A novel member of the BTB/POZ family, PATZ, associates with the RNF4 RING finger protein and acts as a transcriptional repressor.

We have identified a novel human gene encoding a 59-kDa POZ-AT hook-zinc finger protein (PATZ) that interacts with RNF4, a mediator of androgen receptor activity, and acts as a transcriptional repressor. PATZ cDNA was isolated through a two-hybrid interaction screening using the RING finger protein RNF4 as a bait. In vitro and in vivo interaction between RNF4 and PATZ was demonstrated by protein-protein affinity chromatography and coimmunoprecipitation experiments. Such interaction occurred through a small region of PATZ containing an AT-hook DNA binding domain. Immunofluorescence staining and confocal microscopy showed that PATZ localizes in distinct punctate nuclear regions and colocalizes with RNF4. Functional analysis was performed by cotransfection assays: PATZ acted as a transcriptional repressor, whereas its partner RNF4 behaved as a transcriptional activator. When both proteins were overexpressed a strong repression of the basal transcription was observed, indicating that the association of PATZ with RNF4 switches activation to repression. In addition, RNF4 was also found to associate with HMGI(Y), a chromatin-modeling factor containing AT-hook domains

Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES). a multicentre, open-label, randomised trial

Background: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. Methods: We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365. Findings: Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. Interpretation: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. Funding: Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy

Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study

Background Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery. Methods In this multinational retrospective observational study we enrolled adult participants (aged $\ge$18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year followup after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band. Patients with a previous history of bariatric surgery or large delays between scheduled and actual visits were excluded. The training cohort comprised patients from two centres in France (ABOS and BAREVAL). The primary outcome was BMI at 5 years. A model was developed using least absolute shrinkage and selection operator to select variables and the classification and regression trees algorithm to build interpretable regression trees. The performances of the model were assessed through the median absolute deviation (MAD) and root mean squared error (RMSE) of BMI. Findings10 231 patients from 12 centres in ten countries were included in the analysis, corresponding to 30 602 patient-years. Among participants in all 12 cohorts, 7701 (75$\bullet$3%) were female, 2530 (24$\bullet$7%) were male. Among 434 baseline attributes available in the training cohort, seven variables were selected: height, weight, intervention type, age, diabetes status, diabetes duration, and smoking status. At 5 years, across external testing cohorts the overall mean MAD BMI was 2$\bullet$8 kg/m${}^2$ (95% CI 2$\bullet$6-3$\bullet$0) and mean RMSE BMI was 4$\bullet$7 kg/m${}^2$ (4$\bullet$4-5$\bullet$0), and the mean difference between predicted and observed BMI was-0$\bullet$3 kg/m${}^2$ (SD 4$\bullet$7). This model is incorporated in an easy to use and interpretable web-based prediction tool to help inform clinical decision before surgery. InterpretationWe developed a machine learning-based model, which is internationally validated, for predicting individual 5-year weight loss trajectories after three common bariatric interventions.Comment: The Lancet Digital Health, 202

Implementation of Low Glycemic Index Diet Together with Cornstarch in Post-Gastric Bypass Hypoglycemia: Two Case Reports

Post-bariatric hypoglycemia (PBH) is an increasingly recognized long-term complication of bariatric surgery. The nutritional treatment of PBH includes a high-fiber diet and the restriction of soluble and high-glycemic index carbohydrates; however, these measures are not always enough to prevent hypoglycemia. We evaluated the efficacy of uncooked cornstarch, a low-glycemic index carbohydrate characterized by slow intestinal degradation and absorption, in addition to a high-fiber diet, for the treatment of PBH. We report the cases of two young women suffering from severe postprandial and fasting hypoglycemia following Roux-en-Y gastric bypass (RYGB). The patients underwent Continuous Glucose Monitoring (CGM) before and 12–16 weeks after the administration of uncooked cornstarch (respectively 1.25 g/kg b.w. and 1.8 g/kg b.w.) in addition to a high-fiber diet. In both patients, CGM showed more stable glucose levels throughout monitoring, a remarkable reduction of the time spent in hypoglycemia (<55 mg/dL) both during the day (−11% for both patients) and the night (−22% and −32%), and the improvement of all glycemic variability indexes. Our report, within the limit of only two cases, suggests that the implementation of a dietary intervention through the addition of uncooked cornstarch reduces daily glycemic fluctuations and hypoglycemic episodes in patients with PBH

Bariatric surgery and long-term nutritional issues

Bariatric surgery is recognized as a highly effective therapy for obesity since it accomplishes sustained weight loss, reduction of obesity-related comorbidities and mortality, and improvement of quality of life. Overall, bariatric surgery is associated with a 42% reduction of the cardiovascular risk and 30% reduction of all-cause mortality. This review focuses on some nutritional consequences that can occur in bariatric patients that could potentially hinder the clinical benefits of this therapeutic option. All bariatric procedures, to variable degrees, alter the anatomy and physiology of the gastrointestinal tract; this alteration makes these patients more susceptible to developing nutritional complications, namely, deficiencies of macro- and micro-nutrients, which could lead to disabling diseases such as anemia, osteoporosis, protein malnutrition. Of note is the evidence that most obese patients present a number of nutritional deficits already prior to surgery, the most important being vitamin D and iron deficiencies. This finding prompts the need for a complete nutritional assessment and, eventually, an adequate correction of pre-existing deficits before surgery. Another critical issue that follows bariatric surgery is post-operative weight regain, which is commonly associated with the relapse of obesity-related co-morbidities. Nu-tritional complications associated with bariatric surgery can be prevented by life-long nutritional monitoring with the administration of multi-vitamins and mineral supplements according to the patient's needs

Implementation of low glycemic index diet together with cornstarch in post-gastric bypass hypoglycemia: Two case reports

Post-bariatric hypoglycemia (PBH) is an increasingly recognized long-term complication of bariatric surgery. The nutritional treatment of PBH includes a high-fiber diet and the restriction of soluble and high-glycemic index carbohydrates; however, these measures are not always enough to prevent hypoglycemia. We evaluated the efficacy of uncooked cornstarch, a low-glycemic index carbohydrate characterized by slow intestinal degradation and absorption, in addition to a high-fiber diet, for the treatment of PBH. We report the cases of two young women suffering from severe postprandial and fasting hypoglycemia following Roux-en-Y gastric bypass (RYGB). The patients underwent Continuous Glucose Monitoring (CGM) before and 12⁻16 weeks after the administration of uncooked cornstarch (respectively 1.25 g/kg b.w. and 1.8 g/kg b.w.) in addition to a high-fiber diet. In both patients, CGM showed more stable glucose levels throughout monitoring, a remarkable reduction of the time spent in hypoglycemia

Glycemic control and microvascular complications in adults with type 1 diabetes and long-lasting treated celiac disease: A case-control study

Aims: To investigate whether in type 1 diabetes (T1DM) patients the concomitance of long-lasting celiac disease (CD) treated with a gluten free diet (GFD) impacts glycaemic control and the prevalence/severity of microvascular complications. Methods: A case-control, observational study was performed in 34 patients with T1DM and GFD-treated CD and 66 patients with T1DM alone matched for age, gender, and T1DM duration. Anthropometric parameters, glucose control (HbA1c), status of chronic complications and concomitant autoimmune diseases were evaluated. Results: HbA1c level was similar in T1DM + CD and T1DM alone (7.8 ± 1.0 vs 7.7 ± 1.1%, P = 0.57); insulin requirement was significantly higher in T1DM + CD compared with T1DM (P = 0.04). There were no differences in systolic blood pressure while diastolic blood pressure was significantly lower in T1DM + CD (P = 0.003). The prevalence/severity of microvascular complications was similar between the two groups. Glomerular filtration rate (eGFR) was significantly lower in T1DM + CD (100 ± 20 vs 110 ± 16 ml/min/1.73 m2, P = 0.007). Conclusions: In patients with T1DM, the co-occurrence of long-term GFD-treated CD neither worsens glycemic control nor negatively impacts chronic microvascular complications. However, patients with T1DM + CD have lower eGFR values than those with T1DM alone

Glycemic control and microvascular complications in adults with type 1 diabetes and long-lasting treated celiac disease: A case-control study

Dalbulus maidis (DeLong & Wolcott) (Hemiptera: Cicadellidae) is one of the most important pathogen vectors on maize, but its courtship behavior has never been documented. In the present study, we recorded length of courtship and mating periods and behavioral transitions for D. maidis. According to these observations, we built ethograms for both sexes to create a comprehensive description of their courtship behavior. The mean courtship duration was 110.04 (±66.84) min and the mean mating period was 51.61 (±19.75) min. Both sexes showed similar, stereotyped behavioral transitions. However, females exhibited a lower frequency of several behavioral transitions and behaviors compared with males. Before mating, females were more frequently resting or performing an abdomen movement. Less frequently, they were walking or flapping the wings (wing fanning). Meanwhile, males exhibited three main behaviors before mating; the most frequent was wing fanning, followed by walking and approaching. However, during courtship, rapprochement between individuals of both sexes was not common so it is deduced that physical contact is not essential. In this regard, we discuss possible acoustic and chemical communication during the courtship process of D. maidis. © 2014, Springer Science+Business Media New York

Insulin resistance is central to long-term reversal of histologic non-alcoholic steatohepatitis after metabolic surgery

CONTEXT Non-alcoholic steatohepatitis(NASH)is considered as the hepatic counterpart of the metabolic syndrome. OBJECTIVE To investigate the determinants of NASH reversal in patients undergoing biliopancreatic diversion(BPD)in a 5-year follow-up study. DESIGN Prospective Study, Policlinico Universitario Agostino Gemelli. PARTICIPANTS 37 patients underwent fine-needle liver biopsy during BPD. Nine of them had a negative liver biopsy for NASH and were excluded. Ultrasonography-guided percutaneous liver biopsy was obtained at 5 years after operation. INTERVENTION Biliopancreatic Diversion and liver biopsy. MAIN OUTCOME MEASURES The primary outcome of our study was histologic NASH reversal, at 5-years follow-up. To better characterize the clinical variables involved in the resolution of NASH, we also compared patients without histologic NASH resolution at 5 years, with those in whom NASH had disappeared. RESULTS At follow-up, NASH reversed in 56.5% of the patients. NAFLD Activity-Score(NAS)improved from 3.33±1.15 to 1.84±1.10(P<0.0001).Fibrosis reversed in 16% of the patients(P=0.022)and in 32% improved(95% CI, 0.05-0.54).No significant differences in BMI or clinical parameters changes explained the effect of surgery on NASH, apart from the measure insulin sensitivity post-surgery. HOMA-IR decreased from 3.31±1.72 at baseline to 1.73±1.08(P<0.0001)after BPD and Matsuda index improved from 2.66±1.79 to 4.73±3.05(P<0.0001).Lipid profile normalized(total-cholesterol from 4.75±1.18 to 3.32±0.77mmol/l, P<0.0001; LDL-cholesterol from 2.92±0.91 to 1.60±0.51mmol/l, P=0.0001; HDL-cholesterol from 0.97±0.33 to 1.10±0.35mmol/l, P=0.023; triglycerides from 2.52±1.6 to 1.47±0.67 mmol/l, P=0.003).Neural network analysis showed that end-study Matsuda index discriminated between responders and non-responders with high accuracy[receiver operating characteristic curve(ROC)area-under-the curve(AUC)0.98%]. CONCLUSION Remission of NASH is driven by reversal of whole-body insulin resistance post-intervention