Parallel waves of inductive signaling and mesenchyme maturation regulate differentiation of the chick mesonephros

AbstractThe mesonephros is a linear kidney that, in chicken embryos, stretches between the axial levels of the 15th to the 30th somites. Mesonephros differentiation proceeds from anterior to posterior and is dependent on signals from the nephric duct, which migrates from anterior to posterior through the mesonephric region. If migration of the nephric duct is blocked, markers of tubule differentiation, including Lhx1 and Wnt4, are not activated posterior to the blockade. However, activation and maintenance of the early mesonephric mesenchyme markers Osr1, Eya1 and Pax2 proceeds normally in an anterior-to-posterior wave, indicating that these genes are not dependent on inductive signals from the duct. The expression of Lhx1 and Wnt4 can be rescued in duct-blocked embryos by supplying a source of canonical Wnt signaling, although epithelial structures are not obtained, suggesting that the duct may express other tubule-inducing signals in addition to Wnts. In the absence of the nephric duct, anterior mesonephric mesenchyme adjacent to somites exhibits greater competence to initiate tubular differentiation in response to Wnt signaling than more posterior mesonephric mesenchyme adjacent to unsegmented paraxial mesoderm. It is proposed that mesonephric tubule differentiation is regulated by two independent parallel waves, one of inductive signaling from the nephric duct and the other of competence of the mesonephric mesenchyme to undergo tubular differentiation, both of which travel from anterior to posterior in parallel with the formation of new somites

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND:APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self-identified black participants of MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS:Cross-sectional associations of APOL1 genotypes (high-risk=2 alleles; low-risk=0 or 1 allele) with coronary artery calcification, carotid-intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62 years, 55% women, mean cystatin C-based estimated glomerular filtration rate 89 mL/min per 1.73 m2, 12% with albuminuria), 12% had the high-risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid-intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high-risk group was 82% more likely to develop incident heart failure compared with the low-risk group (95% confidence interval, 1.01-3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00-3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03-3.35) slightly attenuated this association. The APOL1 high-risk genotypes were not significantly associated with other clinical CVD outcomes. CONCLUSIONS:Among blacks without baseline CVD, the APOL1 high-risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD

Изучение адсорбции технеция-99м на оксиде алюминия из среды метилэтилкетона в статических и динамических условиях

Исследована адсорбция экстрагированного метилэтилкетоном 99mТс на гамма-оксиде алюминия с различной рН-формой в статических и динамических условиях проведения процесса. Определены коэффициенты распределения 99mТс в системе метилэтилкетон - 99mТс - оксид алюминия. Установлено, что максимальная сорбционная емкость по радионуклиду достигается на оксидах с рН-формой 4,5_6. В этих же условиях наблюдаются наименьшие потери 99mТс при проведении его адсорбции на хроматографической колонке и промывке колонки водой, а также наибольший выход 99mТс (более 95 %) при последующем его выделении в виде раствора натрия пертехнетата,99mТс. Показано, что общая продолжительность процесса отделения 99mТс от экстрагента не превышает 20 мин, что сопоставимо с временем получения элюата 99mТс из традиционных сорбционных генераторов, и, в конечном итоге, обеспечивает возможность создания ресурсоэффективных экологически чистых производств радиофармпрепаратов 99mТс

Sleep homeostasis, seizures, and cognition in children with focal epilepsy

AIM: To investigate the link between sleep disruption and cognitive impairment in childhood epilepsy by studying the effect of epilepsy on sleep homeostasis, as reflected in slow-wave activity (SWA). METHOD: We examined SWA from overnight EEG-polysomnography in 19 children with focal epilepsy (mean [SD] age 11 years 6 months [3 years], range 6 years 6 months-15 years 6 months; 6 females, 13 males) and 18 age- and sex-matched typically developing controls, correlating this with contemporaneous memory consolidation task scores, full-scale IQ, seizures, and focal interictal discharges. RESULTS: Children with epilepsy did not differ significantly from controls in overnight SWA decline (p = 0.12) or gain in memory performance with sleep (p = 0.27). SWA was lower in patients compared to controls in the first hour of non-rapid eye movement sleep (p = 0.021), although not in those who remained seizure-free (p = 0.26). Full-scale IQ did not correlate with measures of SWA in patients or controls. There was no significant difference in SWA measures between focal and non-focal electrodes. INTERPRETATION: Overnight SWA decline is conserved in children with focal epilepsy and may underpin the preservation of sleep-related memory consolidation in this patient group. Reduced early-night SWA may reflect impaired or immature sleep homeostasis in those with a higher seizure burden

Midwives\u27 knowledge, attitudes and learning needs regarding antenatal vaccination

Objective: To determine the knowledge, attitudes and learning needs of midwives regarding antenatal vaccination. Design & Setting: A cross-sectional, paper-based survey of midwives employed at the only public tertiary maternity hospital in the Australian state of XX between November 2015 and July 2016. Participants: 252 midwives providing care in antepartum, intrapartum, and/or postpartum settings. Measurements: Self-reported responses to a 41-item survey. Findings: The vast majority of midwives supported influenza and pertussis vaccination for pregnant women, with 90.0% and 71.7% reporting they would recommend pertussis and influenza vaccine, respectively, to a pregnant friend or family member, and almost all stating that midwives should administer vaccines to pregnant patients (94.8%). Seven out of ten midwives (68.1%) responded correctly to all knowledge items regarding vaccines recommended during pregnancy; 52.8% demonstrated correct knowledge regarding vaccine administration despite only 36.6% having attended an education session on antenatal vaccination in the previous two years. Nearly all midwives (97.3%) expressed a need for more education on vaccine administration. The most commonly reported barrier to administering influenza (61.3%) and pertussis (59.0%) vaccination was having staff available with the certification required to administer vaccines. Key Conclusions: Midwives view antenatal vaccination as their responsibility and are interested and receptive to education. Implications for Practice: There is an unmet need and demand among midwives for professional development that would enable them to recommend and administer vaccines to pregnant women in accordance with national immunisation guidelines and integrate vaccination into routine antenatal care

Sleep homeostasis, seizures, and cognition in children with focal epilepsy

AIM To investigate the link between sleep disruption and cognitive impairment in childhood epilepsy by studying the effect of epilepsy on sleep homeostasis, as reflected in slow-wave activity (SWA). METHOD We examined SWA from overnight EEG-polysomnography in 19 children with focal epilepsy (mean [SD] age 11 years 6 months [3 years], range 6 years 6 months-15 years 6 months; 6 females, 13 males) and 18 age- and sex-matched typically developing controls, correlating this with contemporaneous memory consolidation task scores, full-scale IQ, seizures, and focal interictal discharges. RESULTS Children with epilepsy did not differ significantly from controls in overnight SWA decline (p = 0.12) or gain in memory performance with sleep (p = 0.27). SWA was lower in patients compared to controls in the first hour of non-rapid eye movement sleep (p = 0.021), although not in those who remained seizure-free (p = 0.26). Full-scale IQ did not correlate with measures of SWA in patients or controls. There was no significant difference in SWA measures between focal and non-focal electrodes. INTERPRETATION Overnight SWA decline is conserved in children with focal epilepsy and may underpin the preservation of sleep-related memory consolidation in this patient group. Reduced early-night SWA may reflect impaired or immature sleep homeostasis in those with a higher seizure burden

Population-Based Limits of Urine Creatinine Excretion

Introduction: The validity of a timed urine collection is typically judged by measurement of urine creatinine excretion, but prevailing limits may be unreliable. We sought to empirically derive population-based limits of excretion for evaluating the validity of a timed urine collection. Methods: Covariate and 24-hour urine data were obtained from 3582 participants in the Chronic Renal Insufficiency Cohort (CRIC) study, 814 participants in the Modification of Diet in Renal Disease (MDRD) study, 1010 participants in the Jackson Heart Study (JHS), and 8536 participants in the Prevention of Renal Vascular End Stage Disease (PREVEND) study. Weight, height, age, sex, and serum creatinine concentrations were evaluated as potential predictors of urine creatinine excretion using Akaike Information Criteria, R-squared values, and deviance. Bias and precision of the fitted models were assessed by analyses of residuals. Agreement between 24-hour creatinine clearance and 125I-iothalamate clearance was assessed before and after exclusion of potentially invalid urine samples. Results: A best-fitting model to predict 24-hour urine creatinine excretion among the 9199 discovery cohort members included sex-specific terms for weight, height, and age (R-squared = 0.328). This model had a median bias of +4.3 mg creatinine/day (95% confidence interval −5.6, +13.3 mg/day) in 4599 validation cohort members, and 82% of observed values were within 30% of predicted model. Serum creatinine concentrations only marginally improved model precision but reduced bias in persons with advanced chronic kidney disease (CKD). Conclusion: The limits of urine creatinine excretion derived here represent the most valid and representative data for appraising the adequacy of a timed urine collection

Prednisolone or tetracosactide depot for infantile epileptic spasms syndrome? A prospective analysis of data embedded within two randomised controlled trials

OBJECTIVE: To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS). METHODS: Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis. The main outcome was cessation of spasms (Days 13-14 after randomisation). Lead time to treatment and underlying aetiology were taken into account. Cessation of spasms on Days 14-42 inclusive, electroclinical response (EEG Day 14), plus developmental and epilepsy outcomes (at 14 months in UKISS and 18 months in ICISS) are also reported. Minimum treatment was prednisolone 40 mg per day for two weeks or tetracosactide depot 0·5 mg IM on alternate days for two weeks, all followed by a reducing dose of prednisolone over two weeks. RESULTS: 126 infants were included in this study. On tetracosactide depot, 47 of 62 (76%) were free of spasms on Days 13-14 compared to 43 of 64 (67%) on prednisolone (difference 9%, 95% CI -7·2% to +25·2%, chi square 1·15, p = 0·28). For Day 14-42 cessation of spasms, on tetracosactide depot, 41 of 61 (67%) were free of spasms compared to 35 of 62 (56%) on prednisolone (difference 11%, 95% CI -6·4% to +28·4%, chi square 1·51, p = 0·22). There was no significant difference in mean VABS score between infants who received prednisolone compared with those who received tetracosactide depot (74·8 (SD 18·3) versus 78·0 (SD 20·2) t = -0·91 p = 0·36). The proportion with ongoing epilepsy at the time of developmental assessment was 20 of 61 (33%) in the tetracosactide group compared with 26 out of 63 (41%) in the prednisolone group (difference 8%, 95% CI -9·2% to +25·2%, Chi [2] 0·95, p = 0·33). SIGNIFICANCE: With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome

A trouble shared is a trouble halved : the role of family identification and identification with humankind in well-being during the COVID-19 pandemic

This research was supported by a grant from the German Research Foundation awarded to RvD, NMJ, and JAH (DI 848/15-1 and HA 6455/4-1). The data collection for this study was supported by a grant from the association of friends and supporters (Freunde & Förderer) at Goethe University.The COVID-19 pandemic has triggered health-related anxiety in ways that undermine peoples’ mental and physical health. Contextual factors such as living in a high-risk area might further increase the risk of health deterioration. Based on the Social Identity Approach, we argue that social identities can not only be local that are characterized by social interactions, but also be global that are characterized by a symbolic sense of togetherness and that both of these can be a basis for health. In line with these ideas, we tested how identification with one’s family and with humankind relates to stress and physical symptoms while experiencing health-related anxiety and being exposed to contextual risk factors. We tested our assumptions in a representative sample (N = 974) two-wave survey study with a 4-week time lag. The results show that anxiety at Time 1 was positively related to stress and physical symptoms at Time 2. Feeling exposed to risk factors related to lower physical health, but was unrelated to stress. Family identification and identification with humankind were both negatively associated with subsequent stress and family identification was negatively associated with subsequent physical symptoms. These findings suggest that for social identities to be beneficial for mental health, they can be embodied as well as symbolic.Publisher PDFPeer reviewe

How national leaders keep ‘us’ safe : a longitudinal, four-nation study exploring the role of identity leadership as a predictor of adherence to COVID-19 non-pharmaceutical interventions

This research was supported by a grant from the German Research Foundation awarded to RvD, NMJ and JAH (DI 848/15-1 and HA 6455/4-1).Objectives : To investigate whether citizens’ adherence to health-protective non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic is predicted by identity leadership, wherein leaders are perceived to create a sense of shared national identity. Design : Observational two-wave study. Hypotheses testing was conducted with structural equation modelling. Setting : Data collection during the COVID-19 pandemic in China, Germany, Israel and the USA in April/May 2020 and four weeks later. Participants : Adults in China (n=548, 66.6% women), Germany (n=182, 78% women), Israel (n=198, 51.0% women) and the USA (n=108, 58.3% women). Measures : Identity leadership (assessed by the four-item Identity Leadership Inventory Short-Form) at Time 1, perceived shared national identification (PSNI; assessed with four items) and adherence to health-protective NPIs (assessed with 10 items that describe different health-protective interventions; for example, wearing face masks) at Time 2. Results : Identity leadership was positively associated with PSNI (95% CI 0.11 to 0.30, p<0.001) in all countries. This, in turn, was related to more adherence to health-protective NPIs in all countries (95% CI 0.03 to 0.36, 0.001≤p≤0.017) except Israel (95% CI −0.03 to 0.27, p=0.119). In Germany, the more people saw Chancellor Merkel as engaging in identity leadership, the more they adhered to health-protective NPIs (95% CI 0.04 to 0.18, p=0.002). In the USA, in contrast, the more people perceived President Trump as engaging in identity leadership, the less they adhered to health-protective NPIs (95% CI −0.17 to −0.04, p=0.002). Conclusions : National leaders can make a difference by promoting a sense of shared identity among their citizens because people are more inclined to follow health-protective NPIs to the extent that they feel part of a united ‘us’. However, the content of identity leadership (perceptions of what it means to be a nation’s citizen) is essential, because this can also encourage people to disregard such recommendations.Publisher PDFPeer reviewe