, CI: 0.14-0.52) and longer years of education (PR: 0.83, CI: 0.77-0.88) were associated with a less prevalence. CONCLUSIONS: Slower gait speed was associated with poorer cognitive status in outpatient older adults. Gait speed may be a complementary tool in the cognitive assessment of older adults from resource-limited settings.

Acute Effects of Continuous and Intermittent Blood Flow Restriction on Sprint Interval Performance and Muscle Oxygen Responses.

ABSTRACT: Wizenberg, AM, Gonzalez-Rojas, D, Rivera, PM, Proppe, CE, Laurel, KP, Stout, JR, Fukuda, DH, Billaut, F, Keller, JL, and Hill, EC. Acute effects of continuous and intermittent blood flow restriction on sprint interval performance and muscle oxygen responses. J Strength Cond Res 37(10): e546-e554, 2023-This investigation aimed to examine the acute effects of continuous and intermittent blood flow restriction (CBFR and IBFR, respectively) during sprint interval training (SIT) on muscle oxygenation, sprint performance, and ratings of perceived exertion (RPE). Fifteen men (22.6 ± 2.4 years; 176 ± 6.3 cm; 80.0 ± 12.6 kg) completed in random order a SIT session with CBFR, IBFR (applied during rest), and no blood flow restriction (NoBFR). Each SIT session consisted of two 30-second all-out sprint tests separated by 2 minutes. Peak power (PP), total work (TW), sprint decrement score (S dec ), RPE, and muscle oxygenation were measured during each sprint. A p value ≤0.05 was considered statistically significant. PP decreased to a greater extent from sprint 1 to sprint 2 during CBFR (25.5 ± 11.9%) and IBFR (23.4 ± 9.3%) compared with NoBFR (13.4 ± 8.6%). TW was reduced similarly (17,835.6 ± 966.2 to 12,687.2 ± 675.2 J) from sprint 1 to sprint 2 for all 3 conditions, but TW was lower (collapsed across time) for CBFR (14,320.7 ± 769.1 J) than IBFR (15,548.0 ± 840.5 J) and NoBFR (15,915.4 ± 771.5 J). There were no differences in S dec (84.3 ± 1.7%, 86.1 ± 1.5%, and 87.2 ± 1.1% for CBFR, IBFR, and NoBFR, respectively) or RPE, which increased from sprint 1 (8.5 ± 0.3) to sprint 2 (9.7 ± 0.1). Collective muscle oxygenation responses increased across time and were similar among conditions, whereas increases in deoxy[heme] and total[heme] were greatest for CBFR. Applying BFR during SIT induced greater decrements in PP, and CBFR resulted in greater decrements in work across repeated sprints. The larger increases in deoxy[heme] and total[heme] for CBFR suggested it may induce greater metabolite accumulation than IBFR and NoBFR when combined with SIT.

Effect of glyphosate and ciprofloxacin exposure on enteric bacteria of tadpoles.

The high load of agrochemicals and antibiotics present in agricultural aquatic environments represents a risk for wildlife. Since enteric bacteria, which play a key role in the physiological functioning of their hosts, are sensitive to a wide variety of pollutants, their study allows to evaluate the health of organisms. This study aimed to evaluate the effects of commercial formulations of a glyphosate-based herbicide (GBH) and the antibiotic ciprofloxacin (CIP), individually and in mixture, on the bacterial diversity of the intestinal content of common toad (Rhinella arenarum) tadpoles. The diversity of cultivable fast-growing bacteria with low nutritional requirements was evaluated using classic microbiological tests and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry identification. Bacterial diversity varied among treatments. Taxa diversity increased in the GBH-treated group but decreased in the CIP-treated group. Remarkably, Yersinia spp. and Proteus spp. were only found in the GBH-treated group. The prevalence of Klebsiella spp. and Pseudomonas spp. decreased in the intestinal microbiota of the GBH-CIP-treated group. To our knowledge, this is the first report on the alteration of cultivable enteric bacteria of autochthonous tadpoles due to two pollutants of emerging concern. Our results demonstrate that R. arenarum tadpoles can be used as non-conventional model organisms for environmental pollution monitoring. Our preliminary findings would contribute to understanding how the presence of GBH and CIP in freshwaters may represent a threat to wildlife and human health by causing enteric dysbiosis of part of the bacterial community.

Greater neuromuscular fatigue following low-load blood flow restriction than non-blood flow restriction resistance exercise among recreationally active men.

The purpose of this study was to examine the acute effects of low-load blood flow restriction (LLBFR) and low-load non-BFR (LL) on neuromuscular function after a bout of standardized fatiguing leg extension muscle actions. Fourteen men (mean age ± SD = 23 ± 4 yr) volunteered to participate in this investigation and randomly performed LLBFR and LL on separate days. Resistance exercise consisted of 75 isotonic unilateral leg extension muscle actions performed at 30% of one-repetition maximum. Before (pretest) and after (posttest) performance of each bout of exercise, strength and neural assessments were determined. There were no pretest to posttest differences between LLBFR and LL for maximal voluntary isometric contraction (MVIC) torque or V wave/M wave responses (muscle compound action potentials assessed during a superimposed MVIC muscle action), which exhibited decreases (collapsed across condition) of 41.2% and 26.2%, respectively. There were pretest to posttest decreases in peak twitch torque (36.0%) and surface electromyography amplitude (sEMG) (29.5%) for LLBFR but not LL and larger decreases in voluntary activation for LLBFR (11.3%) than for LL (4.5%). These findings suggested that LLBFR elicited greater fatigue-induced decreases in several indexes of neuromuscular function relative to LL. Despite this, both LLBFR and LL resulted in similar decrements in performance as assessed by maximal strength.NEW & NOTEWORTHY The application of blood flow restriction induces greater acute neuromuscular fatigue relative to nonrestricted conditions. Resistance exercise with blood flow restriction elicited a greater reduction in twitch responses. These neuromuscular differences might explain the more favorable adaptations achieved with blood flow restriction that are likely a function of metabolic stress and subsequent changes in efferent neural drive.

One-year persistent symptoms and functional impairment in SARS-CoV-2 positive and negative individuals.

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

Surgery for Intraductal Papillary Mucinous Neoplasms of the Pancreas: Preoperative Factors Tipping the Scale of Decision-Making.

BACKGROUND: Decision-making in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas depends on scaling the risk of malignancy with the surgical burden of a pancreatectomy. This study aimed to develop a preoperative, disease-specific tool to predict surgical morbidity for IPMNs. METHODS: Based on preoperative variables of resected IPMNs at two high-volume institutions, classification tree analysis was applied to derive a predictive model identifying the risk factors for major morbidity (Clavien-Dindo ≥3) and postoperative pancreatic insufficiency. RESULTS: Among 524 patients, 289 (55.2%) underwent pancreaticoduodenectomy (PD), 144 (27.5%) underwent distal pancreatectomy (DP), and 91 (17.4%) underwent total pancreatectomy (TP) for main-duct (18.7%), branch-duct (12.6%), or mixed-type (68.7%) IPMN. For 98 (18.7%) of the patients, major morbidity developed. The classification tree distinguished different probabilities of major complications based on the type of surgery (area under the surve [AUC] 0.70; 95% confidence interval [CI], 0.63-0.77). Among the DP patients, the presence of preoperative diabetes identified two risk classes with respective probabilities of 5% and 25% for the development of major morbidity, whereas among the PD/TP patients, three different classes with respective probabilities of 15%, 20%, and 36% were identified according to age and body mass index (BMI). Overall, history of diabetes, age, and cyst size segregated three different risk classes for new-onset/worsening diabetes. CONCLUSIONS: In presumed IPMNs, the disease-specific risk of major morbidity and pancreatic insufficiency can be determined in the preoperative setting and used to personalize the possible surgical indication. Age and overweight status in case of PD/TP and diabetes in case of DP tip the scale toward less aggressive clinical management in the absence of features suggestive for malignancy.