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PREMATURE labor, BIRTH weight, LOW birth weight, BIRTH intervals, COHORT analysis, CHORIOAMNIONITIS, and CHILDBIRTH at home

Background: Approximately 20.5 million infants were born weighing <2500 g (defined as low birthweight or LBW) in 2015, primarily in low- and middle-income countries (LMICs). Infants born LBW, including those born preterm (<37 weeks gestation), are at increased risk for numerous consequences, including neonatal mortality and morbidity as well as suboptimal health and nutritional status later in life. The objective of this study was to identify predictors of LBW and preterm birth among infants in rural Uganda. Methods: Data were derived from a prospective birth cohort study conducted from 2014–2016 in 12 districts across northern and southwestern Uganda. Birth weights were measured in triplicate to the nearest 0.1 kg by trained enumerators within 72 hours of delivery. Gestational age was calculated from the first day of last menstrual period (LMP). Associations between household, maternal, and infant characteristics and birth outcomes (LBW and preterm birth) were assessed using bivariate and multivariable logistic regression with stepwise, backward selection analyses. Results: Among infants in the study, 4.3% were born LBW (143/3,337), and 19.4% were born preterm (744/3,841). In multivariable analysis, mothers who were taller (>150 cm) (adjusted Odds Ratio (aOR) = 0.42 (95% CI = 0.24, 0.72)), multigravida (aOR = 0.62 (95% CI = 0.39, 0.97)), or with adequate birth spacing (>24 months) (aOR = 0.60 (95% CI = 0.39, 0.92)) had lower odds of delivering a LBW infant Mothers with severe household food insecurity (aOR = 1.84 (95% CI = 1.22, 2.79)) or who tested positive for malaria during pregnancy (aOR = 2.06 (95% CI = 1.10, 3.85)) had higher odds of delivering a LBW infant. In addition, in multivariable analysis, mothers who resided in the Southwest (aOR = 0.64 (95% CI = 0.54, 0.76)), were ≥20 years old (aOR = 0.76 (95% CI = 0.61, 0.94)), with adequate birth spacing (aOR = 0.76 (95% CI = 0.63, 0.93)), or attended ≥4 antenatal care (ANC) visits (aOR = 0.56 (95% CI = 0.47, 0.67)) had lower odds of delivering a preterm infant; mothers who were neither married nor cohabitating (aOR = 1.42 (95% CI = 1.00, 2.00)) or delivered at home (aOR = 1.25 (95% CI = 1.04, 1.51)) had higher odds. Conclusions: In rural Uganda, severe household food insecurity, adolescent pregnancy, inadequate birth spacing, malaria infection, suboptimal ANC attendance, and home delivery represent modifiable risk factors associated with higher rates of LBW and/or preterm birth. Future studies on interventions to address these risk factors may be warranted. [ABSTRACT FROM AUTHOR]

CHILDREN and AGE

Introduction and Aims: Parental role modelling of alcohol use is known to influence alcohol consumption in adolescence and in later life. This study aimed to assess relationships between parental status, child age and alcohol consumption, which have not been well documented.Design and Methods: Data were sourced from the 2013 Australian National Drug Strategy Household Survey. Analyses were conducted for 25-55 year olds (n = 11 591) by parental status, gender and age of youngest child in the household, controlling for socio-demographic factors.Results: Parents were less likely than non-parents to exceed the alcohol guideline for increased lifetime risk (18.2% vs. 24.2%) and short-term risk: at least weekly (14.2% vs. 21.2%); and at least monthly (27.5% vs. 35.9%). Fathers were just as likely to exceed the guidelines for lifetime risk as other men, but those with children aged 0-2, were less likely to exceed the guideline for short-term risk. Women were least likely to exceed the guideline for lifetime risk if they had children aged 0-2, 6-11 or 15 years and over, or the guideline for short-term risk, if they had children aged 0-2, or 15 years and over in the household. Parents were more likely to report drinking in the home.Discussion and Conclusions: Parents were less likely to exceed alcohol guidelines than non-parents, especially mothers whose youngest child was an infant or in high school or older. Consistent with population rates in men, fathers were more likely to exceed alcohol guidelines than mothers, and this excess consumption warrants public health attention. [ABSTRACT FROM AUTHOR]

TOXOPLASMA, POLYMERS, TUBULINS, MICROTUBULES, XENOPUS, and RELATIVES

Background: TgDCX is a doublecortin-domain protein associated with the conoid fibers, a set of strongly curved non-tubular tubulin-polymers in Toxoplasma. TgDCX deletion impairs conoid structure and parasite invasion. TgDCX contains two tubulin-binding domains: a partial P25α and the DCX/doublecortin domain. Orthologues are found in apicomplexans and their free-living relatives Chromera and Vitrella. Results: We report that isolated TgDCX-containing conoid fibers retain their pronounced curvature, but loss of TgDCX destabilizes the fibers. We crystallized and determined the 3D-structure of the DCX-domain, which is similar to those of human doublecortin and well-conserved among TgDCX orthologues. However, the orthologues vary widely in targeting to the conoid in Toxoplasma and in modulating microtubule organization in Xenopus cells. Several orthologues bind to microtubules in Xenopus cells, but only TgDCX generates short, strongly curved microtubule arcs. EM analysis shows microtubules decorated with TgDCX bundled into rafts, often bordered on one edge by a "C"-shaped incomplete tube. A Chromera orthologue closely mimics TgDCX targeting in Toxoplasma and binds to microtubules in Xenopus cells, but does not generate arcs or "C"-shaped tubes, and fails to rescue the defects of the TgDCX-knockout parasite. Conclusions: These observations suggest that species-specific features of TgDCX enable it to generate strongly curved tubulin-polymers to support efficient host-cell invasion. [ABSTRACT FROM AUTHOR]

INFANT mortality, ANTHROPOMETRY, HUMAN body composition, PLETHYSMOGRAPHY, LOGISTIC regression analysis, and MALNUTRITION in infants

Background: With the greatest burden of infant undernutrition and morbidity in low and middle income countries (LMICs), there is a need for suitable approaches to monitor infants in a simple, low-cost and effective manner. Anthropometry continues to play a major role in characterising growth and nutritional status. Methods: We developed a range of models to aid in identifying neonates at risk of malnutrition. We first adopted a logistic regression approach to screen for a composite neonatal morbidity, low and high body fat (BF%) infants. We then developed linear regression models for the estimation of neonatal fat mass as an assessment of body composition and nutritional status. Results: We fitted logistic regression models combining up to four anthropometric variables to predict composite morbidity and low and high BF% neonates. The greatest area under receiver-operator characteristic curves (AUC with 95% confidence intervals (CI)) for identifying composite morbidity was 0.740 (0.63, 0.85), resulting from the combination of birthweight, length, chest and mid-thigh circumferences. The AUCs (95% CI) for identifying low and high BF% were 0.827 (0.78, 0.88) and 0.834 (0.79, 0.88), respectively. For identifying composite morbidity, BF% as measured via air displacement plethysmography showed strong predictive ability (AUC 0.786 (0.70, 0.88)), while birthweight percentiles had a lower AUC (0.695 (0.57, 0.82)). Birthweight percentiles could also identify low and high BF% neonates with AUCs of 0.792 (0.74, 0.85) and 0.834 (0.79, 0.88). We applied a sex-specific approach to anthropometric estimation of neonatal fat mass, demonstrating the influence of the testing sample size on the final model performance. Conclusions: These models display potential for further development and evaluation in LMICs to detect infants in need of further nutritional management, especially where traditional methods of risk management such as birthweight for gestational age percentiles may be variable or non-existent, or unable to detect appropriately grown, low fat newborns. [ABSTRACT FROM AUTHOR]

ALCOHOL drinking, SCHOOL children, CROSS-sectional method, STUDENT health, DRINKING behavior, FORECASTING, FRIENDSHIP, HEALTH education, SCHOOLS, STUDENTS, and DISEASE prevalence

Background: Alcohol consumption by young people (particularly early initiation) is a predictor for poorer health in later life. In addition, evidence now clearly shows a causal link between alcohol and cancer. This study investigated prevalence, predictors of alcohol consumption among adolescents including perceptions of the link between alcohol and cancer, and the role of parents and peers.Methods: A sample of Australian school students aged 12-17 years participated in a survey (n = 2885). Logistic regression analysis was undertaken to determine predictors.Results: Alcohol use increased with age and by 16, most had tried alcohol with 33.1% of students aged 12-17 reporting that they drank at least occasionally (95% CI = 31.0-35.2). Awareness of the link between alcohol and cancer was low (28.5%). Smoking status and friends' approval were predictive of drinking, whereas parental disapproval was protective. Those aged 14-17 who did not think the link between alcohol and cancer was important were more likely to drink, as were those living in areas of least disadvantage. The only factors that predicted recent drinking were smoking and the perception that alcohol was easy to purchase.Conclusions: An education campaign highlighting the link between alcohol and cancer may have positive flow-on effects for young people, and schools should incorporate this messaging into any alcohol education programs. Consideration should be given to factors that serve to regulate under-aged accessibility of alcohol. [ABSTRACT FROM AUTHOR]

OCCUPATIONAL therapy, PRIMARY care, MEDICAL rehabilitation, PHYSICAL therapy, and MEDICAL care

Background: Primary healthcare (PHC) is central to increased access and transformation in South African healthcare. There is limited literature about services required by occupational therapists in PHC. Despite policy being in place, the implementation of services at grassroots level does not always occur adequately. Objectives: This study aimed at gaining an understanding of the challenges of being disabled and the services required by occupational therapists (OTs) in rural communities in order to better inform the occupational therapy (OT) training curriculum. Method: An exploratory, descriptive qualitative design was implemented using purposive sampling to recruit 23 community healthcare workers from the uGu district. Snowball sampling was used to recruit 37 members of the uGu community, which included people with disability (PWD) and caregivers of PWDs. Audio-recorded focus groups and semi-structured interviews were used to collect data, which were thematically analysed. Ethical approval was obtained from the Biomedical and Research Ethics Committee of the University of KwaZulu-Natal (BE248/14). Results: Two main themes emerged namely: firstly, the challenges faced by the disabled community and secondly appropriate opportunities for intervention in PHC. A snapshot of the social and physical inaccessibility challenges experienced by the community was created. Challenges included physical and sexual abuse, discrimination and marginalisation. Community-based rehabilitation and ideas for health promotion and prevention were identified as possible strategies for OT intervention. Conclusion: The understanding of the intervention required by OT in PHC was enhanced through obtaining the views of various stakeholders' on the role. This study highlighted the gaps in community-based services that OTs should offer in this context. [ABSTRACT FROM AUTHOR]

EDUCATIONAL leadership, EDUCATIONAL planning, HIGHER education, EDUCATIONAL programs, and POSTSECONDARY education

Promoting the development of educational leadership in higher education is essential for strengthening the quality of teaching and learning. Additional research is needed to conceptualize educational leadership, especially within informal roles. We analysed how faculty members in an academic development program conceptualized educational leadership. Five key characteristics emerged that inform the development of educational leadership capacity in postsecondary contexts: affective qualities, mentoring and empowering, action-orientation, teaching excellence, and research and scholarship. Three characteristics of academic programs aimed at developing educational leadership were also identified: funding and resources to implement a change initiative, building interdisciplinary communities, and embracing identity. [ABSTRACT FROM AUTHOR]

ATHEROSCLEROSIS treatment, TYPE 2 diabetes treatment, GLUCOSE intolerance, THERAPEUTIC use of monoclonal antibodies, DISEASE progression, ATHEROSCLEROSIS complications, TYPE 2 diabetes complications, ARTERIES, ATHEROSCLEROSIS, CLINICAL trials, COMPARATIVE studies, INTERLEUKIN-1, RESEARCH methodology, MEDICAL cooperation, MONOCLONAL antibodies, RESEARCH, EVALUATION research, RANDOMIZED controlled trials, BLIND experiment, CHEMICAL inhibitors, and DISEASE complications

Background: Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression.Objectives: The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging.Methods: Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta.Results: There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was -3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (-4.30 mg/dl [range: -8.5 to -0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test.Conclusions: There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930). [ABSTRACT FROM AUTHOR]

CLOSTRIDIUM difficile, GLUTAMATE dehydrogenase, TREATMENT duration, and ENZYME-linked immunosorbent assay

A proportion of patients suspected of Clostridium difficile infection are unnecessarily placed in contact isolation. By introducing a random-access glutamate dehydrogenase (GDH) test for C. difficile, we aimed to reduce isolation time. In addition, we investigated whether the result of the toxin A&B enzyme immunoassay (EIA) was associated with the decision to initiate antibiotic treatment against C. difficile. This retrospective pre- and post-implementation study was from June 3, 2016, to June 4, 2018. Pre-implementation, only a NAAT was performed. In the post-implementation period, a GDH test was performed; if positive, a toxin A&B EIA followed the same day and subsequently a NAAT. Contact isolation for CDI was discontinued when the GDH test was negative. Median time in isolation was 50.8 h pre-implementation (n = 189) versus 28.0 h post-implementation (n = 119), p < 0.001. The GDH test had a negative predictive value of 98.8% (95% CI 97.9–99.4). In 7/31 (22.6%) patients with a positive NAAT and GDH test and a negative toxin A&B EIA, no antibiotics against C. difficile were initiated versus 4/28 (14.3%) patients who were NAAT, GDH and toxin A&B EIA positive. Introducing a random-access screening test resulted in a significant decrease in patient isolation time. The GDH test had a high negative predictive value making it suitable to determine whether contact isolation can be discontinued. Furthermore, the result of a toxin A&B EIA had limited added value on the percentage of patients in whom antibiotic treatment against C. difficile was initiated. [ABSTRACT FROM AUTHOR]

LUNGS, LONGITUDINAL method, HISTORY, and LUNG transplants

Summary: The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post‐transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X‐rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2/FiO2 ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long‐term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized. [ABSTRACT FROM AUTHOR]

SEPTEMBER 11 Terrorist Attacks, 2001, HAZARDOUS substance exposure, MEDICAL screening, HAZARDS, and HEALTH risk assessment

The attack on the World Trade Center (WTC) on September 11th, 2001 exposed thousands of individuals to an unprecedented mix of chemicals, combustion products and micronized building materials. Clinicians at the Mount Sinai Irving Selikoff Center for Occupational and Environmental Medicine, in partnership with affected stakeholder organizations, developed a medical screening program to evaluate the health status of workers and volunteers who spent time at the WTC site and thus sustained exposure in the aftermath of September 11th. Standardized questionnaires were adapted for use in this unique population and all clinicians underwent training to ensure comparability. The WTC Worker and Volunteer Medical Screening Program (MSP) received federal funding in April 2002 and examinations began in July 2002. The MSP and the follow up medical monitoring program has successfully recruited nearly 22,000 responders, and serves as a model for the rapid development of a medical screening program to assess the health of populations exposed to environmental hazards as a result of natural and man-made disasters. The MSP constitutes a successful screening program for WTC responders. We discuss the challenges that confronted the program; the absence of a prior model for the rapid development of a program to evaluate results from mixed chemical exposures; little documentation of the size of the exposed population or of who might have been exposed; and uncertainty about both the nature and potential severity of immediate and long-term health effects. [ABSTRACT FROM AUTHOR]

WORLD Trade Center Bombing, New York, N.Y., 1993, RESCUE work, EMERGENCY medical services, SEPTEMBER 11 Terrorist Attacks, 2001, TERRORISM, MEDICAL screening, HEALTH risk assessment, DIAGNOSTIC services, MEDICAL care, and NEW York (State)

BACKGROUND: Approximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers. METHODS: To characterize WTC-related health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays. RESULTS: Of 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site. CONCLUSION: WTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Long-term medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters. [ABSTRACT FROM AUTHOR]

SEPTEMBER 11 Terrorist Attacks, 2001, PARTICLES, TOXINS, GLASS fibers, POLYCYCLIC aromatic hydrocarbons, DIOXINS, and PUBLIC health

In the aftermath of the September 11 World Trade Center (WTC) attack, a large number of people sustained potential exposures to smoke, dust, particulate matter, and a variety of toxins, including asbestos, pulverized concrete, glass fibers, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated furans and dioxins. Additionally, many had exposure to psychological traumatogens. The most common effects seen to date are respiratory and mental health consequences. The long-term consequences of exposures are not yet known, and there remains concern about the potential for late-emerging diseases such as cancers. This article reviews WTC-related health effects, the spectrum of exposures and how they were documented, and discusses future preventive efforts. [ABSTRACT FROM AUTHOR]

BEER, INTERNATIONAL economic relations, INTERNATIONAL trade, and UNITED States -- Foreign economic relations

Demonstrates how United States and Canadian controls on the alcohol market affect public health. US-Canadian alcohol control; Public health implications; How the trade agreements (GATT, FTA, NAFTA) work; Trade disputes since 1985; The larger meaning of the disputes; Chronology of the US-Canada beer dispute; Glossary; Summary.

SCHOOL children, DYSLEXIC children, EMERGENT literacy, PHONOLOGICAL awareness, NOISE, and ARTIFICIAL satellite tracking

Humans' propensity to acquire literacy relates to several factors, including the ability to understand speech in noise (SiN). Still, the nature of the relation between reading and SiN perception abilities remains poorly understood. Here, we dissect the interplay between (1) reading abilities, (2) classical behavioral predictors of reading (phonological awareness, phonological memory, and rapid automatized naming), and (3) electrophysiological markers of SiN perception in 99 elementary school children (26 with dyslexia). We demonstrate that, in typical readers, cortical representation of the phrasal content of SiN relates to the degree of development of the lexical (but not sublexical) reading strategy. In contrast, classical behavioral predictors of reading abilities and the ability to benefit from visual speech to represent the syllabic content of SiN account for global reading performance (i.e., speed and accuracy of lexical and sublexical reading). In individuals with dyslexia, we found preserved integration of visual speech information to optimize processing of syntactic information but not to sustain acoustic/phonemic processing. Finally, within children with dyslexia, measures of cortical representation of the phrasal content of SiN were negatively related to reading speed and positively related to the compromise between reading precision and reading speed, potentially owing to compensatory attentional mechanisms. These results clarify the nature of the relation between SiN perception and reading abilities in typical child readers and children with dyslexia and identify novel electrophysiological markers of emergent literacy. Humans' propensity to acquire literacy relates to several factors, one of which is the ability to understand speech in noise. This neuroimaging study reveals that reading abilities and neuronal traces of speech processing in noise are related in multiple specific ways. [ABSTRACT FROM AUTHOR]

VESPULA, HONEYDEW (Entomology), COELOSTOMIDIIDAE, ANT communities, and INSECT food

The Avian Convergence Hypothesis states that avian-honeydew associations are likely to develop when biogeographic and/or climatic factors limit the formation of ant-honeydew associations (the dominant association in tropical ecosystems). In this study we examine a honeydew-influenced forest system in an island archipelago where ant diversity is low but invasive Vespula wasp species (Vespidae) are present. We found honeydew production was highly seasonal, with both standing crop and 24-h production peaking in summer. When Vespula wasps were abundant (summer and autumn) they preferentially visited infested trees and fed regularly on honeydew droplets on infested branches. Two ant species occasionally fed on honeydew. No other insects or birds were observed feeding on honeydew during the study period. With the exception of Vespula, honeydew does not appear to be a preferred food source in this community, possibly because of the range of other food resources available in surrounding forest, farmland and gardens. The abundance of Vespula wasps at the site may also have disrupted bird-honeydew associations. We suggest the Avian Convergence Hypothesis could be restated to explicitly include both nectar availability and invasive social insects as both are likely to influence bird use of honeydew. [ABSTRACT FROM AUTHOR]

FLAVONOIDS, TRP channels, INTRACELLULAR calcium, TRADITIONAL medicine, CHROMONES, CALCIUM metabolism, ANIMAL experimentation, CARRIER proteins, CELLS, CHEMICAL elements, COMPARATIVE studies, EPITHELIAL cells, RESEARCH methodology, MEDICAL cooperation, MICE, RESEARCH, RESEARCH funding, and EVALUATION research

Background and Purpose: The TRPC5 proteins assemble to create calcium-permeable, non-selective, cationic channels. We sought novel modulators of these channels through studies of natural products.Experimental Approach: Intracellular calcium measurements and patch clamp recordings were made from cell lines. Compounds were generated by synthetic chemistry.Key Results: Through a screen of natural products used in traditional Chinese medicines, the flavonol galangin was identified as an inhibitor of lanthanide-evoked calcium entry in TRPC5 overexpressing HEK 293 cells (IC50 0.45 μM). Galangin also inhibited lanthanide-evoked TRPC5-mediated current in whole-cell and outside-out patch recordings. In differentiated 3T3-L1 cells, it inhibited constitutive and lanthanide-evoked calcium entry through endogenous TRPC5-containing channels. The related natural flavonols, kaempferol and quercetin were less potent inhibitors of TRPC5. Myricetin and luteolin lacked effect, and apigenin was a stimulator. Based on structure-activity relationship studies with natural and synthetic flavonols, we designed 3,5,7-trihydroxy-2-(2-bromophenyl)-4H-chromen-4-one (AM12), which inhibited lanthanide-evoked TRPC5 activity with an IC50 of 0.28 μM. AM12 also inhibited TRPC5 activity evoked by the agonist (-)-Englerin A and was effective in excised outside-out membrane patches, suggesting a relatively direct effect. It inhibited TRPC4 channels similarly, but its inhibitory effect on TRPC1-TRPC5 heteromeric channels was weaker.Conclusions and Implications: The data suggest that galangin (a natural product from the ginger family) is a TRPC5 inhibitor and that other natural and synthetic flavonoids contain antagonist or agonist capabilities at TRPC5 and closely related channels depending on the substitution patterns of both the chromone core and the phenyl ring. [ABSTRACT FROM AUTHOR]

ON-site evaluation, STREAMING video, VIDEO excerpts, and MEDICAL technology

Introduction: Telecytology using real‐time microscopy has gained popularity for rapid on‐site evaluations (ROSE). Although proficiency testing is routinely used in cytopathology, no established means of competency assessment is currently available for telecytology. Our aim was to determine the feasibility of a dynamic (real‐time) platform to assess telecytology competency. Methods: Remote Medical Technology dynamic (real‐time) video streaming platform for ROSE is used at our institution, and short video clips of telecytology cases were recorded using Camtasia Studio 8 software during different ROSE sessions. Selected MP4 videos (range 13‐88 seconds, mean 33 seconds), along with clinical histories, were used to build a multiple‐choice question test with one training case and 20 test cases, utilising Tutor (Philips) software to host the web‐based test. The test was voluntary for cytopathologists and cytotechnologists. Answers and feedback from test takers were analysed. Results: Thirteen participants—four cytopathologists and nine cytotechnologists—previously trained to use telecytology, volunteered to take the test. Individual scores ranged from 10 (50%) to 19 (95%) with a median of 16 (80%). Most feedback received involved technical difficulties. Conclusions: We present, to the best of our knowledge, the first tool to assess telecytology competency for ROSE using pre‐recorded dynamic streaming videos. Despite technical challenges related to incorporating videos into a web‐based test, the test was feasible and provided users with valuable feedback about their ROSE performance. Future effort will be devoted to establishing a more user‐friendly test platform and establishing a benchmark for passing scores. This paper illustrates that an assessment tool for telecytology competency for ROSE using pre‐recorded dynamic streaming videos is feasible. In addition, the novel test provided users with valuable feedback about their ROSE performance and provides feedback on the challenges related to telecytology ROSE. [ABSTRACT FROM AUTHOR]

STOMATA, LEAF anatomy, PLANT epidermis, PLANT growth, and WATER

Stomata, valves on the plant epidermis, are critical for plant growth and survival, and the presence of stomata impacts the global water and carbon cycle. Although transcription factors and cell-cell signaling components regulating stomatal development have been identified, it remains unclear as to how their regulatory interactions are translated into two-dimensional patterns of stomatal initial cells. Using molecular genetics, imaging, and mathematical simulation, we report a regulatory circuit that initiates the stomatal cell-lineage. The circuit includes a positive feedback loop constituting self-activation of SCREAMs that requires SPEECHLESS. This transcription factor module directly binds to the promoters and activates a secreted signal, EPIDERMAL PATTERNING FACTOR2, and the receptor modifier TOO MANY MOUTHS, while the receptor ERECTA lies outside of this module. This in turn inhibits SPCH, and hence SCRMs, thus constituting a negative feedback loop. Our mathematical model accurately predicts all known stomatal phenotypes with the inclusion of two additional components to the circuit: an EPF2-independent negative-feedback loop and a signal that lies outside of the SPCH•SCRM module. Our work reveals the intricate molecular framework governing self-organizing two-dimensional patterning in the plant epidermis. [ABSTRACT FROM AUTHOR]