Orthorexia nervosa and type 1 diabetes: results of a cross-sectional study.

AIM: Orthorexia nervosa (ON) is a condition characterized by an excessive importance attributed to the intake of healthy foods. This study was aimed at investigating the prevalence of ON in subjects with type 1 diabetes (T1D) compared to control subjects. METHODS: Patient with T1D using either flash glucose monitoring or continuous glucose monitoring were enrolled. For the selection of control group, each patient was asked to indicate one non-diabetic subject of their same sex and approximate age among colleagues at work and school. Patients and controls completed the following questionnaires: ORTO-15, Dusseldorf Orthorexie Scale (DOS), Eating Disorder Examination Questionnaire (EDE-Q) and Brief Symptom Inventory (BSI). The principal outcome was the prevalence of ON among T1D and control subjects. RESULTS: We enrolled 44 patients with T1D aged 39.7 ± 15.7 years, with BMI 24.3 ± 4.3 kg/m2, and mean HbA1c 53.5 [49-57] mmol/mol. Control subjects were similar to T1D with respect to sex, age and BMI. Thirty-two [72%] and 29 [65%] subjects among patients and controls, respectively, had ORTO15 < 40 (between-group p = 0.48). Two (4.5%) and zero subjects among patients and controls, respectively, had DOS ≥ 30 (p = 0.29). Median scores of DOS, but not of ORTO-15, were significantly higher in patients than in controls. None of the metabolic variables showed a correlation with psychometric tests in T1D. CONCLUSION: Although the prevalence of ON was not significantly higher in T1D than in controls, patients with T1D showed higher scores of some, but not all, tests assessing orthorexia, without any significant correlation with metabolic parameters.

SIRT6 is a key regulator of mitochondrial function in the brain.

The SIRT6 deacetylase has been implicated in DNA repair, telomere maintenance, glucose and lipid metabolism and, importantly, it has critical roles in the brain ranging from its development to neurodegeneration. Here, we combined transcriptomics and metabolomics approaches to characterize the functions of SIRT6 in mouse brains. Our analysis reveals that SIRT6 is a central regulator of mitochondrial activity in the brain. SIRT6 deficiency in the brain leads to mitochondrial deficiency with a global downregulation of mitochondria-related genes and pronounced changes in metabolite content. We suggest that SIRT6 affects mitochondrial functions through its interaction with the transcription factor YY1 that, together, regulate mitochondrial gene expression. Moreover, SIRT6 target genes include SIRT3 and SIRT4, which are significantly downregulated in SIRT6-deficient brains. Our results demonstrate that the lack of SIRT6 leads to decreased mitochondrial gene expression and metabolomic changes of TCA cycle byproducts, including increased ROS production, reduced mitochondrial number, and impaired membrane potential that can be partially rescued by restoring SIRT3 and SIRT4 levels. Importantly, the changes we observed in SIRT6-deficient brains are also occurring in aging human brains and particularly in patients with Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis disease. Overall, our results suggest that the reduced levels of SIRT6 in the aging brain and neurodegeneration initiate mitochondrial dysfunction by altering gene expression, ROS production, and mitochondrial decay.

Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling.

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle atrophy in mice. Notably, overexpression of SIRT6 spontaneously decreases the size of primary myotubes in a cell-autonomous manner. On the other hand, SIRT6 depletion increases the diameter of myotubes and protects them against glucocorticoid-induced reduction in myotube size, which is associated with enhanced protein synthesis and repression of atrogenes. In line with this, we find that muscle-specific SIRT6 deficient mice are resistant to glucocorticoid-induced muscle wasting. Mechanistically, we find that SIRT6 deficiency hyperactivates IGF/PI3K/AKT signaling through c-Jun transcription factor-mediated increase in IGF2 expression. The increased activation, in turn, leads to nuclear exclusion and transcriptional repression of the FoxO transcription factor, a key activator of muscle atrophy. Further, we find that pharmacological inhibition of SIRT6 protects against glucocorticoid-induced muscle wasting in mice by regulating IGF/PI3K/AKT signaling implicating the role of SIRT6 in glucocorticoid-induced muscle atrophy.

Effectiveness of low-carbohydrate diets for long-term weight loss in obese individuals: A meta-analysis of randomized controlled trials.

AIM: To assess whether low-carbohydrate (LC) diets are associated with differences in weight loss and well-being in people with obesity, and their cardiovascular and renal safety. MATERIALS AND METHODS: A meta-analysis of randomized controlled trials longer than 3 months, retrieved through an extensive search on MedLine and Embase databases, comparing weight loss with LC and control diets in people with body mass index (BMI) greater than 30 kg/m2 , was conducted. RESULTS: We retrieved 25 trials. Compared with controls, LC diets were associated with significant reduction of body weight at 3-4 (MD -2.59 [-3.93, -1.25] kg) and 6-8 months (MD -2.64 [-4.32, -0.95]), but no difference at 10-14 and 18-30 months, and significantly greater BMI reduction at 3-4 months (-1.66 [-2.70, -0.61] kg/m2 ), but not at other time points. Because only four trials reported data on renal function and psychological variables, renal safety and impact on well-being could not be assessed. Differences in fasting plasma glucose at any time point were not statistically significant. No significant differences in total or LDL cholesterol or blood pressure were found in the long term, whereas a long-term reduction of triglycerides (23.26 [-45.53, -0.98] mg/dl at 18-30 months), and increase of HDL cholesterol (MD 4.94 [0.30, 9.57] mg/dl at 18-30 months), were observed. CONCLUSION: LC diets are associated with greater short-term weight loss than non-carbohydrate-restricted diets and a longer term favourable effect on cardiovascular risk factors. Further evidence on long-term efficacy and renal safety is needed before LC diets can be recommended as the preferred diets in obese people.

Diabetic Foot Syndrome in the COVID-19 era: How to Move from Classical to new Approaches.

Diabetic foot syndrome (DFS) is a major complication of diabetes mellitus. Coronavirus infectious disease 2019 (COVID-19) has created new necessities and priorities in DFS management. These include telemedicine and patient triage to minimise hospitalisation and visits to the clinic. Moreover, new studies will be needed to evaluate whether the lockdown in patients with DFS or in those with high risk of DFS have increased the risk of deteriorating outcomes, including limb loss. Our future challenge will lie in re-organising our world during the pandemic and after its resolution. We need more awareness of the widespread ways of the changes in taking care of patients and to improve education, skills, and behaviour of high-risk patients.

Retrospective Matched Case-Control Study on the Use of CO2 Laser for the Treatment of Nonhealing Diabetic Foot Ulcers: The DULCIS-2 (Diabetic ULcer, CO2 Laser, and Infections) Study.

PURPOSE: Infection, which is one of the possible complications of diabetic foot ulcers (DFUs), makes the treatment of ulcers challenging because of its negative impact on healing processes and the high prevalence of multiresistant germs. This study is aimed at verifying the effect of a surgical CO2 laser (which reduces the bacterial load and allows a more accurate debridement), as compared with the traditional lancets, on the healing rate of DFU. METHODS: The present case-control retrospective analysis was performed on patients with chronic (>6 months) DFU with Texas grade >1, treated with 80 W surgical CO2 laser (DEKA SmartXide2 C80, El.En. Group) and compared with a matched sample of patients with similar characteristics, who were treated with a traditional surgical approach. The debridement was performed trying to achieve the complete removal of nonviable tissues. The principal endpoint was the proportion of patients healed at 6 months. All analyses were carried out with SPSS 25.0. The study protocol was approved by the local ethical committee. RESULTS: This study included 118 patients (59 cases and 59 controls). At 6 months, the proportion of healing patients was 35% and 18% in cases and controls, respectively (P = .034). The corresponding figure at 1 year was 62% and 38% (P = .009), whereas no difference was observed at 1, 2, and 3 months. No serious adverse event was observed. CONCLUSIONS: In this article, we show for the first time that CO2 laser treatment, in comparison with traditional surgical approaches, can be associated with an increased healing rate in patients with DFU.

Assessing kinetics and recruitment of DNA repair factors using high content screens.

Repair of genetic damage is coordinated in the context of chromatin, so cells dynamically modulate accessibility at DNA breaks for the recruitment of DNA damage response (DDR) factors. The identification of chromatin factors with roles in DDR has mostly relied on loss-of-function screens while lacking robust high-throughput systems to study DNA repair. In this study, we have developed two high-throughput systems that allow the study of DNA repair kinetics and the recruitment of factors to double-strand breaks in a 384-well plate format. Using a customized gain-of-function open-reading frame library ("ChromORFeome" library), we identify chromatin factors with putative roles in the DDR. Among these, we find the PHF20 factor is excluded from DNA breaks, affecting DNA repair by competing with 53BP1 recruitment. Adaptable for genetic perturbations, small-molecule screens, and large-scale analysis of DNA repair, these resources can aid our understanding and manipulation of DNA repair.

Efficacy and effects of bariatric surgery in the treatment of obesity: Network meta-analysis of randomized controlled trials.

AIMS: Bariatric surgery (BS) is recommended for subjects with a Body Mass Index (BMI) over of 40 kg/m2 or with a BMI between 35 and 40 kg/m2 with obesity-related comorbidities. Aim of the study was to compare different types of BS with medical therapy (MT) for the treatment of obesity. DATA SYNTHESIS: We conducted a network-meta-analysis (NMA) including randomized clinical trials comparing different BS techniques versus MT in people with obesity, with a duration ≥24 weeks (PROSPERO, #CRD42020160359). Primary endpoint was BMI. Indirect comparisons of different types of surgery were performed by NMA. Types of BS included: laparoscopic adjustable gastric banding (LAGB), Roux-en-Y gastric bypass, sleeve gastrectomy (SG), bilio-pancreatic diversion (BPD); greater curvature plication (GCP); one-anastomosis gastric bypass (OAGB); Laparoscopic Vertical Banded Gastroplasty (LVBG) and duodenal switch (DS). 43 trials were retrieved in this metanalysis. BS was associated with a significant reduction in BMI, systolic blood pressure, triglyceride and fasting glucose, and with a significant increase of HDL cholesterol when compared to MT. In direct comparisons, RYGB was more effective than LAGB, LVBG, and GCP, but less effective than DS, whereas LAGB was less effective than LVBG and SG. In the NMA, DS and BPD appeared to be more effective than other procedures. CONCLUSIONS: BS produces a greater weight loss than MT in morbidly obese patients, inducing a greater improvement of obesity-associated metabolic parameters. Available data are insufficient to assess the effect of BS on mortality. Different surgical procedures are heterogeneous for efficacy and safety.

Obesity as a risk factor for hospitalization in COronaVirus Disease-19 (COVID-19) patients: Analysis of the Tuscany regional database.

BACKGROUND AND AIMS: Aim of the present study is to determine the role of obesity as a risk factor for COronaVirus Disease-19 (COVID-19) hospitalization. METHODS AND RESULTS: This observational study was performed using Istituto Superiore di Sanità (ISS) Tuscany COVID-19 database by the Agenzia Regionale Sanità (ARS), including all COVID-19 cases registered until April 30th, 2020, with reported information on chronic diseases. The principal outcome was hospitalization. An age and gender-adjusted logistic regression model was used to assess the association of clinical and demographic characteristics with hospitalization. Further multivariate models were applied. Of 4481 included subjects (36.9% aged over 70 years), 1907 (42.6%) were admitted to hospital. Obesity was associated with hospitalization after adjusting for age and gender. The association of obesity with hospitalization retained statistical significance in a fully adjusted model, including possible confounders (OR: 2.99 [IC 95% 2.04-4.37]). The effect of obesity was more evident in younger (<70 years) than in older (≥70 years) subjects. CONCLUSIONS: The present data confirm that obesity is associated with an increased risk of hospitalization in patients with COVID-19. Interestingly, the association of obesity with hospitalization was greater in younger (<70 years) patients.

Metabolic surgery for the treatment of type 2 diabetes: A network meta-analysis of randomized controlled trials.

AIM: To compare different types of metabolic surgery (MS) with medical therapy (MT) for the treatment of type 2 diabetes (T2D). MATERIALS AND METHODS: We conducted a network-meta-analysis (NMA) including randomized clinical trials comparing different MS techniques versus MT in people with T2D, with a duration of ≥24 weeks. Primary endpoints were glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and diabetes remission. Indirect comparisons of different types of surgery were performed by NMA. Mean and 95% confidence intervals for continuous variables, and Mantel-Haenzel odds ratios for categorial variables, were calculated using random effect models. Types of MS included: laparoscopic adjustable gastric banding (LAGB), Roux-en-Y gastric bypass, sleeve gastrectomy (SG), bilio-pancreatic diversion (BPD); greater curvature plication (GCP); one-anastomosis gastric bypass (OAGB); and duodenojejunal bypass. RESULTS: The 24 retrieved trials included 1351 patients (1014 with MS and 337 with MT). The mean baseline BMI was 36.8 kg/m2 . MS was associated with significantly greater reductions in HbA1c and FPG and greater diabetes remission when compared to MT. In the NMA, a significant reduction in HbA1c was observed with OAGB and SG. All surgical procedures were associated with a significant increase in diabetes remission, except GCP and LAGB. All procedures were associated with a reduction of body mass index (BMI). CONCLUSIONS: Metabolic surgery is an interesting option for the treatment of T2D, although further data are needed to demonstrate its long-term efficacy and safety. Present data are not sufficient to modify current recommendations, which consider MS a possible treatment for T2D in those with a BMI >35 kg/m2 .

Combined continuous glucose monitoring and subcutaneous insulin infusion versus self-monitoring of blood glucose with optimized multiple injections in people with type 1 diabetes: A randomized crossover trial.

AIM: To investigate the efficacy of a combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) versus an optimized degludec-based multiple daily injections (MDI) regimen + self-monitoring of blood glucose (SMBG) in people with type 1 diabetes with regard to optimizing glucose control. MATERIAL AND METHODS: The trial included 28 individuals who underwent a 4-week run-in phase, and were then randomized 1:1 to: (a) CSII + CGM followed by MDI + SMBG or (b) an MDI basal-bolus regimen followed by CSII + CGM. RESULTS: In patients randomized to the CSII + CGM → MDI + SMBG arm, a significant reduction in glycated haemoglobin (HbA1c) versus baseline was found at the end of the first phase (CSII + CGM) without significant variation in the following MDI + SMBG phase. In the arm randomized to the MDI + SMBG → CSII + CGM sequence, a significant improvement in HbA1c was observed in the first phase (MDI + SMBG), together with a further decrease in the following CSII + CGM phase. In the comparison of the two treatments using a mixed linear model, CSII + CGM was superior to MDI + SMBG with respect to change in HbA1c (P = 0.001). CONCLUSIONS: This study suggests that CSII + CGM improves glycaemic control without relevant safety issues in type 1 diabetes, in comparison with MDI + SMBG.

Nephrolithiasis and sodium-glucose co-transporter-2 (SGLT-2) inhibitors: A meta-analysis of randomized controlled trials.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) decreased serum uric acid in type 2 diabetes. Hyperuricemia is associated with an increased risk of nephrolithiasis. The present meta-analysis, performed on trials with duration ≥52 weeks in comparison with placebo or active comparators, suggests no effects of SGLT-2i on the risk of nephrolithiasis.

The response of cultured meiofaunal and benthic foraminiferal communities to lead exposure: Results from mesocosm experiments.

Lead (Pb) is regarded as a highly toxic element that poses a serious threat to biota. A mesocosm experiment was performed to assess the influence of Pb on meiofaunal (metazoans within 45-500 µm) and benthic foraminiferal (protozoan) communities. To this end, sediments bearing such communities were incubated in mesocosms, exposed to different levels of Pb in seawater, and monitored for up to 8 wk. Concentrations of Pb <1 ppm in water did not promote a significant increase of this metal in sediments. Relatively high concentrations of Pb seemed to affect meiofaunal and benthic foraminiferal communities by reducing their richness or diversity, and the abundance of the most sensitive taxa. The mesocosm approach can be considered an effective method to document the responses of meiofaunal and benthic foraminiferal communities to various kinds and concentrations of pollutants over time. This approach allows the evaluation of dose-response relationships, validates the outcomes of field studies, and possibly confirms the sediment quality guidelines and thresholds. Environ Toxicol Chem 2018;37:2439-2447. © 2018 SETAC.

Assessing the effect of mercury pollution on cultured benthic foraminifera community using morphological and eDNA metabarcoding approaches.

Mercury (Hg) is a highly toxic element for living organisms and is known to bioaccumulate and biomagnify. Here, we analyze the response of benthic foraminifera communities cultured in mesocosm and exposed to different concentrations of Hg. Standard morphological analyses and environmental DNA metabarcoding show evidence that Hg pollution has detrimental effects on benthic foraminifera. The molecular analysis provides a more complete view of foraminiferal communities including the soft-walled single-chambered monothalamiids and small-sized hard-shelled rotaliids and textulariids than the morphological one. Among these taxa that are typically overlooked in morphological studies we found potential bioindicators of Hg pollution. The mesocosm approach proves to be an effective method to study benthic foraminiferal responses to various types and concentrations of pollutants over time. This study further supports foraminiferal metabarcoding as a complementary and/or alternative method to standard biomonitoring program based on the morphological identification of species communities.

Distribution of Cr and Pb in artificial sea water and their sorption in marine sediments: an example from experimental mesocosms.

The uptake of two heavy metals (chromium and lead) in sediments in experimental mesocosms under exposure to different metal concentrations was evaluated by monitoring their concentrations over time both in seawater and in sediment. Two separate experiments under laboratory-controlled conditions were carried out for the two metals. Sediments were collected from a protected natural area characterized by low anthropic influence and were placed in mesocosms that were housed in aquaria each with seawater at a different metal concentration. At pre-established time intervals, seawater and sediment samples were collected from each mesocosm for chemical analyses. Quantification of chromium and lead concentration in seawater and sediment samples was carried out by atomic absorption spectrometer with graphite furnace. Low doses of chromium and lead (<1 mg L-1) do not entail an uptake in sediments and waters. At doses ≥1 mg L-1, evolution of concentrations over time shows significant differences between these two metals: (i) chromium absorption from seawater is twice faster than lead; (ii) lead accumulates in considerable amount in sediments. The different behaviour of the two investigated heavy metals could be ascribed to different interactions existing between metal ions and different components of sediment.

High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX.

The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and transcription. Chromatin-mediated transcription regulation involves DNA methylation, chromatin remodeling, and histone modifications. However, chromatin also contains non-histone chromatin-associated proteins, of which the high-mobility group (HMG) proteins are the most abundant. Although it is known that HMG proteins induce structural changes of chromatin, the processes underlying transcription regulation by HMG proteins are poorly understood. Here we decipher the molecular mechanism of transcription regulation mediated by the HMG AT-hook 2 protein (HMGA2). We combined proteomic, ChIP-seq, and transcriptome data to show that HMGA2-induced transcription requires phosphorylation of the histone variant H2AX at S139 (H2AXS139ph; γ-H2AX) mediated by the protein kinase ataxia telangiectasia mutated (ATM). Furthermore, we demonstrate the biological relevance of this mechanism within the context of TGFß1 signaling. The interplay between HMGA2, ATM, and H2AX is a novel mechanism of transcription initiation. Our results link H2AXS139ph to transcription, assigning a new function for this DNA damage marker. Controlled chromatin opening during transcription may involve intermediates with DNA breaks that may require mechanisms that ensure the integrity of the genome.