Parents\u27 perceptions and concerns about their children\u27s weight

Background: For parents to address overweight or obesity in their children, they first need to perceive their child to be overweight and to show some level of concern. We aimed to: (1) measure the level of misclassification between children&rsquo;s actual and parent-perceived weight status, and (2) determine the level of parent concern about their child&rsquo;s (actual) weight and whether concern varied according to the accuracy of parents&rsquo; perceptions.Methods: Participants were 1711 primary school children aged 5&ndash;12 years from the Barwon-South West region of Victoria, Australia. Height and weight were measured and weight status determined using international standards. Parents completed a Computer Assisted Telephone Interview (CATI) that included questions relating to their child&rsquo;s weight.Results: 448 children (26.2% of sample) were overweight or obese. Of these, weight status for almost half (48%) was underestimated by parents. This &lsquo;bias&rsquo; did not vary according to the child&rsquo;s gender, parent&rsquo;s education, or household socio-economic status but did for child&rsquo;s age and parent-respondent gender. More than half (57%) of the parents of overweight-obese children expressed no concern about their child&rsquo;s weight. Parents who underestimated the weight status of their overweight child were significantly less concerned (P &lt; 0.001) about their child&rsquo;s weight than those who correctly perceived their child as overweight.Conclusions: Parents were relatively poor judges of overweight or obesity in their own child and consequently there was a lack of appropriately directed concern. Education to help parents correctly classify their child&rsquo;s weight status should be part of efforts to prevent unhealthy weight gain.<br /

Role of Mitofusin 2 in the Renal Stress Response

The role of mitofusin 2 (MFN2), a key regulator of mitochondrial morphology and function in the renal stress response is unknown. To assess its role, the MFN2 floxed gene was conditionally deleted in the kidney of mice (MFN2 cKO) by Pax2 promoter driven Cre expression (Pax2Cre). MFN2 cKO caused severe mitochondrial fragmentation in renal epithelial cells that are critical for normal kidney tubular function. However, despite a small (20%) decrease in nephron number, newborn cKO pups had organ or tubular function that did not differ from littermate Cre-negative pups. MFN2 deficiency in proximal tubule epithelial cells in primary culture induced mitochondrial fragmentation but did not significantly alter ATP turnover, maximal mitochondrial oxidative reserve capacity, or the low level of oxygen consumption during cyanide exposure. MFN2 deficiency also did not increase apoptosis of tubule epithelial cells under non-stress conditions. In contrast, metabolic stress caused by ATP depletion exacerbated mitochondrial outer membrane injury and increased apoptosis by 80% in MFN2 deficient vs. control cells. Despite similar stress-induced Bax 6A7 epitope exposure in MFN2 deficient and control cells, MFN2 deficiency significantly increased mitochondrial Bax accumulation and was associated with greater release of both apoptosis inducing factor and cytochrome c. In conclusion, MFN2 deficiency in the kidney causes mitochondrial fragmentation but does not affect kidney or tubular function during development or under non-stress conditions. However, MFN2 deficiency exacerbates renal epithelial cell injury by promoting Bax-mediated mitochondrial outer membrane injury and apoptosis

Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney

Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF

Neuropilin-1 Modulates p53/Caspases Axis to Promote Endothelial Cell Survival

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), one of the crucial pro-angiogenic factors, functions as a potent inhibitor of endothelial cell (EC) apoptosis. Previous progress has been made towards delineating the VPF/VEGF survival signaling downstream of the activation of VEGFR-2. Here, we seek to define the function of NRP-1 in VPF/VEGF-induced survival signaling in EC and to elucidate the concomitant molecular signaling events that are pivotal for our understanding of the signaling of VPF/VEGF. Utilizing two different in vitro cell culture systems and an in vivo zebrafish model, we demonstrate that NRP-1 mediates VPF/VEGF-induced EC survival independent of VEGFR-2. Furthermore, we show here a novel mechanism for NRP-1-specific control of the anti-apoptotic pathway in EC through involvement of the NRP-1-interacting protein (NIP/GIPC) in the activation of PI-3K/Akt and subsequent inactivation of p53 pathways and FoxOs, as well as activation of p21. This study, by elucidating the mechanisms that govern VPF/VEGF-induced EC survival signaling via NRP-1, contributes to a better understanding of molecular mechanisms of cardiovascular development and disease and widens the possibilities for better therapeutic targets

Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD

Apoptosis in brain and gut tissue of mice fed a seed preparation of the cycad Lepidozamia peroffskyana

Apoptosis (programmed cell death) was identified in histological sections of bain and gut tissue of adult mice fed seed preparations from the cycad Lepidozamia peroffskyana. This form of cell death was also found at high levels in brain tissue from neonatal mice born from a cycad-fed mother. The discovery was made during re-appraisal of archival tissue from a study of toxic properties of L. peroffskyana. Ingestion of appropriately prepared food or medicine derived from another cycad, Cycas circinalis, is thought to be associated with several motor neurone and other neurodegenerative disorders of some Pacific island inhabitants. Apoptosis is cell death under gene control. From the present study, presence of apoptosis in brain tissue after cycad toxicity may provide a link between cycad ingestion and development of neurodegenerative disorders and may provide a novel explanation for localization of some neurodegenerative disorders, as some inhabitants may have a genetic susceptibility to apoptosis induced by cycad toxicity

Pontosubicular apoptosis ("necrosis") in human neonates with intrauterine growth retardation and placental infarction

In a previous study of 37 autopsied stillbirths with non-dysmorphic intrauterine growth retardation ( IUGR), 26 cases were associated with placental infarction, a morphologic marker of uteroplacental insufficiency. Nine of the 26 cases with both IUGR and placental infarction, where archival tissue was available, had grey matter ischaemic lesions that were subsequently identified as pontosubicular necrosis. This lesion is now regarded as a localized form of apoptosis. A further eight third trimester stillbirth cases with both IUGR and placental infarction were ascertained prospectively. Sixteen of these 17 cases showed pontosubicular apoptosis, identified morphologically and verified using activated caspase-3 and TUNEL. Five of the 17 cases showed apoptosis in the frontal or temporal cortex as well. In this current study, pontosubicular apoptosis was strongly associated with IUGR and placental infarction in third trimester stillborns, suggesting that uteroplacental insufficiency leading to chronic fetal hypoxaemia may cause cerebral apoptosis

An experimental study evaluating the effect of minoxidil on the growth cycle of hair follicles

The possibility that topically-applied minoxidil might affect the growth cycle of hair follicles was studied in inbred Herston white mice and HRA/Skh1 hairless mice. In the normal follicular cycle, the anagen or growth phase can be followed by autoradiographic demonstration of [3H]thymidine uptake in proliferating matrical cells, and the catagen or regression phase can be recognised, using light microscopy, by the presence of greatly increased death of matrical cells by apoptosis. Using these two markers, the effects of topically-applied minoxidil on follicular kinetics were studied, during neonatal hair growth and the spontaneous wave of hair loss that occurs 16 to 17 days after birth. Minoxidil at strengths of either 1% or 3%, applied daily to the dorsal skin of newborn mice from birth until 25 days of age, was found to have no recognisable effect. Despite this negative result, however, the study does show the potential for the use of apoptosis as a marker for catagen in research in dermatopathology