Parenting Practices Are Associated With Out-of-School Physical Activity in US Adolescents in 2014.

INTRODUCTION: Lack of physical activity (PA) is associated with obesity, diabetes, hypertension, cardiovascular diseases, and cancer. Parenting practices influence PA in young children. However, there is little evidence available for adolescents. We examined whether parenting practices were associated with out-of-school PA (OSPA) in US adolescents. METHODS: This cross-sectional 2019 study analyzed data from the 2014 FLASHE study, a web-based, quota-sampled survey of parent-adolescent dyads. Inclusion required survey completion and parents to live with their teen (ages 12-17 y old). Physically limited adolescents were excluded. Dyads were stratified by teen age. Exposures included parental modeling, monitoring, facilitation, restriction, guided choice, and pressure. The outcomes of interest were OSPA Youth Activity Profile scores. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using adjusted logistic regressions. RESULTS: A total of 1109 dyads were included. Guided choice increased odds of OSPA for 15- to 17-year-olds (OR = 2.12; 95% CI, 1.17-3.84). Facilitation increased odds of OSPA for 12- to 14-year-olds (OR = 2.21; 95% CI, 1.13-4.33). Monitoring decreased odds of OSPA for 15- to 17-year-olds (OR = 0.34; 95% CI, 0.20-0.57) and 12- to 14-year-olds (OR = 0.45; 95% CI, 0.27-0.74). Friend support increased odds of OSPA in 15- to 17-year-olds (OR = 4.03; 95% CI, 2.29-7.08) and 12- to 14-year-olds (OR = 3.05; 95% CI 1.69-5.51). CONCLUSION: Future interventions should prioritize (1) shared decision making for older teens, (2) access to PA opportunities for younger adolescents, and (3) promoting peer PA and friend support for everyone.

Diagnosis, Management And Prevention Of Hepatitis C In Pakistan 2017.

AIMS AND OBJECTIVES: Since the advent of direct acting antiviral agents, there is a revolutionary change in the management of HCV infection. Newer drugs with different mechanism of action are being introduced and are expected to be available in coming few months in Pakistan as well. The main purpose of the guideline is to review and induct the latest research in field of HCV infection in Pakistani perspective so that our healthcare professionals can apply the new recommendations in timely and judicial manner. Target groups of guidelines are general physicians treating hepatitis C, hepatologists and gastroenterologists. Other beneficiaries of these guidelines are public health institutions of Pakistan, which provide free treatment to deserving patients under National Hepatitis Prevention and Control Program and Pakistan Bait-ul- Mal Program. METHODOLOGY: These guidelines are based on the review of National consensus practice guidelines: Diagnosis, Management and Prevention of Hepatitis C Pakistan 2009. Published data in National and International Journals searched with the help of Google search and pub med, and 2015-16 guidelines of HCV by AASLD, EASL, APASL and WHO. Local studies are preferably added with references to enhance the Pakistani perspective. Evidence was also taken from published studies. Recommendations have been based upon evidence from national publications on the subject and scientific presentations at national liver meeting as well from experts' personal experience and opinion.

miR-let-7f-1 regulates SPARC mediated cisplatin resistance in medulloblastoma cells.

Our previous studies indicate that Secreted Protein Acidic and Rich in Cysteine (SPARC) expression suppressed medulloblastoma tumor growth in vitro and in vivo. Here we sought to determine the effect of SPARC expression in medulloblastoma cells to chemotherapeutic agents. In this study, we show that SPARC expression induces cisplatin resistance in medulloblastoma cells. We also demonstrate that the autophagy was involved in SPARC expression mediated resistance to cisplatin. Suppression of autophagy by either autophagy inhibitor, 3-methyladenosine (3MA) or Atg5 siRNA enhanced cisplatin sensitivity in SPARC expressed cells. Further, SPARC expression suppressed miR-let-7f-1 expression which resulted in disrupted repression of High Mobility Group Box 1 (HMGB1), a critical regulator of autophagy. We also show that HMGB1 is a direct target of miR-let-7f-1 and forced expression of HMGB1 cDNA enhanced cisplatin sensitivity in SPARC expressed cells. In summary, our results suggest that SPARC modulates cisplatin resistance by modulating the Let-7f-1 miRNA/HMGB1 axis in medulloblastoma cells.

Heme and FLVCR-related transporter families SLC48 and SLC49.

Heme is critical for a variety of cellular processes, but excess intracellular heme may result in oxidative stress and membrane injury. Feline leukemia virus subgroup C receptor (FLVCR1), a member of the SLC49 family of four paralogous genes, is a cell surface heme exporter, essential for erythropoiesis and systemic iron homeostasis. Disruption of FLVCR1 function blocks development of erythroid progenitors, likely due to heme toxicity. Mutations of SLC49A1 encoding FLVCR1 are noted in patients with a rare neurodegenerative disorder: posterior column ataxia with retinitis pigmentosa. FLVCR2 is highly homologous to FLVCR1 and may function as a cellular heme importer. Mutations of SLC49A2 encoding FLVCR2 are observed in Fowler syndrome, a rare proliferative vascular disorder of the brain. The functions of the remaining members of the SLC49 family, MFSD7 and DIRC2 (encoded by the SLC49A3 and SLC49A4 genes), are unknown, although the latter is implicated in hereditary renal carcinomas. SLC48A1 (heme responsive gene-1, HRG-1), the sole member of the SLC48 family, is associated with the endosome and appears to transport heme from the endosome into the cytosol.

Erythrocyte scaffolding protein p55/MPP1 functions as an essential regulator of neutrophil polarity.

As mediators of innate immunity, neutrophils respond to chemoattractants by adopting a highly polarized morphology. Efficient chemotaxis requires the formation of one prominent pseudopod at the cell front characterized by actin polymerization, while local inhibition suppresses the formation of rear and lateral protrusions. This asymmetric control of signaling pathways is required for directional migration along a chemotactic gradient. Here, we identify the MAGUK protein p55/MPP1 as a mediator of the frontness signal required for neutrophil polarization. We developed a p55 knockout (p55(-/-)) mouse model, and demonstrate that p55(-/-) neutrophils form multiple transient pseudopods upon chemotactic stimulation, and do not migrate efficiently in vitro. Upon agonist stimulation, p55 is rapidly recruited to the leading edge of neutrophils in mice and humans. Total F-actin polymerization, along with Rac1 and RhoA activation, appear to be normal in p55(-/-) neutrophils. Importantly, phosphorylation of Akt is significantly decreased in p55(-/-) neutrophils upon chemotactic stimulation. The activity of immunoprecipitated phosphatidylinositol 3-kinase gamma (PI3Kgamma), responsible for chemoattractant-induced synthesis of PIP(3) and Akt phosphorylation, is unperturbed in p55(-/-) neutrophils. Although the total amount of PIP(3) is normal in p55(-/-) neutrophils, PIP(3) is diffusely localized and forms punctate aggregates in activated p55(-/-) neutrophils, as compared to its accumulation at the leading edge membrane in the wild type neutrophils. Together, these results show that p55 is required for neutrophil polarization by regulating Akt phosphorylation through a mechanism that is independent of PI3Kgamma activity.

Identification of erythrocyte p55/MPP1 as a binding partner of NF2 tumor suppressor protein/Merlin.

Neurofibromatosis type 2 is an inherited disorder characterized by the development of benign and malignant tumors on the auditory nerves and central nervous system with symptoms including hearing loss, poor balance, skin lesions, and cataracts. Here, we report a novel protein-protein interaction between NF2 protein (merlin or schwannomin) and erythrocyte p55, also designated as MPP1. The p55 is a conserved scaffolding protein with postulated functions in cell shape, hair cell development, and neural patterning of the retina. The FERM domain of NF2 protein binds directly to p55, and surface plasmon resonance analysis indicates a specific interaction with a kD value of 3.7 nM. We developed a specific monoclonal antibody against human erythrocyte p55, and found that both p55 and NF2 proteins are colocalized in the non-myelin-forming Schwann cells. This finding suggests that the p55-NF2 protein interaction may play a functional role in the regulation of apico-basal polarity and tumor suppression pathways in non-erythroid cells.

Alternatively spliced exon 5 of the FERM domain of protein 4.1R encodes a novel binding site for erythrocyte p55 and is critical for membrane targeting in epithelial cells.

Direct physical linkage of MAGUKs to the actin cytoskeleton was first established by the interaction of erythrocyte p55 with the FERM domain of protein 4.1R. Subsequently, it was reported that p55 binds to a 51-amino acid peptide, encoded by exon 10, located within the FERM domain of protein 4.1R. In this study, we investigated the nature of the p55-FERM domain binding interface and show that p55 binds to a second 35-amino acid peptide, encoded by an alternatively spliced exon 5, located within the FERM domain of protein 4.1R. Competition and Surface Plasmon Resonance-binding measurements suggest that the peptides encoded by exons 5 and 10 bind to independent sites within the D5 domain of p55. Interestingly, the full length 135 kDa isoform of protein 4.1R containing both exons 5 and 10 was targeted exclusively to the plasma membrane of epithelial cells whereas the same isoform without exon 5 completely lost its membrane localization capacity. Together, these results indicate that p55 binds to two distinct sites within the FERM domain, and the alternatively spliced exon 5 is necessary for the membrane targeting of protein 4.1R in epithelial cells. Since sequences similar to the exon 5-peptide of protein 4.1R and D5 domain of p55 are conserved in many proteins, our findings suggest that a similar mechanism may govern the membrane targeting of other FERM domain containing proteins.