Adeno-associated virus type 2 in US children with acute severe hepatitis.

As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.

Catalytic Asymmetric Synthesis of Zinc Metallacycles.

Transition-metal-catalyzed reductive coupling reactions of alkynes and imines are attractive methods for the synthesis of chiral allylic amines. Mechanistically, these reactions involve oxidative cyclization of the alkyne and the imine to generate a metallacyclic intermediate, which then reacts with H2 or a H2 surrogate to form the product. As an alternative to this hydrogenolysis pathway, here we show that transmetalation to zinc can occur, forming a zinc metallacycle product. This organozinc product serves as a versatile nucleophile for carbon-carbon and carbon-heteroatom coupling reactions. Mechanistic studies based on isotopic labeling experiments and DFT calculations suggest that the key transmetalation step occurs between a Co(II) species and ZnCl2.

Exophytic condyloma: are they as benign as we think?

AIM: As the understanding of anal dysplasia continues to develop, controversy remains regarding treatment of these lesions. The purpose of this study was to evaluate lesion type (flat vs exophytic) and the association between morphology and dysplasia. METHODS: This was a single-centre retrospective analysis of a prospectively collected pathological database of patients > 17 years old who underwent operative excision/biopsies for presumed anal condyloma or dysplasia from 2009 to 2018. The analysis includes comparisons between patient factors, phenotype and grade of dysplasia. RESULTS: Sixty-nine patients had 423 lesions. The mean age of the study population was 48.2 years. 62.3% were men and 46.4% of patients were black. 47.8% of patients were human immunodeficiency virus (HIV) positive and 39.1% were men who have sex with men (MSM). There were 176 (41.6%) flat lesions and 234 (55.3%) exophytic lesions. Exophytic lesions were 2.5-fold more likely to be associated with a higher grade of dysplasia than flat lesions (OR 2.63, 95% CI 1.09-6.32). Neither lesion type nor dysplasia severity was associated with human papillomavirus, lesion location or patient characteristics, including race, MSM or HIV status. DISCUSSION: Exophytic lesions were more than twice as likely to have advanced dysplasia compared with flat lesions. A clearer understanding of the association between gross lesion appearance and dysplasia will allow more appropriate counselling of patients and the development of better screening and treatment guidelines for anal condylomata and dysplasia.

The effects of a loaded rucksack and weighted vest on metabolic cost and stride frequency in female adults.

This study evaluated the metabolic cost and stride frequency during exercise while wearing an evenly distributed weight vest in recreationally fit women. Nine healthy women performed a modified Balke treadmill test until volitional fatigue in one of three conditions; (1) unloaded (2) rucksack and (3) weighted vest. Wearing a weighted vest did not show improvement of V̇O2peak, HRpeak, peak stride frequency or average stride frequency (all p ≥ 0.05). However, total time of exercise was significantly longer in the evenly distributed weight vest condition compared to the rucksack condition (p = 0.024) despite similar V̇O2peak and HRpeak. These results may provide practical information when females in tactical populations are preparing for missions in which heavy loads must be carried. Practitioner summary: This study compared the effects of load carriage mode on metabolic cost and stride frequency during graded exercise in females. The weighted vest showed significantly longer exercise time despite similar V̇O2peak and HRpeak. Development of standardised weight distribution mode may serve as an advantageous strategy for females in tactical settings. Abbreviations: HR: heart rate; V̇O2: oxygen uptake; RPE: rating of perceived exertion; V̇O2peak: peak oxygen uptake; HRpeak: peak heart rate.

Is sarcopenia a better predictor of complications than body mass index? Sarcopenia and surgical outcomes in patients with rectal cancer.

AIM: Sarcopenia, or a reduction of lean muscle mass, is associated with poorer outcomes in cancer patients. Few previous studies have examined this potentially correctable risk factor in patients with locally advanced rectal cancer. METHOD: Skeletal muscle mass index was measured retrospectively on initial staging CT scans of patients undergoing chemoradiation followed by radical resection for rectal cancer for the period 2007-2013. Patients were categorized as sarcopenic or nonsarcopenic and differences in terms of demographics, pre-, peri- and postoperative outcomes were examined. RESULTS: Forty-seven patients were included; their mean age was 59.3 (36-82) years and 61.7% were men. We considered that 55.2% of men and 44.4% of women were sarcopenic; the overall prevalence of sarcopenia was 51.1%. Age, preoperative haemoglobin and albumin were significantly related to sarcopenia. Body mass index (BMI) and obesity (BMI > 30 kg/m2 ) were not associated with sarcopenia. Blood transfusions were more frequent in sarcopenic patients (P = 0.001). Although readmissions and length of stay were not increased, overall postoperative complications were significantly higher in sarcopenic patients (P = 0.03). Neither BMI nor obesity was associated with postoperative complications. CONCLUSION: Sarcopenia was present in over 50% of patients with locally advanced rectal cancer at diagnosis. It was associated with a higher incidence of both blood transfusion and postoperative complications. BMI did not correlate with these negative outcomes. Sarcopenia may be a better predictor of surgical outcomes than BMI or obesity.

Cold-induced vasodilation responses before and after exercise in normobaric normoxia and hypoxia.

PURPOSE: Cold-induced vasodilation (CIVD) is known to protect humans against local cold injuries and improve manual dexterity. The current study examined the effects of metabolic heat production on cold-induced vasodilation responses in normobaric hypoxia and normoxia. METHODS: Ten participants immersed their non-dominant hand into 5 °C water for 15 min. Minimum finger temperature (Tmin), maximum finger temperature (Tmax), onset time, amplitude, and peak time were measured before and after exercise under normoxia (21% O2) and two levels of normobaric hypoxia (17% O2 and 13% O2). RESULTS: Neither Tmin nor amplitude was affected by hypoxia. However, Tmax was significantly decreased by hypoxia while reduction in onset time and peak time trended towards significance. Tmin, Tmax, and amplitude were significantly higher during post-exercise CIVD than pre-exercise CIVD. CONCLUSION: The CIVD response may be negatively affected by the introduction of hypoxia whereas metabolic heat production via exercise may counteract adverse effects of hypoxia and improve CIVD responses.

Pre-Hospital Fast Positive Cases Identified by DFB Ambulance Paramedics: Final Clinical Diagnosis.

Ischaemic stroke clinical outcomes are improved by earlier treatment with intravenous thrombolysis. An existing pathway at the Mater University Hospital for assessment of suspected acute stroke in the Emergency Department was updated, aiming to shorten door-to-needle time. This study examines the final clinical diagnosis of Dublin Fire Brigade Ambulance Paramedic identified Face-Arm-Speech-Test (FAST) positive patients presenting to the Emergency Department over a 7 month period. A retrospective analysis was carried out of 177 consecutive FAST positive patients presenting between March and November 2014. The final clinical diagnosis was acute stroke in 57.1% (n=101) of patients. Of these, 76 were ischaemic strokes of whom 56.5% (n=43) were thrombolysed. In the pre-hospital setting Ambulance Paramedics can identify, with reasonable accuracy, acute stroke using the FAST test. Over half of the ischaemic stroke patients presenting via this pathway can be treated with intravenous thrombolysis.

Postanesthetic death in a cat with myopathy.

There are few reports of naturally occurring muscular dystrophy in domestic animals. Herein, we describe a case of muscular dystrophy in a 4-year-old neutered male American domestic shorthair cat that died unexpectedly following anesthesia for an elective surgical procedure. Macroscopic muscular hypertrophy and histologic evidence of myofiber size variation, mineralization, myofiber degeneration, and necrosis were compatible with a diagnosis of muscular dystrophy. Extensive endomysial fibrosis was noted histologically in the diaphragm. A complete absence of dystrophin protein in Western blot confirmed the diagnosis of Duchenne muscular dystrophy. Immunofluorescence microscopy revealed reduced levels of dystrophin-associated proteins and an upregulation of utrophin at the sarcolemma. Anesthetic deaths can occur in dystrophin-deficient cats, and therefore muscular dystrophy and the associated cardiomyopathy should be considered in the differential diagnoses for perianesthetic death in cats.

Biomacromolecule-tagged nanoscale constructs for crossing the blood-brain barrier.

Access to the brain is restricted by the low permeability of the blood-brain barrier (BBB), greatly hampering modern drug delivery efforts. A promising approach to overcome this boundary is to utilize biomacromolecules (peptides, nucleic acids, carbohydrates) as targeting ligands on nanoscale delivery vehicles to shuttle cargo across the BBB. In this mini-review, we highlight the most recent approaches for crossing the BBB using synthetic nanoscale constructs decorated with members of these general classes of biomacromolecules to safely and selectively deliver therapeutic materials to the brain.

The Effects of Slow Breathing during Inter-Set Recovery on Power Performance in the Barbell Back Squat.

Slow breathing (SB) reduces sympathetic nervous system activity, the heart rate (HR), and blood pressure (BP) and increases parasympathetic nervous system activity, HR variability, and oxygen saturation which may lead to quicker recovery between bouts of exercise. Therefore, the purpose of this study was to examine whether a SB technique using the 4-7-8 method between sets of barbell back squats (SQs) would attenuate drops in power and bar velocity. In a randomized, crossover design, 18 healthy resistance-trained college-aged males (age: 20.7 ± 1.4 years, body height: 178.6 ± 6.4 cm, body mass: 82.2 ± 15.0 kg, 4.5 ± 2.4 years of experience) performed 5 sets of 3 repetitions of SQs with normal breathing (CON) or SB during the 3-min recovery between sets. Peak and average power and bar velocity were assessed using a linear positioning transducer. HR recovery (RHR), systolic BP recovery (RBP), the rating of perceived exertion (RPE) and the rating of perceived recovery score (RS) were assessed after each set. There were no significant differences between conditions for peak and average power and bar velocity, RBP, RPE, and RS (p > 0.211). SB led to a greater RHR after set 2 (SB: 51.0 ± 14.9 bpm vs. CON: 44.5 ± 11.5 bpm, p = 0.025) and 3 (SB: 48.3 ± 13.5 bpm vs. CON: 37.7 ± 11.7 bpm, p = 0.006) compared to the CON condition. SB was well tolerated, did not hinder nor improve training performance and improved RHR after the middle sets of SQs. Further investigations are warranted to examine the effects of other SB techniques and to determine SB's effects on different training stimuli as well as its effects over an entire workout and post-workout recovery metrics.

Metabolic effects of adjunctive aripiprazole in clozapine-treated patients with schizophrenia.

OBJECTIVE: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine-treated patients with schizophrenia. METHOD: In an 8-week randomized, double-blind, placebo-controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole-body dual-energy X-ray absorptiometry (DXA). RESULTS: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. -0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low-density lipoprotein (LDL) levels (-15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (-376 ± 632 vs. -36 ± 301 nm, P = 0.035). Further, there was a significant reduction in the lean mass (-1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole-body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo. CONCLUSION: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine-treated patients with schizophrenia.

Posttraumatic Soft Tissue Coverage of the Lower Leg for the Orthopedic Surgeon.

Soft tissue reconstructive techniques are powerful tools for the orthopedic surgeon caring for lower extremity trauma. This article seeks to inform orthopedic surgeons about useful techniques for skin closure, secondary wound closure techniques, and rotational flaps of the lower leg. Split thickness skin grafting, piecrusting, and the use of negative pressure wound therapy for skin closure, as well as rotational gastrocnemius, soleus, and reverse sural artery flaps are discussed with emphasis on techniques for the nonvascular and nonmicrovascular orthopedic surgeon.

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface.

Emerging infectious diseases present great risks to public health. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become an urgent public health issue of global concern. It is speculated that the virus first emerged through a zoonotic spillover. Basic research studies have suggested that bats are likely the ancestral reservoir host. Nonetheless, the evolutionary history and host susceptibility of SARS-CoV-2 remains unclear as a multitude of animals has been proposed as potential intermediate or dead-end hosts. SARS-CoV-2 has been isolated from domestic animals, both companion and livestock, as well as in captive wildlife that were in close contact with human COVID-19 cases. Currently, domestic mink is the only known animal that is susceptible to a natural infection, develop severe illness, and can also transmit SARS-CoV-2 to other minks and humans. To improve foundational knowledge of SARS-CoV-2, we are conducting a synthesis review of its host diversity and transmission pathways. To mitigate this COVID-19 pandemic, we strongly advocate for a systems-oriented scientific approach that comprehensively evaluates the transmission of SARS-CoV-2 at the human and animal interface.

"Chicken dumping": Motivations and perceptions in shifting poultry production practices.

Non-governmental organizations (NGOs) often implement overseas development aid through intensive small-scale animal agriculture to alleviate food insecurity in low- and middle-income countries. Intensive animal farming can pose unclear outcomes to households engaged in the practice because of the reliance on industrial animal breeds that are reared with antibiotics and raised in higher densities compared to traditional scavenging husbandry systems. As a result, intensive small-scale farming operations that lack proper infrastructure, training, and financial resources could facilitate the spread of antimicrobial resistance and infectious diseases. We applied a mixed-methods framework towards analyzing the effectiveness of small-scale broiler chicken farming in northern Ecuador. First, from May 2016 - May 2017, our observational surveys indicated that intensive small-scale poultry farming follows a boom-and-bust cycle that is extremely vulnerable to environmental stressors. Second, in May 2016, we followed a cohort of households enrolled in a poultry development project led by an NGO. We observed a substantial decline in chicken survivorship from Survey period 1 to 2 (mean chicken count decrease from 50 to 35 corresponding to a 70% survivorship) and from Survey period 2 to 3 (mean chicken count decrease from 35 to 20.3 corresponding to a 58% survivorship). Heads of households were self-reporting broiler chicken survivorship substantially higher than our recorded observations during survey period two (46 compared to 35 respectively) and three (44.3 compared to 20.3 respectively). We speculate that if households continue to inaccurately report poultry demographics, then it could perpetuate a negative feedback loop where NGOs continue to conduct the same intervention practices without receiving accurate outcome metrics. Third, we used semi-structured questionnaires to determine that access to financial resources was the major motivation for determining when to farm broiler chickens. Intensive small-scale poultry farming can be unreliable and disease-enhancing, yet also associated with dubious self-reports of success.

Arthroscopic Fixation of Knee Femoral Condyle Osteochondritis Dissecans Fragment With Bone Marrow Aspirate Concentrate.

This article reviews a technique for arthroscopic fixation of an osteochondritis dissecans fragment with bone marrow aspirate concentrate augmentation. This technique involves safe harvest of bone marrow arthroscopically from the intercondylar notch, proper preparation and debridement of the parent bone, reduction of the progeny osteochondritis dissecans fragment, insertion of the bone marrow aspirate concentrate, and placement of multiple headless compression screws for fixation.

Spatial analysis of chronic wasting disease in free-ranging white-tailed deer (Odocoileus virginianus) in Illinois, 2008-2019.

Understanding the geographic distribution and clustering of chronic wasting disease (CWD) among free-ranging white-tailed deer (Odocoileus virginianus) populations can inform disease management practices. We used a retrospective analysis of surveillance data to evaluate CWD's spatial and temporal dynamics within 16 CWD-infected northern Illinois counties. Of 42,541 deer samples collected and tested for CWD from recreational hunter harvest between 2008 and 2019, we recorded 359 (0.84%) CWD-positive samples. We observed variability in CWD cases over time and space. By county, the median CWD-positive proportion was 0.84%, varying from a minimum of 0.14% in McHenry County to a maximum of 6.28% in Boone County. Across years, there were differences among CWD-positive proportions with a median of 0.90%, ranging from a minimum of 0.27% in 2012 to a maximum of 1.60% in 2019. We used a retrospective discrete Poisson scan statistic model to evaluate the space-time clustering of CWD-positive deer. We identified a statistically significant (p < .001) primary cluster C1 (area = 23.59 km2 ; RR = 10.48), occurring from 2010 to 2015 in the north-central part of the study area, and a secondary cluster C2, occurring from 2014 to 2019 (area = 9.27 km2 ; RR = 3.88) in the north-west of the study area. Detected CWD-positive space-time clusters suggest that the risk of CWD is not random. Space-time clusters of CWD can be used to evaluate the effectiveness of the Illinois CWD management programme. The area surrounding the older C1 cluster has undergone longer and more intense CWD management compared with C2. Currently, the older C1 cluster is no longer as high risk compared with the newer cluster C2, suggesting that management efforts in C2 should be increased. However, all CWD clusters should be targeted with surveillance, prevention and management programmes, including reducing deer densities to limit further spread of CWD.

A Review of Antimicrobial Resistance in Poultry Farming within Low-Resource Settings.

The emergence, spread, and persistence of antimicrobial resistance (AMR) remain a pressing global health issue. Animal husbandry, in particular poultry, makes up a substantial portion of the global antimicrobial use. Despite the growing body of research evaluating the AMR within industrial farming systems, there is a gap in understanding the emergence of bacterial resistance originating from poultry within resource-limited environments. As countries continue to transition from low- to middle income countries (LMICs), there will be an increased demand for quality sources of animal protein. Further promotion of intensive poultry farming could address issues of food security, but it may also increase risks of AMR exposure to poultry, other domestic animals, wildlife, and human populations. Given that intensively raised poultry can function as animal reservoirs for AMR, surveillance is needed to evaluate the impacts on humans, other animals, and the environment. Here, we provide a comprehensive review of poultry production within low-resource settings in order to inform future small-scale poultry farming development. Future research is needed in order to understand the full extent of the epidemiology and ecology of AMR in poultry within low-resource settings.

Packed bed compression visualisation and flow simulation using an erosion-dilation approach.

X-ray computed tomography has been demonstrated to be capable of imaging 1 mL (5 mm diameter, 50 mm height) chromatography packed beds under compression, visualising the 3D structure and measuring changes to geometry of the packing. 1 mL pre-packed columns did not exhibit any structural changes at vendor specified flow rate limits, however cellulose beds did compress at higher flow rates that were imaged before, during and after flow. This was used to visualise and quantitate changes to porosity, tortuosity and permeability based on simulation of flow through the packed bed structure using the imaging data. When using a high flow rate it was found that a decrease in porosity could be measured during compression before reverting after flow had ceased, with corresponding changes to tortuosity and permeability also occurring. X-ray CT imaging of packed beds and individual beads exposed to foulant-rich process streams resulted in considerable image quality loss, associated with residual biological material. In order to address this, digital processing using an erosion-dilation method was applied at bead and bed scales to computationally alter the porosity by adding or removing material from the existing surface to calculate the impact upon tortuosity factor. The eroded and dilated bead volumes of agarose, cellulose and ceramic materials were used to simulate diffusivity whilst mimicking internal bead pore constriction and blocking mechanisms.

Food Safety Considerations Related to the Consumption and Handling of Game Meat in North America.

Emerging foodborne pathogens present a threat to public health. It is now recognized that several foodborne pathogens originate from wildlife as demonstrated by recent global disease outbreaks. Zoonotic spillover events are closely related to the ubiquity of parasitic, bacterial, and viral pathogens present within human and animal populations and their surrounding environment. Foodborne diseases have economic and international trade impacts, incentivizing effective wildlife disease management. In North America, there are no food safety standards for handling and consumption of free-ranging game meat. Game meat consumption continues to rise in North America; however, this growing practice could place recreational hunters and game meat consumers at increased risk of foodborne diseases. Recreational hunters should follow effective game meat food hygiene practices from harvest to storage and consumption. Here, we provide a synthesis review that evaluates the ecological and epidemiological drivers of foodborne disease risk in North American hunter populations that are associated with the harvest and consumption of terrestrial mammal game meat. We anticipate this work could serve as a foundation of preventive measures that mitigate foodborne disease transmission between free-ranging mammalian and human populations.

Psychophysiological Responses in Emergency Medical Technician Students during Simulated Work Activities in a Hot Environment.

This study compared physiological responses and cognitive performance during simulated work activities in heat to a thermoneutral condition. First responders perform physically demanding activities in a hot environment which may impose additional burdens on tactical personnel during daily tasks. Ten healthy (8 men and 2 women) participants performed two consecutive simulated work activities with two repetitions of each activity (10 min walking on treadmill and 15 sandbag lifts) under heat and thermoneutral conditions. A Stroop color word test (SCWT) and total mood disturbance (TMD) were obtained at first and second baseline (B1, B2), after a 30-min resting period (B3), and recovery (R1). At the end of the trial, core temperature (Tc), skin temperature (tsk), and mean body temperature (Tb) were higher in the heat condition compared to neutral condition (all p ≤ 0.05), whereas oxygen uptake, heart rate, and mean arterial pressure were not significantly different between conditions. There were no differences in scores of SCWT and TMD between conditions. However, TMD was significantly improved after two successive bouts of exercise compared to B3 (all p ≤ 0.05). This investigation shows that two successive simulated work activities did not induce the detrimental influence on thermoregulatory and cognitive responses. Extended work activities in a hot and humid environment may impose a psychophysiological burden and need to be investigated.