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Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

Abstract Cu(In,Ga)(S,Se)2 absorbers with a bandgap in the near-infrared region are ideal candidates for a bottom cell in multi-junction solar cell architectures. In flexible and lightweight form factors, such devices could help power many applications through integrated solar cells. Here, we show the use of a two-step method to synthesize Cu(In,Ga)(S,Se)2, with a bandgap between 1.00 and 1.13 eV, on bendable ultra-thin glass, with minority carrier lifetimes approaching 100 ns, in a homogenous and repeatable fashion. We also report on conventional and alternative device fabrication methods with very low waste and toxicity footprints. Champion solar cells are fabricated based on absorbers with a graded bandgap between 1.05 and 1.1 eV, and an open circuit voltage approaching 600 mV. Our results show a way for scalable fabrication of all thin-film, flexible tandem solar cells, by means of industrially relevant processing steps in a low cost and sustainable fashion.

The global Coronavirus disease 2019 (COVID-19) pandemic and associated restrictions on indoor gatherings posed considerable challenges to the delivery of courses that traditionally have relied on hands-on learning in their laboratory components. Here, our experiences converting a senior instrumental analysis course to remote online learning in the Fall 2020 semester are described. The main objective was the production of laboratory videos in lieu of in-person experiments that maintained a high level of authenticity. Videos of six instrumental analysis experiments were created. Experiments were performed and recorded using a headband or tripod mounted "GoPro Hero8" camera by a teaching assistant, providing students with a first-person perspective. The videos were edited in "Camtasia" software and posted on the course's "Desire2Learn" (D2L) Web site for students to view on-demand. This allowed lectures to be coordinated with the experiment schedule, which permitted the discussion of theory(in the lecture) and experiments (in the online laboratory) to be tightly integrated. Student performance (assessed through summative oral exams) and student feedback from anonymous electronic surveys were generally positive, though course completion rates dropped. The laboratory videos were utilized when the laboratory returned to in-person delivery in the Fall 2021 and 2022 semesters. The availability of first-person videos was found to enrich the students' experience, improve preparation, reduce anxiety, and foster a more inclusive environment by allowing for the scheduling of online makeup laboratories (in case of missed lab experiments), hence representing a valuable tool for student success.

Harsh environments, such as those with breaking waves and turbulent flows, present extreme challenges to organismal survival. Many animals exploiting these habitats possess adaptations to maintain position under dynamic flow conditions, such as reversible or permanent attachment systems. However, some station-holding fishes (e.g. sculpins) instead rely on morphological and behavioural modifications of their pectoral fins to increase friction with the substrate and combat drag. Despite epidermal microstructures on the fins of other benthic fishes, little exploration of pectoral fin surfaces at the microscopic scale has been undertaken in sculpins. Using scanning electron microscopy, we discovered microscopic, fibrillar projections contained within single cells on the ventral surfaces of the paired fin rays of two intertidal and two subtidal species of marine sculpins. In contrast to subtidal species, the intertidal species possessed epidermal cells with discrete channels separating groups of fibrillar projections. These features bear a striking resemblance to epidermal microstructures described in other fishes but have distinct morphological differences. We suggest the hypothesis that these previously overlooked features contribute to sculpin station-holding performance via enhanced mechanical interactions with the substrate, suggesting new taxa within which to explore potential mechanisms of underwater friction enhancement and adhesion.

Aim: Percutaneous transluminal angioplasty (PTA) for peripheral artery disease (PAD) commonly leads to dissections which are associated with higher target lesion revascularization (TLR) rates. Clinical and economic consequences of dissection management in the femoropopliteal artery following PTA, and specifically the potential economic benefit of focal dissection repair using the novel Tack Endovascular System, remain unknown. Methods: A decision-analytic model was used to estimate 24-month clinical events, costs and quality-adjusted life year (QALY) gain for a Tack-supported versus status-quo PTA strategy. Patient and lesion characteristics and TLR rates were derived from the PTA cohort of the TOBA II clinical trial, an observational cohort, and literature. Cost–effectiveness was determined from a US payer and provider perspective separately for the non-severe (grade A or B), severe (grade C and higher) and the entire dissection cohort. Results: TLR rates were lower for the Tack-supported strategy compared with PTA (7.7 vs 27.4% in the non-severe, 13.9 vs 25.8% in the severe and 12.0 vs 26.3% in the entire dissection cohort). Cost and QALY differences were +$297/ + 0.0110 in the non-severe dissection cohort and - $1602/ + 0.0067 in the severe dissection cohort, resulting in an incremental cost–effectiveness ratio (ICER) of $25,622 in the non-severe cohort and dominance in the severe cohort and the entire cohort. Conclusion: Compared with a ‘status-quo’ approach, proactive focal stenting may lead to fewer reinterventions and improved quality of life. There appears to be a graded economic benefit of focal dissection treatment, being cost-effective in non-severe dissections and even cost saving in severe dissections.

Abstract Background Combination anti‐obesity medications (AOMs) to treat postoperative bariatric surgery weight regain have limited data on their use in the clinical setting. Understanding the optimal treatment protocol in this cohort will maximize weight loss outcomes. Methods A retrospective review of bariatric surgery patients (N = 44) presenting with weight regain at a single academic multidisciplinary obesity center who were prescribed AOM(s) plus intensive lifestyle modification for 12 months. Results Age: 28–76 years old, 93% female, mean weight 110.2 ± 20.3 kg, BMI 39.7 ± 7.4 kg/m2, presenting 5.2 ± 1.6 years post‐bariatric surgery [27 (61.4%), 14 (31.8%), and 3 (6.8%) laparoscopic Roux‐en‐Y gastric bypass (RYGB), laparoscopic vertical sleeve gastrectomy (VSG), and open RYGB, respectively], with 15.1 ± 11.1 kg mean weight gain from nadir. Mean weight loss after medical intervention at 3‐, 6‐, and 12‐month time points was 4.4 ± 4.6 kg, 7.3 ± 7.0 kg, and 10.7 ± 9.2 kg, respectively. At 12 months, individuals prescribed 3 or more AOMs lost more weight than those prescribed one (−14.5 ± 9.0 kg vs. −4.9 ± 5.7 kg, p

Objective: We estimated the acute effects of acute beer consumption on non-linear HR Variability (HRV) behavior after submaximal aerobic exercise. Equipment and methods: This is a transversal, crossover, randomized and controlled trial. Fifteen healthy female and 17 healthy male adults were included in the final sample. Subjects performed two protocols on two randomized days: Water (300 mL) and Beer (300ml). The subjects underwent 15 minutes seated at rest, followed by aerobic exercise on a treadmill (five minutes at 50-55% of maximum HR and 25 minutes 60-65% of maximum HR) and then remained seated for 60 minutes during recovery from the exercise. Water or beer was consumed between four and ten minutes after exercise cessation. Results: The symbolic analysis (0V% and 2LV%), the fractal analysis by Detrended Fluctuation Analysis and the Sample Entropy demonstrated a late recovery in males in the beer protocol. In the women's group, the results were contradictory among the HR fragmentation analysis indexes. Beer consumption by males after a submaximal aerobic test was able to delay recovery of non-linear HRV behavior.

Abstract Ultraviolet-C (UVC) photodetector has appealed to a numerous number of research owing to its manifold applications in wireless communication, flame monitoring, and medicine. However, in addition to superior performance and high stability of recent studies, scalability and production cost are important factors for commercialization and practical implementation. In this study, a halide perovskite-based UVC photodetector was fabricated using spin-coating process and low-temperature annealing. Corning® Willow® Glass was selected as the substrate for the bottom-illuminated device due to its flexibility and exceptional optical transmission (approximately 60%) in the deep-UV region. The device had a vertical structure with a large active area (1 cm2) owing to the judicious utilization of electrodes. Under bent state with a curvature radius of 25 mm, the as-fabricated device exhibited high response and repeatability with an on/off ratio of 9.57 × 103, a fast response speed of 45/46 ms (rise/fall times) at zero bias under the illumination of a 254-nm UV lamp. The results are based on a flexible and lightweight photodetector without the utilization of notable metal electrodes.

Abstract Leptin exerts its effects on energy balance by inhibiting food intake and increasing energy expenditure via leptin receptors in the hypothalamus. While LepR neurons in the arcuate nucleus of the hypothalamus, the primary target of leptin, have been extensively studied, LepR neurons in other hypothalamic nuclei remain understudied. LepR neurons in the lateral hypothalamus contribute to leptin's effects on food intake and reward, but due to the low abundance of this population it has been difficult to study their molecular profile and responses to energy deficit. We here explore the transcriptome of LepR neurons in the LH and their response to energy deficit. Male LepR-Cre mice were injected in the LH with an AAV carrying Cre-dependent L10:GFP. Few weeks later the hypothalami from fed and food-restricted (24-h) mice were dissected and the TRAP protocol was performed, for the isolation of translating mRNAs from LepR cells in the LH, followed by RNA sequencing. After mapping and normalization, differential expression analysis was performed with DESeq2. We confirm that the isolated mRNA is enriched in LepR transcripts and other known neuropeptide markers of LepRLH neurons, of which we investigate the localization patterns in the LH. We identified novel markers of LepRLH neurons with association to energy balance and metabolic disease, such as Acvr1c, Npy1r, Itgb1, and genes that are differentially regulated by food deprivation, such as Fam46a and Rrad. Our dataset provides a reliable and extensive resource of the molecular makeup of LH LepR neurons and their response to food deprivation.

Resumo Fundamento Tem-se sugerido que o consumo de bebidas energéticas (BEs) possa afetar a atividade cardiovascular. Objetivos Investigar os efeitos agudos da ingestão de BE sobre a variabilidade da frequência cardíaca (VFC) recuperação cardiovascular após exercício aeróbico moderado em homens de diferentes capacidades cardiorrespiratórias. Métodos Este é um estudo randomizado, duplo cego, crossover, controlado por placebo. Vinte e oito jovens adultos foram divididos em dois grupos de acordo com o pico de consumo de oxigênio (pico de VO2): (1) pico de VO2 alto (AO) – pico de VO2 > 52,15 mL/Kg/min, e (2) pico de VO2 baixo (BO) - pico de VO2

Abstract The roughness and wettability of surfaces exploited by free-ranging geckos can be highly variable and attachment to these substrates is context dependent (e.g., presence or absence of surface water). Although previous studies focus on the effect of these variables on attachment independently, geckos encounter a variety of conditions in their natural environment simultaneously. Here, we measured maximum shear load of geckos in air and when their toes were submerged underwater on substrates that varied in both surface roughness and wettability. Gecko attachment was greater in water than in air on smooth and rough hydrophobic substrates, and attachment to rough hydrophilic substrates did not differ when tested in air or water. Attachment varied considerably with surface roughness and characterization revealed that routine measurements of root mean square height can misrepresent the complexity of roughness, especially when measured with single instruments. We used surface roughness power spectra to characterize substrate surface roughness and examined the relationship between gecko attachment performance across the power spectra. This comparison suggests that roughness wavelengths less than 70 nm predominantly dictate gecko attachment. This study highlights the complexity of attachment in natural conditions and the need for comprehensive surface characterization when studying biological adhesive system performance.

BackgroundEffective dissemination of research to health and social care practitioners enhances clinical practice and evidence-based care. Social media use has potential to facilitate dissemination to busy practitioners. ObjectiveThis is a protocol for a systematic review that will quantitatively synthesize evidence of the effectiveness of social media, compared with no social media, for dissemination of research evidence to health and social care practitioners. Social media platforms, formats, and sharing mechanisms used for effective dissemination of research evidence will also be identified and compared. MethodsElectronic database searches (MEDLINE, PsycINFO, CINAHL, ERIC, LISTA, and OpenGrey) will be conducted from January 1, 2010, to January 10, 2023, for studies published in English. Randomized, nonrandomized, pre-post study designs or case studies evaluating the effect of social media on dissemination of research evidence to postregistration health and social care practitioners will be included. Studies that do not involve social media or dissemination or those that evaluate dissemination of nonresearch information (eg, multisource educational materials) to students or members of the public only, or without quantitative data on outcomes of interest, will be excluded. Screening will be carried out by 2 independent reviewers. Data extraction and quality assessment, using either the Cochrane tool for assessing risk of bias or the Newcastle-Ottawa Scale, will be completed by 2 independent reviewers. Outcomes of interest will be reported in 4 domains (reach, engagement, dissemination, and impact). Data synthesis will include quantitative comparisons using narrative text, tables, and figures. A meta-analysis of standardized pooled effects will be undertaken, and subgroup analyses will be applied, if appropriate. ResultsSearches and screening will be completed by the end of May 2023. Data extraction and analyses will be completed by the end of July 2023, after which findings will be synthesized and reported by the end of October 2023. ConclusionsThis systematic review will summarize the evidence for the effectiveness of social media for the dissemination of research evidence to health and social care practitioners. The limitations of the evidence may include multiple outcomes or methodological heterogeneity that limit meta-analyses, potential risk of bias in included studies, and potential publication bias. The limitations of the study design may include potential insensitivity of the electronic database search strategy. The findings from this review will inform the dissemination practice of health and care research. Trial RegistrationPROSPERO CRD42022378793; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=378793 International Registered Report Identifier (IRRID)DERR1-10.2196/45684

Introduction and objectives: Studies assessing the effects of caffeine (CAF) on the cardiovascular system have demonstrated that CAF can delay cardiac recovery following exercise. This study intended to assess the impact of CAF intake before physical exercise on heart rate variability (HRV) and cardiovascular parameters. Methods: This is a prospective, crossover, controlled clinical trial conducted at the University of Pernambuco, Petrolina, PE, Brazil. The experimental protocol was split into three stages with a minimum of 48 hours between them. Exercises intensity was standardized based on the one repetition maximum test (1RM), obtaining the load of each volunteer for the intensity of 75% of 1RM. In the second and third phases, the control protocols were applied and 300 mg caffeine was given 45 minutes before training. HRV indices were determined at the subsequent times: 0 to 5 minutes of rest (before) and during 30 minutes of recovery (Rec) (after exercise), divided into six intervals, each of 5 minutes. Results: The final sample involved 30 volunteers. CAF delayed HRV recovery after resistance exercise. In general, CAF impaired recovery of HRV after resistance exercise. Significant changes were observed in the RMSSD, SDNN, TINN, SD1, low frequency and high frequency indices between the control and CAF group. Conclusion: CAF protocol delayed parasympathetic regulation of heart rhythm following exercise, slowing recovery of HR, blood pressure and HRV indices after exercise. Resumo: Introdução e objetivos: Estudos avaliando os efeitos da cafeína (CAF) sobre o sistema cardiovascular mostraram que a CAF pode retardar a recuperação dos batimentos cardíacos ao estado de repouso após o exercício. Este estudo teve como objetivo avaliar o impacto da ingestão de cafeína (CAF) antes do exercício físico de força sobre variabilidade da frequência cardíaca (VFC) na recuperação. Metodologia: Trata-se de um ensaio clínico prospetivo, controlado por cruzamento, realizado na Universidade de Pernambuco, em Petrolina, PE. Está registrado no ClinicalTrials.gov (Number NCT03899675). O procedimento experimental foi dividido em três etapas com um mínimo de 48 horas entre elas. A intensidade do exercício foi padronizada com base no teste de 1 repetição máxima (1RM), obtendo-se a carga de cada voluntário para a intensidade de 75% de 1RM. Na segunda e terceira fase da pesquisa, os protocolos de controle e cafeína (300 mg) foram aplicados. A ingestão de cafeína aconteceu 45 minutos antes do treinamento. Os índices de VFC foram determinados nos seguintes tempos: 0 a 5 minutos de repouso (antes) e durante 30 minutos de recuperação (Rec) (após o exercício), divididos em seis intervalos de 5 minutos cada. Resultados: A amostra final foi composta por 30 voluntários. No geral, a cafeína prejudicou a recuperação da VFC no período de recuperação após o exercício resistido. Diferenças significativas foram observadas nos índices RMSSD, SDNN, TINN, SD1, LF e HF entre o grupo controle e o grupo CAF. Conclusão: O protocolo CAF foi capaz de intensificar reduções na atividade parassimpática após o exercício, causando atraso na recuperação da FC, pressão arterial e índices de VFC após o exercício.

Abstract The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0–3.0 × 107 genomic copies per µl of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.

Mucorales infections are increasing in frequency and are a One Health pathogen of concern. In humans and domestic animals, risk factors include being immunocompromised, elevated circulating serum iron, contaminated open wounds, or metabolic diseases such as ketoacidosis or uncontrolled diabetes. Mucormycosis was first identified in 2012 in Pacific Northwest marine mammals, predominantly in harbor porpoises. We performed an assessment to determine the overall qualitative risk, or risk score, of mucormycosis in harbor porpoises. Risk factors for this disease are unknown in aquatic mammals. In a separate risk factor analysis, potential risk factors such as pollutants, trace metals (e.g., iron), and co-infection with other pathogens (e.g., viruses and Brucella spp.) were examined in mucormycosis cases and noncases using a matched case-control study design, to determine the presence and strength of association of these factors with mucormycosis. Disease severity (gross and histopathology) and exposure scores were multiplied together to obtain the overall risk scores of 9 -16 which corresponded to moderate and severe, respectively. In the risk factor analysis, the factors most strongly associated with a mucormycosis case, relative to a control, were elevated liver iron, decreased blubber thickness, and the decreased ratio of the sum of PCB congeners/sum of PBDE congeners. The results of this study suggest that mucormycosis may pose an inordinately high risk to harbor porpoises (and potentially sympatric species in the Salish Sea such as southern resident killer whales) based on the detected prevalence and the severity of lesions observed at necropsy. However, the risk may be greater on an individual basis compared to the overall population, and is likely related to other factors such as increased POP and heavy metal burdens.

Abstract The impact of birth weight (BW) on adult health has been studied, related to the autonomic nervous system, and implicated in cardiovascular risk. We investigated cardiorespiratory and heart rate (HR) autonomic recovery after moderate effort in healthy term-born adults with different BWs. We studied 28 healthy physically active women aged between 18 to 30 years split equally into two groups according to BW: G1 (n = 14), BW between 2500 g and 3200 g and G2 (n = 14), BW > 3200 g. The groups remained seated at rest for 15 min, followed by aerobic exercise on a treadmill (five minutes at 50–55% of maximum HR and 25 min 60–65% of maximum HR) and then remained seated for 60 min during recovery from the exercise. Cardiorespiratory parameters and HR variability (HRV) [RMSSD, HF (ms2)] were assessed before and during recovery from exercise. In G1, HR was increased from 0 to 20 min after exercise whilst in G2 HR was higher from 0 to 7 min following exercise. In G1, short-term HRV was increased from 5 to 10 min after exercise but in G2 it recovered prior to 5 min following effort. In conclusion, healthy term-born women with low normal BW present slower HR autonomic recovery after exercise.

Abstract Background Invasive species are of substantial concern because they may threaten ecosystem stability and biodiversity worldwide. Not surprisingly, studies examining the drivers of biological invasion have increased in number over the past few decades in an effort to curtail invasive species success by way of informing management decisions. The common house gecko, Hemidactylus frenatus, has successfully invaded the Pacific islands where it appears to thrive in and dominate non-natural habitats offering high food availability (i.e., well-lit human dwellings) compared to native geckos. Previous work demonstrated that H. frenatus can outperform the native gecko, Lepidodactylus lugubris, in terms of maximal sprint speed on relatively simple planar surfaces (e.g., building walls). Lepidodactylus lugubris and other native geckos, however, may have superior locomotor performance in three-dimensional, structurally complex habitats. Results Here we compared the locomotor behaviour and exertion capacity of the native gecko, Gehyra oceanica, and the invasive gecko, Hemidactylus frenatus, on the island of Mo’orea, French Polynesia, on fabricated structures simulating structurally complex substrates. We found that the native gecko exhibits improved locomotor performance compared to the invasive gecko on structurally complex substrates. We also completed encounter surveys to document free-ranging habitat use and behaviour of these two species. We discovered that H. frenatus were more common in natural habitats than previously observed and used similar substrates as G. oceanica, although G. oceanica appeared to use substrates with greater perch heights (i.e., trees). Conclusions Our findings revealed that locomotor performance in complex environments may contribute to the previously observed habitat segregation between native and invasive Pacific island geckos. Furthermore, our locomotor and habitat use data are consistent with the hypothesis that G. oceanica may be resistant to invasion of H. frenatus in natural environments. Our study calls for more detailed ecophysiological and ecomorphological studies of both native and invasive Pacific gecko species.

Abstract Previous studies have demonstrated that regular avocado consumption presents advantageous effects on cardiovascular system. However, little attention has been paid to the use of avocado as a dietary supplement, in particular, for individuals involved in physical exercise training. Therefore, this study aims to evaluate the effect of acute avocado pulp intake on cardiovascular and autonomic recovery subsequent to moderate exercise. Using a crossover, randomized, double-blind and placebo-controlled trial design, 16 healthy female adults underwent two protocols: Avocado pulp (600 mg in capsule) and placebo (600 mg starch in capsule). After the ingestion of Avocado pulp or placebo, the subjects were seated for 60 min at rest, followed by running on a treadmill at a submaximal level and then remained seated for 60 min during recovery from the exercise. Heart rate (HR), heart rate variability (HRV) [rMSSD, SD1, HF (ms2)] and skin conductance were evaluated before and during exercise, as well as during recovery. HR, systolic blood pressure, HRV and skin conductance recovered faster when subjects were given avocado pulp prior to exercise. In conclusion, avocado pulp improved cardiovascular and autonomic recovery after exercise, suggesting a reduced risk of cardiovascular events after exertion. The current results support the beneficial effects of ingestion of avocado prior to submaximal treadmill running.

Abstract Background This study utilized a chicken model of chronic physiological stress mediated by corticosterone (CORT) administration to ascertain how various host metrics are altered upon challenge with Clostridium perfringens. Necrotic enteritis (NE) is a disease of the small intestine of chickens incited by C. perfringens, which can result in elevated morbidity and mortality. The objective of the current study was to investigate how physiological stress alters host responses and predisposes birds to subclinical NE. Results Birds administered CORT exhibited higher densities of C. perfringens in their intestine, and this corresponded to altered production of intestinal mucus. Characterization of mucus showed that C. perfringens treatment altered the relative abundance of five glycans. Birds inoculated with C. perfringens did not exhibit evidence of acute morbidity. However, histopathologic changes were observed in the small intestine of infected birds. Birds administered CORT showed altered gene expression of tight junction proteins (i.e. CLDN3 and CLDN5) and toll-like receptors (i.e. TLR2 and TLR15) in the small intestine. Moreover, birds administered CORT exhibited increased expression of IL2 and G-CSF in the spleen, and IL1β, IL2, IL18, IFNγ, and IL6 in the thymus. Body weight gain was impaired only in birds that were administered CORT and challenged with C. perfringens. Conclusion CORT administration modulated a number of host functions, which corresponded to increased densities of C. perfringens in the small intestine and weight gain impairment in chickens. Importantly, results implicate physiological stress as an important predisposing factor to NE, which emphasizes the importance of managing stress to optimize chicken health.

BackgroundThere are still no studies of the cardiovascular safety of the isolated use of Citrus aurantium in aerobic submaximal exercise.ObjectiveTo evaluate the effect of C. aurantium supplementation on the recovery of cardiorespiratory and autonomic parameters following a session of submaximal aerobic exercise.MethodsTwelve healthy male adults achieved a crossover, randomized, double-blind, and placebo-controlled trial. C. aurantium (600 mg, p-synephrine at 30% amount [180 mg]) or placebo (600 mg of starch) were ingested 90 min before evaluation in randomized days. We evaluated systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), heart rate (HR) and, HR variability indexes at Rest and during 60 min of recovery from exercise.ResultsCitrus aurantium ingestion accelerated the reduction in SBP after exercise, anticipated the return of vagal modulation of the heart after exercise via the HF (ms2), pNN50 (%), and 2 UV% indices. Moreover, rushed the output of sympathetic modulation after exercise via the 0V% index. No unfavorable cardiovascular effects were achieved for HR, DBP, PP, and MAP parameters.ConclusionsCitrus aurantium was shown to be safe for the cardiovascular and autonomic systems alongside submaximal aerobic exercise in healthy males.

BackgroundAlthough there are a considerable number of clinical studies on nitrate (NO3) rich beetroot juice (BRJ) and hypertension, it is difficult to indicate the real effects of NO3 from BRJ on the BP of hypertensive patients because there are still no estimates of the effects of NO3 derived from BRJ on the BP of hypertension patients.ObjectiveTo clarify these effects, we developed a systematic literature review with a meta-analysis of randomized clinical trials (RCTs).DesignThe searches were accomplished through EMBASE, Cochrane Library, MEDLINE, CINAHL, Web of Science, and LILACS databases. The study included single or double-blinded RCTs and participants older than 18 years with hypertension [systolic BP (SBP) > 130 mmHg and diastolic BP (DBP) > 80 mmHg]. NO3 BRJ was required to be consumed in a format that possibly blinded participants/researchers. These studies should also report the SBP and DBP values (mmHg) measured before and after the treatment. Risk of Bias tools and GRADE were enforced.ResultsSeven studies were included (218 participants). BRJ intervention time ranged from 3 to 60 days with daily dosages of 70–250 mL of BRJ. After the intervention with NO3 from BRJ, SBP underwent significant changes (p < 0.001) of −4.95 (95% CI: −8.88; −1.01) (GRADE: ⊕⊕⊕○ Moderate), but not for DBP (p = 0.06) −0.90 mmHg (95% CI: −3.16; 1.36) (GRADE: ⊕⊕⊕○ Moderate), compared to the control group.ConclusionsThe NO3 derived from BRJ reduces SBP, but not DBP in patients with arterial hypertension.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=269339.

Animal cell migration is predominantly driven by the coordinated, yet stochastic, polymerization of thousands of nanometer-scale actin filaments across micron-scale cell leading edges. It remains unclear how such inherently noisy processes generate robust cellular behavior. We employed high-speed imaging of migrating neutrophil-like HL-60 cells to explore the fine-scale shape fluctuations that emerge and relax throughout the process of leading edge maintenance. We then developed a minimal stochastic model of the leading edge that reproduces this stable relaxation behavior. Remarkably, we find lamellipodial stability naturally emerges from the interplay between branched actin network growth and leading edge shape – with no additional feedback required – based on a synergy between membrane-proximal branching and lateral spreading of filaments. These results thus demonstrate a novel biological noise-suppression mechanism based entirely on system geometry. Furthermore, our model suggests that the Arp2/3-mediated ~70–80° branching angle optimally smooths lamellipodial shape, addressing its long-mysterious conservation from protists to mammals.

Introduction: Due to functional and autonomic difficulties faced by individuals with Duchenne Muscular Dystrophy (DMD), the use of assistive technology is critical to provide or facilitate functional abilities. The key objective was to investigate acute cardiac autonomic responses, by application of Heart Rate Variability (HRV), during computer tasks in subjects with DMD via techniques based on non-linear dynamics.Method: HRV was attained via a Polar RS800CX. Then, was evaluated by Chaotic Global Techniques (CGT). Forty-five male subjects were included in the DMD group and age-matched with 45 in the healthy Typical Development (TD) control group. They were assessed for 20 min at rest sitting, and then 5 min whilst performing the maze task on a computer.Results: Both TD and DMD subjects exhibited a significantly reduced HRV measured by chaotic global combinations when undertaking the computer maze paradigm tests. DMD subjects presented decreased HRV during rest and computer task than TD subjects.Conclusion: While there is an impaired HRV in subjects with DMD, there remains an adaptation of the ANS during the computer tasks. The identification of autonomic impairment is critical, considering that the computer tasks in the DMD community may elevate their level of social inclusion, participation and independence.

OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P

10‐nitro‐9(E)‐octadec‐9‐enoic acid (CXA‐10), a novel nitro fatty acid compound, demonstrates potential as a therapeutic agent in multiple disease indications in which oxidative stress, inflammation, fibrosis, and/or direct tissue toxicity play significant roles. Phase I studies were conducted in healthy and obese subjects to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of oral CXA‐10 after single and multiple doses in the fed and fasted states that would confirm the mechanisms of action of CXA‐10. After single and multiple ascending doses, CXA‐10 demonstrated dose‐proportional increases in plasma exposure. CXA‐10 decreased levels of biomarkers associated with altered inflammation and metabolic stress observed from nonclinical studies. In CXA‐10‐202, a consistent decrease from baseline was observed with CXA‐10 150 mg dose, but not 25 or 450 mg doses, for biomarkers of altered inflammation and metabolic dysfunction, including leptin, triglycerides, cholesterol, MCP‐1, and IL‐6. In CXA‐10‐203, after coadministration with CXA‐10, geometric mean peak plasma concentration (Cmax) and area under the plasma concentration‐time curve from time point 0 to the end of the dosing interval (AUC0−t) decreased 20% and 25% for pravastatin, increased 10% and 25% for simvastatin, and decreased 20% and 5% for ezetimibe. These findings are consistent with the pharmacological effects of CXA‐10. Adverse events (AEs) were dose‐related, and the most frequently reported AEs (>10% of subjects) were diarrhea, abdominal pain, and nausea. CXA‐10 was safe and well‐tolerated with no clinically significant abnormalities reported on physical examination, vital signs, clinical laboratory evaluations, or electrocardiographic evaluation. Phase II studies are underway in patients with focal segmental glomerulosclerosis and pulmonary arterial hypertension to investigate the efficacy and tolerability of CXA‐10 75–300 mg once daily.

Regulation of the plant immune system is important for controlling the specificity and amplitude of responses to pathogens and in preventing growth-inhibiting autoimmunity that leads to reductions in plant fitness. In previous work, we reported that SRFR1, a negative regulator of effector-triggered immunity, interacts with SNC1 and EDS1. When SRFR1 is non-functional in the Arabidopsis accession Col-0, SNC1 levels increase, causing a cascade of events that lead to autoimmunity phenotypes. Previous work showed that some members of the transcriptional co-repressor family TOPLESS interact with SNC1 to repress negative regulators of immunity. Therefore, to explore potential connections between SRFR1 and TOPLESS family members, we took a genetic approach that examined the effect of each TOPLESS member in the srfr1 mutant background. The data indicated that an additive genetic interaction exists between SRFR1 and two members of the TOPLESS family, TPR2 and TPR3, as demonstrated by increased stunting and elevated PR2 expression in srfr1 tpr2 and srfr1 tpr2 tpr3 mutants. Furthermore, the tpr2 mutation intensifies autoimmunity in the auto-active snc1-1 mutant, indicating a novel role of these TOPLESS family members in negatively regulating SNC1-dependent phenotypes. This negative regulation can also be reversed by overexpressing TPR2 in the srfr1 tpr2 background. Similar to TPR1 that positively regulates snc1-1 phenotypes by interacting with SNC1, we show here that TPR2 directly binds the N-terminal domain of SNC1. In addition, TPR2 interacts with TPR1 in vivo, suggesting that the opposite functions of TPR2 and TPR1 are based on titration of SNC1-TPR1 complexes by TPR2 or altered functions of a SNC1-TPR1-TPR2 complex. Thus, this work uncovers diverse functions of individual members of the TOPLESS family in Arabidopsis and provides evidence for the additive effect of transcriptional and post-transcriptional regulation of SNC1.

Research on gecko-based adhesion has become a truly interdisciplinary endeavour, encompassing many disciplines within the natural and physical sciences. Gecko adhesion occurs by the induction of van der Waals intermolecular (and possibly other) forces between substrata and integumentary filaments (setae) terminating in at least one spatulate tip. Gecko setae have increasingly been idealized as structures with uniform dimensions and a particular branching pattern. Approaches to developing synthetic simulacra have largely adopted such an idealized form as a foundational template. Observations of entire setal fields of geckos and anoles have, however, revealed extensive, predictable variation in setal form. Some filaments of these fields do not fulfil the morphological criteria that characterize setae and, problematically, recent authors have applied the term ‘seta’ to structurally simpler and likely non-adhesively competent fibrils. Herein we briefly review the history of the definition of squamate setae and propose a standardized classificatory scheme for epidermal outgrowths based on a combination of whole animal performance and morphology. Our review is by no means comprehensive of the literature regarding the form, function, and development of the adhesive setae of squamates and we do not address significant advances that have been made in many areas (e.g. cell biology of setae) that are largely tangential to their classification and identification. We contend that those who aspire to simulate the form and function of squamate setae will benefit from a fuller appreciation of the diversity of these structures, thereby assisting in the identification of features most relevant to their objectives.

Recent years have witnessed a multitude of studies focusing on gekkotan adhesion. Intense interest in this phenomenon was triggered by the discovery of the manner and magnitude of the forces generated by the hair-like filaments (setae) on the toe pads and inspired the development of the next generation of smart, reversible synthetic adhesives. Most studies pursuing these goals have concentrated on the generalized form and properties of gekkotan setae outlined in those key early studies, resulting in the fabrication of synthetic filaments of uniform dimensions. Although there are over 1,800 species of extant geckos, and hundreds of species of anoles (a separate lizard lineage that has convergently evolved adhesive toe pads), most investigations have used relatively few species as the source of basic information, the Tokay gecko (Gekko gecko) being the most prominent among these. Such exemplar taxa generally exhibit structurally intricate setae and morphologically complex configurations of the adhesive apparatus. Setal structure taken to be characteristic of these taxa is generally reported by singular statements of maximal length, diameter, density and branching pattern. Contemporaneous work focusing on the configuration of setae at locations across the toe pads and upon the evolutionary origin of adhesively competent digits in anoles and specific lineages of geckos, however, has revealed extensive variation of setal structure within individuals, information about how setae may have arisen from non-adhesive filamentous precursors, and how newly adhesively competent digits have been integrated into pre-existing patterns of locomotor mechanics and kinematics. Such observations provide insights into what is minimally necessary for adhesively competent digits to function and reveal the simplest configuration of components that make this possible. We contend that information gleaned from such studies will assist those seeking to employ the principles of fibrillar-based adhesion, as exemplified by lizards, for bio-inspired applications.

Summary: Disrupted chromatin regulatory processes contribute to the development of cancer, in particular pancreatic ductal adenocarcinoma. The assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) is typically used to study chromatin organization. Here, we present a revised ATAC-seq protocol to study chromatin accessibility in adherent patient-derived cell lines. We provide details on how to calculate the library molarity using Agilent’s Bioanalyzer and an analysis pipeline for peak calling and transcription factor mapping.For complete details on the use and execution of this protocol, please refer to Brunton et al. (2020).

Primary fungal diseases in marine mammals are rare. Mucormycosis, a disease caused by fungi of the order Mucorales, has been documented in few cetaceans and pinnipeds. In 2012, the first case of mucormycosis in the Pacific Northwest was documented in a dead stranded harbor porpoise (Phocoena phocoena) in Washington state. Since then, mucormycosis has been detected in a total of 21 marine mammals; fifteen harbor porpoises, five harbor seals (Phoca vitulina), and one southern resident killer whale (Orcinus orca). Infected animals were predominately found in the inland waters of Washington and British Columbia, and one harbor seal was recovered in northern Oregon. Fungal hyphae were detected histologically in a variety of tissues, including brain, lung, spleen, pancreas, kidneys, muscle, lymph nodes, and skin. Three fungal species were identified from seven cases by PCR screening or fungal culture; Rhizomucor pusillus (four cases), Lichtheimia corymbifera (two cases), and Cunninghamella bertholletiae. Underlying conditions such as emaciation, current or recent pregnancy, multisystemic parasitism, protozoal infection, and herpesvirus were found in several affected animals. Reasons for the appearance and subsequent increase of these fungal infections in marine mammals are unknown. The emergence of this disease as a source of marine mammal mortality in the Pacific Northwest is of particular concern for endangered southern resident killer whales that spend time in this region. Current population-level stressors such as insufficient prey, high levels of contaminants, and noise pollution, could predispose them to these fatal infections.

Processing of sound signals is an important factor for conscious human communication and such sound signals may be assessed through cortical auditory evoked potentials. Heart rate variability provides information about heart rate autonomic regulation. The association between resting heart rate variability and cortical auditory evoked potentials was investigated. Resting heart rate variability in the time and frequency domain and the cortical auditory evoked potential components were investigated. Subjects remained at rest for 10 minutes for recording of heart rate variability. Cortical auditory evoked potential examinations were then undertaken through frequency and duration protocols in both ears. Linear regression indicated that the amplitude of the N2 wave of the cortical auditory evoked potentials in the left ear (not right ear) was significantly influenced by the standard deviation of normal-to-normal heart beats (17.7%) and percentage of adjacent heart beat intervals with a difference of duration greater than 50 milliseconds (25.3%) for the time domain heart rate variability indices in the frequency protocol. In the duration protocol and in the left ear the latency of the P2 wave was significantly influenced by low (20.8%) and high frequency bands in normalized units (21%) and low frequency/high frequency ratio (22.4%) indices of heart rate variability spectral analysis. The latency of the N2 wave was significantly influenced bylow frequency (25.8%), high frequency (25.9%) and low frequency/high frequency ratio (28.8%). In conclusion, it is proposed that resting heart rhythm is associated with thalamo-cortical, cortical-cortical and auditory cortex pathways involved with auditory processing in the right hemisphere.

Peroxy and peroxyacyl nitrates (PNs and PANs) are important trace gas constituents of the troposphere which are challenging to quantify by differential thermal dissociation with NO2 detection in polluted (i.e., high-NOx) environments. In this paper, a thermal dissociation peroxy radical chemical amplification cavity ring-down spectrometer (TD-PERCA-CRDS) for sensitive and selective quantification of total peroxynitrates (ΣPN  =  ΣRO2NO2) and of total peroxyacyl nitrates (ΣPAN  =  ΣRC(O)O2NO2) is described. The instrument features multiple detection channels to monitor the NO2 background and the ROx ( =  HO2 + RO2 + ΣRO2) radicals generated by TD of ΣPN and/or ΣPAN. Chemical amplification is achieved through the addition of 0.6 ppm NO and 1.6 % C2H6 to the inlet. The instrument's performance was evaluated using peroxynitric acid (PNA) and peroxyacetic or peroxypropionic nitric anhydride (PAN or PPN) as representative examples of ΣPN and ΣPAN, respectively, whose abundances were verified by iodide chemical ionization mass spectrometry (CIMS). The amplification factor or chain length increases with temperature up to 69 ± 5 and decreases with analyte concentration and relative humidity (RH). At inlet temperatures above 120 and 250 °C, respectively, PNA and ΣPAN fully dissociated, though their TD profiles partially overlap. Furthermore, interference from ozone (O3) was observed at temperatures above 150 °C, rationalized by its partial dissociation to O atoms which react with C2H6 to form C2H5 and OH radicals. Quantification of PNA and ΣPAN in laboratory-generated mixtures containing O3 was achieved by simultaneously monitoring the TD-PERCA responses in multiple parallel CRDS channels set to different temperatures in the 60 to 130 °C range. The (1 s, 2σ) limit of detection (LOD) of TD-PERCA-CRDS is 6.8 pptv for PNA and 2.6 pptv for ΣPAN and significantly lower than TD-CRDS without chemical amplification. The feasibility of TD-PERCA-CRDS for ambient air measurements is discussed.

Abstract Background Epidemiological studies have linked exposures to ambient fine particulate matter (PM2.5) and traffic with autonomic nervous system imbalance (ANS) and cardiac pathophysiology, especially in individuals with preexisting disease. It is unclear whether metabolic syndrome (MetS) increases susceptibility to the effects of PM2.5. We hypothesized that exposure to traffic-derived primary and secondary organic aerosols (P + SOA) at ambient levels would cause autonomic and cardiovascular dysfunction in rats exhibiting features of MetS. Male Sprague Dawley (SD) rats were fed a high-fructose diet (HFrD) to induce MetS, and exposed to P + SOA (20.4 ± 0.9 μg/m3) for 12 days with time-matched comparison to filtered-air (FA) exposed MetS rats; normal diet (ND) SD rats were separately exposed to FA or P + SOA (56.3 ± 1.2 μg/m3). Results In MetS rats, P + SOA exposure decreased HRV, QTc, PR, and expiratory time overall (mean effect across the entirety of exposure), increased breathing rate overall, decreased baroreflex sensitivity (BRS) on three exposure days, and increased spontaneous atrioventricular (AV) block Mobitz Type II arrhythmia on exposure day 4 relative to FA-exposed animals receiving the same diet. Among ND rats, P + SOA decreased HRV only on day 1 and did not significantly alter BRS despite overall hypertensive responses relative to FA. Correlations between HRV, ECG, BRS, and breathing parameters suggested a role for autonomic imbalance in the pathophysiologic effects of P + SOA among MetS rats. Autonomic cardiovascular responses to P + SOA at ambient PM2.5 levels were pronounced among MetS rats and indicated blunted vagal influence over cardiovascular physiology. Conclusions Results support epidemiologic findings that MetS increases susceptibility to the adverse cardiac effects of ambient-level PM2.5, potentially through ANS imbalance.

The genus Exophiala is composed of ubiquitous, pigmented, saprotrophic fungi and includes both terrestrial and waterborne species. Though Exophiala species are generally considered opportunistic pathogens, exophialosis can be an important cause of morbidity and mortality in aquatic and semi-aquatic species. Over a 6-year period, a captive 32-year-old male eastern hellbender (Cryptobranchus alleganiensis alleganiensis), was treated for recurring, slow growing, ventral midline cutaneous masses. Excisional biopsies were characterized histologically by granulomatous dermatitis with low numbers of intralesional, pigmented fungal conidia and hyphae. Bacterial and fungal cultures of the masses and skin were negative on two separate submissions. Polymerase chain reaction amplification of a short fragment of the fungal 28S large subunit (LSU) ribosomal RNA was positive with 100% nucleotide sequence identity to several species of Exophiala. Following recurrence after successive rounds of antifungal therapy, euthanasia was elected. At necropsy, similar dermal granulomatous inflammation and intralesional pigmented fungal elements as observed in excisional biopsies formed a thick band in the dermis and extended through the coelomic body wall. Visceral dissemination was noted in the lung and kidney. Postmortem DNA sequence analysis of a large portion of the fungal LSU as well as the internal transcribed spacer (ITS) from a portion of frozen affected dermis identified the fungus as a novel species, Exophiala sp. 1 (UTHSCSA R-5437).

In this paper, measurements of C9 – C16 biogenic volatile organic compounds (BVOCs) in the headspaces above near-shore marine vegetation samples of Fucus gardneri (rock weed), Ulva spp. (sea lettuce), Callophyllis spp. (red sea fans), Alaria marginata (winged kelp), and Nereocystis luetkeana (bull kelp) collected on the west coast of Vancouver Island, British Columbia, Canada, are presented. Numerous BVOCs were observed in the headspace samples, including n-alkanes (e.g., n-dodecane, n-tridecane, n-tetradecane and n-pentadecane) and oxygenated hydrocarbons (e.g., octanal, nonanal, geranyl acetone, and 6-methyl-hepten-2-one), though the majority of VOCs emitted was not identified. The emissions from Ulva spp., Callophyllis spp. and F. gardneri samples contained a similar assortment of n-alkanes and oxygenated BVOCs (e.g., n-aldehydes) as observed at Mace Head, Ireland, whereas the headspaces above N. luetkeana and A. marginata contained monoterpenes, foremost limonene, and toluene. Further studies are needed to constrain emissions of BVOCs from near-coastal vegetation as they have the potential to substantially impact coastal O3 budgets and the organic content of marine derived aerosol. Keywords: BVOC emissions, Kelp, Seaweed, Monoterpenes, Limonene, Hydrocarbons