Obesity with associated developmental delay and/or learning disability in patients exhibiting additional features: Report of novel pathogenic copy number variants

Obesity is a major threat to public health worldwide, and there is now mounting evidence favoring a role for the central nervous system (CNS) in weight control. A causal relationship has been recognized in both monogenic (e.g., BDNF, TRKB, and SIM1 deficiencies) and syndromic forms of obesity [e.g., Prader–Willi syndrome (PWS)]. Syndromic obesity arising from chromosomal abnormalities, that typically also affect learning and development, are often associated with congenital malformations and behavioral characteristics. We report on nine unrelated patients with a diagnosis of learning disability and/or developmental delay (DD) in addition to obesity that were found to have copy number variants (CNVs) by single nucleotide polymorphism array‐based analysis. Each patient also had a distinct and complex phenotype, and most had hypotonia and other neuroendocrine issues, such as hyperphagia and hypogonadism. Molecular and clinical characterization of these patients enabled us to determine with confidence that the CNVs we observed were pathogenic or likely to be pathogenic. Overall, the CNVs reported here encompassed a candidate gene or region (e.g., SIM1) that has been reported in patients associating obesity and DD and/or intellectual disability (ID) and novel candidate genes and regions. © 2013 Wiley Periodicals, Inc.     

Effects of 980-nm diode laser on the ultrastructure and fracture resistance of dentine

Few reports have addressed the effects of diode laser irradiation at 980 nm on the morphology and fracture resistance of dentine. The purpose of this study is to evaluate the effects of 980-nm diode laser on the ultrastructure and fracture resistance of root dentine. The roots of 90 extracted canine teeth were divided into three groups according to the type of irrigating solution (water, NaOCl, and NaOCl/EDTA) and subdivided into three subgroups (n?=?10) according to the amount of laser irradiation (without irradiation, 1.5 W/100 Hz and 3.0 W/100 Hz). The roots were filled with an epoxy resin-based sealer and gutta-percha and then subjected to a fracture resistance test. Data were analyzed by ANOVA and the Tukey test (p?<?0.05). Additionally, 18 canine teeth were prepared using the same irrigation/irradiation protocols and evaluated by scanning electron microscopy (SEM). The SEM showed greater changes when the laser power increased, and the changes also varied according to the irrigating solution. A modified smear layer was observed in specimens that were treated with water and then laser-irradiated. The laser treatment did not alter the fracture resistance of roots treated with 1.5 W/100 Hz (246.3?±?29.5 N) and 3.0 W/100 Hz (215.3?±?25.1 N) laser power. The roots treated with NaOCl were more susceptible to fracture (199.4?±?15.1 N) than those irrigated with water (254.2?±?23.0 N) (p?<?0.05). The 980-nm diode laser altered the morphology of the dentine but did not affect the fracture resistance of the roots.     

Factors that influence basal insulin requirement in type 2 diabetes

In clinical practice, basal insulin dosage (BID) for the treatment for type 2 diabetes given as slow-acting analogues or NPH insulin varies widely when adjusted for body weight (UI/kg). In this study, we investigated the interrelationship between BID and anthropometric, laboratory and clinical parameters. A total of 681 type 2 diabetic patients, treated with bedtime insulin in association with other antidiabetic drugs (preprandial insulin and/or oral agents), were studied. Anthropometric, clinical and biochemical parameters, as well as micro- and macrovascular complications, were evaluated. Non-alcoholic fatty liver disease (NAFLD) was assessed by liver ultrasound. BID was titrated to achieve a fasting blood glucose target of ≤6.7?mmol/L (120?mg/dL). In the multivariate analysis, BID was significantly associated with waist circumference (p?=?0.04) and the insulin treatment duration (p?=?0.004) as the type of insulin treatment ("basal-bolus" regimen vs. basal insulin only, p?相似文献   

Role of sex hormones in modulation of brown adipose tissue activity

The recent demonstration that metabolically active brown adipose tissue (BAT) is present with a high prevalence in humans undoubtedly represents one of the major advancements in the field of metabolic research in the last few years. The increasing interest in BAT is justified by preclinical observations highlighting an important role of this tissue in energy dissipation and metabolic clearance of substrates from the blood. These findings imply that stimulation of BAT activity may represent a new therapeutic approach for obesity and associated comorbidities. However, before proposing BAT as a target organ for therapeutics in a clinical setting, many further notions about BAT function and modulation need to be explored. Keeping in mind the importance of sex dimorphism in energy metabolism control under physiological and pathological conditions, sex hormones may play a relevant role in the regulation of BAT activity in both males and females. Much of the evidence acquired in the past supports the concept of an important role for different sex hormones in BAT thermogenesis and indicates that this tissue mediates the ability of sex hormones to modulate energy balance. These findings make it plausible that a modified interaction between BAT and sex hormones may contribute to the development and the maintenance of obesity and associated metabolic complications.     

Reduction of volumetric bone mineral density in postmenopausal women with hepatitis C virus-correlated chronic liver disease: A peripheral quantitative computed tomography (pQCT) study

BackgroundThe prevalence of osteoporosis in chronic liver disease (CLD) varies considerably among the studies, depending on patient selection and diagnostic criteria. We aimed to measure bone turnover markers and volumetric bone mineral density (BMD) in a group of postmenopausal women with CLD using both dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), in comparison with age-matched healthy subjects.MethodsThirty-five postmenopausal patients with HCV-correlated CLD and 35 healthy postmenopausal women, as controls, underwent a DXA scan at lumbar and femoral level and a pQCT measurement of the nondominant forearm. Serum concentrations of biochemical markers relevant to bone turnover were also measured.ResultsPatients showed no differences in DXA values either at lumbar or femoral level compared to controls. On the contrary, pQCT geometrical (cortical cross-sectional area) and volumetric (total and trabecular volumetric BMD) parameters were significantly reduced in the CLD women. Also the Strength–Strain Index (SSI), an estimate of diaphyseal bone resistance to bending and torsion, was significantly lower in patients than in controls. Patients with CLD presented an unbalanced bone turnover, with increased bone resorption markers.ConclusionsThe bone geometrical and volumetric parameters measured in our CLD postmenopausal women, by pQCT, show a reduced bone mineral quality and stiffness. Conversely, DXA-measurements seem unable to appreciate the bone alterations in these patients. This would encourage further studies to validate pQCT analysis as a diagnostic tool for a correct estimate of bone involvement in CLD.     

Cardiovascular disease in asthma and COPD: a population-based retrospective cross-sectional study

We conducted a large population-based retrospective cross-sectional study for determining the extent of clinically recognized chronic obstructive pulmonary disease (COPD) and asthma, and the prevalence of associated cardiovascular diseases (CVDs), using information obtained from the Health Search Database (HSD) owned by the Italian College of General Practitioners (SIMG). Our study provides further evidence that patients with the diagnosis of COPD are at increased association with the diagnosis of most CVDs. It also documents that age clusters between 35 and 54 years are those at highest association of simultaneous presence of the diagnosis of CVD and that of COPD, with a progressive significant reduction in older age clusters. Moreover, it shows that the diagnosis of asthma is modestly associated with the diagnosis of different CV morbidities.     

Videocapillaroscopy study of post traumatic lower limb loss of tissue treated with and without acellular dermal substitute

A 46 years old male with a post traumatic loss of tissue localized on the anterior surface of the right thigh and knee due to a road accident, was treated with different surgical reconstructive techniques. Combined use of autologous skin graft and acellular dermal substitute Integra? allowed the satisfactory recovery of the patient who was discharged after 82 days from the trauma. To analyse the characteristics and the quality of the healing tissues we performed a videocapillaroscopy study to assess the microcirculatory pattern of the autologous skin grafted on the dermal substitute in comparison with the autologous skin grafted on granulation tissue. The videocapillaroscopy was performed in the zone skin grafted directly on granulation tissue, Zone 1 (Z1); on the region of the lesion in the knee, treated with dermal substitute and autologous skin graft, Zone 2 (Z2), and on the undamaged controlateral knee skin. Zone 3 (Z3). The results showed that the capillary density was similar between Z2 and Z3, while in Z1, the zone skin grafted on the granulation tissue without Integra? the capillary density was significatively reduced. These preliminary observations within the clinical data may be an useful contribute to better understand the tissue healing process.     

Impacto de la infección por el nuevo coronavirus en los pacientes con uveítis asociada a una enfermedad autoinmune: resultado de la encuesta COVID-19-GEAS pacientes

IntroductionThe objetive of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey.Material and methodsInternal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population.ResultsA total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet's disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive.ConclusionsBoth asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.