The Background of Mitochondrial DNA Haplogroup J Increases the Sensitivity of Leber's Hereditary Optic Neuropathy Cells to 2,5-Hexanedione Toxicity

Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad implications for other neurodegenerative disorders such as Parkinson's disease

Efeitos maternos e perinatais com utilização de floral no trabalho de parto: ensaio clínico randomizado

Objetivo: Avaliar os efeitos clínicos, obstétricos maternos e perinatais com o uso de essências florais no trabalho de parto, frente a fatores que o potencializam.Método: Ensaio clínico, randomizado, controlado, em 164 parturientes divididas em dois grupos, essências florais e placebo, respectivamente, avaliadas pré e pós intervenção. Realizado em centro de parto normal, na cidade de São Paulo, de maio a outubro de 2018. Os dados foram analisados por estatística descritiva, teste t de Student hipótese bilateral, t crítico observado negativo e positivo, Qui-quadrado de Pearson, Exato de Fisher.Resultados: Observou-se no Grupo Experimental, moderada elevação da pressão arterial sistólica (p=0,046) da frequência (p=0,055) e intensidade das contrações (p=0,031), assim como, redução do tempo ao nascimento (194 minutos), maior número de partos vaginais (p=0,038) e melhor padrão de vitalidade fetal.Conclusão: Evidenciou-se ação positiva da Essência Floral perante os fatores potencializadores do trabalho de parto, sendo efetiva nas repercussões clínicas e obstétricas maternas, bem como perinatais. Palavras-chave: Trabalho de parto. Terapias complementares. Essências florais. Ensaio clínico

Successful radiotherapy for local control of progressively increasing metastasis of gastrointestinal stromal tumor

Gastrointestinal stromal tumors (GISTs) are known to be poorly responsive to conventional chemotherapy and historically considered resistant to radiotherapy. In the past the mainstay of GIST treatment was surgery, but the introduction of tyrosine kinase inhibitors (TKIs) imatinib and sunitinib marked the beginning of a new era in the treatment of GIST patients. To date, radiotherapy for GIST has not been administered in clinical practice except for limited palliative settings and there are no clear data on the administration of radiotherapy, alone or in combination with TKIs, with a purely cytoreductive intent. We describe the clinical case of a 48-year-old woman with metastatic GIST treated with external radiotherapy in a critical supraclavicular tumor localization progressively increasing in size with several symptoms and not responsive to systemic TKI therapies. We obtained an initial shrinkage of the mass and subsequent stabilization with an immediate and clear clinical benefit. Although the historical medical literature considered GISTs resistant to radiation therapy, our clinical case suggests this treatment may be appropriate in selected patients

Perfluorooctanesulfonate and perfluorooctanoic acid exposures of the Italian general population

The serum concentrations of perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) were determined in 230 subjects of the Italian general population. Participants were enrolled in 2008 in two Italian towns (Brescia, Northern Italy, and Rome, Central Italy) and belonged to the three age ranges: 20-35. years, 36-50. years, and 51-65. years.PFOS and PFOA were quantified by HPLC interfaced to a mass spectrometer operating in the electrospray negative mode. Data were acquired using multiple reaction monitoring (MRM). The isotope dilution technique was applied throughout.The median serum concentrations of all participants were 6.31ngg-1 and 3.59ngg-1 for PFOS and PFOA, respectively, and the pertinent 90th percentiles were 12.38 and 6.92.Men had higher concentrations of PFOS and PFOA than women, regardless of age. The differences were statistically significant in the 20-35 and 36-50. years groups, but not in the 51-65 group.An increase of PFOS and PFOA serum concentrations with age was observed. The Median test showed a statistically significant difference (p≪0.01) between the three age groups for both PFOS and PFOA when applied to the entire dataset (males and females). When the test was applied to the groups of males and females separately, a significant difference was observed for females (p≪0.005) but not for males (p>0.1).The observed strong correlation between PFOS and PFOA concentrations suggests same or similar exposure routes. © 2010 Elsevier Ltd

Bariatric Surgery Reduces Oxidative Stress by Blunting 24-h Acute Glucose Fluctuations in Type 2 Diabetic Obese Patients

OBJECTIVE - We evaluated the efficacy of malabsorptive bariatric surgery on daily blood glucose fluctuations and oxidative stress in type 2 diabetic obese patients. RESEARCH DESIGN AND METHODS - The 48-h continuous subcutaneous glucose monitoring was assessed in type 2 diabetic patients before and 1 month after biliopancreatic diversion (BPD) (n = 36), or after diet-induced equivalent weight loss (n = 20). The mean amplitude of glycemic excursions and oxidative stress (nitrotyrosine) were evaluated during continuous subcutaneous glucose monitoring. During a standardized meal, glucagon-like peptide (GLP)-1, glucagon, and insulin were measured. RESULTS - Fasting and postprandial glucose decreased equally in surgical and diet groups. A marked increase in GLP-1 occurred during the interprandial period in surgical patients toward the diet group (P < 0.01). Glucagon was more suppressed during the interprandial period in surgical patients compared with the diet group (P < 0.01). Mean amplitude of glycemic excursions and nitrotyrosine levels decreased more after BPD than after diet (P < 0.01). CONCLUSIONS - Oxidative stress reduction after biliopancreatic diversion seems to be related to the regulation of glucose fluctuations resulting from intestinal bypass. © 2010 by the American Diabetes Association

Firm Survival: An Empirical Study Concerning Insurance Agencies

This paper analyzes the relevance of firm size, region, sales network, organizational structure, and auditing on the survival likelihood of a specific firm typology, the insurance agency. By applying a configurational comparative method, namely fuzzy-set qualitative analysis (fsQCA), to a unique dataset of 52 insurance agents, representing 52 active Italian insurance agencies, this study demonstrates that, when combined with other variables, organizational structure provides sufficient conditions for insurance agency survival. The different relevance of some specific management areas according to the insurance agency location is highlighted

Anti-obesity drug therapy in clinical practice: Evidence of a poor prescriptive attitude

Obesity is a worldwide growing problem for the health care systems and its treatment is strongly recommended. Orlistat, naltrexone/bupropion, and liraglutide are approved for weight loss in Italy in patients with a Body Mass Index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 with concomitant diseases. However, the prescription of these drugs is significantly low worldwide. General practitioners (GPs) play a key role in the early diagnosis and appropriate management of obesity. The aim of the study was to investigate the management of obesity and the prescriptive attitude of anti-obesity drugs in a general practice setting.All patients registered in lists of 8 GPs with a recorded diagnosis of obesity or BMI values ≥ 30 kg/m2 in the period 2017–2018, were recruited. A descriptive analysis of demographic and clinical characteristic was carried out. The Spearman's correlation rank test was applied to identify correlations between BMI and all the variables of interest.Among 1301 obese patients, only 66.1 % had been diagnosed and 29.4 % had no registered BMI value. Patients with recorded BMI, were overweight (7.8 %) or in the obesity class I (38.8 %), class II (14.1 %), and class III (7.1 %), respectively.The obese patients (class 1–3) were older [66 (55–76) vs 49 (32–59); p < 0.01], and had more concurrent diseases [5 (3−8) vs 4 (2–6); p < 0.01] than patients who reached a BMI < 30 Kg/m2. Moreover, most of obese were high cardiovascular risk (HCVr) patients (67.0 % vs 31.9 %; p < 0.01). The BMI was directly related to age (rs 0.14; p < 0.01), diabetes (rs 0.19; p < 0.01), hypertension (rs 0.14; p < 0.01), heart failure (rs 0.09; p < 0.01), HCVr (rs 0. 12; p < 0.01) and number of comorbidities (rs 0.08; p = 0.01). No prescriptions of orlistat or naltrexone/bupropion were found. Liraglutide was prescribed only in 7 patients because of the concomitant presence of diabetes.Our results suggest a low adherence to guide line recommendations for obesity management and confirm an under-prescription of anti-obesity drugs in Italy

Experience of women in labor with the use of flowers essences / Vivência de mulheres em trabalho de parto com o uso de essências florais

OBJETIVO: O estudo descreve a vivencia de mulheres submetidas ao uso de essências florais como terapia não farmacológica para o alivio da dor e ansiedade durante o trabalho de parto. MÉTODOS: Pesquisa descritiva exploratória, de conteúdo qualitativo, realizada com 30 parturientes, em um centro de parto normal público, intra-hospitalar da cidade de São Paulo. RESULTADOS: Constatou-se que os efeitos da terapia floral, atuaram em sinergia, na redução dos sintomas de estresse-medo-tensão, além do aumento do bem-estar emocional proporcionando às parturientes a oportunidade de protagonizar o seu próprio trabalho de parto e parto. CONCLUSÃO: Conclui-se que o uso da essência floral, no trabalho de parto, proporcionou calma, relaxamento, concentração e coragem às mulheres, emoções estas que possibilitaram melhor controle da dor e da ansiedade

Experience of women in labor with the use of flowers essences / Vivência de mulheres em trabalho de parto com o uso de essências florais

OBJETIVO: O estudo descreve a vivencia de mulheres submetidas ao uso de essências florais como terapia não farmacológica para o alivio da dor e ansiedade durante o trabalho de parto. MÉTODOS: Pesquisa descritiva exploratória, de conteúdo qualitativo, realizada com 30 parturientes, em um centro de parto normal público, intra-hospitalar da cidade de São Paulo. RESULTADOS: Constatou-se que os efeitos da terapia floral, atuaram em sinergia, na redução dos sintomas de estresse-medo-tensão, além do aumento do bem-estar emocional proporcionando às parturientes a oportunidade de protagonizar o seu próprio trabalho de parto e parto. CONCLUSÃO: Conclui-se que o uso da essência floral, no trabalho de parto, proporcionou calma, relaxamento, concentração e coragem às mulheres, emoções estas que possibilitaram melhor controle da dor e da ansiedade