Feasibility of using teleradiology to improve tuberculosis screening and case management in a district hospital in Malawi.

Malawi has one of the world's highest rates of human immunodeficiency virus (HIV) infection (10.6%), and southern Malawi, where Thyolo district is located, bears the highest burden in the country (14.5%). Tuberculosis, common among HIV-infected people, requires radiologic diagnosis, yet Malawi has no radiologists in public service. This hinders rapid and accurate diagnosis and increases morbidity and mortality

Spatial variability of nitrogen dioxide and formaldehydeand residential exposure of children in the industrial area of Viadana, Northern Italy

Chipboard production is a source of ambient air pollution. We assessed the spatial variability of outdoor pollutants and residentialexposure of children living in proximity to the largest chipboard industry in Italy and evaluated the reliability of exposureestimates obtained from a number of available models. We obtained passive sampling data on NO2and formaldehyde collectedby the Environmental Protection Agency of Lombardy region at 25 sites in the municipality of Viadana during 10 weeks (2017-2018) and compared NO2measurements with average weekly concentrations from continuous monitors. We compared interpo-lated NO2and formaldehyde surfaces with previous maps for 2010. We assessed the relationship between residential proximity tothe industry and pollutant exposures assigned using these maps, as well as other available countrywide/continental models basedon routine data on NO2, PM10, andPM2.5. The correlation between NO2concentrations from continuous and passive samplingwas high (Pearson'sr= 0.89), although passive sampling underestimated NO2especially during winter. For both 2010 and 2017-2018, we observed higher NO2and formaldehyde concentrations in the south of Viadana, with hot-spots in proximity to theindustry. PM10and PM2.5exposures were higher for children at 3.5 km to theindustry, whereas NO2exposure was higher at 1-1.7 km to the industry. Road and population densities were also higher close tothe industry. Findings from a variety of exposure models suggest that children living in proximity to the chipboard industry inViadana are more exposed to air pollution and that exposure gradients are relatively stable over time

Congenital hypothyroidism due to a new deletion in the sodium/iodide symporter protein.

OBJECTIVE: Iodide transport defect (ITD) is a rare disorder characterised by an inability of the thyroid to maintain an iodide gradient across the basolateral membrane of thyroid follicular cells, that often results in congenital hypothyroidism. When present the defect is also found in the salivary glands and gastric mucosa and it has been shown to arise from abnormalities of the sodium/iodide symporter (NIS). PATIENT: We describe a woman with hypothyroidism identified at the 3rd month of life. The diagnosis of ITD was suspected because of nodular goitre, and little if any iodide uptake by the thyroid and salivary glands. Treatment with iodide partially corrected the hypothyroidism; however, long-term substitution therapy with L-thyroxine was started. MEASUREMENTS: Thyroid radioiodide uptake was only 1.4% and 0.3% at 1 and 24 h after the administration of recombinant human TSH. The saliva to plasma I- ratio was 1.1 indicating that the inability of the thyroid gland to concentrate I- was also present in the salivary glands. RESULTS: Analysis of the patient's NIS gene revealed a 15 nucleotide (nt) deletion of the coding sequence (nt 1314 through nt 1328) and the insertion of 15 nt duplicating the first 15 nt of the adjacent intron. The patient was homozygous for this insertion/deletion, while both consanguineous parents were heterozygous. This deletion predicts the production of a protein lacking the five terminal amino acids of exon XI (439-443) which are located in the 6th intracellular loop. COS-7 cells transfected with a vector expressing the mutant del-(439-443) NIS failed to concentrate iodide, suggesting that the mutation was the direct cause of the ITD in this patient. CONCLUSION: In conclusion we describe the first Italian case of congenital hypothyroidism due to a new deletion in the NIS gene

Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique

As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care

Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test

The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative

Distinguishable DNA methylation defines a cardiac-specific epigenetic clock

BACKGROUND The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG

Metabolic reprogramming by malat1 depletion in prostate cancer

The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes growth and progression in prostate cancer (PCa); however, little is known about its possible impact in PCa metabolism. The aim of this work has been the assessment of the metabolic reprogramming associated with MALAT1 silencing in human PCa cells and in an ex vivo model of organotypic slice cultures (OSCs). Cultured cells and OSCs derived from primary tumors were transfected with MALAT1 specific gapmers. Cell growth and survival, gene profiling, and evaluation of targeted metabolites and metabolic enzymes were assessed. Computational analysis was made considering expression changes occurring in metabolic markers following MALAT1 targeting in cultured OSCs. MALAT1 silencing reduced expression of some metabolic enzymes, including malic enzyme 3, pyruvate dehydrogenase kinases 1 and 3, and choline kinase A. Consequently, PCa metabolism switched toward a glycolytic phenotype characterized by increased lactate production paralleled by growth arrest and cell death. Conversely, the function of mitochondrial succinate dehydrogenase and the expression of oxidative phosphorylation enzymes were markedly reduced. A similar effect was observed in OSCs. Based on this, a predictive algorithm was developed aimed to predict tumor recurrence in a subset of patients. MALAT1 targeting by gapmer delivery restored normal metabolic energy pathway in PCa cells and OSCs