Calcineurin/NFAT Activation-Dependence of Leptin Synthesis and Vascular Growth in Response to Mechanical Stretch

Background and Aims- Hypertension and obesity are important risk factors of cardiovascular disease. They are both associated with high leptin levels and have been shown to promote vascular hypertrophy, through the RhoA/ROCK and ERK1/2 phosphorylation. Calcineurin/NFAT activation also induces vascular hypertrophy by upregulating various genes. This study aimed to decipher whether a crosstalk exists between the RhoA/ROCK pathway, Ca+2/calcineurin/NFAT pathway, and ERK1/2 phosphorylation in the process of mechanical stretch-induced vascular smooth muscle cell (VSMC) hypertrophy and leptin synthesis. Methods and Results- Rat portal vein (RPV) organ culture was used to investigate the effect of mechanical stretch and exogenous leptin (3.1 nM) on VSMC hypertrophy and leptin synthesis. Results showed that stretching the RPV significantly upregulated leptin secretion, mRNA and protein expression, which were inhibited by the calcium channel blocker nifedipine (10 μM), the selective calcineurin inhibitor FK506 (1 nM) and the ERK1/2 inhibitor PD98059 (1 μM). The transcription inhibitor actinomycin D (0.1M) and the translation inhibitor cycloheximide (1 mM) significantly decreased stretch-induced leptin protein expression. Mechanical stretch or leptin caused an increase in wet weight changes and protein synthesis, considered as hypertrophic markers, while they were inhibited by FK506 (0.1 nM; 1 nM). In addition, stretch or exogenous leptin significantly increased calcineurin activity and MCIP1 expression whereas leptin induced NFAT nuclear translocation in VSMCs. Moreover, in response to stretch or exogenous leptin, the Rho inhibitor C3 exoenzyme (30 ng/mL), the ROCK inhibitor Y-27632 (10 μM), and the actin depolymerization agents Latrunculin B (50 nM) and cytochalasin D (1 μM) reduced calcineurin activation and NFAT nuclear translocation. ERK1/2 phosphorylation was inhibited by FK506 and C3. Conclusions- Mechanical stretch-induced VSMC hypertrophy and leptin synthesis and secretion is mediated by Ca2+/calcineurin/NFAT activation. RhoA/ROCK and ERK1/2 activation are critical for mechanical stretch-induced calcineurin activation

Colorectal Cancer Screening: Impact of COVID-19 Pandemic and Possible Consequences

Colonoscopy procedure has been the key screening method to detect colorectal cancer (CRC). As a fatal disease, CRC needs early detection. The COVID-19 pandemic caused screening tests (colonoscopy) to be halted and delayed. As a result, there could be dire consequences such as later-stage or missed diagnosis or greater mortality. This report will analyze scientific literature pertaining to interrupted CRC screenings due to COVID-19 while drawing historical parallels from the 1918 flu pandemic. We conducted literature searches in the PubMed database as well as in Google Scholar. One of the main lessons learned from the 1918 flu pandemic was to employ social distancing to stop the spread of the virus. So, the global response at the start and peak of the COVID-19 pandemic was decreased hospital visits for any non-emergency cases. That led to a halt and delays in cancer (including CRC) screenings. The Medical community predicted this lag will cause more CRC cases and deaths in the future. However, reorganizing and changing screening method strategies were helpful during the ongoing pandemic. In conclusion, COVID-19 greatly affected CRC screening, including how we view the future of CRC screening. We can learn from this prospect to better prepare for future pandemics or other public health crises.http://deepblue.lib.umich.edu/bitstream/2027.42/171056/2/life-11-01297.pdfPublished onlin

Promoting healthy eating and physical activity among school children: findings from Health-E-PALS, the first pilot intervention from Lebanon

Background: In Lebanon, childhood obesity doubled during the past decade. Preventive measures should start early in life and Schools are considered an important environment to promote energy balance health behaviours. School-based programmes promoting healthy lifestyles are lacking. The purpose of this study was to evaluate the feasibility and effectiveness of a multicomponent school-based intervention to promote healthy eating and physical activity (and prevent obesity) with school children aged 9–11 years in Lebanon. Methods: The intervention was developed based on the constructs of the Social Cognitive Theory and adapted to the culture of Lebanese and Arab populations. It consisted of three components: class curriculum, family involvement and food service. Eight schools were purposively selected from two communities of different socioeconomic status (SES) in Beirut and, within each school type, were matched on SES, religious sect profile, and then randomly assigned to either the intervention or control group. Anthropometric measurements and questionnaires on determinants of behavioural change, eating and physical activity habits were completed by the students in both groups at baseline and post intervention. Focus group interviews were conducted in intervention schools at the end of the study. Challenges encountered during the programme implementation were also identified, since Lebanon is considered a country with political unrest and no similar research projects were conducted in the area. Results: Students in the intervention group reported purchasing and consuming less chips and sweetened drinks post-intervention compared with controls (86% & 88% less respectively p < 0.001). Knowledge and self-efficacy scores increased for the intervention (+2.8 & +1.7 points respectively p < 0.001) but not for the control group. There was no difference in physical activity and screen time habits and no changes in BMI between groups at post intervention. Interview data from focus groups showed that the programme was generally well accepted. Limitations for better outcomes include the length of the programme and the school environment. Conclusion: “Health-E-PALS” intervention is a promising innovative, theory-based, culturally sensitive intervention to promote healthy eating habits and physical activity in Lebanese school children with a potential to be scaled up, replicated and sustained

Texture-Based Analysis of Fetal Organs in Fetal Growth Restriction

Fetal growth restriction (FGR) is common, affecting around 10% of all pregnancies. Growth restricted fetuses fail to achieve their genetically predetermined size and often weigh &lt;10th centile for gestation. However, even appropriately grown fetuses can be affected, with the diagnosis of FGR missed before birth. Babies with FGR have a higher rate of stillbirth, neonatal morbidity such as breathing problems, and neurodevelopmental delay. FGR is usually due to placental insufficiency leading to poor placental perfusion and fetal hypoxia. MRI is increasingly used to image the fetus and placenta. Here we explore the use of novel multi-compartment Intravoxel Incoherent Motion Model (IVIM)-based models for MRI fetal and placental analysis, to improve understanding of FGR and quantify abnormalities and biomarkers in fetal organs. In 12 normally grown and 12 FGR gestational-age matched pregnancies (Median 28+ 4 wks±3+ 3 wks) we acquired T2 relaxometry and diffusion MRI datasets. Decreased perfusion, pseudo-diffusion coefficient, and fetal blood T2 values in the placenta and fetal liver were significant features distinguishing between FGR and normal controls (p-value &lt;0.05). This may be related to the preferential shunting of fetal blood away from the fetal liver to the fetal brain that occurs in placental insufficiency. These features were used to predict FGR diagnosis and gestational age at delivery using simple machine learning models. Texture analysis was explored to compare Haralick features between control and FGR fetuses, with the placenta and liver yielding the most significant differences between the groups. This project provides insights into the effect of FGR on fetal organs emphasizing the significant impact on the fetal liver and placenta, and the potential of an automated approach to diagnosis by leveraging simple machine learning models

Effects of a brief mindfulness-based intervention on emotional regulation and levels of mindfulness in senior students

Mindfulness-based interventions have been applied in diverse populations and achieved mental health benefits. This study examined the effects of a brief mindfulness program for emotional regulation and levels of mindfulness on senior students in Brazil. The intervention consisted of six weekly meetings attended by 30 participants. It is a pre-experimental research, with pre- and post-test comparative and correlation measurements. The preliminary results, which relied on parametrical and non-parametrical tests, revealed a reduction in total emotional regulation difficulties (p = 0.0001; r = − 0.55). Also, there was an increase in the levels of mindfulness in the subtests for both dimensions under evaluation: “Awareness” (p = 0.0001; d = 0.77) and “Acceptance” (p = 0.048; d = 0.37). By associating the amount of meditative practices performed by students with the variables, a significant positive correlation was found with the mindfulness dimension “Awareness” (rP = 0.422; p = 0.020), and there was a significant negative correlation with Difficulties in emotion regulation (rS = − 0.478; p = 0.008) and with its respective subscales “Non-acceptance” (rS = − 0.654; p = 0.0001) and “Clarity” (rS = − 0.463; p = 0.010). In conclusion, the application of a brief mindfulness-based intervention is promising in Brazilian university contexts; moreover, it can bring benefits to students, e.g., an increase in emotion regulation as well as in levels of mindfulness. We suggest that further research should use an experimental design and follow-up.info:eu-repo/semantics/publishedVersio

High-spin States in \u3csup\u3e191, 193\u3c/sup\u3eAu and \u3csup\u3e192\u3c/sup\u3ePt: Evidence for Oblate Deformation and Triaxial Shapes

High-spin states of 191, 193Au and 192Pt have been populated in the 186W(11B, xn) and 186W(11B, p4n) reactions, respectively, at a beam energy of 68 MeV and their γ decay was studied using the YRAST Ball detector array at the Wright Nuclear Structure Laboratory at Yale University. The level scheme of 193Au has been extended up to Iπ = 55/2+. New transitions were observed also in 191Au and 192Pt. Particle-plus-Triaxial-Rotor (PTR) and Total Routhian Surface (TRS) calculations were performed to determine the equilibrium deformations of the Au isotopes. The predictions for oblate deformations in these nuclei are in agreement with the experimental data. Development of nonaxial shapes is discussed within the framework of the PTR model

Socio-demographic disparities in receipt of clinical health care services during the COVID-19 pandemic for Canadian children with disability

Background: Little is known about the experience of receiving in-person and virtual clinical health care services during the COVID-19 pandemic for Canadian children with developmental disabilities and delays facing multiple layers of vulnerability (e.g., low income, low educational attainment families). We examined the relationship between socio-demographic factors and the receipt of these services (physical and mental health services) during COVID-19 for Canadian children with these conditions. Methods: Data collected in Canada for the Global Report on Developmental Delays, Disorders and Disabilities were used. The survey: (1) was developed and disseminated in collaboration with caregivers of children with disabilities, (2) included topics such as response to the pandemic and receipt of services and supports, and (3) documented the experiences of a non-random convenience sample of caregivers of children (any age) with these conditions during and prior to the pandemic. We used four logistic regression models to assess the association between socio-demographic factors and receipt of services. Results: Being a single parent, having low educational attainment (high school or less), having low income (making less than $40,000 per year), working less than full time (working part-time, working reduced hours due to COVID, retired, stay home parent or student), as well as male gender and older age of the child with disability were factors associated with decreased likelihood of receiving services. Conclusion: Our findings point to the need for tailoring services for families of children with disabilities, particularly low socioeconomic status families, to ensure continuity of care during public health emergencies

Value Functions and Transversality Conditions for Infinite-Horizon Optimal Control Problems

This paper investigates the relationship between the maximum principle with an infinite horizon and dynamic programming and sheds new light upon the role of the transversality condition at infinity as necessary and sufficient conditions for optimality with or without convexity assumptions. We first derive the nonsmooth maximum principle and the adjoint inclusion for the value function as necessary conditions for optimality that exhibit the relationship between the maximum principle and dynamic programming. We then present sufficiency theorems that are consistent with the strengthened maximum principle, employing the adjoint inequalities for the Hamiltonian and the value function. Synthesizing these results, necessary and sufficient conditions for optimality are provided for the convex case. In particular, the role of the transversality conditions at infinity is clarified