Topical 5‐azacytidine accelerates skin wound healing in rats

The development of new methods to improve skin wound healing may affect the outcomes of a number of medical conditions. Here, we evaluate the molecular and clinical effects of topical 5‐azacytidine on wound healing in rats. 5‐Azacytidine decreases the expression of follistatin‐1, which negatively regulates activins. Activins, in turn, promote cell growth in different tissues, including the skin. Eight‐week‐old male Wistar rats were submitted to 8.0‐mm punch‐wounding in the dorsal region. After 3 days, rats were randomly assigned to receive either a control treatment or the topical application of a solution containing 5‐azacytidine (10 mM) once per day. Photo documentation and sample collection were performed on days 5, 9, and 15. Overall, 5‐azacytidine promoted a significant acceleration of complete wound healing (99.7% ± 0.7.0 vs. 71.2% ± 2.8 on day 15; n = 10; p < 0.01), accompanied by up to threefold reduction in follistatin expression. Histological examination of the skin revealed efficient reepithelization and cell proliferation, as evaluated by the BrdU incorporation method. 5‐Azacytidine treatment also resulted in increased gene expression of transforming growth factor‐beta and the keratinocyte markers involucrin and cytokeratin, as well as decreased expression of cytokines such as tumor necrosis factor‐alpha and interleukin‐10. Lastly, when recombinant follistatin was applied to the skin in parallel with topical 5‐azacytidine, most of the beneficial effects of the drug were lost. Thus, 5‐azacytidine acts, at least in part through the follistatin/activin pathway, to improve skin wound healing in rodents.     

Serum levels of 17-β-estradiol are not predictive of prostate cancer diagnosis and aggressiveness: Results from an Italian biopsy cohort

ObjectivesTo explore the association between serum levels of 17-β-estradiol (17BE) and prostate cancer (PCa) risk in men undergoing prostate biopsy.Methods and materialsBetween 2006 and 2012, we prospectively enrolled 894 patients, with no history of PCa, undergoing prostate biopsy. Before biopsy was performed, general data, digital rectal examination (DRE), body mass index, 17BE, and prostate-specific antigen (PSA) were recorded. The risk of detecting cancer and high-grade cancer was assessed as a function of 17BE using crude and adjusted logistic regressions.ResultsSerum levels of 17BE were not associated with an increased risk of PCa or high-grade disease. Age (odds ratio [OR] 1.05; 95% confidence interval [CI]: 1.03–1.07; P = 0.000), DRE(OR 2.81; 95% CI: 1.98–4.00; P = 0.000), and PSA(OR 1.07; 95% CI: 1.04–1.10; P = 0.000) were found to be independent predictors of PCa risk. Age (OR 1.05; 95% CI: 1.01–1.09; P = 0.007), DRE (OR 3.04; 95% CI: 1.79–5.17; P = 0.000), body mass index (OR 1.07; 95% CI: 1.01–1.150; P = 0.040), and PSA (OR 1.08; 95% CI: 1.03–1.12; P = 0.000) were found to be independent predictors of high-grade disease.ConclusionIn our cohort of patients, serum levels of 17BE are not predictive of PCa or high-grade disease. In patients at risk of PCa, 17BE should not be considered a reliable marker to predict poorly differentiated PCa in the setting of initial prostate biopsy.     

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco,Brazil

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common—and clinically important—endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.     

Non-invasive methods for iron overload evaluation in dysmetabolic patients

IntroductionAlthough hyperferritinemia may reflect the inflammatory status of patients with non-alcoholic fatty liver disease (NAFLD), approximately 33% of hyperferritinemia cases reflect real hepatic iron overload.AimTo evaluate a non-invasive method for assessing mild iron overload in patients with NAFLD using 3T magnetic resonance imaging (MRI) relaxometry, serum hepcidin, and the expression of ferritin subunits.MethodsThis cross-sectional study assessed patients with biopsy-proven NAFLD. MRI relaxometry was performed using a 3T scanner in all patients, and the results were compared with iron content determined by liver biopsy. Ferritin, hepcidin, and ferritin subunits were assessed and classified according to ferritin levels and to siderosis identified by liver biopsy.ResultsA total of 67 patients with NAFLD were included in the study. MRI revealed mild iron overload in all patients (sensitivity, 73.5%; specificity, 70%). For mild (grade 1) siderosis, the transverse relaxation rate (R₂*) threshold was 58.9 s^?1 and the mean value was 72.5 s^?1 (SD, 33.9), while for grades 2/3 it was 88.2 s^?1 (SD, 31.9) (p < 0.001). The hepcidin threshold for siderosis was > 30.2 ng/mL (sensitivity, 87%; specificity, 82%). Ferritin H and ferritin L subunits were expressed similarly in patients with NAFLD, regardless of siderosis. There were no significant differences in laboratory test results between the groups, including glucose parameters and liver function tests.ConclusionsMRI relaxometry and serum hepcidin accurately assessed mild iron overload in patients with dysmetabolic iron overload syndrome.     

Manual Therapy as Treatment for Chronic Musculoskeletal Pain in Female Breast Cancer Survivors: A Systematic Review and Meta-Analysis

ObjectiveThe purpose of this systematic review was to investigate the effectiveness of manual therapy (MT) for chronic musculoskeletal pain (CMP) in the upper limbs and thorax of female breast cancer survivors and to investigate the changes in the quality of life and function of these patients.MethodsSystematic searches were performed in the databases MEDLINE/PubMed, Cumulative Index of Nursing and Allied Health/EBSCO, Web of Science, and Physiotherapy Evidence Database, through March 2018, to identify randomized controlled trials investigating whether MT was effective to treat CMP pain in female breast cancer survivors (PROSPERO number CDR42017074175).ResultsThe database searches retrieved 1562 titles, and after screening, 5 papers were included for full analysis. The manual therapy techniques described in the included studies involved myofascial induction, myofascial release, classic massage, ischemic compression of trigger points, and myofascial therapy. A meta-analysis, using a fixed-effects model, found that MT decreased CMP intensity (standardized mean difference: 0.32; 95% CI 0.06-0.57), but no significant difference was observed in quality of life after the MT intervention in comparison with a control condition (standardized mean difference: 0.14; 95% CI 0.17-0.46).ConclusionCurrent evidence suggests that MT is considered effective for treating CMP in the upper limbs and thorax of female breast cancer survivors.     

Colonic duplication in an adult mimicking a tumor of pancreas

Duplications of the alimentary tract are uncommon congenital malformations that can present diagnostic difficulties. We report a rare case of a cystic colonic duplication in a female adult. Preoperative investigations were suggestive of pancreatic tumor. The diagnosis was established based on the histopathological examination of the resected specimen. We concluded that, though uncommon, intestinal duplication should be considered in differential diagnosis of abdominal mass.     

Gastric emptying before and after cholecystectomy in patients with cholecystolithiasis

BACKGROUND/AIMS: The objective of the present study was to measure gastric emptying time of solids and semisolids in dyspeptic individuals with cholecystolithiasis before and 6 months after cholecystectomy in order to determine whether cholecystectomy interferes with gastric emptying. METHODOLOGY: A prospective, self-pairing study was conducted on 29 patients selected according to appropriate inclusion and exclusion criteria. Gastric emptying time of solids and semisolids was determined before and six months after laparoscopic cholecystectomy by the 13C-octanoic acid and 13C-acetate breath tests, respectively. The samples were analyzed by infrared spectrometry. The gastric retention time (lag phase) and gastric emptying half-time of solid and semisolid were determined and the results obtained before and after surgery were compared in the same patient. In addition, the effects of surgery on dyspeptic symptoms were assessed. RESULTS: No significant differences (p>0.05) in gastric retention time and gastric emptying half-time of solid and semisolid test meals were observed before and after cholecystectomy. Dyspeptic symptoms (pain, upper abdominal gases, early satiety, nausea and vomiting) improved after surgery. CONCLUSIONS: Laparoscopic cholecystectomy does not interfere with the gastric emptying time of solids or semisolids in dyspeptic individuals with cholecystolithiasis.