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Abstract Background Zearalenone (ZEN), a secondary metabolite of Fusarium fungi, is one of the most common mycotoxins in global food supplies such as cereal grains and processed food. ZEN and its metabolites are commonly referred to as mycoestrogens, due to their ability to directly bind nuclear estrogen receptors α (ER-α) and β (ER-β). Zeranol, a synthetic mycoestrogen, is administered to U.S. cattle as a growth promoter. Despite widespread human exposure and ample evidence of adverse reproductive impacts in vitro and in vivo, there has been little epidemiological research on the health impacts of ZEN exposure during pregnancy. The objective of our study was to examine associations between ZEN and gestational weight gain (GWG). Methods Urine samples were collected in each trimester from pregnant participants in the UPSIDE cohort (n = 286, Rochester, NY, USA). High performance liquid chromatography and high-resolution tandem mass spectrometry were used to quantify concentrations of ZEN as well as ∑mycoestrogens (composite sum of ZEN metabolites; ng/ml). Maternal weights at clinical visits were abstracted from medical records. We fitted longitudinal models of specific-gravity adjusted, log-transformed ZEN and ∑mycoestrogens in relation to total GWG (kilograms) and GWG rate (kilograms/week). We additionally examined risk of excessive GWG (in relation to Institute of Medicine guidelines) and considered effect modification by fetal sex. Results ZEN and ∑mycoestrogens were detected in > 93% and > 95% of samples, respectively. Mycoestrogen concentrations were positively associated with total GWG (ZEN β:0.50 kg; 95%CI: 0.13, 0.87) and GWG rate (ZEN β:0.20 kg/week; 95%CI: 0.01, 0.03). Associations tended to be stronger among participants carrying male (versus female) fetuses and results were robust to adjustment for diet. Conclusions Mycoestrogen exposure during pregnancy may contribute to greater GWG. Future research is needed to understand potential influences on downstream maternal and offspring health.

Abstract Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and bioinformatic experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in non-invasive and invasive breast cancer cell lines. In human triple-negative breast cancer biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in non-invasive compared to invasive regions. Similarly, bioinformatics analysis of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free, and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces the formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective therapeutic modality to limit recurrence in breast cancer patients.

ABSTRACT Objectives To evaluate the validity of the Golden Proportion, Golden Percentage, and Recurring Esthetic Dental (RED) Proportion among Kenyans of African descent with naturally well‐aligned teeth. Materials and Methods Standardized frontal photographic images of the smiles of 175 participants aged 18–35 years were obtained, and Adobe Photoshop was used to analyze and measure the frontal widths of the maxillary central and lateral incisors and canines in triplicate. The average teeth widths were calculated to determine the existence of the Golden Proportion, Golden Percentage, and RED Proportion, and their validity using independent sample t‐tests to compare the differences in the mean teeth widths at α

The study presents a concise overview on the main effects on satellites due to space weather drivers compared to the well-known interplanetary, magnetospheric and ground-based consequences. The solar-activity-driven influences include specific physics-based effects on the spacecraft surface and on-board electronics due to electromagnetic emission and energetic particles as well as complex effects due to geomagnetic storms which may endanger the mission performance and spacecraft longevity. We select as test examples the Starlink satellites in the period 2019–2022 and present the temporal correspondence between their launches and the space weather phenomena. Based on comparative analysis, we discuss whether the occurrence vs. the intensity of solar and interplanetary drivers of space weather can be considered as a cause for orbital stability problems and satellite loss. The results suggest that a sequence of geomagnetic disturbances together with multiple weak space weather events could lead to severe levels of atmospheric drag ending in a service or satellite loss.

Abstract Recently, much attention has been paid to the relationship between solar and seismic activities toward earthquake (EQ) prediction. Some researchers believe in the existence of a connection between them; however, others completely refuse the existence of such a connection. In this study, the correlation between solar disturbances and occurrence of EQs during two consecutive solar cycles (SCs) 23 & 24 from 1996 to 2019 was investigated to explore such a relationship. The study was performed on both global and local scales. On a global scale, we studied the temporal variations of EQs number and the corresponding solar activity, represented by sunspot number. On the other hand, we selected several seismic zones characterized with high seismic activities and shallow depth EQs. For each zone we examined the day-to-day variations in the number of EQs and explored the space weather “chain of action” from the Sun to Earth in order to examine whether these events have an influence to increase the number of EQs or not. Results showed that, for the whole global seismicity, no clear correlation is found between EQs occurrence and solar activity, while for small active seismic zones, the connection between them is significant. An increase in the number of shallow EQs in the studied seismic zones is observed in association with the variations of examined space weather indices. Thus, the current study suggests a possible connection between solar activity and localized seismic activities. However, the solar-magnetosphere-lithosphere coupling and interaction during solar events need further study and investigation for a better understanding of their EQ triggering effects.

The study presents the compilation of a comprehensive catalog of solar energetic protons (SEPs) in solar cycles (SCs) 23 and 24 (1996–2019) in 10 energy channels from about 20 to 100 MeV based on data from the Energetic and Relativistic Nuclei and Electron (ERNE) instrument aboard Solar and Heliospheric Observatory (SOHO). For comparison, we added previously reported SEP fluxes by a number of different sources. We identified the SEP-solar origin in terms of solar flares and coronal mass ejections and calculated the statistical correlations (Pearson and partial) as a function of the SEP energy.

Background/Objectives: Puerto Ricans (PRs) face significant challenges in accessing essential parenting resources and support due to language barriers and lack of culturally appropriate healthcare services, perpetuating health disparities. Cultural adaptation of psychosocial measurement tools is crucial for promoting health equity and improving health outcomes. This study describes the cultural adaptation of two parenting discipline assessment measures for use with Spanish-speaking PR mothers of 2–4-year-old children. Methods: We used a community-engaged, mixed-methods approach to measurement adaptation that involved independent translations (n = 2), back-translations (n = 2), and an adaptation committee (n = 6, including all translators) who reviewed, appraised, and modified survey versions. We conducted cognitive interviews (n = 20) to pretest the semi-finalized Spanish measures and assess mothers’ understanding of survey items. Results: Mothers had a mean age of 28.6 years. Most were married/cohabitating (70%), had a high school diploma or GED (90%), and a household income of less than $40,000 (68%). Indexed children’s mean age was 2.9 years, with most identified by mothers as female (60%). Feedback from the adaptation committee and pretesting participants led to specific changes like rephrasing culturally specific terms and adjusting examples to better fit the daily experiences of PR mothers. Most mothers found the Spanish version of the measures to be clear and culturally relevant. This cultural adaptation process addressed translation inconsistencies and design issues, and better captured culturally relevant discipline practices. Conclusions: Engaging communities in measurement adaptations ensures culturally and linguistically tailored measures that respect participant preferences, strengthen partnerships, and enable interventions to address health disparities, thereby promoting child health.

Poor sleep quality and psychological distress in pregnancy are important health concerns. Serotonin and melatonin levels may underlie variation in these adverse outcomes. In this study, we examined dietary nutrients involved in serotonin and melatonin synthesis in relation to maternal sleep quality and affective symptoms during pregnancy. Pregnant women at no greater than normal medical risk at enrollment completed 24-hour dietary recalls in mid-late pregnancy. Usual intakes of vitamin B6, vitamin D, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and tryptophan were estimated from dietary intake of foods and supplements using the National Cancer Institute (NCI) method. Sleep quality, depression, and anxiety were measured using validated questionnaires. Associations between nutrient intakes, sleep quality, and affective symptoms were estimated using generalized estimating equation models adjusting for potential confounding factors. In minimally adjusted models, EPA + DHA and tryptophan intakes were associated with a lower score indicating better sleep quality (b: −1.07, 95% CI: −2.09, −0.05) and (b: −12.40, 95% CI: −24.60, −0.21), respectively. EPA + DHA and tryptophan intakes were also associated with a lower odds of shorter sleep duration and sleep disturbances. In addition, tryptophan was associated with a lower odds of higher sleep latency. However, associations were attenuated and nonsignificant after adjustment for demographic and lifestyle factors. In conclusion, intakes of EPA + DHA and tryptophan were associated with improved sleep quality, but these associations were confounded by maternal demographic and lifestyle characteristics. This study highlights the need to consider dietary intake and pregnancy health in the context of demographic characteristics and lifestyle behaviors.

Abstract During a few solar energetic particle (SEP) events, solar protons were trapped within the geomagnetic field and reached the outer edge of the inner radiation belt. We reproduced this phenomenon by modeling the proton flux distribution at the Low‐Earth Orbit (LEO) for different geomagnetic conditions during solar particle events. We developed a three‐dimensional relativistic test particle simulation code to compute the 70–180 MeV solar proton Lorentz trajectories in low L‐shell range from 1 to 3. The Tsyganenko model (T01) generated the background static magnetic field with the IGRF (v12) model. We have selected three Dst index values: −7, −150, and −210 nT, to define quiet time, strong, and severe geomagnetic storms and to generate the corresponding inner magnetic field configurations. Our results showed that the simulated solar proton flux was more enhanced in the high‐latitude regions and more expanded toward the lower latitude range as long as the geomagnetic storm was intensified. Satellite observations and geomagnetic cutoff rigidities confirmed the numerical results. Furthermore, the LEO proton flux distribution was deformed, so the structure of the proton flux inside the South Atlantic Anomaly (SAA) became longitudinally extended as the Dst index decreased. Moreover, we have assessed the corresponding radiation environment of the LEO mission. We realized that, for a higher inclined LEO mission during an intense geomagnetic storm (Dst = −210 nT), the probability of the occurrence of the Single Event Upset (SEU) rates increased by 19% and the estimated accumulated absorbed radiation doses increased by 17% in comparison with quiet conditions.

The key postulate of the prion paradigm is that some proteins can take on unconventional conformations and pass these conformations to newly synthesized protein molecules with the same primary structure [...]

Background: A fall after total hip arthroplasty (THA) that results in a periprosthetic femoral fracture (PPF) can have devastating functional and psychological consequences in older adults. There are few studies that have evaluated both functional and psychological outcomes of PPF post-THA in the same cohort. Methods: This is a retrospective study of 130 people who underwent revision THA between 2005 and 2019 due to PPF. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC), Harris Hip Score (HHS), and Short Form-12 (SF-12) assessed physical function, hip joint function, and psychological well-being, respectively. Descriptive statistics using means and standard deviation or frequencies and percentages were used to define the sample. The association between baseline demographic, clinical, and surgical factors on WOMAC, HHS, and SF-12 scores at 1-year post-PPF surgery was modelled using multivariable linear regression. The mean age (n = 130) was 80.6 ± 9.0 years, and 55.4% (n = 72) were female. The mortality rate was 15.4% (n = 20) at 1-year post-PPF surgery. One-year follow-up data were available for 35.4% (n = 46) of patients. Results: The WOMAC (n = 37), HHS (n = 32), and SF-12 mental component summary (n = 46) scores at 1-year post-PPF surgery were 67.9 ± 20.3, 78.3 ± 15.0, and 52.7 ± 9.1, respectively. No significant association was found among age, gender, previous history of lower extremity surgery, Vancouver classification, and femoral bone grafting on WOMAC, HHS, and SF-12 scores. Conclusions: Our study found that patients with PPF have fair hip joint function, poor physical function and psychological well-being, and a high mortality rate at 1-year post-PPF surgery.

ObjectiveSex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes.MethodsRetrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels.ResultsIn adjusted models, first trimester total testosterone (β=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (β=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (β=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone.ConclusionEarly-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors.

Each year in Canada, a substantial number of adults undergo limb amputation, with lower limb amputation (LLA) the most prevalent. Enhancing walking ability is crucial for optimizing rehabilitation outcomes, promoting participation, and facilitating community reintegration. Overcoming challenges during the acute post-amputation phase and sub-acute rehabilitation necessitates alternative approaches, such as motor imagery and mental practice, to maximize rehabilitation success. However, the current evidence on activation patterns using motor imagery in individuals with LLA is limited. The primary objective was to assess the feasibility of observing brain activation during imagined walking in individuals with LLA utilizing 3T functional magnetic resonance imaging (fMRI). Eight individuals with LLA and 11 control subjects participated. Consistent with representations of the lower limbs, both control and amputee groups demonstrated bilateral activation in the medial surface of the primary motor and somatosensory cortices. However, individuals with lower limb amputations exhibited significantly greater activation during imagined walking, particularly in frontal regions and the medial surface of the primary motor and supplementary motor cortices. Furthermore, the volume of activation in the bilateral primary motor cortices was higher for participants with amputations compared to controls. The protocol developed in this study establishes a foundation for evaluating the effects of a gait training program that incorporates mental imagery alongside conventional rehabilitation practices, in contrast to standard care alone. This pilot investigation holds potential to enhance our understanding of brain plasticity in individuals with LLA and pave the way for more effective rehabilitation strategies to optimize functional recovery and community reintegration.

Abstract Honey bees process nectar into honey by active evaporation on the tongue and passive evaporation involving nest ventilation and fanning behaviour, as well as enzymatic action. The elimination of excess water from nectar carries considerable energetic costs. The concentration of the nectar load is assumed to remain constant during transport. However, some of this water elimination may occur before foragers return to the nest and pass their nectar loads to receiver bees. In honey bees captured while foraging in Macadamia orchards, we show that the nectar in their crops has approximately twice the sugar concentration of the fresh nectar in flowers. This was true for four Macadamia cultivars, with up to 75% of the initial water content being removed. There is a further concentration increase in the crops of returning bees captured at the hive entrance. The only possible route of water elimination from the crop is via evaporation from the mouthparts. We calculate the savings in honey processing costs to be on average 35 times more than the reduction in flight costs due to reduced body mass. Pre-concentration of nectar in foraging honey bees may be widespread, and of crucial importance for honey storage.

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results. Consequently, a cautionary statement regarding belimumab use in this population was added to the product label. To alleviate concerns that belimumab may not be safe and effective for patients of Black African ancestry, the Efficacy and Safety of Belimumab in Black Race Patients with SLE (EMBRACE) study was conducted in a post‐marketing commitment to the Food and Drug Administration. The study recruited only patients who self‐identified as being of Black race; its findings led to the removal of the cautionary labeling of belimumab use in patients of Black African ancestry. Our manuscript highlights the critical lessons learned from the successes and failures of the EMBRACE study. It also provides suggestions for overcoming health disparities, highlighting strategies for conducting well‐designed clinical trials to overcome systematic barriers to diversity in recruitment, with a focus on enacting long‐term support to ensure equity in the process, products, and benefits from drug development and clinical trials.

Whether or not primates are behaviorally affected by the presence of visitors in a zoo setting is a question of great relevance to zoo animal well-being. The situation imposed by the COVID-19 pandemic provided an unusual opportunity to examine how the absence of visitors impacts behavior. We took advantage of this opportunity to study the behavior of a gorilla troop during periods of no-visitors compared to our long-term database on gorilla behavior during normal zoo operations. While there were notable individual differences in response to visitors, we found no significant relationship between presence of visitors and behavior. These results suggest that the presence of visitors does not have a significant impact on behavior and well-being of zoo-housed gorillas.

Abstract Background Research has demonstrated an increased risk of falls after total hip arthroplasty (THA). Yet, people’s knowledge on falls risk factors and how falls prevention strategies are being used after THA have not been examined. If a person’s knowledge of falls and self-efficacy about falls prevention strategies is low this would indicate a pressing need for interventions to lessen risk. The study objectives were: 1) to determine the falls knowledge and what fall prevention strategies people used after (THA) and 2) to determine the outcomes of a falls risk assessment at 12-months after unilateral THA. Methods Overall, 108 people completed the Falls Risk for Older People – Community Setting (FROP-Com) scale, a falls questionnaire (covered occurrence of falls, knowledge on falls risk factors, falls prevention strategies implemented after THA surgery), 6-m Walk Test (6mWT), 30-Second Chair Stand Test (30CST), Timed-up and Go (TUG) Test, and Activities-specific Balance Confidence Scale (ABC). Results Twenty-five (23.2%) people fell at least once in the 12 months after THA. Scores on the FROP-Com ranged from 2–20 with an average of 8.2 ± 3.6 indicating a mild falls risk. The importance of falling compared to other health concerns was rated as moderate to high (6.8 ± 2.9) and the majority of participants (n = 98, 90.7%) believed falls can be prevented after THA. Total scores on the ABC scale ranged from 30.6% to 100.0% with an average score of 84.4 ± 15.5%, indicating high function. Only 47 people (43.5%) reported receiving falls prevention education. A total of 101 falls prevention strategies were completed by 67 people (62%), the most common strategy was environmental modifications (e.g., installation of grab bars) at 37.4%, while exercise was mentioned by only 2%. The majority of people had functional deficits in 30CST (62%) and TUG (76.9%) at 12-months after unilateral THA. Conclusions Almost a quarter of the sample had experienced a fall in the 12-months after THA and functional deficits were common. The majority of the sample had proactively implemented falls prevention strategies after the surgery. Yet importantly, people after THA had limited exposure to falls prevention education and implemented a limited range of prevention strategies.

Abstract Objective Binge eating, a core diagnostic symptom in binge eating disorder and bulimia nervosa, increases the risk of multiple physiological and psychiatric disorders. The neurotransmitter dopamine is involved in food craving, decision making, executive functioning, and impulsivity personality trait; all of which contribute to the development and maintenance of binge eating. The objective of this paper is to review the associations of dopamine levels/activities, dopamine regulator (e.g., dopamine transporter, degrading enzymes) levels/activities, and dopamine receptor availability/affinity with binge eating. Methods A literature search was conducted in PubMed and PsycINFO to obtain human and animal studies published since 2010. Results A total of 31 studies (25 human, six animal) were included. Among the human studies, there were 12 case–control studies, eight randomized controlled trials, and five cross-sectional studies. Studies used neuroimaging (e.g., positron emission tomography), genetic, and pharmacological (e.g., dopamine transporter inhibitor) techniques to describe or compare dopamine levels/activities, dopamine transporter levels/activities, dopamine degrading enzyme (e.g., catechol-O-methyltransferase) levels/activities, and dopamine receptor (e.g., D1, D2) availability/affinity among participants with and without binge eating. Most human and animal studies supported an altered dopaminergic state in binge eating (26/31, 83.9%); however, results were divergent regarding whether the altered state was hyperdopaminergic (9/26, 34.6%) or hypodopaminergic (17/26, 65.4%). The mixed findings may be partially explained by the variability in sample characteristics, study design, diagnosis criteria, and neuroimaging/genetic/pharmacological techniques used. However, it is possible that instead of being mutually exclusive, the hyperdopaminergic and hypodopaminergic state may co-exist, but in different stages of binge eating or in different individual genotypes. Conclusions For future studies to clarify the inconsistent findings, a homogenous sample that controls for confounders that may influence dopamine levels (e.g., psychiatric diseases) is preferable. Longitudinal studies are needed to evaluate whether the hyper- and hypo-dopaminergic states co-exist in different stages of binge eating or co-exist in individual phenotypes. Plain Language Summary Binge eating is characterized by eating a large amount of food in a short time and a feeling of difficulty to stop while eating. Binge eating is the defining symptom of binge eating disorder and bulimia nervosa, both of which are associated with serious health consequences. Studies have identified several psychological risk factors of binge eating, including a strong desire for food, impaired cognitive skills, and distinct personality traits (e.g., quick action without careful thinking). However, the physiological markers of binge eating remain unclear. Dopamine is a neurotransmitter that is heavily involved in feeding behavior, human motivation, cognitive ability, and personality. Therefore, dopamine is believed to play a critical role in binge eating. This review synthesized study findings related to the levels and activities of dopamine, dopamine regulators, and dopamine receptors in the context of binge eating. The primary finding is that most studies that used neuroimaging, genetic, or drug techniques found an altered dopaminergic state related to binge eating. However, the literature is inconsistent concerning the direction of the alteration. Considering the mixed findings and the limitations in study design, future studies, especially those that include repeated measurements, are needed to clarify the role of dopamine in binge eating.

OBJECTIVES:. Children presenting with acute myocarditis may experience rapid clinical deterioration requiring extracorporeal membrane oxygenation (ECMO); however, our understanding of best practices and timing of ECMO initiation are lacking. We explored the relationships between pre-cannulation factors and survival in this high-acuity patient population. DESIGN:. Retrospective review of a large international registry. Primary outcome was survival to hospital discharge, stratified by incident cardiac arrest (CA) prior to ECMO and time to cannulation after intubation. SETTING AND SUBJECTS:. The Extracorporeal Life Support Organization registry was queried for patients less than or equal to 18 years old receiving ECMO support for myocarditis between 2007 and 2018. Exclusion criteria included being nonindex runs, non-venoarterial ECMO or missing data points for main variables studied. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Population characteristics and survival were compared using t test, Wilcoxon rank-sum test, or Fisher exact test. Multivariable logistic regression was used for significant factors in the unadjusted logistic regression. Among 506 index ECMO runs in pediatric patients with myocarditis, survival for the cohort was 72%, with no difference between early and late eras (2007–2012 vs 2013–2018; p = 0.69). Survivors demonstrated higher pre-ECMO pH levels as well as shorter intubation-to-cannulation (ITC) times (3 hr [interquartile range (IQR)], 1–14 hr vs 6 hr [IQR, 2–20 hr]; p = 0.021). CA occurred within 24 hours prior to ECMO cannulation, including extracorporeal cardiopulmonary resuscitation, in 54% of ECMO runs (n = 273). Accounting for the interaction between pre-ECMO CA occurrence and ITC time, longer ITC time remained associated with lower survival for patients who did not experience a CA prior to ECMO, with adjusted odds ratio of 0.09 (IQR, 0.02–0.40; p = 0.002) for ITC time greater than or equal to 18 hours. CONCLUSIONS:. The results of this multicenter analysis of ECMO utilization and outcomes for pediatric myocarditis suggest that patients approaching ECMO cannulation who have not experienced CA may have better survival outcomes if cannulated onto ECMO early after intubation.

We present a comprehensive catalog of geomagnetic storms (GSs) with a Dst index ≤−50 nT detected during solar cycles (SCs) 23 and 24 (1996–2019). About 550 events were identified in the Kyoto database and used as a starting point for this study. The solar origin of the GSs, in terms of coronal mass ejections (CMEs), solar flares (SFs), and in situ-observed energetic particles, was identified where possible using temporal constraints and wide Earth-directed ejecta. In addition, any accompanied interplanetary (IP) sources, such as ICMEs and IP shock waves detected at 1 AU, are also considered. The resulting occurrence rates and correlation plots are presented and discussed in the space weather framework.

Abstract Objective The importance of the central and peripheral serotonin systems in regulating energy balance and obesity development has been highlighted in animal models. Yet, the role of both serotonin systems has not been systematically assessed in humans. The purpose of this study was to investigate the association of genes within both serotonin systems with obesity outcomes in black adolescents. Methods African–American adolescents (n = 1052) whose mothers participated the Memphis New Mother's Study were assessed. In total, 110 polymorphisms mapped to 10 serotonin genes were examined for their associations with standardized body mass index (BMI‐z) scores and waist circumferences using generalized estimating equation models. Results Over 39% of adolescents were overweight or had obesity. Three single nucleotide polymorphisms (SNPs) within TPH2, HTR3B, and SLC6A4, were significantly associated with BMI‐z scores (p

Abstract Purpose Ready-to-eat fast food vending outlets provide a cheap and readily available food. Foodborne diseases have been previously reported in Embu, Kenya, but data on the prokaryotic metagenome in vended foods is scanty. This study aimed to determine the prokaryotic diversity in fruits, vegetable salad, African sausage, chips (potato fries), fried fish, roasted beef (meat), smokies, samosa, soil, and water collected from food vendors and the surrounding environment in Embu Town and Kangaru Market. Methods The study used 454 pyrosequencing, Illumina high-throughput sequencing of 16S rRNA gene in the analysis of total community DNA extracted from samples using the phenol-chloroform method. The 16S rRNA gene variable region (V4-V7) of the extracted DNA was amplified and library construction performed. Sequence analysis was done using QIIME2. Hierarchical clustering of samples, diversity indices, rarefaction curves, and Venn diagrams were generated using the R programming language in R software version 3.6.3. Results Bacterial operational taxonomic units (OUTs) were distributed in Proteobacteria (52.81%), Firmicutes (31.16%), and Lentisphaerae (0.001%). The OTUs among archaea were Candidatus Nitrososphaera (63.56%) and Nitrososphaera spp. (8.77%). Brucella spp. and Bacillus cereus associated with foodborne diseases were detected. Potential pathogens, Rickettsia spp. in risk group 2 and Brucella spp. in risk group 3, were detected. Uncultured Candidatus Koribacter and Candidatus Solibacter were also detected in the food samples. There was a significant difference in the microbial community structure among the sample types (P

Abstract In spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived cross-links was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.

To control HIV infection there is a need for vaccines to induce broad, potent and long-term B and T cell immune responses. With the objective to accelerate and maintain the induction of substantial levels of HIV-1 Env-specific antibodies and, at the same time, to enhance balanced CD4 and CD8 T cell responses, we evaluated the effect of concurrent administration of MF59-adjuvanted Env protein together with DNA or NYVAC vectors at priming to establish if early administration of Env leads to early induction of antibody responses. The primary goal was to assess the immunogenicity endpoint at week 26. Secondary endpoints were (i) to determine the quality of responses with regard to RV144 correlates of protection and (ii) to explore a potential impact of two late boosts. In this study, five different prime/boost vaccination regimens were tested in rhesus macaques. Animals received priming immunizations with either NYVAC or DNA alone or in combination with Env protein, followed by NYVAC + protein or DNA + protein boosts. All regimens induced broad, polyfunctional and well-balanced CD4 and CD8 T cell responses, with DNA-primed regimens eliciting higher response rates and magnitudes than NYVAC-primed regimens. Very high plasma binding IgG titers including V1/V2 specific antibodies, modest antibody-dependent cellular cytotoxicity (ADCC) and moderate neutralization activity were observed. Of note, early administration of the MF59-adjuvanted Env protein in parallel with DNA priming leads to more rapid elicitation of humoral responses, without negatively affecting the cellular responses, while responses were rapidly boosted after repeated immunizations, indicating the induction of a robust memory response. In conclusion, our findings support the use of the Env protein component during priming in the context of an heterologous immunization regimen with a DNA and/or NYVAC vector as an optimized immunization protocol against HIV infection.

Abstract Cells interpret cues from and interact with fibrous microenvironments through the body based on the mechanics and organization of these environments and the phenotypic state of the cell. This in turn regulates mechanoactive pathways, such as the localization of mechanosensitive factors. Here, we leverage the microscale heterogeneity inherent to engineered fiber microenvironments to produce a large morphologic data set, across multiple cells types, while simultaneously measuring mechanobiological response (YAP/TAZ nuclear localization) at the single cell level. This dataset describing a large dynamic range of cell morphologies and responses was coupled with a machine learning approach to predict the mechanobiological state of individual cells from multiple lineages. We also noted that certain cells (e.g., invasive cancer cells) or biochemical perturbations (e.g., modulating contractility) can limit the predictability of cells in a universal context. Leveraging this finding, we developed further models that incorporate biochemical cues for single cell prediction or identify individual cells that do not follow the established rules. The models developed here provide a tool for connecting cell morphology and signaling, incorporating biochemical cues in predictive models, and identifying aberrant cell behavior at the single cell level.

Abstract Background Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of inflammation through cell death and proinflammatory cytokine production. This multicenter, randomized, double-blind (sponsor-unblinded), placebo-controlled, experimental medicine study evaluated the safety, pharmacokinetics (PK), and preliminary efficacy of GSK2982772, a RIPK1 inhibitor, in moderate to severe rheumatoid arthritis (RA). Methods Patients with moderate to severe RA who had received ≥12 weeks’ stable-dose conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy were randomized (2:1) to GSK2982772 60 mg or placebo orally 2 or 3 times daily for 84 days. Safety, PK, disease activity, joint damage, and pharmacodynamic (PD) biomarkers were assessed at days 43 and 85. Results A total of 52 patients were randomized (placebo, 18; GSK2982772, 34). Adverse events (AEs) were reported in 13 (72%) in patients in the placebo group (n = 3 b.i.d; n = 10 t.i.d.) and 20 (61%) in the GSK2982772 group (n = 3 b.i.d; n = 17 t.i.d.). All treatment-related AEs were mild/moderate, except one severe case of alopecia areata at day 49 and retinal vein thrombosis at day 66 (which led to withdrawal from the study) in patients receiving GSK2982772 t.i.d. Disease Activity Score in 28 Joints–C-reactive protein (DAS28-CRP) scores, ACR20/50/70 response, and rates of low disease activity and remission were similar between placebo and GSK2982772 arms. Conclusions These results suggest that inhibition of RIPK1 activity at the GSK2982772 exposure levels evaluated do not translate into meaningful clinical improvement of RA. Trial registration ClinicalTrials.gov Identifier: NCT02858492 . Registered 8 August 2016.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is often accompanied by impaired emotion regulation (ER). There has been increasing emphasis on developing evidence-based approaches to improve ER in ASD. Electroencephalography (EEG) has shown success in reducing ASD symptoms when used in neurofeedback-based interventions. Also, certain EEG components are associated with ER. Our overarching goal is to develop a technology that will use EEG to monitor real-time changes in ER and perform intervention based on these changes. As a first step, an EEG-based brain computer interface that is based on an Affective Posner task was developed to identify patterns associated with ER on a single trial basis, and EEG data collected from 21 individuals with ASD. Accordingly, our aim in this study is to investigate EEG features that could differentiate between distress and non-distress conditions. Specifically, we investigate if the EEG time-locked to the visual feedback presentation could be used to classify between WIN (non-distress) and LOSE (distress) conditions in a game with deception. Results showed that the extracted EEG features could differentiate between WIN and LOSE conditions (average accuracy of 81%), LOSE and rest-EEG conditions (average accuracy 94.8%), and WIN and rest-EEG conditions (average accuracy 94.9%).

Objective: To determine which intrinsic and extrinsic exertional heat illness (EHI) risk factors exist in youth American football players and observe perceptual and physiological responses of players during events (games and practices). Methods: Cross-sectional cohort study observing 63 youth football players, varying in position. Independent variables were league (weight-restricted (WR, n = 27) and age-restricted (AR, n = 36)) and event type. Dependent variables were anthropometrics, work-to-rest ratio, and wet bulb globe temperature. Descriptive variables included preparticipation examination and uniform configuration. A subset of 16 players participated in physiological variables (heart rate and gastrointestinal temperature). Data collection occurred on 7 AR and 8 WR nonconsecutive practices and the first 3 games of the season. Results: Mean values for anthropometric variables were higher (p < 0.05) in the AR league than the WR league. Work time (χ2 (1,111) = 4.232; p = 0.039) and rest time (χ2 (1,111) = 43.41; p < 0.001) were significantly greater for games, but ratios were significantly higher for practices (χ2 (1,111) = 40.62; p < 0.001). The majority of events (77%) observed were in black and red flag wet bulb globe temperature risk categories. A total of 57% of the players had a preparticipation examination, and up to 82% of events observed were in full uniforms. Individual gastrointestinal temperature and heart rate responses ranged widely and no players reached critical thresholds. Conclusion: Extrinsic (disproportionate work ratios, environmental conditions) and intrinsic (higher body mass index) EHI risk factors exist in youth football. Certain risk factors may be influenced by event and league type. National youth football organizations need to create thorough guidelines that address EHI risk factors for local leagues to adopt.

Abstract Background Balance and gait problems are common and progressive in dementia. Use of a mobility aid provides physical support and confidence. Yet, mobility aid use in people with dementia increases falls three-fold. An assessment tool of mobility aid safety in people with dementia does not currently exist. The objectives of this study were: 1) to develop a tool for the evaluation of physical function and safe use of a 4-wheeled walker in people with dementia, and 2) to evaluate its construct and criterion validity, inter-rater and test-retest reliability and minimal detectable change. Methods Healthcare professionals (HCP) experienced in rehabilitation of people with dementia participated in focus groups for item generation of the new tool, The Safe Use of Mobility Aid Checklist (SUMAC). The SUMAC evaluates physical function (PF) and safe use of the equipment (EQ) on nine tasks of daily life. Reliability was evaluated by HCP (n = 5) scored participant videos of people with dementia (n = 10) using a 4-wheeled walker performing the SUMAC. Inter-rater and test-retest reliability was assessed using intra-class correlation coefficients (ICC). Construct validity evaluated scores of the HCPs to a consensus HCP panel using Spearman’s rank-order correlations. Criterion validity evaluated SUMAC-PF to the Performance-Oriented Mobility Assessment (POMA) gait subscale using Spearman’s rank-order correlations. Results Three focus groups (n = 17) generated a tool comprised of nine tasks and the components within each task for physical function and safe use. Inter-rater reliability was statistically significant for SUMAC-PF (ICC = 0.92, 95%CI (0.81, 0.98), p

In this study, we give correlations between the geomagnetic storm (GS) intensity and parameters of solar and interplanetary (IP) phenomena. We also perform 3D geometry reconstructions of geo-effective coronal mass ejections (CMEs) using the recently developed PyThea framework and compare on-sky and de-projected parameter values, focusing on the reliability of the de-projection capabilities. We utilize spheroid, ellipsoid and graduated cylindrical shell models. In addition, we collected a number of parameters of the GS-associated phenomena. A large variation in 3D de-projections is obtained for the CME speeds depending on the selected model for CME reconstruction and observer subjectivity. A combination of fast speed and frontal orientation of the magnetic structure upon its arrival at the terrestrial magnetosphere proves to be the best indicator for the GS strength. More reliable estimations of geometry and directivity, in addition to de-projected speeds, are important for GS forecasting in operational space weather schemes.

The expression of life-history traits, such as lifespan or reproductive effort, is tightly correlated with the amount and blend of macronutrients that individuals consume. In a range of herbivorous insects, consuming high protein to carbohydrate ratios (P:C) decreases lifespan but increases female fecundity. In other words, females face a resource-based trade-off between lifespan and fecundity. Redox metabolism may help mediate this trade-off, if oxidative damage is elevated by reproductive investment and if this damage, in turn, reduces lifespan. Here, we test how diets varying in P:C ratio affect oxidative damage and antioxidant protection in female and male of the marula fly, Ceratitis cosyra (Diptera: Tephritidae). We use replicated lines that have been subjected to experimental evolution and differ in their lifespan and reproductive scheduling. We predicted that high fecundity would be associated with high oxidative damage and reduced antioxidant defences, while longer lived flies would show reduced damage and elevated antioxidant defences. However, higher levels of oxidative damage were observed in long-lived control lines than selection lines, but only when fed the diet promoting lifespan. Flies fed diets promoting female fecundity (1:4 and 1:2 P:C) suffered greater oxidative damage to lipids than flies fed the best diet (0:1 P:C) for lifespan. Total antioxidant capacity was not affected by the selection regime or nutrition. Our results reiterate the importance of nutrition in affecting life-history traits, but suggest that in C. cosyra, reactive oxygen species play a minimal role in mediating dietary trade-offs between lifespan and reproduction.

In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medical clinical practice, with the goal of developing strategies for curing or preventing disease and ameliorating pain and suffering in companion animals and humans alike. Veterinary clinical trials in client-owned companion animals affected with naturally occurring, spontaneous disease can inform human clinical trials and significantly improve their outcomes. Innovative cell therapies are an area of rapid development that can benefit from non-traditional and clinically relevant animal models of disease. This manuscript outlines cell types and therapeutic applications that are currently being investigated in companion animals that are affected by naturally occurring diseases. We further discuss how such investigations impact translational efforts into the human medical field, including a critical evaluation of their benefits and shortcomings. Here, leaders in the field of veterinary regenerative medicine argue that experience gained through the use of cell therapies in companion animals with naturally occurring diseases represent a unique and under-utilized resource that could serve as a critical bridge between laboratory/preclinical models and successful human clinical trials through a One-Health approach.

The goal of this study was to translate and adapt the original 9-item of the Contextual Assessment of Social Skills (CASS) to a Dutch version and assess its psychometric qualities. Autistic adolescents aged 12 to 18 years (n = 99) took part in a randomized controlled trial. In this study, pre-intervention data were utilized. The original CASS was adapted to ensure cultural relevance and the content validity was assessed. Data was used to assess reliability and structural validity, using confirmatory factor analysis. 4-item were added to the CASS during the adaptation to better align with the objectives of the experimental intervention. The original 9-item had inter-item correlations between 0.01 and 0.70. The Cronbach's alpha for the original 4-item total score was moderate ([alpha] = 0.69), while for a 7-item total score, it was high ([alpha] = 0.86). This 7-item total score had a sufficient model fit (Comparative Fit Index = 0.90). This total score had a significant correlation with the Assertion subscale of the Social Skills Improvement System-Adolescent (SSIS-A) (r = 0.26, p < 0.01), and the Social Responsiveness Scale-2 (SRS-2) total score (r = - 0.21, p = 0.04) indicating sufficient convergent validity. The CASS total score was not correlated with the Repetitive and Restricted Behavior scale of the SRS-2 (r = - 0.08, p = 0.43), indicating sufficient divergent validity. The Dutch CASS can be considered a conceptually sound and reliable observational instrument for assessing social conversational skills in Dutch autistic youth. Further evaluation of its feasibility when implemented in practice, outside of clinical research, is needed.

Systematic data collection has become increasingly important in zoos as it facilitates evidence-based decision-making. Here, we describe the results of a two-year study on exhibit use and pair-bonding in a colony of Humboldt penguins. We used two different data collection apps to evaluate their effectiveness and suitability for evaluating pair-bond strength. Data were collected using instantaneous scan sampling and all-occurrence sampling 2–3 times per week for 2 years for a total of nearly 240 h of observation (19 h with one system and 219 h with the other system). The activity patterns (in particular, time spent in the water) differed amongst penguins and between the two data collection tools. Patterns of courtship-related behaviors varied tremendously across individuals. The longer pairs had been bonded, the more time they spent in close proximity. We highlight two important considerations for institutions aiming to collect such systematic data. First, it is critical to interpret all findings in context by incorporating husbandry details and keeper insights to highlight explanations that may not be readily apparent from the data. Second, one must explore all aspects of any data collection system before committing to its use—system setup, ease of data collection, format and accessibility of exported data. Not doing so may negate the value of systematic data collection by limiting the use and interpretability of the data.

When human TDP-43 is overexpressed in yeast it is toxic and forms cytoplasmic aggregates. The mechanism of this toxicity is unknown. Genetic screens for TDP-43 toxicity modifiers in the yeast system previously identified proteins, including PBP1, that enhance TDP-43 toxicity. The determination in yeast that deletion of PBP1 reduces TDP-43 toxicity while overexpression enhances toxicity, led to the discovery that its human homolog, ATXN2, is associated with ALS risk. Thus, the yeast system has relevance to human disease. We now show that deletion of a new yeast gene, tip41Δ, likewise suppresses TDP-43 toxicity. We also found that TDP-43 overexpression and toxicity is associated with reduced autophagy. This is consistent with findings in other systems that increasing autophagy reduces TDP-43 toxicity and is in contrast to a report of enhanced autophagy when TDP-43 was overexpressed in yeast. Interestingly, we found that deletions of PBP1 and TIP41, which reduced TDP-43 toxicity, eliminated TDP-43′s inhibition of autophagy. This suggests that toxicity of TDP-43 expressed in yeast is in part due to its inhibition of autophagy and that deletions of PBP1 and TIP41 may reduce TDP-43 toxicity by preventing TDP-43 from inhibiting autophagy.

Abstract The purpose of this consensus document was to develop feasible, evidence‐based occupational heat safety recommendations to protect the US workers that experience heat stress. Heat safety recommendations were created to protect worker health and to avoid productivity losses associated with occupational heat stress. Recommendations were tailored to be utilized by safety managers, industrial hygienists, and the employers who bear responsibility for implementing heat safety plans. An interdisciplinary roundtable comprised of 51 experts was assembled to create a narrative review summarizing current data and gaps in knowledge within eight heat safety topics: (a) heat hygiene, (b) hydration, (c) heat acclimatization, (d) environmental monitoring, (e) physiological monitoring, (f) body cooling, (g) textiles and personal protective gear, and (h) emergency action plan implementation. The consensus‐based recommendations for each topic were created using the Delphi method and evaluated based on scientific evidence, feasibility, and clarity. The current document presents 40 occupational heat safety recommendations across all eight topics. Establishing these recommendations will help organizations and employers create effective heat safety plans for their workplaces, address factors that limit the implementation of heat safety best‐practices and protect worker health and productivity.

Objective: In regard to locating clinical trials for a systematic review, limited information is available about how librarians locate clinical trials in biomedical databases, including (1) how much information researchers provide librarians to assist with the development of a comprehensive search strategy, (2) which tools librarians turn to for information about study design methodology, and (3) librarians’ confidence levels in their knowledge of study design methodology. A survey was developed to explore these aspects of how a medical librarian locates clinical trials when facilitating systematic reviews for researchers. Methods: In this cross-sectional study, a 21-question survey was sent to medical librarians via several email listservs during April 2020. Respondents were limited to librarians who make the decisions on search terms for systematic reviews. Results: Responses (n=120) indicated that librarians were often asked to search for various types of clinical trials. However, there was not a consistent method for creating search strategies that locate diverse types of clinical trials. Multiple methods were used for search strategy development, with hedges being the most popular method. In general, these librarians considered themselves to be confident in locating trials. Different resources were used to inform study types, including textbooks, articles, library guides and websites. Discussion: Medical librarians indicated that while they felt confident in their searching skills, they did not have a definitive source of information about the various types of clinical trials, and their responses demonstrated a clear need and desire for more information on study design methodology.

Summary: The major lineages of nectar-feeding birds (hummingbirds, sunbirds, honeyeaters, flowerpiercers, and lorikeets) are considered examples of convergent evolution. We compared sucrose digestion capacity and sucrase enzymatic activity per unit intestinal surface area among 50 avian species from the New World, Africa, and Australia, including 20 nectarivores. With some exceptions, nectarivores had smaller intestinal surfaces, higher sucrose hydrolysis capacity, and greater sucrase activity per unit intestinal area. Convergence analysis showed high values for sucrose hydrolysis and sucrase activity per unit intestinal surface area in specialist nectarivores, matching the high proportion of sucrose in the nectar of the plants they pollinate. Plants pollinated by generalist nectar-feeding birds in the Old and New Worlds secrete nectar in which glucose and fructose are the dominant sugars. Matching intestinal enzyme activity in birds and nectar composition in flowers appears to be an example of convergent coevolution between plants and pollinators on an intercontinental scale.

The prevalence of diabetes is consistently rising worldwide. Diabetic nephropathy is a leading cause of chronic renal failure. The present study aimed to explore the crosstalk among the different cell types inside diabetic glomeruli, including glomerular endothelial cells, mesangial cells, podocytes, and immune cells, by analyzing an online single-cell RNA profile (GSE131882) of patients with diabetic nephropathy. Differentially expressed genes in the glomeruli were processed by gene enrichment and protein-protein interactions analysis. Glomerular endothelial cells, as well as podocytes, play a critical role in diabetic nephropathy. A subgroup of glomerular endothelial cells possesses characteristic angiogenesis genes, indicating that angiogenesis takes place in the progress of diabetic nephropathy. Immune cells such as macrophages, T lymphocytes, B lymphocytes, and plasma cells also contribute to the disease progression. By using iTALK, the present study reports complicated cellular crosstalk inside glomeruli. Dysfunction of glomerular endothelial cells and immature angiogenesis result from the activation of both paracrine and autocrine signals. The present study reinforces the importance of glomerular endothelial cells in the development of diabetic nephropathy. The exploration of the signaling pathways involved in aberrant angiogenesis reported in the present study shed light on potential therapeutic target(s) for diabetic nephropathy.

Summary: Mutations in the p53 tumor suppressor are frequent causes of cancer. Because p53 aggregates appear in some tumor cells, it has been suggested that p53 could also cause cancer by forming self-replicating protein aggregates (prions). Here, using yeast, we show that transient p53 overexpression induced the formation of p53 prion aggregates that were transmitted for >100 generations, found in lysate pellets, stained with Thioflavin T, and transmitted by cytoplasmic transfer, or transfection with lysates of cells carrying the prion or with p53 amyloid peptide. As predicted for a prion, transient interruption of p53 expression caused permanent p53 prion loss. Importantly, p53 transcription factor activity was reduced by prion formation suggesting that prion aggregation could cause cancer. p53 has also been found in liquid-like nuclear droplets in animal cell culture. In yeast, we found that liquid-like p53 foci appear in response to stress and disappear with stress removal.

Una introducción al número extraordinario sobre la economía mexicana, escrita por los editores invitados Gerardo Esquivel y Susan W. Parker.

A new series of N-acyl hydrazones (4a-g) derived from indole-3-propionic acid (IPA) were synthesized. These N-acyl hydrazones were prepared by the reaction of 3-(1H-indol-3-yl) propane hydrazide and aldehyde in the existence of glacial acetic acid as a catalyst. 1HNMR and FT-IR analyses were used to identify the synthesized compounds and they were in vitro evaluated as antibacterial agents against six different types of microorganisms by using well diffusion method. All the tested N-acyl hydrazones (4a-g) displayed moderate activity against the Gram-negative E.coli, comparable to that of Amoxicillin. Some of the tested N-acyl hydrazones also exhibited intermediate activity against some of the examined Gram-positive and Gram-negative bacteria. While no activity was exhibited by any of the examined compounds against the Gram-positive S. aureus.

The first comprehensive analysis between the in situ detected solar energetic electrons (SEEs) from ACE/EPAM satellite and remotely observed radio signatures in solar cycles (SCs) 23 and 24 (1997–2019) is presented. The identified solar origin of the SEEs (in terms of solar flares, SFs, and coronal mass ejections, CMEs) is associated with solar radio emission of types II, III and IV, where possible. Occurrence rates are calculated as a function of the radio wavelength, from the low corona to the interplanetary space near Earth. The tendencies of the different burst appearances with respect to SC, helio-longitude, and SEE intensity are also demonstrated. The corresponding trends of the driver (in terms of median values of the SF class and CME projected speed) are also shown. A comparison with the respective results when using solar energetic protons is presented and discussed.

Aim: This was a systematic review conducted to evaluate the analgesic drugs and techniques used in the management of pain in dogs undergoing ovariohysterectomy. Materials and Methods: Systematic searches in PubMed, Google Scholar, and ScienceDirect were conducted for peer-reviewed articles written in English and published from 1995 to 2015. The key search words were dogs, ovariohysterectomy, pain, and analgesics. This was followed by a manual search of the references within the primary data sources. Inclusion and exclusion of studies and data extraction were performed independently by two reviewers. All randomized studies evaluating the effects of analgesics during ovariohysterectomy in dogs were included. Results: A total of 31 trials met the criteria and were, therefore, included in the study. Data on the type of analgesic drugs used, the technique of administration, and the need for rescue analgesia were extracted from the papers. Individual analgesic protocols were used in 83.9% of the studies compared to multimodal drug therapy, which was used in 16.1% of the studies. Opioids were used in 39.0% of studies, nonsteroidal anti-inflammatory drugs (NSAIDs) in 19.4%, a combination of NSAIDs and opioids in 19.4%, local analgesics in 6.5%, and acupuncture in 3.2% of the studies. Drug administration was done using three approaches that included pre-operative (64.5%), post-operative (22.6%) as well as combined pre- and post-operative approach (12.9%). In 77.4% of the studies, administration of analgesics was done once, while in 12.9%, it was done as a 72-h post-operative course. 24-h and 48-h courses of post-operative pain therapy were done in 6.5% and 3.2% of the studies, respectively. About 57% of the dogs in the control groups required rescue analgesia as compared to 21.6% in the single and 11.3% in multimodal drug therapy groups. The requirement for rescue analgesics was highest in dogs treated using acupuncture (43.8%) and lowest in dogs treated using NSAID-opioid combination (8.6%). Fewer dogs among those that received pain medication preoperatively and postoperatively required rescue analgesia compared to those in groups given drugs before and after surgery only. More dogs (26.4%) among those given analgesics only once postoperatively required rescue analgesia as compared to those that received analgesics daily for 72 h (4.4%). Conclusions: This study provides evidence that opioids are the mainstream analgesic drugs used in managing acute post-operative pain in dogs' post-ovariohysterectomy. In addition, multimodal drug therapy, particularly, NSAID-opioids combination is more effective for pain management than single drug administration. Administering analgesics both before and after surgery is associated with better outcomes and so is a protracted course of post-operative pain therapy. Although these practices should be encouraged, controlled studies should be conducted to conclusively determine the best practices for pain management in dogs undergoing ovariohysterectomy.

Abstract Background Cognition is a key factor in the regulation of normal walking and dual-task gait assessment is an accepted method to evaluate the relationship. The objective of this study was to create a framework for task complexity of concurrent motor and cognitive tasks with gait in people with mild cognitive impairment (MCI). Methods Community-dwelling people with MCI (n = 41, mean age = 76.20 ± 7.65 years) and cognitively normal controls (n = 41, mean age = 72.10 ± 3.80 years) participated in this study. Gait velocity was collected using an instrumented walkway under one single task and six combined tasks of motor and cognitive activities. The cognitive cost was the difference between the single gait task and each of the concurrent motor and cognitive challenges. A repeated two-way measure ANOVA assessed the effect of cognitive group and walking test condition for each gait task test. Results Gait velocity was significantly slower in the MCI group under all tasks. For both groups, the concurrent motor task of carrying a glass of water conferred a challenge not different from the cognitive task of counting backwards by ones. Performance of the complex cognitive task of serial seven subtractions reduced gait velocity in both groups, but produced a greater change in the MCI group (31.8%). Conclusions Not all concurrent tasks challenge cognition-motor interaction equivalently. This study has created a framework of task difficulty which allows for the translation of dual-task test conditions to future research and clinical practice to ensure the accuracy of assessing patient deficits and risk.

Abstract Background Excessive gestational weight gain (GWG) is common and contributes to the development of obesity in women and their offspring. Electronic or e-health interventions have the potential to reach large groups of women and prevent excessive GWG, but their effectiveness has not been demonstrated. The purpose of this study was to evaluate, in a real-world setting, the effectiveness of a self-directed, integrated online and mobile phone behavioral intervention in preventing excessive GWG. Methods This effectiveness trial was a double-blind, three-arm trial with a parallel group design. Two arms received the same e-health intervention during pregnancy with the third arm serving as the placebo control. The intervention was based on a previously efficacious non-digital intervention that was adapted to electronic format. It included three behavior change tools: a weight gain tracker, and separate diet and physical activity goal-setting and self-monitoring tools. Both treatment conditions received access to informational tools, event reminders, and a blogging feature. Healthy pregnant women age 18-35 years with body mass indexes (BMI) ≥18.5 and

A comprehensive statistical analysis on the properties and accompanied phenomena of all M-class solar flares (as measured in soft X-rays) in the last two solar cycles (1996–2019) is presented here with a focus on their space weather potential. The information about the parent active region and the underlying sunspot (Hale) type is collected for each case, where possible, in order to identify photospheric precondition as precursors for the solar flare eruption or confinement. Associations with coronal mass ejections, solar energetic particles, and interplanetary radio emissions are also evaluated and discussed as possible proxies for flare eruption and subsequent space weather relevance. The results show that the majority (∼80%) of the analyzed M-class flares are of β, β-γ, and β-γ-δ magnetic field configuration. The M-class population of flares is accompanied by CMEs in 41% of the cases and about half of the flare sample has been associated with radio emission from electron beams. A much lower association (≲10%) is obtained with shock wave radio signatures and energetic particles. Furthermore, a parametric scheme is proposed in terms of occurrence rates between M-class flares and a variety of accompanied solar phenomena as a function of flare sub-classes or magnetic type. This study confirms the well-known reduced but inevitable space weather importance of M-class flares.

The purpose of this study is to investigate if feedback related negativity (FRN) can capture instantaneous elevated emotional reactivity in autistic adolescents. A measurement of elevated reactivity could allow clinicians to better support autistic individuals without the need for self-reporting or verbal conveyance. The study investigated reactivity in 46 autistic adolescents (ages 12-21 years) completing the Affective Posner Task which utilizes deceptive feedback to elicit distress presented as frustration. The FRN event-related potential (ERP) served as an instantaneous quantitative neural measurement of emotional reactivity. We compared deceptive and distressing feedback to both truthful but distressing feedback and truthful and non-distressing feedback using the FRN, response times in the successive trial, and Emotion Dysregulation Inventory (EDI) reactivity scores. Results revealed that FRN values were most negative to deceptive feedback as compared to truthful non-distressing feedback. Furthermore, distressing feedback led to faster response times in the successive trial on average. Lastly, participants with higher EDI reactivity scores had more negative FRN values for non-distressing truthful feedback compared to participants with lower reactivity scores. The FRN amplitude showed changes based on both frustration and reactivity. The findings of this investigation support using the FRN to better understand emotion regulation processes for autistic adolescents in future work. Furthermore, the change in FRN based on reactivity suggests the possible need to subgroup autistic adolescents based on reactivity and adjust interventions accordingly.