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Arsenic exposure is associated with elevated sweat chloride concentration and airflow obstruction among adults in Bangladesh: A cross-sectional study
No full textArsenic is associated with lung disease and experimental models suggest that arsenic-induced degradation of the chloride channel CFTR (cystic fibrosis transmembrane conductance regulator) is a mechanism of arsenic toxicity. We examined associations between arsenic exposure, sweat chloride concentration (measure of CFTR function), and pulmonary function among 269 adults in Bangladesh. Participants with sweat chloride ≥ 60 mmol/L had higher arsenic exposures than those with sweat chloride \u3c 60 mmol/L (water: median 77.5 µg/L versus 34.0 µg/L, p = 0.025; toenails: median 4.8 µg/g versus 3.7 µg/g, p = 0.024). In linear regression models, a one-unit µg/g increment in toenail arsenic was associated with a 0.59 mmol/L higher sweat chloride concentration, p \u3c 0.001. Among the entire study population, after adjusting for covariates including age, sex, smoking, education, and height, toenail arsenic concentration was associated with increased odds of airway obstruction (OR: 1.97, 95%: 1.06, 3.67, p = 0.03); however, sweat chloride concentration did not mediate this association. Our findings suggest that sweat chloride concentration may serve as novel biomarker for arsenic exposure, warranting further investigation in diverse populations, and that arsenic likely acts on the lung through mechanisms other than inducing CFTR dysfunction. Alternative mechanisms by which environmental arsenic exposure may lead to obstructive lung disease, such as arsenic-induced direct lung injury and/or increase lung proteinase activity, require additional exploration in future work
Enhancing the MMC Addiction Medicine Elective Curriculum for Medical Students
Get PDFEnhancing a trauma-informed addiction medicine curriculum for Tufts medical students by defining course objectives, creating learner assignments and improving hands-on training.https://knowledgeconnection.mainehealth.org/mite/1001/thumbnail.jp
Period Poverty: Breaking the Cycle
No full textDATE OF PRESENTATION: January 2, 2025
CME available for 1 year after presentation
CME Text Code: 97000
In order to claim CME credit, please complete an evaluation in CloudCME for each presentation.https://knowledgeconnection.mainehealth.org/pediatrics_gr/1065/thumbnail.jp
Tools for Improving Access to Subspecialty Care Among Rural Children
No full textChildren living in rural areas encounter unique, significant barriers to the receipt of health care, including pediatric specialty care. In this article, the authors review these barriers and evaluate the advantages and limitations of various access tools intended to better connect children to specialty care. They highlight the potential of some access tools to increase rural primary care physicians\u27 skill and involvement in their patient care, but also the risks of increasing rural primary care providers\u27 workload and responsibilities without increasing their resources. They contextualize these benefits and risks within the quintuple aims advanced by the Institute of Healthcare Improvement
January 15th, 2025: Three Thyroid Hormone Stories: On Injury Response, Congenital Defects and Neurodevelopmental and Endocrine Disease
No full texthttps://knowledgeconnection.mainehealth.org/medicine_gr/1032/thumbnail.jp
DERM-SUCCESS FDA Pivotal Study: A Multi-Reader Multi-Case Evaluation of Primary Care Physicians\u27 Skin Cancer Detection Using AI-Enabled Elastic Scattering Spectroscopy
No full textBACKGROUND: Elastic Scattering Spectroscopy (ESS), an optical tissue sampling technique, distinguishes between benign and malignant tissue in vivo without the need to perform a surgical biopsy. A handheld device that employs ESS enabled with an artificial intelligence algorithm was developed as an objective tool to aid primary care physicians (PCPs) in their management of lesions suspicious for skin cancer. The aim of this study was to assess and compare the diagnostic and management performance of PCPs with and without the use of the ESS device in detecting skin cancer. METHODS: In this clinical utility study, 108 PCPs evaluated 100 skin lesion cases (50 aided with the device output and 50 unaided by the device). For each case, PCPs provided a diagnosis, management decision, and level of confidence in that decision initially without, and then subsequently with, device output. Sensitivity, specificity, AUC, and confidence in their assessment prior to, and then with, device output were compared. RESULTS: With visual assessment assisted by device output, diagnostic sensitivity increased significantly from 71.1% to 81.7% (P = .0085) and referral sensitivity increased significantly from 82.0% to 91.4% (P = .0027) compared to visual assessment only. Device-aided diagnostic specificity decreased from 60.9% to 54.7% (P = .1896), and referral specificity decreased from 44.2% to 32.4% (P = .0256). Overall management performance (ie, AUC) also increased from 0.708 to 0.762, and increased from 0.567 to 0.682 for lesions which physicians reported low confidence in their unassisted management decision. Physicians reporting high confidence in their management assessment increased from 36.8% to 53.4%. CONCLUSION: Use of the ESS device output by PCPs significantly improved their diagnostic and management sensitivities as well as their overall management performance. The findings suggest the ESS device can improve PCP skin cancer detection and confidence in their skin lesion evaluation and management
Altered metabolomics and inflammatory transcriptomics in human bone marrow adipocytes after acute high calorie diet and acute fasting
No full textExpansion of bone marrow (BM) adipocytes has been linked to nutritional pressures, suggesting that BM is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here, we investigated BM metabolism in response to acute overnutrition (high calorie diet; HCD) and calorie deprivation (fasting). Participants underwent a 10-day HCD followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting. BM adipocytes and sera were collected before and after each dietary intervention for each participant. Using comprehensive and integrated analyses, we characterized nutritional influences on BM adiposity. BM adipocytes after HCD showed an upregulation of FOXP3, the transcription factor that controls the development of Tregs, which are critical in reducing inflammatory immune responses. After fasting, BM adipocytes had an upregulation of inflammatory genes (CP, CFH, VCAN, and IGFBP3). Proteomic analysis after HCD showed that BM serum had an upregulation of proteins related to an inflammatory/complement pathway. After fasting, in the BM serum, there was a significant downregulation of inflammatory/complement pathway proteins. Despite both interventions causing BM adipose tissue expansion, the mechanism for adipogenesis appears to be dependent on nutrient availability. After HCD, lipid-mediated signaling and lipid storage, and lipid droplet biogenesis were significantly downregulated. In contrast, after fasting, lipid-mediated signaling and lipid storage, and lipid droplet biogenesis were significantly upregulated. Overall, our results demonstrate key differences in inflammatory response and lipid metabolism between HCD and fasting, despite a nearly identical BM adipose phenotype. Further analyses are needed to understand the effects nutritional pressures have on BM adipogenesis and immune responses
Non-insulin therapies in management of type 1 diabetes
No full textWith increasing prevalence of double diabetes (features of type 2 diabetes in people with type 1 diabetes (T1D)), there is a growing interest in using non-insulin therapies to improve glycemic outcomes, promote weight loss, and reduce cardiovascular risk in T1D. In this narrative review, we summarize current literature and provide practical guidance for clinicians when considering these therapies. Using a PubMed literature search, we identified 51 randomized clinical trials investigating sodium glucose co-transporter inhibitors (SGLTi :9), glucagon like peptide 1 receptor agonist (GLP1RA: 13), metformin (13), dipeptidyl peptidase-4 inhibitor (DPP-4i: 9), pramlintide (4), bromocriptine (1) and combination therapies (2) in T1D. Outcomes of interest included change in HbA1c, weight, total daily dose (TDD) of insulin, surrogate cardiovascular outcomes and safety parameters. Data shows that GLP-1RAs and SGLTi have demonstrated the greatest efficacy in reducing HbA1c up to 0.7% and 0.5% respectively compared to placebo. GLP-1RAs reduced TDD of insulin by up to 18.5% and weight up to 9.3% (8.3kg). SGLTi reduced insulin TDD by up to 15.3% and weight 5.3% (4.3kg). Neither class increased the risk of severe hypoglycemia but SGLTi had a two-to-fivefold higher risk of diabetic ketoacidosis (DKA). Other agents (metformin, DPP-4i and bromocriptine) failed to demonstrate a sustained glycemic efficacy in T1D. In summary, GLP-1RA has a great potential as adjunct therapy in T1D. SGLTi could be another beneficial therapy in T1D, however, more research is needed to improve DKA risk with this therapy. Efficacy trials of weekly GLP-1RA and its potential cardio-renal benefits in T1D are much needed
Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome.
No full textCONTEXT: Bardet-Biedl syndrome (BBS) is a rare genetic disease associated with disruptions in melanocortin-4 receptor pathway signaling that can contribute to increased risk for metabolic syndrome and obesity-related comorbidities.
OBJECTIVE: Here, MetS-Z-BMI scores, a continuous measure based on body mass index (BMI), were calculated to determine metabolic syndrome severity and response to treatment with the melanocortin-4 receptor agonist setmelanotide in BBS.
METHODS: All patients from a phase 3 study (NCT03746522) of setmelanotide with data required for the calculation of MetS-Z-BMI scores were included. Mean MetS-Z-BMI score was determined at baseline and Week 52; subgroup analyses were conducted by sex, age, genotype, and response to setmelanotide.
RESULTS: MetS-Z-BMI scores were evaluable for 22 of 32 patients enrolled. Baseline mean (SD) MetS-Z-BMI score across patients was 1.1 (0.5); baseline mean (SD) odds ratios of future cardiovascular disease or type 2 diabetes were 3.1 (1.5) and 3.7 (1.7), respectively, for adults and 10.2 (4.7) and 2.8 (1.3), respectively, for pediatric patients. Overall, mean (SD) MetS-Z-BMI score at Week 52 was reduced by 0.34 (0.62). Mean (SD) MetS-Z-BMI scores significantly differed depending on achievement of predetermined weight-based thresholds of ≥10% weight loss (patients aged ≥18 years) or ≥0.3-point reduction in BMI Z score (patients aged \u3c 18 years) at Week 52 (achievers, -0.64 [0.54]; nonachievers, 0.08 [0.47]; P = .0043). No significant difference was observed with other subgroup comparisons.
CONCLUSION: MetS-Z-BMI score reductions were observed after 52 weeks of treatment, suggesting that setmelanotide may decrease metabolic syndrome severity and risk of future obesity-related comorbidities in those with BBS
Importance of Interdepartmental Communication in Relation to Patient Outcomes
No full texthttps://knowledgeconnection.mainehealth.org/nurseresidency/1134/thumbnail.jp