How can the kinetics of human blastocyst expansion be used to evaluate an embryo's ploidy identified using preimplantation genetic testing for aneuploidy (PGT-A)?
This was a retrospective ...observational study of 188 autologous blastocysts from 34 sequential treatment cycles using PGT-A and blastocyst biopsy. Using time-lapse imaging, blastocyst expansion was evaluated using a quantitative standardized expansion assay (qSEA). Trophectoderm cell division was examined in selected, unbiopsied embryos (n = 7) to evaluate the contribution of mitosis to the expansion rate.
The averaged euploid blastocyst expansion rate was significantly (52.8%) faster than in aneuploid blastocysts (P = 0.0041). Scatterplots, representing ‘expansion maps’, revealed that both populations showed a similarly overlapping distribution of blastocyst formation times at 80–140 h from fertilization. Euploidy and aneuploidy were better distinguished in regions of higher and lower expansion, respectively, in expansion maps. Based upon the expansion slopes, rank-ordering of individual embryos within cohorts resulted in more than 90% euploid embryos in the first two ranks in patients less than 35 years of age. Additional detailed time-lapse image analysis provided evidence that rapid expansion was associated with robust, integrative cellular mitosis in trophectoderm cells.
The kinetics of human blastocyst expansion are related to an embryo's ploidy. These preliminary observations describe a new quantitative, non-invasive approach to embryo assessment that may be useful to identify single blastocysts for transfer, particularly in younger patient groups. However, this approach may also be useful for euploid embryo selection after PGT-A. The results support the hypothesis that aneuploidy universally impairs general cellular processes, including cell division, in differentiated cells.
Measures of the built environment such as neighborhood walkability have been associated with health behaviors such as physical activity, the lack of which in turn may contribute to the development of ...diseases such as obesity, diabetes, cardiovascular disease, and cancer. However, limited research has examined these measures in association with health-related quality of life (HR-QoL), particularly in minoritized populations. We examined the relationship between perceived neighborhood environment and HR-QoL in a sample of mostly Black and Latino residents in New York City (NYC).
This study utilized the baseline survey data from the Physical Activity and Redesigned Community Spaces (PARCS) Study among 1252 residents 34.6% Black, 54.1% Latino, 80.1% female, mean(±SD) age = 38.8 ± 12.5) in 54 park neighborhoods in NYC. Perceived built environment was measured using Neighborhood Environment and Walkability Survey, and mental and physical HR-QoL was estimated using Short Form (SF)-12. Using factor analysis, we identified two subscales of neighborhood walkability: enablers (e.g., trails, sidewalks, esthetics) vs. barriers (e.g., high crime and traffic). In addition, we included a third subscale on neighborhood satisfaction. Generalized Estimating Equation models adjusted for demographics and BMI and accounted for the clustering effect within neighborhood. Multiple imputation was used to account for missing data.
Mental HR-QoL was associated with barriers of walkability (β ± SE = - 1.63 ± 0.55, p < 0.01) and neighborhood satisfaction (β ± SE = 1.55 ± 0.66, p = 0.02), after adjusting for covariates. Physical HR-QoL was associated with only barriers of walkability (β ± SE = - 1.13 ± 0.57, p < 0.05).
Among NYC residents living in minoritized neighborhoods, mitigating negative aspects of the neighborhood environment may be more crucial than adding positive features in terms of HR-QoL. Our study points to the need to investigate further the role of the built environment in urban, minoritized communities.
The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain‐derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational ...studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies.
Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
Four-dimensional (4D) printing relies on multimaterial printing, reinforcement patterns, or micro/nanofibrous additives as programmable tools to achieve desired shape reconfigurations. However, ...existing programming approaches still follow the so-called origami design principle to generate reconfigurable structures by self-folding stacked 2D materials, particularly at small scales. Here, we propose a programmable modular design that directly constructs 3D reconfigurable microstructures capable of sophisticated 3D-to-3D shape transformations by assembling 4D micro-building blocks. 4D direct laser writing is used to print two-photon polymerizable, stimuli-responsive hydrogels to construct building blocks at micrometer scales. Denavit-Hartenberg (DH) parameters, used to define robotic arm kinematics, are introduced as guidelines for how to assemble the micro-building blocks and plan the 3D motion of assembled chain blocks. Last, a 3D-printed microscaled transformer capable of changing its shape from a race car to a humanoid robot is devised and fabricated using the DH parameters to guide the motion of various assembled compartments.
Objective: To compare relative associations of eating patterns and dietary composition with body mass index (BMI) in younger (aged 20-59 years, n=1792) and older (aged 60-90 years, n=893) ...participants in the Continuing Survey of Food Intakes by Individuals, collected 1994-1996. Methods: Data from two 24-h dietary recalls from individuals reporting physiologically plausible energy intake (within +/-22% of predicted energy requirements, based on previously published methods) were used. Results: Mean reported energy intake was 96 and 95% of predicted energy requirements in younger and older subjects, respectively. Older subjects were less likely than younger subjects to skip a meal, but snacking was common in both age groups. Fiber density was significantly higher in the older group. A higher BMI in both age groups was associated with a higher total daily energy intake, and higher energy intakes at all eating occasions. In both age groups, eating frequency was positively associated with energy intake, and eating more than three times a day was associated with being overweight or obese. In the younger group but not the older group, a lower fiber density coupled with higher percentage of energy from fat was independently associated with having a higher BMI. Conclusions: While no one eating occasion contributes more than any other to excess adiposity, eating more often than three times a day may play a role in overweight and obesity in both younger and older persons. A reduced satiety response to dietary fiber in addition to lower energy expenditure may potentially further contribute to weight gain in older persons.
Type 2 diabetes is a significant and increasing burden in adolescents and young adults. Clear strategies for research, prevention, and treatment of the disease in these vulnerable patients are ...needed. Evidence suggests that type 2 diabetes in children is different not only from type 1 but also from type 2 diabetes in adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as well as the risk of complications and the psychosocial impact, will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate both current and future research, treatment, and prevention approaches. This Consensus Report characterizes type 2 diabetes in children, evaluates the fundamental differences between childhood and adult disease, describes the current therapeutic options, and discusses challenges to and approaches for developing new treatments.
Pulmonary function tests (PFTs) are usually interpreted by clinicians using rule-based strategies and pattern recognition. The interpretation, however, has variabilities due to patient and ...interpreter errors. Most PFTs have recognizable patterns that can be categorized into specific physiological defects. In this study, we developed a computerized algorithm using the python package (pdfplumber) and validated against clinicians' interpretation. We downloaded PFT reports in the electronic medical record system that were in PDF format. We digitized the flow volume loop (FVL) and extracted numeric values from the reports. The algorithm used FEV1/FVC<0.7 for obstruction, TLC<80%pred for restriction and <80% or >120%pred for abnormal DLCO. The algorithm also used a small airway disease index (SADI) to quantify late expiratory flattening of the FVL to assess small airway dysfunction. We devised keywords for the python Natural Language Processing (NLP) package (spaCy) to identify obstruction, restriction, abnormal DLCO and small airway dysfunction in the reports. The algorithm was compared to clinicians' interpretation in 6,889 PFTs done between March 1st, 2018, and September 30th, 2020. The agreement rates (Cohen's kappa) for obstruction, restriction and abnormal DLCO were 94.4% (0.868), 99.0% (0.979) and 87.9% (0.750) respectively. In 4,711 PFTs with FEV1/FVC≥0.7, the algorithm identified 190 tests with SADI < lower limit of normal (LLN), suggesting small airway dysfunction. Of these, the clinicians (67.9%) also flagged 129 tests. When SADI was ≥ LLN, no clinician's reports indicated small airway dysfunction. Our results showed the computerized algorithm agreed with clinicians' interpretation in approximately 90% of the tests and provided a sensitive objective measure for assessing small airway dysfunction. The algorithm can improve efficiency and consistency and decrease human errors in PFT interpretation. The computerized algorithm works directly on PFT reports in PDF format and can be adapted to incorporate a different interpretation strategy and platform.
Viral papain-like cysteine protease (PLpro, NSP3) is essential for SARS-CoV-2 replication and represents a promising target for the development of antiviral drugs. Here, we used a combinatorial ...substrate library and performed comprehensive activity profiling of SARS-CoV-2 PLpro. On the scaffold of the best hits from positional scanning, we designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro. We determined crystal structures of two of these inhibitors in complex with SARS-CoV-2 PLpro that reveals their inhibitory mechanisms and provides a molecular basis for the observed substrate specificity profiles. Last, we demonstrate that SARS-CoV-2 PLpro harbors deISGylating activity similar to SARSCoV-1 PLpro but its ability to hydrolyze K48-linked Ub chains is diminished, which our sequence and structure analysis provides a basis for. Together, this work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repurposing.
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