Whole genome sequencing in ROHHAD trios proved inconclusive: what's beyond?

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a rare, life-threatening, pediatric disorder of unknown etiology, whose diagnosis is made difficult by poor knowledge of clinical manifestation, and lack of any confirmatory tests. Children with ROHHAD usually present with rapid onset weight gain which may be followed, over months or years, by hypothalamic dysfunction, hypoventilation, autonomic dysfunction, including impaired bowel motility, and tumors of neural crest origin. Despite the lack of evidence of inheritance in ROHHAD, several studies have been conducted in recent years that have explored possible genetic origins, with unsuccessful results. In order to broaden the search for possible genetic risk factors, an attempt was made to analyse the non-coding variants in two trios (proband with parents), recruited in the Gaslini Children's Hospital in Genoa (Italy). Both patients were females, with a typical history of ROHHAD. Gene variants (single nucleotide variants, short insertions/deletions, splice variants or in tandem expansion of homopolymeric tracts) or altered genomic regions (copy number variations or structural variants) shared between the two probands were searched. Currently, we have not found any potentially pathogenic changes, consistent with the ROHHAD clinical phenotype, and involving genes, regions or pathways shared between the two trios. To definitively rule out the genetic etiology, third-generation sequencing technologies (e.g., long-reads sequencing, optical mapping) should be applied, as well as other pathways, including those associated with immunological and autoimmune disorders, should be explored, making use not only of genomics but also of different -omic datasets.

Influence of the MCT1-T1470A polymorphism (rs1049434) on repeated sprint ability and blood lactate accumulation in elite football players: a pilot study.

PURPOSE: The aim of this study is to investigate the influence of the MCT1 T1470A polymorphism (rs1049434) on repeated sprint ability (RSA) and lactate accumulation after RSA testing. METHODS: Twenty-six elite Italian male football players (age: 17.7 ± 0.78 years; height: 179.2 ± 7.40 cm; weight: 72.1 ± 5.38 kg) performed RSA testing (6 × 30-m sprints with an active recovery between sprints), and lactate measurements were obtained at 1, 3, 5, 7, and 10 min post-exercise. Genotyping for the MCT1 T1470A polymorphism was performed using PCR. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium, being 42% wildtype (A/A), 46% heterozygotes (T/A), and 12% mutated homozygotes (T/T). Significant differences between genotypic groups were found in the two final sprint times of the RSA test. Under a dominant model, carriers of the major A-allele (Glu-490) in the dominant model showed a significantly lower sprint time compared to footballers with the T/T (Asp/Asp) genotype (5th Sprint time: A/A + T/A = 4.60 s vs TT = 4.97 s, 95% CI 0.07-0.67, p = 0.022; 6th Sprint: A/A + T/A = 4.56 s vs T/T = 4.87 s, 95% CI 0.05-0.57, p = 0.033). CONCLUSIONS: The T1470A (Glu490Asp) polymorphism of MCT1 was associated with RSA. Our findings suggest that the presence of the major A-allele (Glu-490) is favourable for RSA in football players.

Assessing hand hygiene compliance among healthcare workers in six Intensive Care Units.

INTRODUCTION: Healthcare associated infections (HAIs) are a cause of high morbidity, disability and reduced quality of life, as well as mortality and rising costs for health systems. Preventing the HAI risk by planning and implementing effective preventive strategies is important to safeguard patient health. METHODS: The study aimed to evaluate the presence of procedures and protocols for infection control, to assess the adhesion to the different aspects of hand hygiene (HH) and hand washing technique by healthcare workers in six ICUs. A perspective observational study was conducted in six ICUs. In each ICU, the adherence by health care workers to both hand hygiene practices and standard precautions was assessed, as well as the presence of procedures and written protocols. RESULTS: The findings showed that in all the involved ICUs, 73 of 142 required protocols and procedures were available. Specifically, 59 of 79 were available for general measure of risk control, 12 of 15 for hand hygiene, and 24 of 48 for standard precautions and isolation measures. Also, the results showed highly variable levels of adherence to the best hygiene practices in all the ICUs involved in the study, with compliance rates ranging from 3% to 100%, and 73 of 142 required protocols were available at the study time. CONCLUSIONS: Overall, the involved ICUs showed low levels of adherence to best hygiene practices. This suggests the need to implement immediate strategies for infection control in the ICUs. A multidisciplinary intervention could be effective in preventing and control the HAI risk.score was reached only by the third year students with regard to the proper HH. The level of knowledge about HAI was inadequate.A periodically check of nursing students' knowledge would be advisable in order to fill any gaps, improve training, reduce HAI and increase prevention measures compliance.

Influence of the COL5A1 rs12722 on musculoskeletal injuries in professional soccer players.

AIM: The aim of this study was to investigate whether COL5A1 rs12722 polymorphism is associated with musculoskeletal injuries in elite soccer players. METHODS: Fifty-four male professional soccer players of European origin (25.9±4.3 years) were recruited from a team participating at the Official Italian Professional Championship during four consecutive seasons (2009-2013). The incidence and severity of musculoskeletal injuries and its relationship to COL5A1 rs12722 polymorphism were analyzed. DNA was extracted from buccal swab. The cohort was genotyped for the COL5A1 rs12722 single nucleotide polymorphism (SNP) through PCR and enzyme digestion with BstUI, and musculoskeletal injuries data were collected during the four seasons. Injuries were categorized under 5 degrees of severity based on the number of days' absence, while musculoskeletal injuries incidence was calculated per 1,000 hours of exposure to training and matches ((∑ injuries/∑ exposure hours) x 1000). RESULTS: No significant differences were found among genotypes for incidence of musculoskeletal injuries (P=0.683). Participants with TT genotype (3.71±0.5, N.=4) showed a trend (P=0.193) versus an higher severity of injuries than individuals with TC (2.98±0.8, N.=10) or CC (2.75±0.95, n=4) genotypes. The COL5A1 rs12722 accounted for 44% of severity of injuries (P=0.002). CONCLUSION: In conclusion, the COL5A1 rs12722 was found to be associated with severity of musculoskeletal injuries but not with incidence of musculoskeletal injuries in top-level soccer players.

Physical activity levels and health-related quality of life in young Italian population.

AIM: Significant levels of physical activity (PA) have benefit in reducing chronic diseases in the general adults, but little is known on the association between health-related quality of life (HRQoL) and PA levels among young population. This study aims to investigate the association between different levels of PA and HRQoL in a random sample of 155 Italian University students (age range: 18-30 years old). METHODS: We used the short version of IPAQ and SF-36 to assess PA levels and HRQoL, respectively. Differences in HRQoL scores between the three IPAQ categories (low, moderate and high) were evaluated by the analysis of covariance (with age and BMI as covariates). Forward stepwise multiple regression analysis was used to determine the most predictive variables for a good HRQoL. RESULTS: A significant relationship between PA (Kcal/week and METs/week) and Physical Functioning, Role Physical, General Health, and Physical Summary Component scores was observed in women, while the Role Physical, and the Vitality were associated with PA in men. The amount of PA (day/week, Kcal/week and METs/week) significantly predicted the HRQoL scores and the variance explained by the function ranged from 5.75% to 14.24% for women and from 5.41% to 10.95% for men. The regular frequency of PA during the week was the most important positive predictors for the highest scores in most of HRQoL domains. CONCLUSION: Our results confirm that the highest PA Levels were associated with more favorable scores in HRQoL dimensions, also among young Italian population.

Genetic markers and explosive leg-muscle strength in elite Italian soccer players.

AIM: The aim of the present paper was to investigate the relationships between polymorphisms in ACTN3, ACE and BDKRB2 genes, soccer performance, and explosive leg-muscle strength in Italian soccer players. METHODS: We examined 42 top-level Italian soccer players (S) and 106 sedentary healthy Italians, as a control group (C). χ2 test was used to look for the difference in genotype distribution of ACTN3, ACE and BDKRB2 between groups. The data were evaluated by forward stepwise multiple regression analysis with the Squat Jump (SJ) and Counter Movement Jump (CMJ) as dependent variables, as well as competition level (CL), ACTN-3, ACE and BDKRB2 genotypes as independent variables. RESULTS: No significant difference was found between groups for ACE, ACTN-3 and BDKRB2 genotype distributions. Forward stepwise multiple regression analysis suggests a significant relationship between a) SJ vs. CL, ACE, and ACTN-3 and b) CMJ vs. CL. For SJ, the multivariate model combining genotypic data and competition level significantly predicted explosive leg-muscle strength in soccer players and variance explained by the function was 23.92%. CONCLUSION: An interaction of two polymorphisms (ACE and ACTN-3) might be able to discriminate quantitative traits crucial for the elite soccer performance, however the contribution of genetic factors to soccer performance is not so high.

Continuous subcutaneous insulin infusion (CSII) in pregnant diabetic patients.

The efficacy of the insulin infusion pump (CSII) in pregnancy was examined in 12 diabetic patients and compared with intermittent insulin therapy (IIT). In patients poorly controlled on IIT constant and rapid equilibrium was achieved with CSII (mean of glucose levels: CSII versus IIT = 84 versus 137 mg/dl; S.D. = 36 versus 63 mg/dl; mean amplitude of glycemic excursion (MAGE) = 65 versus 112 mg/dl. In patients well controlled on IIT, CSII led to a reduction in the variation of glucose excursions (S.D. = 29 versus 36 mg/dl; MAGE = 48 versus 76 mg/dl). CSII generally produced a reduction of 20-37 per cent of daily insulin dose (in three cases there was an increase of dose with the achievement of glycemic control). Furthermore in CSII treated-patients amniotic glucose, insulin and C-peptide concentrations were found to be in the normal range (22.1 +/- 10.1 mg/dl; 5.2 +/- 2.7 microU/ml; 1.25 +/- 0.71 ng/ml, respectively). All infants were born at or near-term, had no macrosomia or neonatal problems. It is concluded that CSII is a highly efficient way to achieve normal glucose levels in pregnancy, not only in type I, but also in type II or gestational diabetes.

Continuous subcutaneous insulin infusion (CSII) in pregnant diabetic women.

Insulin infusion pump treatment (CSII) in pregnancy was compared with conventional therapy (IIT) in 12 pregnant diabetic women. In patients poorly controlled on IIT a plasma glucose equilibrium was achieved with CSII (mean of: glucose levels = 84 vs 137 mg/dl; SD = 36 vs 63 mg/dl; MAGE = 65 vs 112 mg/dl). In patients well controlled on IIT, CSII led to a reduction in the variation of glucose excursions (SD = 29 vs 36 mg/dl; MAGE = 48 vs 76 mg/dl). CSII generally led to a reduction of 20-37% of daily insulin dose but in 3 cases there was an increase of dose with the achievement of glycaemic control. A significant relation between bolus/basal ratio of insulin daily dose and the quality of glycaemic control was also found during CSII. All infants were born at or near to term and none were macrosomic or had neonatal complications. It is concluded that CSII is highly efficient in pregnancy not only in type I but also in type II or gestational diabetes.

Pulsatile Gn-Rh induced ovulatory cycles: echographic and endocrine aspects.

Five patients with primary hypogonadotrophic amenorrhea were treated for the induction of ovulation with I.V. pulsatile Gn-Rh doses ranging from 2.5 to 12.5 micrograms/90 min) for 15 cycles. Ovulation occurred during Gn-Rh treatment in 7 cycles (A) or after i.m. HGC administration (5,000-10,000 IU) (B = 6) (ovulation rate = 86%). Four pregnancies (A = 2; B = 2) were obtained (in one case there was a twin pregnancy). Echographic and endocrine patterns were evaluated. Ovulatory follicular diameter was 18.3 +/- 6.0 mm, no difference between A and B (21.8 +/- 5.6 and 16.0 +/- 5.1 mm, respectively) was observed. In addition E2 preovulatary plasma levels were similar in the two groups examined (334 +/- 131 and 300 +/- 89 pg/ml, respectively). Also endocrine and echographic profiles of conceptive (C) and non conceptive (NC) cycles were similar. Furthermore all doses resulted effective in determining the ovarian response and no difference was found at different dosage used. It is concluded that pulsatile GnRh is a "physiological" way of inducing ovulation in PHA patients. By analysis of the present data we consider it advisable to induce ovulation by the enhancement of the endogenous LH peak which occurs during Gn-Rh administration (A group) and then periodic injections of HCG can be used for maintaining the luteal function.