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The article is a response to a previous article on the perspective of dietitians in fostering momentum for planetary health change. The authors agree with the importance of integrating planetary health (PH) education into the curriculum of health professional programs. They highlight the recent update to the Australian Medical Council's accreditation standards, which now includes a significant focus on PH. The authors discuss their own approach to incorporating sustainability themes into the curriculum at the University of Sydney and mention other international medical schools' efforts in this area. They emphasize the need for collaboration and further development in integrating PH content into health professional programs. [Extracted from the article]

Background and purpose: Mutations in the early growth response 2 gene (EGR2) cause demyelinating, but also axonal, neuropathies differing in severity and age of onset. Except for one family, all reported cases have autosomal dominant inheritance and mutations are localized within the three zinc finger (ZNF) DNA‐binding domain. The aim of this study was to provide a clinical and molecular analysis of a novel recessive mutation in EGR2. Methods: Clinical and electrophysiological assessments of three affected patients, from a consanguineous family, were performed. Genetic analyses of EGR2 were carried out by Sanger sequencing. Functional effects of clinical recessive mutations were assessed using a mammalian two‐hybrid assay. Results: A novel missense mutation (c.791C>T; p.P264L) in the homozygous state was detected outside the ZNF domains of the EGR2 gene. Three affected siblings presented with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. Respiratory compromise and cranial nerve dysfunction were also found. Our data indicate that the p.P264L mutation prevents interaction of EGR2 transcription factor with NAB corepressors, suggesting that a disruption of the NAB‐EGR2 protein interactions can result in dramatic neuropathy. Conclusion: Mutations in, or next to, the R1 domain of EGR2 should be considered with extreme caution for genetic counseling, since these could cause a severe neuropathy with an autosomal recessive manner of transmission. [ABSTRACT FROM AUTHOR]

Objectives: To describe the population of women having bariatric surgery and compare the pregnancy outcomes for women having bariatric surgery with a non-bariatric surgery population having a first and second pregnancy.Design: Population-based record linkage study.Setting: New South Wales (NSW), Australia.Population: All women aged 15-45 years with a hospital record in NSW (2002-2014) and all women giving birth in NSW (1994-2015; n = 1 606 737 women).Methods: Pregnancy and birth outcomes were compared between first and second pregnancies using repeated-measures logistic regression and paired Student's t-tests. Bariatric and non-bariatric groups were also compared.Main Outcome Measures: Maternal diabetes, preterm birth (<37 weeks of gestation) and large for gestational age.Results: There was a 13-fold increase in hospitalisations for primary bariatric surgery during 2002-2014. Compared with the general birthing population, women who had bariatric surgery experienced higher rates of hypertension, diabetes, and preterm birth. Among women who had bariatric surgery between a first and second pregnancy, there were reduced rates of hypertension (OR 0.39, 95% CI 0.29-0.53), spontaneous preterm birth (OR 0.37, 95% CI 0.16-0.86), infants that were large for gestational age (OR 0.63, 95% CI 0.44-0.88), and the admission of infants to a special care nursery or neonatal intensive care (OR 0.64, 95% CI 0.46-0.90) in the second pregnancy. Rates for small-for-gestational age and gestational diabetes following surgery were 8.3 and 11.4%, respectively CONCLUSIONS: Bariatric surgery between a first and second pregnancy was associated with reductions in obesity-related adverse pregnancy outcomes. Bariatric surgery performed for the management of obesity in accordance with current clinical criteria is associated with improved pregnancy outcomes in a subsequent pregnancy.Tweetable Abstract: Bariatric surgery for obesity may improve pregnancy and birth outcomes in a subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: While guidelines support metformin as a therapeutic option for diabetic patients with mild‐to‐moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008‐2015). Associations (adjusted hazard ratio, 95% LCLaHR95% UCL) of diabetes regimens (with and excluding metformin) in the first year post‐transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post‐transplant; most also received diabetes comedications. Compared to those who received insulin‐based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin‐based regimens were associated with significantly lower adjusted all‐cause (aHR 0.180.410.91), malignancy‐related (aHR 0.450.450.99), and infection‐related (aHR 0.120.320.85) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin‐based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients. [ABSTRACT FROM AUTHOR]

In this double blind, unicentre, randomized, placebo controlled study, we evaluated the changes in 25-hydroxyvitamin D (25(OH)D) serum levels in 150 young Belgian adults (18.30 years), monthly supplemented with 50,000 IU of vitamin D (VTD) or placebo for 6 months, from November 2010 to May 2011. At T0, 30% of the population presented 25(OH)D serum levels below 20 ng/mL. In the VTD-treated group, mean serum levels increased from 21.2 ± 8.2 to 30.6 ± 8.8 ng/mL (P < 0.001) at T3mo and to 36.0 ± 9.2 ng/mL (P < 0.001) at T6mo. Despite documented VTD intake, no changes in serum levels were, however, observed in 10% of the treated group. In the placebo group, mean 25(OH)D serum levels decreased from 22.8 ± 8.5 to 14.0 ± 6.9 ng/mL at T3mo (P < 0.001) but returned to values not significantly different from those observed at T0 (23.5 ± 8.6 ng/mL) at T6mo. No difference between serum calcium levels was observed between the groups throughout the study. In conclusion, monthly supplementation with 50,000 UI of VTD in winter can warrant serum 25(OH) Dlevels above 20ng/mL in 96.2% of those healthy young adults without inducing unacceptably high 25(OH)D concentration. This supplementation is safe and may be proposed without 25(OH)D testing. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a bifunctional protein comprising a TRP ion channel segment linked to an α-type protein kinase domain. TRPM7 is essential for proliferation and cell growth. Up-regulation of TRPM7 function is involved in anoxic neuronal death, cardiac fibrosis and tumour cell proliferation. The goal of this work was to identify non-toxic inhibitors of the TRPM7 channel and to assess the effect of blocking endogenous TRPM7 currents on the phenotype of living cells. EXPERIMENTAL APPROACH We developed an aequorin bioluminescence-based assay of TRPM7 channel activity and performed a hypothesis-driven screen for inhibitors of the channel. The candidates identified were further assessed electrophysiologically and in cell biological experiments. KEY RESULTS TRPM7 currents were inhibited by modulators of small conductance Ca2+-activated K+ channels (KCa2.1-2.3; SK) channels, including the antimalarial plant alkaloid quinine, CyPPA, dequalinium, NS8593, SKA31 and UCL 1684. The most potent compound NS8593 (IC50 1.6 µM) specifically targeted TRPM7 as compared with other TRP channels, interfered with Mg2+-dependent regulation of TRPM7 channel and inhibited the motility of cultured cells. NS8593 exhibited full and reversible block of native TRPM7-like currents in HEK 293 cells, freshly isolated smooth muscle cells, primary podocytes and ventricular myocytes. CONCLUSIONS AND IMPLICATIONS This study reveals a tight overlap in the pharmacological profiles of TRPM7 and KCa2.1-2.3 channels. NS8593 acts as a negative gating modulator of TRPM7 and is well-suited to study functional features and cellular roles of endogenous TRPM7. [ABSTRACT FROM AUTHOR]

Investigations into Drosophila mutants with impaired vision due to mutations in the transient receptor potential gene ( trp) initiated a systematic search for TRP homologs in other species, finally leading to the discovery of a whole new family of plasma membrane cation channels involved in multiple physiological processes. Among the recently discovered TRP cation channels two homologous proteins, TRPM6 and TRPM7, display unique domain compositions and biophysical properties. These remarkable genes are vital for Mg2+ homeostasis in vertebrates and, if disrupted, lead to cell death or human disease. [ABSTRACT FROM AUTHOR]

Background: Comorbidity is an important prognostic factor for elderly patients with head and neck cancer. Investigators are faced with the dilemma of selecting the appropriate comorbidity instrument for outcomes research in cancer. The goal of this study was to compare 2 general comorbidity indices with 2 disease-specific indices.Methods: The Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database was used to identify 15,493 patients with incident squamous cell carcinomas of the oral cavity, pharynx, and larynx first diagnosed between December 1983 and December 1994. Comorbid ailments were identified through the use of the International Classification of Diseases, 9th edition codes in the Medicare inpatient and outpatient claims for 7131 patients. The overall severity of comorbidity was classified according to 2 general comorbidity indices: the Charlson Comorbidity Index and the Klabunde Index, and 2 disease-specific indices: the Washington University Head and Neck Index and the Head and Neck Cancer Index. Overall survival was the primary end point. Cox proportional hazards analysis was used to assess the performance and discrimination of the comorbidity indices.Results: For each of the 4 comorbidity indices, there was a weak trend of worse survival with higher levels of comorbidity. The 2 general indices performed as well as the 2 disease-specific indices and no instrument clearly performed better than the others.Conclusion: Both the general and disease-specific comorbidity indices provided important prognostic information. The disease-specific indices did not perform better than the general indices. In this claims-based analysis, there was no apparent advantage to using a disease-specific index when attempting to predict overall survival. [ABSTRACT FROM AUTHOR]

To study the role of endothelial ATP-sensitive K+ channels in the regulation of vascular tone we examined the intracellular calcium concentration ([Ca2+]i) in coronary capillaries consisting only of endothelial cells. Coronary capillary fragments were isolated enzymatically from the guinea-pig heart and [Ca2+]i was determined by microfluorometry of fura-2 loaded cells. Low concentrations of the K+ channel opener diazoxide, which caused pronounced glibenclamide-sensitive hyperpolarization in capillaries, induced a rapid, transient rise in [Ca2+]i followed by a sustained elevation of [Ca2+]i (19 of 40 experiments). [Ca2+]i in the endothelial cells increased from 32 ± 7 nM at rest to 66 ± 11 nM at the peak ( n = 19). One third of the [Ca2+]i-transients showed irregular oscillations of [Ca2+]i. No significant difference in the [Ca2+]i-response induced by 100 nM or 1 μM diazoxide was found. Similar results were obtained with the K+ channel opener rilmakalim. Simultaneous measurements of the membrane potential and [Ca2+]i with fluorometric methods indicated that the hyperpolarization but not the [Ca2+]i-transient could be repeatedly induced in a single capillary by the K+ channel openers. Electrophysiological recordings of the membrane potential using the ”perforated patch” method ( n = 4), showed that rilmakalim (1 μM) induced hyperpolarization of capillaries towards the K+ equilibrium potential, confirming our fluorometric measurements. In conclusion, for the first time, these data indicate that K+ channel openers induce [Ca2+]i-transients in microvascular endothelial cells. This raises the possibility that these drugs not only act as synthetic vasoactive factors via hyperpolarizing smooth muscle cells but also via NO release of microvascular endothelial cells. Interestingly, only 100 nM diazoxide was sufficient for a maximal response, suggesting the expression of a new type of KATP-channel in coronary capillaries characterised by high sensitivity to diazoxide. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) DNA levels were measured by quantitative-competitive polymerase chain reaction (PCR) in weekly leukocyte samples from 50 renal transplant recipients, including 23 with symptomatic and 27 with asymptomatic CMV infection. Peak and week 4 CMV DNA levels were higher in symptomatic subjects (P = .07 and .02, respectively). In a logistic regression model, the logarithm of the week 4 level independently predicted symptomatic infection (odds ratio, 1.78 for a 1 log10 increase; 95% confidence interval, 1.14-2.78; P = .01). All subjects whose week 4 level exceeded 1000 copies/100,000 leukocytes developed symptoms. In subjects with adequate samples for analysis, CMV levels declined exponentially with ganciclovir treatment, with an average half-life of 3.3 days. Levels exceeding 10,000 copies were associated with prolonged time to clearing of CMV DNA. Potential clinical applications of quantitative CMV PCR include predicting occurrence of symptomatic first episodes after transplantation and individualizing duration of antiviral therapy. [ABSTRACT FROM AUTHOR]

Background Modern immunosuppression therapies (ISx) have many side effects, and transplant recipients must take an array of “comedications” to help mitigate complications. Comedication use patterns are not well described in large, representative samples because of lack of data. Methods We integrated national U.S. transplant registry data with pharmacy records (2005–2010) from a large pharmaceutical claims clearinghouse to examine treatments for anemia, metabolic disorders, and infections in relation to ISx regimens in months 6–12 post-transplantation (N = 22,453). Associations of ISx with comedication use (adjusted odds ratio [aOR]) were quantified with multivariate logistic regression including adjustment for recipient, donor, and transplant factors. Results Compared to a reference regimen of tacrolimus, mycophenolic acid, and prednisone, sirolimus-based ISx was associated with significantly more common use of erythropoiesis-stimulating agents (aOR 2.52, 95% confidence interval [CI] 2.06–3.09), iron (aOR 2.26, 95% CI 1.92–2.65), statins (aOR 1.47, 95% CI 1.33–1.63), fibrates (aOR 2.35, 95% CI 1.90–2.90), and phosphorous binders (aOR 2.85, 95% CI 1.80–4.50). Patterns were similar after adjustment for first-year estimated glomerular filtration rate, except the association with phosphorous binders was no longer significant. Cyclosporine-based ISx was associated with more common erythropoiesis-stimulating agent use, including after estimated glomerular filtration rate adjustment (aOR 1.61, 95% CI 1.24–2.10). Compared to those who were being administered triple ISx, recipients receiving tacrolimus-based dual and monotherapies had lower use of statins, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs), and antibacterial agents. Recipients of steroid-free ISx were less commonly treated for post-transplantation diabetes. Conclusions Alternate ISx regimens are associated with varying treatment requirements for hematologic, metabolic. and infectious complications. Comedication use should be considered in the cost-effectiveness and individualization of ISx regimens. [ABSTRACT FROM AUTHOR]