Reversion of Steatosis by SREBP-1c Antisense Oligonucleotide did not Improve Hepatic Insulin Action in Diet-induced Obesity Mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The literature has associated hepatic insulin action with NAFLD. In this sense, treatments to revert steatosis and improve hepatic insulin action become important. Our group has demonstrated that inhibition of Sterol Regulatory Element Binding Proteins-1c (SREBP-1c) reverses hepatic steatosis. However, insulin signals after NAFLD reversion require better investigation. Thus, in this study, we investigated if the reversal of NAFLD by SREBP-1c inhibitor results in improvement in the hepatic insulin signal in obesity mice. After installation/achievement of diet-induced obesity and insulin resistance, Swiss mice were divided into 3 groups: i) Lean, ii) D-IHS, diet-induced hepatic steatosis [no treatment with antisense oligonucleotide (ASO)], and iii) RD-IHS, reversion of diet-induced hepatic steatosis (treated with ASO). The mice were treated with ASO SREBP-1c as previously described by our group. After ASO treatment, one set of animals was anesthetized and used for in vivo test, and another mice set was anesthetized and used for histology and Western blot analysis. Reversion of diet-induced hepatic steatosis did not change blood glucose, glucose decay constant (k(ITT)), body weight, or serum insulin levels. In addition, results showed that the protocol did not improve insulin pathway signaling, as confirmed by the absence of changes in IR, IRS1, Akt and Foxo1 phosphorylation in hepatic tissue. In parallel, no alterations were observed in proinflammatory molecules. Thus, our results suggest that the inhibition of SREBP-1c reverts steatosis, but without improving insulin hepatic resistance.4412885890Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Santa Catarina (FAPESC)Universidade do Extremo Sul Catarinense (UNESC)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Appropriate criteria for identification of near-miss maternal morbidity in tertiary care facilities: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>The study of severe maternal morbidity survivors (near miss) may be an alternative or a complement to the study of maternal death events as a health care indicator. However, there is still controversy regarding the criteria for identification of near-miss maternal morbidity. This study aimed to characterize the near miss maternal morbidity according to different sets of criteria.</p> <p>Methods</p> <p>A descriptive study in a tertiary center including 2,929 women who delivered there between July 2003 and June 2004. Possible cases of near miss were daily screened by checking different sets of criteria proposed elsewhere. The main outcome measures were: rate of near miss and its primary determinant factors, criteria for its identification, total hospital stay, ICU stay, and number and kind of special procedures performed.</p> <p>Results</p> <p>There were two maternal deaths and 124 cases of near miss were identified, with 102 of them admitted to the ICU (80.9%). Among the 126 special procedures performed, the most frequent were central venous access, echocardiography and invasive mechanical ventilation. The mean hospital stay was 10.3 (± 13.24) days. Hospital stay and the number of special procedures performed were significantly higher when the organ dysfunction based criteria were applied.</p> <p>Conclusion</p> <p>The adoption of a two level screening strategy may lead to the development of a consistent severe maternal morbidity surveillance system but further research is needed before worldwide near miss criteria can be assumed.</p

Does training with amplitude modulated tones affect tone-vocoded speech perception?

Temporal-envelope cues are essential for successful speech perception. We asked here whether training on stimuli containing temporal-envelope cues without speech content can improve the perception of spectrally-degraded (vocoded) speech in which the temporal-envelope (but not the temporal fine structure) is mainly preserved. Two groups of listeners were trained on different amplitude-modulation (AM) based tasks, either AM detection or AM-rate discrimination (21 blocks of 60 trials during two days, 1260 trials; frequency range: 4Hz, 8Hz, and 16Hz), while an additional control group did not undertake any training. Consonant identification in vocoded vowel-consonant-vowel stimuli was tested before and after training on the AM tasks (or at an equivalent time interval for the control group). Following training, only the trained groups showed a significant improvement in the perception of vocoded speech, but the improvement did not significantly differ from that observed for controls. Thus, we do not find convincing evidence that this amount of training with temporal-envelope cues without speech content provide significant benefit for vocoded speech intelligibility. Alternative training regimens using vocoded speech along the linguistic hierarchy should be explored

Physical Exercise Decreases Fasting Hyperglycemia in Diabetic Mice Through AMPK Activation

Introduction: The deficiency in glucose uptake in peripheral tissues and increased hepatic gluconeogenesis are physiopathological phenomena observed in type 2 diabetes patients. Physical exercise plays an important role in the improvement of glycemic profile in diabetic patients; however, the mechanisms involved in these processes have not been fully elucidated. Objective: to assess the role of AMPK protein in the glycemic control of diabetic mice after exercise. Methods: During fasting condition, the insulin tolerance test (ITT) and Western blot technique, were combined to assess the glucose homeostasis in diabetic mice (ob/ob and db/db) after a single swimming session. Results: Fasting hyperglycemia, severe insulin resistance and deficiency in the AMPk/ACC signaling in muscle and liver observed in the diabetic mice were reversed after the exercise session. The restoration of AMPK/ACC signaling reduced the expression of the gluconeogenic enzyme, PEPCk in the liver, and increased the translocation of GLUT4 in the skeletal muscle. These data indicate that the activation of AMPK/ACC pathway induced by physical exercise is important to reduce fasting glucose levels in experimental models of type 2 diabetes. These data open new insights for determination of physical activity control on the glucose homeostasis in diabetic patients.15317918

Systematic review of the magnitude and case fatality ratio for severe maternal morbidity in sub-Saharan Africa between 1995 and 2010

<p>Abstract</p> <p>Background</p> <p>Analysis of severe maternal morbidity (maternal near misses) provides information on the quality of care. We assessed the prevalence/incidence of maternal near miss, maternal mortality and case fatality ratio through systematic review of studies on severe maternal morbidity in sub-Saharan Africa.</p> <p>Methods</p> <p>We examined studies that reported prevalence/incidence of severe maternal morbidity (maternal near misses) during pregnancy, childbirth and postpartum period between 1996 and 2010. We evaluated the quality of studies (objectives, study design, population studied, setting and context, definition of severe acute obstetric morbidity and data collection instruments). We extracted data, using a pre-defined protocol and criteria, and estimated the prevalence or incidence of maternal near miss. The case-fatality ratios for reported maternal complications were estimated.</p> <p>Results</p> <p>We identified 12 studies: six were cross-sectional, five were prospective and one was a retrospective review of medical records. There was variation in the setting: while some studies were health facility-based (at the national referral hospital, regional hospital or various district hospitals), others were community-based studies. The sample size varied from 557 women to 23,026. Different definitions and terminologies for maternal near miss included acute obstetric complications, severe life threatening obstetric complications and severe obstetric complications. The incidence/prevalence ratio and case-fatality ratio for maternal near misses ranged from 1.1%-10.1% and 3.1%-37.4% respectively. Ruptured uterus, sepsis, obstructed labor and hemorrhage were the commonest morbidities that were analyzed. The incidence/prevalence ratio of hemorrhage ranged from 0.06% to 3.05%, while the case fatality ratio for hemorrhage ranged from 2.8% to 27.3%. The prevalence/incidence ratio for sepsis ranged from 0.03% to 0.7%, while the case fatality ratio ranged from 0.0% to 72.7%.</p> <p>Conclusion</p> <p>The incidence/prevalence ratio and case fatality ratio of maternal near misses are very high in studies from sub-Saharan Africa. Large differences exist between countries on the prevalence/incidence of maternal near misses. This could be due to different contexts/settings, variation in the criteria used to define the maternal near misses morbidity, or rigor used carrying out the study. Future research on maternal near misses should adopt the WHO recommendation on classification of maternal morbidity and mortality.</p

Pre-validation of the WHO organ dysfunction based criteria for identification of maternal near miss

<p>Abstract</p> <p>Background</p> <p>To evaluate the performance of the WHO criteria for defining maternal near miss and identifying deaths among cases of severe maternal morbidity (SMM) admitted for intensive care.</p> <p>Method</p> <p>Between October 2002 and September 2007, 673 women with SMM were admitted, and among them 18 died. Variables used for the definition of maternal near miss according to WHO criteria and for the SOFA score were retrospectively evaluated. The identification of at least one of the WHO criteria in women who did not die defined the case as a near miss. Organ failure was evaluated through the maximum SOFA score above 2 for each one of the six components of the score, being considered the gold standard for the diagnosis of maternal near miss. The aggregated score (Total Maximum SOFA score) was calculated using the worst result of the maximum SOFA score. Sensitivity, specificity, positive and negative predictive values of these WHO criteria for predicting maternal death and also for identifying cases of organ failure were estimated.</p> <p>Results</p> <p>The WHO criteria identified 194 cases of maternal near miss and all the 18 deaths. The most prevalent criteria among cases of maternal deaths were the use of vasoactive drug and the use of mechanical ventilation (≥1 h). For the prediction of maternal deaths, sensitivity was 100% and specificity 70.4%. These criteria identified 119 of the 120 cases of organ failure by the maximum SOFA score (Sensitivity 99.2%) among 194 case of maternal near miss (61.34%). There was disagreement in 76 cases, one organ failure without any WHO criteria and 75 cases with no failure but with WHO criteria. The Total Maximum SOFA score had a good performance (area under the curve of 0.897) for prediction of cases of maternal near miss according to the WHO criteria.</p> <p>Conclusions</p> <p>The WHO criteria for maternal near miss showed to be able to identify all cases of death and almost all cases of organ failure. Therefore they allow evaluation of the severity of the complication and consequently enable clinicians to build a plan of care or to provide an early transfer for appropriate reference centers.</p

Illustrating risk difference and number needed to treat from a randomized controlled trial of spinal manipulation for cervicogenic headache

<p>Abstract</p> <p>Background</p> <p>The number needed to treat (NNT) for one participant to benefit is considered a useful, clinically meaningful way of reporting binary outcomes from randomized trials. Analysis of continuous data from our randomized controlled trial has previously demonstrated a significant and clinically important difference favoring spinal manipulation over a light massage control.</p> <p>Methods</p> <p>Eighty participants were randomized to receive spinal manipulation or a light massage control (n = 40/group). Improvements in cervicogenic headache pain (primary outcome), disability, and number in prior four weeks were dichotomized into binary outcomes at two thresholds: 30% representing minimal clinically important change and 50% representing clinical success. Groups were compared at 12 and 24-week follow-up using binomial regression (generalized linear models) to compute the adjusted risk difference (RD) between groups and number needed to treat (NNT) after adjusting for baseline differences between groups. Results were compared to logistic regression results.</p> <p>Results</p> <p>For headache pain, clinically important improvement (30% or 50%) was more likely for spinal manipulation: adjusted RD = 17% to 27% and NNT = 3.8 to 5.8 (p = .005 to .028). Some statistically significant results favoring manipulation were found for headache disability and number.</p> <p>Conclusion</p> <p>Spinal manipulation demonstrated a benefit in terms of a clinically important improvement of cervicogenic headache pain. The use of adjusted NNT is recommended; however, adjusted RD may be easier to interpret than NNT. The study demonstrated how results may depend on the threshold for dichotomizing variables into binary outcomes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NLM identifier NCT00246350.</p