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To investigate the diagnostic accuracy of ultrasound microcalcifications for the detection of malignancy in thyroid nodules and determine the validity of the concept that ultrasound microcalcification reflects the presence of psammoma body calcification in thyroid nodules.The laboratory information system at University Hospital Galway, a tertiary referral hospital, was used to compile a list of patients who underwent thyroid lobectomy or complete thyroidectomy over a continuous 12-month period with both preoperative ultrasound and postoperative histology available (n=106) from January to December 2019. The haematoxylin and eosin-stained histology slides of each case were sourced and reviewed under light microscopy by a histopathologist to determine the presence of psammoma body calcification within both benign and malignant thyroid nodules. Two radiologists reviewed preoperative thyroid ultrasound images of each case independently and blindly, and reported on the presence of ultrasonographic microcalcification.There was a strong and significant relationship between the presence of preoperative ultrasound microcalcification and thyroid malignancy (p0.001). Ultrasound microcalcification had a high specificity (93%) and positive predictive value (75%) for thyroid malignancy, with a diagnostic accuracy of 76%. Negative predictive value was high at 76.7%, while sensitivity was low at 42.8%. There was a strong and significant association between the presence of preoperative ultrasound microcalcification in thyroid nodules and the presence of pathological psammoma bodies on histology (p0.001).Ultrasound microcalcification has a strong and significant association with malignancy in thyroid nodules. This study supported the theory that ultrasound microcalcification occurs secondary to the presence of psammoma bodies within thyroid nodules.

Aim This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. Methods A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure Chest pain is a frequent cause for emergency department visits in the United States. The “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain” provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.

Behavioral responses such as social distancing are important in the fight to contain COVID‐19 transmission, yet motivating such responses is an overwhelming, resource‐intensive task. Using multi‐wave data from 23,735 US adults collected in May/September 2020, and January 2021, this study examines how financial preparedness in the form of savings influences the relationship predicted by the Health Belief Model between the degree of concern for COVID‐19 and engagement in social distancing. Findings indicate that general concern for COVID‐19 is related to the decision to engage in social distancing for individuals who have less saved. Curiously, higher levels of financial preparedness are associated with a lower likelihood of social distancing at least among people who had been laid off during the pandemic. The findings suggest a tradeoff between protecting one's standard of living and their health. Government and public health agencies should consider financial preparedness in the design of public health communications. [ABSTRACT FROM AUTHOR] Copyright of Journal of Consumer Affairs is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Family accommodation (FA) has been shown to relate to poorer treatment outcomes in pediatric obsessive compulsive disorder (OCD), yet few studies have examined the trajectory of change in FA throughout treatment and its relation to treatment outcomes. This study examined change in FA in relation to change in symptom severity and impairment in 63 youth receiving a family-based intervention for early-onset OCD. FA, symptom severity and functional impairment were assessed at baseline, week 5, week 9, and post-treatment (week 14). Results suggested that changes in FA in the beginning stages of treatment preceded global symptom improvement (but not OCD specific improvement) whereas changes in functional impairment preceded changes in FA. In the latter half of treatment, changes in FA preceded improvement in global and OCD specific symptom severity as well as functional impairment. These findings highlight the importance of reducing FA, especially in the later stages of treatment, in order to optimize treatment outcomes in early-onset OCD.

Background: Palliative care plays an important role in improving the quality of life for patients with cancer and their caregivers and has been associated with increased patient satisfaction. However, palliative care knowledge in the general population is limited, and often physician referral occurs late in prognosis. The objective of this analysis was to examine factors associated with palliative care knowledge. Method: Using data from the 2018 NCI's Health Information National Trends Survey (HINTS) 5 Cycle 2, descriptive statistics, bivariate analyses, and multivariable logistic regressions were used to assess factors associated with respondents' palliative care knowledge using ORs and 95% confidence intervals as measures of association. The outcome of interest was measured with the item “How would you describe your level of knowledge about palliative care?” Possible response selections were “I've never heard of it,” “I know a little bit about palliative care,” and “I know what palliative care is and could explain it to someone else.” To reduce the risk of type 1 error, jackknife variance estimations with repeated replications were used. All analyses were conducted with the SURVEYLOGISTIC command using SAS 9.4 (SAS Institute Inc.), and the statistical significance level was set at P < 0.05. Results: A total of 3,450 respondents (weighted sample size: 249,489,772) met the inclusion criteria. About 89% (n = 3,000) of all respondents had inadequate knowledge of palliative care. Multivariable analyses indicated that frequent health care utilization as defined as ≥ 2 times per year [OR, 3.01; 95% confidence interval (CI), 2.65–3.58], female gender (OR, 2.15; 95% CI, 1.31–3.59), being married (OR, 2.02; 95% CI, 1.14–3.59), having a college degree or higher (OR, 13.83; 95% CI, 1.71–12.04), and having a regular source of care (OR, 2.67; 95% CI, 1.37–1.90) had greater odds of adequate palliative care knowledge. Those without a cancer diagnosis were less likely to have adequate knowledge of palliative care (OR, 0.49; 95% CI, 0.41–0.89). Conclusions: Knowledge of palliative care in the United States is low, particularly for those not already actively using their available healthcare system. Public health education efforts are needed to target subgroups of the U.S. population identified by this analysis to increase palliative care knowledge. Impact: Healthcare providers have a major role to play in improving palliative care knowledge.

BACKGROUND Strategy training, a rehabilitation intervention, reduces disability and improves functional skills associated with goal-directed behavior. Stroke lesions impacting selected ventromedial regions of interest associated with initiation of goal-directed behavior may attenuate intervention response. If so, strategy training may not be optimal for people with stroke lesions in these regions. OBJECTIVE To examine whether ventromedial regions of interest attenuate changes in disability status attributed to strategy training. DESIGN Secondary analysis of data from two randomized controlled clinical trials. SETTING Inpatient stroke rehabilitation. PARTICIPANTS People with acute stroke diagnosis and available diagnostic studies enrolled in inpatient rehabilitation randomized controlled studies between 2009 and 2017. INTERVENTION Participants were randomized to strategy training or a control condition in addition to the usual care during inpatient rehabilitation. MAIN OUTCOME MEASURES Diagnostic magnetic resonance imaging studies were retrieved from electronic medical records, and stroke lesion location was characterized by a neuroradiologist. Intervention response was defined by Functional Independence Measure change scores of 22 points or greater. RESULTS Only 186 of 275 participants had diagnostic studies available; 13 patients showed no apparent lesion on their diagnostic study. Among 173 cases, 156 had complete data at discharge (strategy training n = 71, control n = 85). Twenty-five cases had a lesion within a region of interest (strategy training n = 14, control n = 11). Intervention response was attenuated in the strategy training group for those with lesions in regions of interest [χ2 (1, n = 71) = 4.60, P = .03], but not for those in the control group [Fisher exact test, n = 85, P = .19). CONCLUSIONS Lesions in the ventromedial regions of interest may attenuate response to strategy training.

Theoretical conceptualizations of “aggressive-victims” portray them as more emotionally dysregulated and socially inept than adolescents who are either aggressive or victimized. The purpose of this systematic review is to synthesize the literature comparing the psychosocial adjustment of aggressor/victim subgroups (i.e., aggressive-victims, predominant-aggressors, predominant-victims, and youth with limited involvement) and determine whether empirical findings are consistent with theory, particularly regarding whether aggressive-victims possess unique and shared characteristics relative to those with other patterns of involvement in aggression. This review focuses on studies with early adolescent samples given the heightened vulnerability for aggression and victimization and the need for more effective interventions during this developmental period. A systematic search of three databases (PubMed, PsycINFO, Academic Search Complete) identified 25 studies, which varied in their sample characteristics, approach to defining subgroups, and findings regarding the unique and shared characteristics of aggressive-victims. I propose several guidelines for future research in this area and highlight several gaps in our existing knowledge. Implications for theory and prevention efforts are discussed.

Background Lumbar spine fusion surgery is traditionally performed with rigid fixation. Because the rigidity is often supraphysiologic, semirigid rods were developed. To the best of our knowledge, a comprehensive evaluation of rod material type on surgical outcomes has yet to be conducted. Methods A systematic review based on PRISMA guidelines was conducted across 3 electronic databases. After examination for inclusion and exclusion criteria, data were extracted from the studies. Results Seventeen studies, including 1399 patients, were included in this review. The mean rigid rod fusion rate is 92.2% and 95.5% for semirigid rods (P = 0.129). The mean improvement in back pain was 60.6% in rigid rods and 71.6% in semirigid rods. The improvement in leg pain was 81.9% and 77.2%, respectively. There were no differences in visual analog scale back pain score (P = 0.098), visual analog scale leg pain score (P = 0.136), or in functional improvement between rigid and semirigid rods (P = 0.143). There was no difference (P = 0.209) in the reoperation rate between rigid rods (13.1%) and semirigid rods (6.5%). There was a comparable incidence of adjacent segment disease (3%), screw fracture (1.7%), and wound infection (1.9%) between rod material types. Conclusions There is a moderate level of evidence supporting that surgical intervention results in high fusion rates regardless of rod material type. Surgical intervention improves back pain, leg pain, and function, with neither material type showing clear superiority. There are comparable rates of reoperation, development of adjacent segment disease, development of mechanical complications, and incidence of infection in both rigid and semirigid rods. Further studies regarding rod material type are warranted.

The prone transpsoas approach is a relatively new technique to correct segmental kyphosis and global sagittal imbalance in a minimally invasive fashion. Here, we provide a detailed case report using the prone transpsoas approach to address adjacent segment disease and flatback deformity. This technique allows considerable restoration of segmental lordosis with lateral interbody placement and posterior decompression and fusion using a single position approach. Our experience with the surgical technique and the advantages and challenges unique to this approach are discussed.

Contains fulltext : 229297.pdf (Publisher’s version ) (Open Access) Globozoospermia is a rare form of male infertility where men produce round-headed sperm that are incapable of fertilizing an oocyte naturally. In a previous study where we undertook a whole exome screen to define novel genetic causes of globozoospermia, we identified homozygous mutations in the gene PDCD2L Two brothers carried a p.(Leu225Val) variant predicted to introduce a novel splice donor site, thus presenting PDCD2L as a potential regulator of male fertility. In this study, we generated a Pdcd2l knockout mouse to test its role in male fertility. Contrary to the phenotype predicted from its testis-enriched expression pattern, Pdcd2l null mice died during embryogenesis. Specifically, we identified that Pdcd2l is essential for post-implantation embryonic development. Pdcd2l(-/-) embryos were resorbed at embryonic days 12.5-17.5 and no knockout pups were born, while adult heterozygous Pdcd2l males had comparable fertility to wildtype males. To specifically investigate the role of PDCD2L in germ cells, we employed Drosophila melanogaster as a model system. Consistent with the mouse data, global knockdown of trus, the fly ortholog of PDCD2L, resulted in lethality in flies at the third instar larval stage. However, germ cell-specific knockdown with two germ cell drivers did not affect male fertility. Collectively, these data suggest that PDCD2L is not essential for male fertility. By contrast, our results demonstrate an evolutionarily conserved role of PDCD2L in development.

OBJECTIVE Although yoga shows promise as a treatment for posttraumatic stress disorder (PTSD), there are few randomized controlled trials that demonstrate significant benefits for individuals with PTSD. The present study addresses this need by comparing the effects of a holistic yoga program (HYP) to that of a wellness lifestyle program (WLP) on PTSD symptom severity with a randomized clinical trial. METHOD The sample consisted of 209 participants (91.4% veterans; 66% male; 61.7% White) who met diagnostic criteria for PTSD at baseline. Participants were randomly assigned to attend one of the 2 weekly interventions for 16 weeks. The HYP consisted of yoga instruction, while the WLP consisted of didactics, discussions, and walking. PTSD severity was measured using the Clinician Administered PTSD Scale (CAPS-5) and the PTSD Checklist (PCL-5). RESULTS Analyses revealed that the HYP reduced PTSD severity measured by the CAPS-5 significantly more than the WLP at treatment end (mean difference = -5.4, effect size = 0.46, p < .001), but not at 7-month follow up (mean difference = -0.9, p = .603). Similarly, the HYP reduced PTSD severity measured by the PCL-5 significantly more than the WLP at treatment end (difference = -6.0, p = .001), but not at 7-month follow up (mean difference = -1.0, p = .682). CONCLUSION Yoga may be an effective intervention for PTSD in addition to standard treatments. Future yoga trials should consider adding a social component to interventions or booster classes to maintain effects long term. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The purpose of this study was to identify subgroups of adolescents with distinct perceptions of parental messages supporting fighting and nonviolence. Latent class analysis identified four subgroups among 2,619 urban middle school students (90% African American; 52% female): messages supporting fighting (32%), messages supporting nonviolence (29%), mixed messages (23%), and no messages (16%). We found significant differences across subgroups in their frequency of physical aggression and peer victimization and beliefs about the use of aggressive and nonviolent responses to peer provocation. Beliefs significantly mediated the relation between parental messages subgroups and both aggression and victimization. Findings illustrate the heterogeneity in the messages urban adolescents perceive from their parents, as well as relations with adolescents' beliefs and behavior.

Despite significant advances in treatment, chronic obstructive pulmonary disease (COPD) remains a chronic and progressive disease that frequently leads to premature mortality. COPD is associated with a constellation of significant symptoms, including dyspnea, cough, wheezing, pain, fatigue, anxiety, depression, and insomnia, and is associated with increased morbidity. Palliative care is appropriate to support these patients. However, historically, palliative care has focused on supporting patients with malignant disease, rather than progressive chronic diseases such as COPD. Therapies for COPD often result in functional and symptomatic improvements, including health-related quality of life (HRQL), and palliative care may further improve symptoms and HRQL. Provision of usual palliative care therapies for this patient population requires understanding the pathogenesis of COPD and common disease-targeted pharmacotherapies, as well as an approach to balancing life-prolonging and HRQL care strategies. This review describes COPD and current targeted therapies and their effects on symptoms, exercise tolerance, HRQL, and survival. It is important to note that medications commonly used for symptom management in palliative care can interact with COPD medications resulting in increased risk of adverse effects, enhanced toxicity, or changes in clearance of medications. To address this, we review pharmacologic interactions with and precautions related to use of COPD therapies in conjunction with commonly used palliative care medications.

Identifying the factors stimulating prostate cancer cells migration and invasion has the potential to bring new therapeutic targets to the clinic. Cysteine-rich secretory protein 3 (CRISP3) is one of the most highly upregulated proteins during the transition of a healthy human prostatic epithelium to prostate cancer. Here we show using a genetically engineered mouse model of prostate cancer that CRISP3 production greatly facilitates disease progression from carcinoma in situ to invasive prostate cancer in vivo. This interpretation was confirmed using both human and mouse prostate cancer cell lines, which showed that exposure to CRISP3 enhanced cell motility and invasion. Further, using mass spectrometry, we show that CRISP3 induces changes in abundance of a subset of cell-cell adhesion proteins, including LASP1 and TJP1 both in vivo and in vitro. Collectively, these data identify CRISP3 as being pro-tumorigenic in the prostate and validate it as a potential target for therapeutic intervention.

Iridoids are plant-derived terpenoids with a rich array of bioactivities. The key step in iridoid skeleton formation is the reduction of 8-oxogeranial by certain members of the progesterone 5β-reductase/iridoid synthase (PRISE) family of short-chain alcohol dehydrogenases. Other members of the PRISE family have previously been implicated in the biosynthesis of the triterpenoid class of cardenolides, which requires the reduction of progesterone. Here, we explore the occurrence and activity of PRISE across major lineages of plants. We observed trace activities toward either 8-oxogeranial or progesterone in all PRISEs, including those from nonseed plants and green algae. Phylogenetic analysis, coupled with enzymatic assays, show that these activities appear to have become specialized in specific angiosperm lineages. This broad analysis of the PRISE family provides insight into how these enzymes evolved in plants and also suggests that iridoid synthase activity is an ancestral trait in all land plants, which might have contributed to the rise of iridoid metabolites.

Few studies have considered academic vocabulary interventions for students who have learning disabilities (LD) and also are English learners (EL). This research explored the effects of the third year of the Creating Habits that Accelerate Academic Language of Students (CHAAOS) vocabulary intervention for eighth-grade students who received English Language Arts instruction (ELA) in special education classes. Over 70% of student participants had LD and over half were EL. Special education teachers delivered 12 weeks of intervention spaced across 7 months to 36 students. Researchers compared outcomes on receptive and expressive measures with 17 students in business-as-usual (BAU) special education ELA. Students receiving the CHAAOS intervention learned the 48 taught words better than students in BAU conditions, retained their knowledge of words 4 weeks following the close of the intervention, and ended the year with higher vocabulary scores on a standardized measure than students in BAU classes. Students who were EL performed similarly on receptive knowledge of words to students who were native English speakers. This study documents the effectiveness of explicit vocabulary routines for students who have LD and are also EL.

Cognitive impairment may be greater in HIV-positive (HIV+) women than in HIV+ men. Whether sex-specific differences exist in brain microstructure of HIV+ individuals is unknown and was evaluated.39 HIV+ (21 men, 18 women) and 45 seronegative (SN, 20 men, 25 women) participants were assessed with brain diffusion tensor imaging and cognitive assessments (7 neuropsychological domains). Fractional anisotropy (FA) and mean diffusivity (MD) were measured with an automated atlas in selected brain regions. Group comparisons were assessed with linear mixed effects models, with sub-regions and hemisphere (left/right) as repeated factors for each region.HIV+ women, but not HIV+ men, were slower than sex-matched SN controls on sensorimotor function (Dominant-hand: interaction-p = 0.007; Non-dominant hand: interaction-p = 0.039). Similarly, only HIV+ women had lower FA in the globus pallidus (GP, interaction-p = 0.011). Additionally, regardless of sex, the HIV+ group had poorer Fluency, Speed, and Attention than SN-controls (p = 0.006-0.008), as well as lower FA and higher MD in multiple brain regions (p = 0.001-0.044). Across all participants, performance on Attention was predicted by uncinate-FA (p 0.001, r = 0.5) and corpus callosum (CC)-FA (p = 0.038, r = 0.23), while the Speed of Information Processing was predicted by CC-FA (p = 0.009, r = 0.3). Furthermore, faster sensorimotor function correlated with higher CC-FA and uncinate-FA in men but not in women (Sex*DTI-interaction-p = 0.03-0.06).The relatively poorer sensorimotor function and abnormally lower GP_FA, suggesting lesser neuronal integrity, in HIV+ women demonstrate sex-specific effects from HIV-infection on these measures. These findings may be related to the greater immune activation and neuroinflammation in HIV+ women compared to HIV+ men. Graphical Abstract.

This study was supported by Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq, Proc. PDE 204792/2018-5 and PQ 307382/2019-2), Funda??o de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, 16/2551-000485-7) and the Biotechnology and Biological Sciences Research Council UK (BB/K008226/1). University of Kent. School of Biosciences. Canterbury, UK; Universidade Federal do Rio Grande do Sul. Instituto de Bioci?ncias. Departamento de Gen?tica. Laborat?rio de Citogen?tica e Evolu??o. Rio Grande do Sul, RS, Brazil. Universidade Federal do Pampa. Laborat?rio de Diversidade Gen?tica Animal. Rio Grande do Sul, RS, Brazil. Universidade Federal do Pampa. Laborat?rio de Diversidade Gen?tica Animal. Rio Grande do Sul, RS, Brazil. Universidade Federal do Rio Grande do Sul. Instituto de Bioci?ncias. Departamento de Gen?tica. Laborat?rio de Citogen?tica e Evolu??o. Rio Grande do Sul, RS, Brazil. Universidade Federal de S?o Carlos. Centro de Ci?ncias Biol?gicas e da Sa?de. Departamento de Gen?tica e Evolu??o. Laborat?rio de Citogen?tica de Peixes. S?o Carlos, SP, Brazil. Universidade Federal de S?o Carlos. Centro de Ci?ncias Biol?gicas e da Sa?de. Departamento de Gen?tica e Evolu??o. Laborat?rio de Citogen?tica de Peixes. S?o Carlos, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Exatas e Naturais. Bel?m, PA, Brazil. University of Kent. School of Biosciences. Canterbury, UK. University of Kent. School of Biosciences. Canterbury, UK. Abstract: Although cytogenetics studies in cuckoos (Aves, Cuculiformes) have demonstrated an interesting karyotype variation, such as variations in the chromosome morphology and diploid number, their chromosome organization and evolution, and relation with other birds are poorly understood. Hence, we combined conventional and molecular cytogenetic approaches to investigate chromosome homologies between chicken and the smooth-billed ani (Crotophaga ani). Our results demonstrate extensive chromosome reorganization in C. ani, with interchromosomal rearrangements involving macro and microchromosomes. Intrachromosomal rearrangements were observed in some macrochromosomes, including the Z chromosome. The most evolutionary notable finding was a Robertsonian translocation between the microchromosome 17 and the Z chromosome, a rare event in birds. Additionally, the simple short repeats (SSRs) tested here were preferentially accumulated in the microchromosomes and in the Z and W chromosomes, showing no relationship with the constitutive heterochromatin regions, except in the W chromosome. Taken together, our results suggest that the avian sex chromosome is more complex than previously postulated and revealed the role of microchromosomes in the avian sex chromosome evolution, especially cuckoos.

Aim:This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.Methods:A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.Structure:Chest pain is a frequent cause for emergency department visits in the United States. The “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain” provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.

A Mediterranean-style eating pattern (MED-EP) may include moderate red meat intake. However, it is unknown if the pro-atherogenic metabolite trimethylamine N-oxide (TMAO) is affected by the amount of red meat consumed with a MED-EP. The results presented are from a secondary, retrospective objective of an investigator-blinded, randomised, crossover, controlled feeding trial (two 5-week interventions separated by a 4-week washout) to determine if a MED-EP with 200 g unprocessed lean red meat/week (MED-CONTROL) reduces circulating TMAO concentrations compared to a MED-EP with 500 g unprocessed lean red meat/week (MED-RED). Participants were seventy-seven women and twelve men (n 39 total) who were either overweight or obese (BMI: mean (30·5) (sem 0·3) kg/m2). Serum samples were obtained following an overnight fast both before (pre) and after (post) each intervention. Fasting serum TMAO, choline, carnitine and betaine concentrations were measured using a targeted liquid chromatography-MS. Data were analysed to assess if (a) TMAO and related metabolites differed by intervention and (b) if changes in TMAO were associated with changes in Framingham 10-year risk score. Serum TMAO was lower post-intervention following MED-CONTROL compared with MED-RED intervention (post-MED-CONTROL 3·1 (sem 0·2) µmv. post-MED-RED 5·0 (sem 0·5) µm, P < 0·001), and decreased following MED-CONTROL (pre- v. post-MED-CONTROL, P = 0·025). Exploratory analysis using mixed model ANCOVA identified a positive association between changes in TMAO and changes in homoeostatic model assessment of insulin resistance (P = 0·036). These results suggest that lower amounts of red meat intake lead to lower TMAO concentrations in the context of a MED-EP.

BACKGROUND: Standardized methods are needed to investigate intake patterns of processed meat subtypes, considering health concerns surrounding processed meat intake. OBJECTIVES: The objectives of this study were to create a standardized method of disaggregating processed meat into processed red meat and processed poultry and describe intake patterns of the US population aged ≥2 y. METHODS: Two researchers independently manually disaggregated processed meat from the Food Patterns Equivalents Database into processed red meat and processed poultry based on available information from the Foods and Nutrient Database for Dietary Studies. We created an SAS program (called Processed Meat Categories) to mimic the manual coding. We used the program to describe intake patterns and trends over time of processed red meat and processed poultry using 24-h recalls from 2007–2008 through 2017–2018 NHANES data with SAS survey-weighted procedures for complex surveys. RESULTS: The SAS program had high agreement with the manual code (Pearson concordance correlation ≥0.95). Of the US population aged ≥2 y, 46.8% (95% CI: 45.3, 48.2%) reported consuming any processed meat, 42.5% (95% CI: 41.0, 43.9%) reported consuming processed red meat, and 11.3% (95% CI: 10.2, 12.4%) reported consuming processed poultry. Most [74.1 ± 0.13% (SEM)] processed meat reported was red meat compared with poultry, and 32.1 ± 0.01% of total red meat and 13.7 ± 0.01% of total poultry reported were processed. Prevalence of processed poultry intake increased from 9.5% (95% CI: 8.9, 10.1%) in 2007–2010 to 11.3% (95% CI: 10.2, 12.4%) in 2015–2018 (P

Funder: Fight for Sight UK; doi: http://dx.doi.org/10.13039/501100000615, Funder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100004440, Wolfram syndrome (WS) is an ultra-rare progressive neurodegenerative disorder defined by early-onset diabetes mellitus and optic atrophy. The majority of patients harbour recessive mutations in the WFS1 gene, which encodes for Wolframin, a transmembrane endoplasmic reticulum protein. There is limited availability of human ocular and brain tissues, and there are few animal models for WS that replicate the neuropathology and clinical phenotype seen in this disorder. We, therefore, characterised two wfs1 zebrafish knockout models harbouring nonsense wfs1a and wfs1b mutations. Both homozygous mutant wfs1a−/− and wfs1b−/− embryos showed significant morphological abnormalities in early development. The wfs1b−/− zebrafish exhibited a more pronounced neurodegenerative phenotype with delayed neuronal development, progressive loss of retinal ganglion cells and clear evidence of visual dysfunction on functional testing. At 12 months of age, wfs1b−/− zebrafish had a significantly lower RGC density per 100 μm2 (mean ± standard deviation; 19 ± 1.7) compared with wild-type (WT) zebrafish (25 ± 2.3, p < 0.001). The optokinetic response for wfs1b−/− zebrafish was significantly reduced at 8 and 16 rpm testing speeds at both 4 and 12 months of age compared with WT zebrafish. An upregulation of the unfolded protein response was observed in mutant zebrafish indicative of increased endoplasmic reticulum stress. Mutant wfs1b−/− zebrafish exhibit some of the key features seen in patients with WS, providing a versatile and cost-effective in vivo model that can be used to further investigate the underlying pathophysiology of WS and potential therapeutic interventions.

Intracranial abscesses are rare lesions with an incidence of approximately 4 per 1 million people. The optimal surgical management of these lesions is still unclear. We present the case of a patient who was discovered to have an intracranial abscess after presenting with right-sided weakness. He was treated via a combination of open craniotomy and continuous antibiotic irrigation using an IRRAflow® catheter (IRRAS, Stockholm, Sweden). Use of the IRRAflow® in this fashion has not yet been described in the literature. This novel approach appears to be safe and resulted in continued decrease in the abscess burden following surgical drainage.

PIWI-interacting small RNAs (piRNAs) maintain genome stability in animal germ cells, with a predominant role in silencing transposable elements. Mutations in the piRNA pathway in the mouse uniformly lead to failed spermatogenesis and male sterility. By contrast, mutant females are fertile. In keeping with this paradigm, we previously reported male sterility and female fertility associated with loss of the enzyme HENMT1, which is responsible for stabilising piRNAs through the catalysation of 3′-terminal 2′-O-methylation. However, the Henmt1 mutant females were poor breeders, suggesting they could be subfertile. Therefore, we investigated oogenesis and female fertility in these mice in greater detail. Here, we show that mutant females indeed have a 3- to 4-fold reduction in follicle number and reduced litter sizes. In addition, meiosis-II mutant oocytes display various spindle abnormalities and have a dramatically altered transcriptome which includes a down-regulation of transcripts required for microtubule function. This down-regulation could explain the spindle defects observed with consequent reductions in litter size. We suggest these various effects on oogenesis could be exacerbated by asynapsis, an apparently universal feature of piRNA mutants of both sexes. Our findings reveal that loss of the piRNA pathway in females has significant functional consequences.

Here we present a novel application of cortical bone trajectory (CBT) fixation utilizing robotic guidance in a previously instrumented spine with a traditional pedicle screw (PS), obviating the need for a larger posterior incision, reducing the risk of infection, muscular dissection, and likely decreasing hospital length of stay. A 60-year-old woman with prior left L3-L4 extreme lateral interbody fusion and unilateral percutaneous PS placed at L3 to L5 presented with progressive bilateral lower-extremity pain and diminished sensation in the S1 dermatome secondary to adjacent segment disease (ASD). The patient underwent an L5-S1 anterior lumbar interbody fusion for indirect decompression and restoration of segmental lordosis. After the first stage was completed, she was turned prone for posterior percutaneous instrumentation. Given prior instrumentation at L3-L5 on the left side, a robot planning software was used to plan a cortical bone screw on the left L5 pedicle. A left S1 PS was then planned with the screw head aligning with the left L5 cortical bone screw. Instrumentation was then placed percutaneously using the robot bilaterally without issue. Intraoperative fluoroscopic imaging demonstrated accurate placement of PS, and postoperative computed tomography demonstrated the excellent positioning of all PSs. This report is the first documented case of a robotically placed CBT screw placed in the same pedicle as a prior traditional PS for ASD. This method expands the surgical options for ASD to include robotic percutaneous placement of posterior instrumentation at the same level as previous instrumentation.

Fertilization requires sperm to travel long distances through the complex environment of the female reproductive tract. Despite the strong association between poor motility and infertility, the kinetics of sperm tail movement and the role individual proteins play in this process is poorly understood. Here, we use a high spatiotemporal sperm imaging system and an analysis protocol to define the role of CRISPs in the mechanobiology of sperm function. Each of CRISP1, CRISP2, and CRISP4 is required to optimize sperm flagellum waveform. Each plays an autonomous role in defining beat frequency, flexibility, and power dissipation. We thus posit that the expansion of the CRISP family from one member in basal vertebrates, to three in most mammals, and four in numerous rodents, represents an example of neofunctionalization wherein proteins with a common core function, boosting power output, have evolved to optimize different aspects of sperm tail performance.

Katanin microtubule-severing enzymes are crucial executers of microtubule regulation. Here, we have created an allelic loss-of-function series of the katanin regulatory B-subunit KATNB1 in mice. We reveal that KATNB1 is the master regulator of all katanin enzymatic A-subunits during mammalian spermatogenesis, wherein it is required to maintain katanin A-subunit abundance. Our data shows that complete loss of KATNB1 from germ cells is incompatible with sperm production, and we reveal multiple new spermatogenesis functions for KATNB1, including essential roles in male meiosis, acrosome formation, sperm tail assembly, regulation of both the Sertoli and germ cell cytoskeletons during sperm nuclear remodelling, and maintenance of seminiferous epithelium integrity. Collectively, our findings reveal that katanins are able to differentially regulate almost all key microtubule-based structures during mammalian male germ cell development, through the complexing of one master controller, KATNB1, with a ‘toolbox’ of neofunctionalised katanin A-subunits.

The purification of individual male germ cell populations is integral for the molecular and biochemical characterisation of specific spermatogenic phases. Although a number of more contemporary techniques have been developed, velocity sedimentation using the STAPUT method remains as a gold standard for this purpose. The gentle nature of the technique, wherein germ cell subpopulations are separated by sedimentation at unit gravity, results in the isolation of viable and high-purity cells. We provide an updated and simplified step-by-step version of the STAPUT protocol for the purification of mouse male germ cells. As per the original method, the protocol described herein allows for the purification of mouse spermatocyte and round spermatids, however it also allows for successful purification of elongating, and elongated spermatid populations, and is optimised for the preservation of cellular ultrastructure. This method yields sufficient numbers of high-purity cells from one adult mouse for RNA or protein extraction or for immunolocalisation studies.

The present study examined how perceptions of school climate differ across subgroups of early adolescents with distinct patterns of involvement in aggression and victimization. We identified subgroups among 800 sixth-grade students (87% African American, 51% female) based on latent class analysis of items assessing aggression and victimization. Consistent with previous research, we found support for a four-class solution that identified the following subgroups: aggressive-victims (8%), predominant-victims (12%), predominant-aggressors (28%), and youth with limited involvement (52%). Predominant-aggressors and aggressive-victims reported lower levels of teacher support and consistency and clarity of school rules than nonaggressive subgroups. Among male adolescents, aggressive-victims reported more positive perceptions of peer interactions than predominant-aggressors. Findings provide evidence that perceptions of school climate are related to early adolescents’ pattern of involvement in aggression and victimization, which has implications for school-based interventions targeting aggressive behavior.

peer-reviewed Teagasc Publication Irish Journal of Agricultural and Food Research | Volume 58: Issue 1 Prediction of 24-hour milk yield and composition in dairy cows from a single part-day yield and sample S. McParlandemail , B. Coughlan , B. Enright , M. O’Keeffe , R. O’Connor , L. Feeney and D.P. Berry DOI: https://doi.org/10.2478/ijafr-2019-0007 | Published online: 09 Aug 2019 PDF       Abstract Article PDF References Recommendations Abstract The objective was to evaluate the accuracy of predicting 24-hour milk yield and composition from a single morning (AM) or evening (PM) milk weight and composition. A calibration dataset of 37,481 test-day records with both AM and PM yields and composition was used to generate the prediction equations; equations were validated using 4,644 test-day records. Prediction models were developed within stage of lactation and parity while accounting for the inter-milking time interval. The mean correlation between the predicted 24-hour yields and composition of milk, fat and protein and the respective actual values was 0.97 when based on just an AM milk yield and composition with a mean correlation of 0.95 when based on just a PM milk yield and composition. The regression of predicted 24-hour yield and composition on the respective actual values varied from 0.97 to 1.01 with the exception of 24-hour fat percentage predicted from a PM sample (1.06). A single AM sample is useful to predict 24-hour milk yield and composition when the milking interval is known.

The American College of Emergency Physicians (ACEP) organized a multidisciplinary effort to create a clinical practice guideline specific to unscheduled, time-sensitive procedural sedation, which differs in important ways from scheduled, elective procedural sedation. The purpose of this guideline is to serve as a resource for practitioners who perform unscheduled procedural sedation regardless of location or patient age. This document outlines the underlying background and rationale, and issues relating to staffing, practice, and quality improvement.

Background: Findings among randomized controlled trials evaluating the effect of red meat on cardiovascular disease risk factors are inconsistent. We provide an updated meta-analysis of randomized controlled trials on red meat and cardiovascular risk factors and determine whether the relationship depends on the composition of the comparison diet, hypothesizing that plant sources would be relatively beneficial. Methods: We conducted a systematic PubMed search of randomized controlled trials published up until July 2017 comparing diets with red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets. Results: Thirty-six studies totaling 1803 participants were included. There were no significant differences between red meat and all comparison diets combined for changes in blood concentrations of total, low-density lipoprotein, or high-density lipoprotein cholesterol, apolipoproteins A1 and B, or blood pressure. Relative to the comparison diets combined, red meat resulted in lesser decreases in triglycerides (weighted mean difference [WMD], 0.065 mmol/L; 95% CI, 0.000–0.129; P for heterogeneity P P =0.003). In comparison with fish, red meat yielded greater decreases in low-density lipoprotein (WMD, –0.173 mmol/L; 95% CI, –0.260 to –0.086; P P =0.004). In comparison with carbohydrates, red meat yielded greater decreases in triglycerides (WMD, –0.181 mmol/L; 95% CI, –0.349 to –0.013). Conclusions: Inconsistencies regarding the effects of red meat on cardiovascular disease risk factors are attributable, in part, to the composition of the comparison diet. Substituting red meat with high-quality plant protein sources, but not with fish or low-quality carbohydrates, leads to more favorable changes in blood lipids and lipoproteins.

Objective To study the differences between robot-guided (Mazor X, Mazor Robotics Ltd., Caesarea, Israel) and 3-dimensional (3D) computed tomography (CT) navigation (O-arm Surgical Imaging System, Medtronic, Minneapolis, Minnesota, USA) for the insertion of pedicle screws. Methods We reviewed the charts of 50 patients who underwent robot-guided pedicle screw insertion (between May 2017–October 2017), and 49 patients who underwent 3D-CT navigation pedicle screw insertion (between September 2015–August 2016). Variables included were age, sex, body mass index, blood loss, length of stay, lumbar level(s), operation time, fluoroscopy time, radiation dose, accuracy, and time-per-screw placement. Results Mean ages were 59.3 years in the robotic group and 58.2 years in the 3D-CT navigation group. Mean was 30.7 kg/m2 in the robotic group and 32.1 kg/m2 in the 3D-CT navigation group. Mean time-per-screw placement was 3.7 minutes for the robotic group and 6.8 minutes for the 3D-CT navigation group, P Conclusions Both technologies are safe and accurate. Robotic technology exposed patients to less fluoroscopy time, decreased time-per-screw placement and shorter hospital stay than 3D-CT navigation. Further studies are warranted to verify our results.

Introduction There has been a surge in robot utilization in spine surgery over the past five years with the rapid development of new spine robotic platforms. This study aimed to compare a new robotic spine platform from Fusion RoboticsTM (Fusion Robotics, Helena, MT) with the widely used Mazor-XTM Stealth Edition robotic platform (Medtronic, Dublin, Ireland) in terms of workflow and lumbar pedicle screw placement accuracy. Methods A cadaver lab was conducted, which included four procedures with single-level lumbar pedicle screw placement using the Fusion RoboticsTM system. These four procedures were compared to four propensity-score matched cases with single-level lumbar pedicle screw placement using the Mazor-XTM Stealth Edition. A single surgeon performed all surgeries. The cases were matched in terms of demographics (age, sex, race, BMI) and comorbidities (Charlson Comorbidity Index score). The primary outcome measure was the operative workflow efficiency (duration as measured with a stopwatch by an independent observer). The secondary outcome measures were pedicle screw accuracy and accuracy to plan. Results After propensity-score matching, there were four cases in each group with no significant between-group differences in terms of sex, race, BMI, or surgical levels; however, there were significant differences in terms of age (p=0.01) and comorbidities (p

OBJECTIVES: To develop a tool for researchers to augment the ASA24 database and include novel foods, beverages, and supplements for use in their study. METHODS: ASA24 uses nutrient values for foods and beverages from USDA's Food and Nutrient Database for Dietary Studies (FNDDS) and supplement values from the National Health and Nutrition Examination Survey Dietary Supplement Database (NHANES DSD). Novel items, such as medical food products, regional or international foods, and proprietary supplement blends may not be present in FNDDS and NHANES DSD, causing researchers to decide not to use ASA24. The ASA24 software engineering and dietary assessment teams analyzed system components including the hierarchal structured database and software code to determine how researcher-provided data for novel items could be incrementally integrated into the complex, “big data” system. The staff evaluated several approaches and technologies to allow researchers to define specific foods, beverages, and supplements against a set of defined evaluation criteria that addressed usability and technical requirements. RESULTS: The ASA24 new foods tool is an Excel workbook comprised of 19 worksheets. Excel macros validate data and facilitate navigation through the workbook. The worksheets are comprised of instructions, data entry templates, completed data entry templates for example purposes, and reference data. Researchers specify food, beverage, and supplement terms, portion amount probes and associated images, nutrient and Food Pattern Equivalents Database values, allowing the novel item to be added to the ASA24 system, and ultimately available to respondents using ASA24 to report dietary intake. The tool has undergone multiple rounds of usability testing and refinements to address issues. The integration process includes the maintenance of a master copy of foods, beverages, and supplements that will be available to researchers interested in adding these items to their own studies. CONCLUSIONS: The ASA24 new foods tool provides researchers with a cost-effective means to add novel foods, beverages, and supplements to their study. This tool can expand the utility of ASA24 to previously understudied groups. FUNDING SOURCES: This project has been funded in whole or in part by the NIH.

OBJECTIVES: To develop a sleep assessment module in ASA24 to capture self-reported sleep behavior as an optional enhancement to the ASA24 Dietary Assessment Tool for adults. METHODS: Multiple self-reported sleep assessment tools were considered in module development, including the National Sleep Foundation Sleep Diary, the Activities Completed over Time in 24-hours (ACT24), Munich Chronotype Questionnaire (MCTQ), and the Consensus Sleep Diary (CSD) Core. Priority was given to minimal need for adaptation, questionnaire length to reduce survey fatigue, incorporating plain language, and optimizing for implementation in 24 hour recalls (24HR) and food records. Researchers with expertise in meal timing and sleep were consulted for feedback on content and utility and programmers with expertise in survey design were consulted on implementation. Lastly, the online data collection process and ASA24 System's output data files were tested for accuracy. RESULTS: The ASA24 sleep module contains ten questions and can be administered immediately following dietary assessment. Eight CSD Core questions were adapted to assess time in bed, time trying to go to sleep, and length of time to fall asleep; number and duration of nocturnal awakenings; wake time and time out of bed for the day; and perceived sleep quality. Two questions were added to capture sleep quality and comparability of reported sleep to a usual night's sleep. For users completing a 24HR, the module includes two questions on time of awakening and sleep quality immediately preceding the first reported meal; all 10 sleep questions are asked for the sleep period immediately following the last meal (i.e., 12 questions total), allowing for assessment of the impact of diet on sleep. In contrast, a food record is completed on the same day users consume the food, and thus all sleep questions address the sleep window prior to the first meal; a single record can be used to assess the impact of sleep on diet. Consecutive days of records can also be collected to capture sleep pre- and post-eating windows. CONCLUSIONS: The ASA24 sleep module can assess sleep timing and quality and will be available in Fall 2021. Researchers can soon leverage this novel resource to examine the association of sleep with timing of eating and other chrononutrition variables. FUNDING SOURCES: This project has been funded by the NIH.

The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro‐evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post‐meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2077-0383/10/11/2227 En esta investigación también participan: Mar Valero Vello, Silvia M. Sanz González, José E. O'Connor, David Galarreta Mira, María D. Pinazo-Durán y Vicente Zanón Moreno. Este artículo pertenece al número especial "Recent Clinical Research on Glaucoma". Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18–22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND.

Intraventricular hemorrhage (IVH) is a devastating neurosurgical condition associated with high rates of morbidity and mortality. It can occur as the result of several pathologies and typically presents with mental status changes, neurologic deficits, seizures, headaches, and decreased Glasgow Coma Scale score. These patients are often treated with placement of an external ventricular drain, which helps decrease the clot burden; however, they commonly clot off leading to multiple exchanges. We present a case in which drainage, irrigation, and fibrinolytic (DRIFT) therapy using IRRAflow® (IRRAS) irrigating catheter was used to treat a patient with severe IVH secondary to aneurysmal subarachnoid hemorrhage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CLpro (Mpro). The drug candidate PF-00835231 is the active compound of the first anti-3CLpro regimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the pre-clinical 3CLpro inhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A549+ACE2 cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A549+ACE2 cells and validates PF-00835231's early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations. Finally, we show that the efflux transporter P-glycoprotein, which was previously suggested to diminish PF-00835231's efficacy based on experiments in monkey kidney Vero E6 cells, does not negatively impact PF-00835231 efficacy in either A549+ACE2 cells or human polarized airway epithelial cultures. Thus, our study provides in vitro evidence for the potential of PF-00835231 as an effective SARS-CoV-2 antiviral and addresses concerns that emerged based on prior studies in non-human in vitro models.Importance:The arsenal of SARS-CoV-2 specific antiviral drugs is extremely limited. Only one direct-acting antiviral drug is currently approved, the viral polymerase inhibitor remdesivir, and it has limited efficacy. Thus, there is a substantial need to develop additional antiviral compounds with minimal side effects and alternate viral targets. One such alternate target is its main protease, 3CLpro (Mpro), an essential component of the SARS-CoV-2 life cycle processing the viral polyprotein into the components of the viral polymerase complex. In this study, we characterize a novel antiviral drug, PF-00835231, which is the active component of the first-in-class 3CLpro-targeting regimen in clinical trials. Using 3D in vitro models of the human airway epithelium, we demonstrate the antiviral potential of PF-00835231 for inhibition of SARS-CoV-2.

This study identified subgroups of adolescents with distinct patterns of involvement with overt and relational in-person and cyber aggression and victimization. We also assessed subgroup similarities and differences in exposure to adverse childhood experiences (ACEs), exposure to community violence, and trauma symptoms. Using latent class analysis, we identified three subgroups among 265 adolescents (M(age) = 14.3 years; 57% female; 96% African American) residing in three urban high-burden communities that included youth who reported: (a) combined (cyber and in-person) aggression and victimization (17%), (b) in-person aggression and victimization (51%), and (c) adolescents with limited involvement (32%). Youth in the combined aggressive-victims subgroup had the highest probability of endorsing exposure to community violence, trauma symptoms, and a higher number of ACEs overall as well as higher rates of both verbal and physical abuse compared to the other subgroups. Our results indicated that the adolescents who reported the highest frequencies of aggressive behavior were also the most victimized and traumatized. These findings provide context to aggressive behavior among adolescents living in high-burden, urban communities and underscore the need for trauma-informed prevention interventions.

Simple Summary The COVID-19 pandemic has contributed to elevated rates of mental health problems and distress among the U.S. population. Pets may be an important source of social support to combat social isolation. This cross-sectional study used latent profile analysis to identify subgroups of U.S. pet owners based on their perceived mental health symptoms prior to and after the onset of the pandemic. Latent transition analysis was used to determine the stability of subgroup membership and examine the effect of attachment to pets on transition probabilities. Five subgroups were identified: low symptoms, mild symptoms, moderate symptoms, high symptoms, and severe symptoms. Evidence of moderation was found, X2(16) = 41.47, p = 0.04. Specifically, results indicated that attachment to pets functioned as a protective factor for individuals exhibiting moderate and high levels of mental health symptoms, as above average attachment to pets was associated with greater odds of transitioning to a less severe symptom profile. However, individuals with severe symptom profiles and high attachment to pets fared worst in the context of COVID-19 restrictions. This study has important implications for future research investigating the role of pets on mental health and for those providing services to pet owners during the COVID-19 pandemic. Abstract This cross-sectional study examined whether, and to what extent, attachment to pets was associated with changes in latent patterns of adults’ perceived mental health symptoms during the COVID-19 pandemic (n = 1942). We used latent transition analysis to determine the stability of subgroup membership pre- and post-COVID and the effect of attachment to pets on transition probabilities. Mental health before COVID-19 was measured retrospectively. Five subgroups were identified: low symptoms, mild symptoms, moderate symptoms, high symptoms, and severe symptoms. Among individuals in the moderate and high symptoms subgroups, those who reported high attachment to pets generally had greater odds of transitioning to a less severe symptom profile (OR = 2.12) over time than those with low attachment to pets (OR = 1.39). However, those who had a severe symptom profile and high attachment to pets had lower odds of transitioning to a less severe symptom profile (OR = 0.30) and higher odds of maintaining a severe symptom profile (OR = 3.33) than those with low attachment to pets. These findings suggest that the protective and risk effects of attachment to pets differ based on individuals’ psychological symptom patterns across multiple indicators. We discuss the implications of these findings for research, policy, and practice.