Bodybuilders' accounts of synthol use: The construction of lay expertise online.

Synthol is an injectable oil used by bodybuilders to make muscles appear bigger. Widely available on the Internet, it is reported to carry a wide range of health risks and side effects such as localised skin problems, nerve damage and oil-filled cysts, as well as muscle damage and the development of scar tissue. Given the tension between health risk and quick muscle enlargement, how lay users explain and justify their synthol intake becomes an important question. Drawing on discourse analysis, we focus on how lay expertise is worked up by users in the absence of available specialist knowledge by invoking medical and pharmaceutical discourses as legitimation, providing novices with support, gaining trust through positive personal narratives and thus gaining credibility as experts. Results have clear implications for health promotion interventions with bodybuilders

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Oxygen Sensing in Drosophila: Multiple Isoforms of the Prolyl Hydroxylase Fatiga Have Different Capacity to Regulate HIFα/Sima

Background: The Hypoxia Inducible Factor (HIF) mediates cellular adaptations to low oxygen. Prolyl-4-hydroxylases are oxygen sensors that hydroxylate the HIF alpha-subunit, promoting its proteasomal degradation in normoxia. Three HIFprolyl hydroxylases, encoded by independent genes, PHD1, PHD2, and PHD3, occur in mammals. PHD2, the longest PHD isoform includes a MYND domain, whose biochemical function is unclear. PHD2 and PHD3 genes are induced in hypoxia to shut down HIF dependent transcription upon reoxygenation, while expression of PHD1 is oxygen-independent. The physiologic significance of the diversity of the PHD oxygen sensors is intriguing. Methodology and Principal Findings: We have analyzed the Drosophila PHD locus, fatiga, which encodes 3 isoforms, FgaA, FgaB and FgaC that are originated through a combination of alternative initiation of transcription and alternative splicing. FgaA includes a MYND domain and is homologous to PHD2, while FgaB and FgaC are shorter isoforms most similar to PHD3. Through a combination of genetic experiments in vivo and molecular analyses in cell culture, we show that fgaB but not fgaA is induced in hypoxia, in a Sima-dependent manner, through a HIF-Responsive Element localized in the first intron of fgaA. The regulatory capacity of FgaB is stronger than that of FgaA, as complete reversion of fga loss-of-function phenotypes is observed upon transgenic expression of the former, and only partial rescue occurs after expression of the latter. Conclusions and Significance: Diversity of PHD isoforms is a conserved feature in evolution. As in mammals, there are hypoxia-inducible and non-inducible Drosophila PHDs, and a fly isoform including a MYND domain co-exists with isoforms lacking this domain. Our results suggest that the isoform devoid of a MYND domain has stronger regulatory capacity than that including this domain.Fil:Acevedo, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Centanin, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Dekanty, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

PHD3 regulates differentiation, tumour growth and angiogenesis in pancreatic cancer

pancreatic cance

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

Balanced Schnyder woods for planar triangulations: an experimental study with applications to graph drawing and graph separators

In this work we consider balanced Schnyder woods for planar graphs, which are Schnyder woods where the number of incoming edges of each color at each vertex is balanced as much as possible. We provide a simple linear-time heuristic leading to obtain well balanced Schnyder woods in practice. As test applications we consider two important algorithmic problems: the computation of Schnyder drawings and of small cycle separators. While not being able to provide theoretical guarantees, our experimental results (on a wide collection of planar graphs) suggest that the use of balanced Schnyder woods leads to an improvement of the quality of the layout of Schnyder drawings, and provides an efficient tool for computing short and balanced cycle separators.Comment: Appears in the Proceedings of the 27th International Symposium on Graph Drawing and Network Visualization (GD 2019

Macrophage Migration Inhibitory Factor Activates Hypoxia-Inducible Factor in a p53-Dependent Manner

All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately

Profiling of cardio-metabolic risk factors and medication utilisation among Type II diabetes patients in Ghana: a prospective cohort study

Background: Type II diabetes mellitus (T2DM) is complicated by multiple cardio-metabolic risk factors. Controlling these factors requires lifestyle modifications alongside utilisation of anti-diabetic medications. Different glucose lowering [(biguanides (BIGs), sulfonylureas (SUAs), thiazolidinediones (TNZ)], lipid lowering (statins), and anti-hypertensive medicines [angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs) and central acting drugs (CADs)] have been approved for controlling hyperglycaemia, dyslipidaemia and hypertension respectively. Here, we examined factors that characterise T2DM and explored the response to medication therapy among T2DM patients. Methods: This prospective cohort study recruited 241 T2DM patients reporting at a clinic in Ghana, from January through to August, 2016. Each patient’s demographic, medications and anthropometric data was obtained while information on medication adherence was captured using Morisky adherence scale-8 (MMAS-8). Fasting blood samples were collected for biochemical analysis. Results: The mean age of participants was 57.82 years for baseline and six-month follow-up. Physical activity differed at baseline and follow up (p \u3c 0.05) but not body mass index (BMI). BIG alone, or in combination with SUA and TNZ did not improve glycaemic status at follow up (p \u3e 0.05). Many participants using either ACEI or ARB were able to control their blood pressures. Among dyslipidaemia patients under statin treatment, there was an improved lipid profile at follow-up. Conclusions: Statin medications are effective for reducing dyslipidaemia in T2DM patients. However, control of modifiable risk factors, particularly blood glucose and to a lesser degree blood pressure is suboptimal. Addressing these will require concomitant interventions including education on medication adherence and correct dietary plans, lifestyle modifications and physical activity

The present and future burden of urinary bladder cancer in the world

Urinary bladder cancer (UBC) is a common disease worldwide. At any point in time 2.7 million people have a history of UBC. The incidence of UBC varies over the world with highest rates in developed communities. But the burden of UBC will increase in less developed areas of the world. These changes can be attributed to global changes in exposure to risk factors for UBC and growth and aging of the world population