Conectar
by John Efromson, Giuliano Ferrero, Aurélien Bègue, Thomas Jedidiah Jenks Doman, Clay Dugo, Andi Barker, Veton Saliu, Paul Reamey, Kanghyun Kim, Mark Harfouche, Jeffrey A. Yoder
Normal development of the immune system is essential for overall health and disease resistance. Bony fish, such as the zebrafish (Danio rerio), possess all the major immune cell lineages as mammals and can be employed to model human host response to immune challenge. Zebrafish neutrophils, for example, are present in the transparent larvae as early as 48 hours post fertilization and have been examined in numerous infection and immunotoxicology reports. One significant advantage of the zebrafish model is the ability to affordably generate high numbers of individual larvae that can be arrayed in multi-well plates for high throughput genetic and chemical exposure screens. However, traditional workflows for imaging individual larvae have been limited to low-throughput studies using traditional microscopes and manual analyses. Using a newly developed, parallelized microscope, the Multi-Camera Array Microscope (MCAM™), we have optimized a rapid, high-resolution algorithmic method to count fluorescently labeled cells in zebrafish larvae in vivo. Using transgenic zebrafish larvae, in which neutrophils express EGFP, we captured 18 gigapixels of images across a full 96-well plate, in 75 seconds, and processed the resulting datastream, counting individual fluorescent neutrophils in all individual larvae in 5 minutes. This automation is facilitated by a machine learning segmentation algorithm that defines the most in-focus view of each larva in each well after which pixel intensity thresholding and blob detection are employed to locate and count fluorescent cells. We validated this method by comparing algorithmic neutrophil counts to manual counts in larvae subjected to changes in neutrophil numbers, demonstrating the utility of this approach for high-throughput genetic and chemical screens where a change in neutrophil number is an endpoint metric. Using the MCAM™ we have been able to, within minutes, acquire both enough data to create an automated algorithm and execute a biological experiment with statistical significance. Finally, we present this open-source software package which allows the user to train and evaluate a custom machine learning segmentation model and use it to localize zebrafish and analyze cell counts within the segmented region of interest. This software can be modified as needed for studies involving other zebrafish cell lineages using different transgenic reporter lines and can also be adapted for studies using other amenable model species.by Ronald McDowell, Liam Heaney, Thomas Brown, Brendan Bunting, Hassan Burhan, Rekha Chaudhuri, Paddy Dennison, Shoaib Faruqi, Robin Gore, David J. Jackson, Andrew Menzies-Gow, Thomas Pantin, Mitesh Patel, Paul Pfeffer, Salman Siddiqui, John Busby, on behalf of the UK Severe Asthma Registry
BackgroundThe Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown.
MethodsData was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed.
ResultsA one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p Conclusion
The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.
by Magdalena Grzonkowska, Mariusz Baumgart, Michał Kułakowski, Michał Szpinda
Detailed numerical data about the development of primary ossification centers in human fetuses may influence both better evaluation and early detection of skeletal dysplasias, which are associated with delayed development and mineralization of ossification centers. To the best of our knowledge, this is the first report in the medical literature to morphometrically analyze the primary ossification center of the squamous part of temporal bone in human fetuses based on computed tomography imaging. The present study offers a precise quantitative foundation for ossification of the squamous part of temporal bone that may contribute to enhanced prenatal care and improved outcomes for fetuses with inherited cranial defects and skeletodysplasias. The examinations were carried out on 37 human fetuses of both sexes (16 males and 21 females) aged 18–30 weeks of gestation, which had been preserved in 10% neutral formalin solution. Using CT, digital image analysis software, 3D reconstruction and statistical methods, the size of the primary ossification center of the squamous part of temporal bone was evaluated. With neither sex nor laterality differences, the best-fit growth patterns for the primary ossification center of the squamous part of temporal bone was modelled by the linear function: y = −0.7270 + 0.7682 × age ± 1.256 for its vertical diameter, and the four-degree polynomial functions: y = 5.434 + 0.000019 × (age)4 ± 1.617 for its sagittal diameter, y = −4.086 + 0.00029 × (age)4 ± 2.230 for its projection surface area and y = −25.213 + 0.0004 × (age)4 ± 3.563 for its volume. The CT-based numerical data and growth patterns of the primary ossification center of the squamous part of temporal bone may serve as age-specific normative intervals of relevance for gynecologists, obstetricians, pediatricians and radiologists during screening ultrasound scans of fetuses. Our findings for the growing primary ossification center of the squamous part of temporal bone may be conducive in daily clinical practice, while ultrasonically monitoring normal fetal growth and screening for inherited cranial faults and skeletodysplasias.by Linda J. Paul, Aaron C. Ericsson, Frank M. Andrews, Zachary McAdams, Michael L. Keowen, Michael P. St Blanc, Heidi E. Banse
Equine glandular gastric disease (EGGD) is a common disease among athletic horses that can negatively impact health and performance. The pathophysiology of this EGGD remains poorly understood. Previous studies using controlled populations of horses identified differences in the gastric glandular mucosal microbiome associated with disease. The objective of this study was to compare the gastric microbiome in horses with EGGD and those without across multiple barns and differing management practices. We hypothesized that alterations in the microbiome of the gastric glandular mucosa are associated with EGGD. A secondary objective was to perform a risk factor analysis for EGGD using the diet and management data collected. Microbial populations of biopsies from normal pyloric mucosa of horses without EGGD (control biopsies), normal pyloric mucosa of horses with EGGD (normal biopsies) and areas of glandular mucosal disruption in horses with EGGD (lesion biopsies) were compared. Lesion biopsies had a different microbial community structure than control biopsies. Control biopsies had a higher read count for the phylum Actinomycetota compared to lesion biopsies. Control biopsies also had an enrichment of the genera Staphylococcus and Lawsonella and the species Streptococcus salivarius. Lesion biopsies had an enrichment of the genera Lactobacillus and Actinobacillus and the species Lactobacillus equigenerosi. These results demonstrate differences in the gastric glandular microbiome between sites of disrupted mucosa in horses with EGGD compared to pyloric mucosa of horses without EGGD. Risk factor analysis indicated that exercise duration per week was a risk factor for EGGD.by Kenneth S. Noguchi, Kevin Moncion, Elise Wiley, Ashley Morgan, Eric Huynh, Marla K. Beauchamp, Stuart M. Phillips, Lehana Thabane, Ada Tang
BackgroundStroke impacts nearly 14 million people annually. Muscle strength and physical function are often affected by stroke and important determinants of stroke recovery. Resistance exercise training (RT) has been shown to improve muscle strength, but RT prescriptions may be suboptimal for other aspects of stroke recovery. Parameters such as frequency, intensity, type, and duration may influence the effectiveness of RT interventions but have not been systematically evaluated.
Objectives1) To determine the effects of RT on stroke recovery, and 2) to examine the influence of RT parameters on intervention effects.
Eligibility criteriaRandomized controlled trials examining the effects of RT will be eligible for this systematic review if they: 1) included only adults with stroke or transient ischemic attack, 2) compared RT to no exercise or usual care, and 3) did not apply a co-intervention.
Study selectionEight databases (MEDLINE, EMBASE, EMCARE, AMED, PsychINFO, CINAHL, SPORTDiscus, and Web of Science) and 2 clinical trials registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) will be searched from inception. Two independent pairs of authors will compare titles, abstracts, and full-text reports against the eligibility criteria. Conflicts will be resolved by consensus or third author.
Main outcome measuresThe construct of interest is stroke recovery. An advisory group of clinicians, researchers, and partners with lived experience of stroke will be consulted to determine specific outcome measures of interest, and to rank their relative importance. We expect to include measures of physical function, strength, cognition, and quality of life. Random-effects meta-analyses will be used to pool results for each outcome across studies, and RT parameters (frequency, intensity, type, and duration) will be used as covariates in meta-regression analyses.
ConclusionThe results of this review will inform the optimal RT prescription parameters for promoting stroke recovery.
by Alexia Loste, Marc Clément, Sandrine Delbosc, Kevin Guedj, Jean Sénémaud, Anh-Thu Gaston, Marion Morvan, Guillaume Even, Grégory Gautier, Alexander Eggel, Michel Arock, Emanuele Procopio, Catherine Deschildre, Liliane Louedec, Jean-Baptiste Michel, Lydia Deschamps, Yves Castier, Raphaël Coscas, Jean-Marc Alsac, Pierre Launay, Giuseppina Caligiuri, Antonino Nicoletti, Marie Le Borgne
AimsIgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression.
Methods and resultsThrough histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression.
ConclusionsOur data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.
by Sari Aaltonen, Mia Urjansson, Anni Varjonen, Henri Vähä-Ypyä, Paula Iso-Markku, Sara Kaartinen, Tommi Vasankari, Urho M. Kujala, Karri Silventoinen, Jaakko Kaprio, Eero Vuoksimaa
BackgroundResearch on device-based physical activity in the oldest-old adults is scarce. We examined accelerometer-measured physical activity and sedentary behavior in nonagenarians. We also investigated how the accelerometer characteristics associate with nonagenarians’ self-reported physical activity, anthropometric, sociodemographic, health and cognitive characteristics.
MethodsNonagenarians from a population-based cohort study (N = 38, mean age 91.2) used accelerometers during the waking hours for seven days. They also participated in a health survey and cognitive telephone interview. The Wald test and Pearson and polyserial correlations were used to analyze the data.
ResultsThe participants’ average day consisted of 2931 steps, 11 minutes of moderate-to-vigorous physical activity and 13.6 hours of sedentary time. Physical activity bouts less than 3 minutes per day and sedentary time bouts of 20–60 minutes per day were the most common. No sex differences were found. Many accelerometer-measured and self-reported physical activity characteristics correlated positively (correlations ≥0.34, p-values Conclusions
Nonagenarians were mostly sedentary and low in physical activity, but individual variability existed. Accelerometer-measured and self-reported physical activity had a good consistency. Education, dizziness and fear of falling were consistently related to accelerometer-measured characteristics in nonagenarians.
by Víctor Manuel Enriquez Estrada, Neftali Eduardo Antonio-Villa, Omar Yaxhemen Bello-Chavolla, Carlos Fredy Cuevas-García, Pedro Luis Vargas Gutiérrez, Irma Sau-Yen Corlay Noriega, Luis Rey García-Cortés
BackgroundMobbing, particularly in medical residencies, can lead to psychological terror with lasting mental and physical health consequences. Its impact on Mexican residents, however, remains underexplored.
AimThis study aimed to investigate the prevalence and associated factors of psychological terror among medical residents at a medical center in Mexico City.
MethodsIn a cross-sectional study, medical residents from various specialties were assessed for mobbing domains, quality of life, and anxiety/depression using the Leymann Inventory of Psychological Terror (LIPT), 36-Item Short Form Health Survey, Beck Depression Inventory-II, and Beck Anxiety Inventory, respectively. Psychological terror was defined as a LIPT score ≥ p80. Linear and binomial logistic regression models were used to explore independent predictors of mobbing and psychological terror.
ResultsOf the 349 participants included (median age: 28; IQR: 27–30 years), 19.5% (95% CI: 15.5%-24.0%) were identified with psychological terror. Furthermore, 39% reported higher-degree trainees as mobbing perpetrators. Women in surgical residencies in their second or fifth year were found to experience higher levels of mobbing. Manifested bullying, workplace stigma, and inappropriate tasks were the most impacted mobbing domains. Anxiety, diminished mental health quality of life, and higher degree of medical specialization were independent predictors of mobbing. Meanwhile, increased anxiety, affiliation to surgical specialties, and being in the second or fifth year of training were identified as predictors of psychological terror.
ConclusionsMobbing and psychological terror are prevalent conditions among medical residents in Mexico. Identification of occupational conditions and adverse psychological stressors can help to improve quality of life and training of medical residents.
by Tasnim F. Imran, Ali A. Khan, Phinnara Has, Alexis Jacobson, Stephanie Bogin, Mahnoor Khalid, Asim Khan, Samuel Kim, Sebhat Erqou, Gaurav Choudhary, Karen Aspry, Wen-Chih Wu
BackgroundAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
ObjectiveThe purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
MethodsUsing Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
ResultsIn all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12–52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p Conclusion
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
by Ann S. Lauterbach, Tobias Tober, Florian Kunze, Marius R. Busemeyer
Many workers are experiencing the downsides of being exposed to an overload of information and communication technology (ICT), highlighting the need for resources to cope with the resulting technostress. This article offers a novel cross-level perspective on technostress by examining how the context of the welfare state influences the relationship between income and technostress. Showing that individuals with higher income experience less technostress, this study argues that the welfare state represents an additional coping resource, in particular in the form of unemployment benefits. Since unemployment benefits insure income earners in the case of job loss, the negative effect of income on technostress should increase with higher levels of unemployment generosity. In line with these expectations, empirical results based on original survey data collected in collaboration with the OECD show that the impact of income on technostress varies across welfare state contexts. Implications for public health and policymakers are being discussed.by Jibonayan Raychaudhuri, Ada Wossink
We examine the effect of the 2008 economic recession on consumers’ observed expenditures for eco-labelled grocery products. Traditional price theory predicts that consumers change their spending during an economic downturn and we would expect the sales share of eco-labelled products to fall since these are relatively more expensive than non-labelled products. We use supermarket loyalty card data from the UK and show that the recession had widely different effects on the expenditure share of different eco-labelled grocery products. We confirm, empirically, that expenditure shares on organic products declined over the time period under study but the expenditures share for fair-trade products increased over the same period. We evaluate alternative models of decision making to explain our results, viz., a salience model and a model of reputation signalling. We find that both of these models give a plausible explanation of our empirical results.by Izabel Alves das Chagas Valóta, Rafael Rodrigo da Silva Pimentel, Ana Paula Neroni Stina Saura, Rodrigo Marques da Silva, Ana Lucia Siqueira Costa Calache, Marcelo José dos Santos
The aim of this study was to analyze levels of fatigue and resilience of Brazilian graduate students during the COVID-19 pandemic and to determine whether there is an association between fatigue and resilience and sociodemographic and academic factors. Data were analyzed using descriptive and inferential statistics, and it was discovered that the variables associated with higher levels of resilience were age; having children; being retired; receiving income above five minimum wages; having had greater problems in other phases of the research schedule; coming from private universities; being from the north of Brazil; studying the area of Health; and having their research schedule unaffected during the pandemic. On the other hand, lack of resilience was associated with not having children; being less well-off financially; being younger; being a woman; studying in a public university; and having to postpone part of the research during the pandemic. The conclusion of the study indicated the need for graduate programs to design strategies to deal with fatigue and promote resilience in Master’s and PhD students.by Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Saurav Mallik, Zhongming Zhao
Chronic kidney disease (CKD) has become a major global health crisis, causing millions of yearly deaths. Predicting the possibility of a person being affected by the disease will allow timely diagnosis and precautionary measures leading to preventive strategies for health. Machine learning techniques have been popularly applied in various disease diagnoses and predictions. Ensemble learning approaches have become useful for predicting many complex diseases. In this paper, we utilise the boosting method, one of the popular ensemble learnings, to achieve a higher prediction accuracy for CKD. Five boosting algorithms are employed: XGBoost, CatBoost, LightGBM, AdaBoost, and gradient boosting. We experimented with the CKD data set from the UCI machine learning repository. Various preprocessing steps are employed to achieve better prediction performance, along with suitable hyperparameter tuning and feature selection. We assessed the degree of importance of each feature in the dataset leading to CKD. The performance of each model was evaluated with accuracy, precision, recall, F1-score, Area under the curve-receiving operator characteristic (AUC-ROC), and runtime. AdaBoost was found to have the overall best performance among the five algorithms, scoring the highest in almost all the performance measures. It attained 100% and 98.47% accuracy for training and testing sets. This model also exhibited better precision, recall, and AUC-ROC curve performance.by Ana Carolina Cavalcante Rodrigues, Caroline Vitória de Lima Moreira, Camila Carlos Prado, Luan Silvestro Bianchini Silva, Rafael Fernandes Costa, Adesina Paul Arikawe, Gustavo Rodrigues Pedrino, Elson Alves Costa, Osmar Nascimento Silva, Hamilton Barbosa Napolitano, Iranse Oliveira-Silva, James Oluwagbamigbe Fajemiroye
Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels [CORT] and behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter [CORT], FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated [CORT], but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence [CORT] as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.by Rafaella Rabelo Polato, Cristino Carneiro Oliveira, Yuri Augusto de Sousa Miranda, Leandro Ferracini Cabral, Carla Malaguti, Anderson José
IntroductionSeveral individuals with post-COVID-19 syndrome referred for pulmonary rehabilitation did not participate. This study aimed to explore individuals’ barriers to participating in posthospitalization COVID-19 rehabilitation.
Materials and methodsThis was a qualitative, multicenter study performed using semistructured interviews. This study included 20 individuals hospitalized for COVID-19 who refused to participate in a pulmonary rehabilitation program at a university hospital.
ResultsIndividuals reported difficulties accessing the rehabilitation center, mainly due to distance, transport costs and conditions, and lack of companions. Health problems (e.g., surgeries, pain, and mobility difficulties) and lack of time due to work, commuting, and household work were also reported. Another reported theme was not perceiving the need for rehabilitation due to feeling well. Minor themes included the need for more information about rehabilitation and a lack of interest, motivation, and medical encouragement.
ConclusionIndividuals hospitalized for COVID-19 faced several barriers to participating in a pulmonary rehabilitation program. These barriers included difficulties in accessing the rehabilitation center, health problems, lack of time, and the perception that rehabilitation was unnecessary. There is a need for actions to overcome these barriers to make the program available to a larger number of individuals.
by Joseph B. Kahan, Patrick Burroughs, Logan Petit, Christopher A. Schneble, Peter Joo, Jay Moran, Maxwell Modrak, William Mclaughlin, Adam Nasreddine, Jonathan N. Grauer, Michael J. Medvecky
ObjectivesThe purpose of this study was to compare the rates of secondary knee surgery for patients undergoing meniscus repair with or without concurrent anterior cruciate ligament reconstruction (ACLr).
MethodsUtilizing a large national database, patients with meniscal repair with or without concurrent arthroscopic ACLr were identified. The two cohorts were then queried for secondary surgical procedures of the knee within the following 2 years. Frequency, age distribution, rates of secondary surgery, and type of secondary procedures performed were compared.
ResultsIn total, 1,585 patients were identified: meniscus repair with ACLr was performed for 1,006 (63.5%) and isolated meniscal repair was performed for 579 (36.5%). Minimum of two year follow up was present for 487 (30.7% of the overall study population).Secondary surgery rates were not significantly different between meniscus repair with concurrent ACLr and isolated meniscus repairs with an overall mean follow up of 13 years (1.5–24 years) (10.6% vs. 13.6%, p = 0.126). For the 2 year follow up cohort, secondary surgery rates were not significantly different (19.3% vs. 25.6%, p = 0.1098). There were no differences in survivorship patterns between the two procedures, both in the larger cohort (p = 0.2016), and the cohort with minimum 2-year follow-up (p = 0.0586).
ConclusionThe current study assessed secondary surgery rates in patients undergoing meniscus repair with or without concurrent ACLr in a large patient database. Based on this data, no significant difference in rates of secondary knee surgery was identified.
by Andrea D. Tyler, Jane McAllister, Helen Stapleton, Penny Gauci, Kym Antonation, David Thirkettle-Watts, Cindi R. Corbett
From pathogen detection to genome or plasmid closure, the utility of the Oxford Nanopore Technologies (ONT) MinION for microbiological analysis has been well documented. The MinION’s small footprint, portability, and real-time analytic capability situates it well to address challenges in the field of unbiased pathogen detection, as a component of a security investigation. To this end, a multicenter evaluation of the effect of alternative analytical approaches on the outcome of MinION-based sequencing, using a set of well-characterized samples, was explored in a field-based scenario. Three expert scientific response groups evaluated known bacterial DNA extracts as part of an international first responder (Chemical, Biological, Radiological) training exercise. Samples were prepared independently for analysis using the Rapid and/or Rapid PCR sequencing kits as per the best practices of each of the participating groups. Analyses of sequence data were in turn conducted using varied approaches including ONTs What’s in my pot (WIMP) architecture and in-house computational pipelines. Microbial community composition and the ability of each approach to detect pathogens was compared. Each group demonstrated the ability to detect all species present in samples, although several organisms were detected at levels much lower than expected with some organisms even falling below 1% abundance. Several ‘contaminant’ near neighbor species were also detected, at low abundance. Regardless of the sequencing approach chosen, the observed composition of the bacterial communities diverged from the input composition in each of the analyses, although sequencing conducted using the rapid kit produced the least distortion when compared to PCR-based library preparation methods. One of the participating groups generated drastically lower sequencing output than the other groups, likely attributed to the limited computer hard drive capacity, and occasional disruption of the internet connection. These results provide further consideration for conducting unbiased pathogen identification within a field setting using MinION sequencing. However, the benefits of this approach in providing rapid results and unbiased detection must be considered along with the complexity of sample preparation and data analytics, when compared to more traditional methods. When utilized by trained scientific experts, with appropriate computational resources, the MinION sequencing device is a useful tool for field-based pathogen detection in mixed samples.by Irene Boateng, Beth Stuart, Taeko Becque, Bruce Barrett, Jennifer Bostock, Robin Bruyndonckx, Lucy Carr-Knox, Emily J. Ciccone, Samuel Coenen, Mark Ebell, David Gillespie, Gail Hayward, Katarina Hedin, Kerenza Hood, Tin Man Mandy Lau, Paul Little, Dan Merenstein, Edgar Mulogo, Jose Ordóñez-Mena, Peter Muir, Kirsty Samuel, Nader Shaikh, Sharon Tonner, Alike W. van der Velden, Theo Verheij, Kay Wang, Alastair D. Hay, Nick Francis
BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. ‘Antibiotic targeting’ ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.
AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.
MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.
Trial registrationPROSPERO Registration number: CRD42023376769.
by Alba Ferré, François Chauvigné, Cinta Zapater, Roderick Nigel Finn, Joan Cerdà
Aquaporin-mediated oocyte hydration is a developmentally regulated adaptive mechanism that co-occurs with meiosis resumption in marine teleosts. It provides the early embryos with vital water until osmoregulatory systems develop, and in the majority of marine teleosts causes their eggs to float. Recent studies have shown that the subdomains of two water channels (Aqp1ab1 and Aqp1ab2) encoded in a teleost-specific aquaporin-1 cluster (TSA1C) co-evolved with duplicated Ywhaz-like (14-3-3ζ-like) binding proteins to differentially control their membrane trafficking for maximal egg hydration. Here, we report that in species that encode the full TSA1C, in-frame intronic splice variants of Aqp1ab1 result in truncated proteins that cause dominant-negative inhibition of the canonical channel trafficking to the plasma membrane. The inhibition likely occurs through hetero-oligomerization and retention in the endoplasmic reticulum (ER) and ultimate degradation. Conversely, in species that only encode the Aqp1ab2 channel we found an in-frame intronic splice variant that results in an intact protein with an extended extracellular loop E, and an out-of frame intronic splice variant with exon readthrough that results in a truncated protein. Both isoforms cause dominant-negative enhancement of the degradation pathway. However, the extended and truncated Aqp1ab2-type variants can also partially escape from the ER to reach the oocyte plasma membrane, where they dominantly-negatively inhibit water flux. The ovarian follicular expression ratios of the Aqp1ab2 isoforms in relation to the canonical channel are lowest during oocyte hydration, but subsequently highest when the canonical channel is recycled, thus leaving the eggs endowed with >90% water. These findings suggest that the expression of inhibitory isoforms of Aqp1ab1 and Aqp1ab2 may represent a new regulatory mechanism through which the cell-surface expression and the activity of the canonical channels can be physiologically modulated during oocyte hydration in marine teleosts.by Auttawit Sirichoat, Orawee Kaewprasert, Yothin Hinwan, Kiatichai Faksri
Mycobacterium avium complex (MAC) infections are a significant clinical challenge. Determining drug-susceptibility profiles and the genetic basis of drug resistance is crucial for guiding effective treatment strategies. This study aimed to determine the drug-susceptibility profiles of MAC clinical isolates and to investigate the genetic basis conferring drug resistance using whole-genome sequencing (WGS) analysis. Drug-susceptibility profiles based on minimum inhibitory concentration (MIC) assays were determined for 38 MAC clinical isolates (12 Mycobacterium avium and 26 Mycobacterium intracellulare). Mutations associated with drug resistance were identified through genome analysis of these isolates, and their phylogenetic relationships were also examined. Drug resistance, based on MIC values, was most commonly observed for moxifloxacin (81.6%), followed by linezolid (78.9%), clarithromycin (44.7%) and amikacin (36.8%). We identified specific mutations associated with resistance to amikacin. These include the rrs mutation at C464T in amikacin intermediate-resistance M. avium, and two mutations at T250A and G1453T in amikacin non-susceptible M. intracellulare. Mutations in rrl at A2058G, A2059C and A2059G were potentially linked to clarithromycin resistance. MAC clinical isolates not susceptible to linezolid exhibited mutations in rplC at G237C and C459T, as well as two rplD mutations at G443A and A489G. GyrB substitution Thr521Ala (T521A) was identified in moxifloxacin non-susceptible isolates, which may contribute to this resistance. A phylogeny of our MAC isolates revealed high levels of genetic diversity. Our findings suggest that the standard treatment regimen for MAC infections using moxifloxacin, linezolid, clarithromycin and amikacin may be driving development of resistance, potentially due to specific mutations. The combination of phenotypic and genotypic susceptibility testing can be valuable in guiding the clinical use of drugs for the treatment of MAC infections.
FreshRSS