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Context Silver-Russell syndrome (SRS) is a clinical and molecular heterogeneous disorder associated with short stature, typical facial gestalt, and body asymmetry. Though molecular causes of SRS can be identified in a significant number of patients, about one-half of patients currently remain without a molecular diagnosis. However, determination of the molecular cause is required for a targeted treatment and genetic counselling. Objective The aim of this study was to corroborate the role of HMGA2 as an SRS-causing gene and reevaluate its mode of inheritance. Design, Setting, Patients Patients were part of an ongoing study aiming on SRS-causing genes. They were classified according to the Netchine-Harbison clinical scoring system, and DNA samples were investigated by whole exome sequencing. Common molecular causes of SRS were excluded before. Results Three novel pathogenic HMGA2 variants were identified in 5 patients from 3 SRS families, and fulfilling diagnostic criteria of SRS. For the first time, homozygosity for a variant in HMGA2 could be identified in a severely affected sibpair, whereas parents carrying heterozygous variants had a mild phenotype. Treatment with recombinant growth hormone led to a catch-up growth in 1 patient, whereas all others did not receive growth hormone and stayed small. One patient developed type 2 diabetes at age 30 years. Conclusions Identification of novel pathogenic variants confirms HMGA2 as an SRS-causing gene; thus, HMGA2 testing should be implemented in molecular SRS diagnostic workup. Furthermore, inheritance of HMGA2 is variable depending on the severity of the variant and its consequence for protein function.

Gastrointestinal (GI) problems are common in Phelan-McDermid syndrome (PMS). Chewing and swallowing difficulties, dental problems, reflux disease, cyclic vomiting, constipation, incontinence, diarrhoea, and nutritional deficiencies have been most frequently reported. Therefore, this review summarises current findings on GI problems and addresses the fundamental questions, which were based on parental surveys, of how frequent GI problems occur in PMS, what GI problems occur, what consequences (e.g., nutritional deficiencies) GI problems cause for individuals with PMS, and how GI problems can be treated in individuals with PMS. Our findings show that gastrointestinal problems have a detrimental effect on the health of people with PMS and are a significant burden for their families. Therefore, we advise evaluation for these problems and formulate care recommendations.

Multicenter long-term studies of predictors for the effectiveness of continuous subcutaneous insulin infusion (CSII) in clinical practice are lacking. We hypothesized that there are substantially greater reductions in hemoglobin A1c (HbA1c) in patients with poor glycemic control and that other predictors may also exist.We used data from 10 outpatient diabetic clinics in Sweden and studied CSII treatment over 5 years. Patients with HbA1c values available ≤ 6 months before starting CSII and at 5 years were included (n = 272, 82% of CSII patients) along with 2,437 contemporaneous controls on multiple daily insulin injections (MDI). Baseline variables evaluated were age, sex, diabetes duration, insulin dose, body mass index (BMI), HbA1c at baseline, and outpatient clinical care unit.At 5 years, significantly greater reductions in HbA1c by CSII compared with MDI were found for patients with higher baseline HbA1c (P = 0.032) and lower baseline BMI (P = 0.013). For baseline HbA1c levels of 7.0%, 8.0%, and 9.0% and a BMI of 25 kg/m(2), the reduction in HbA1c level by CSII was 0.08% (difference not significant), 0.16% (95% confidence interval, 0.03-0.29%), and 0.25% (95% confidence interval, 0.11-0.39%), respectively. Corresponding analyses for the change in HbA1c level from start to 1 and 2 years revealed a significant interaction of insulin pump therapy only with baseline HbA1c levels (P0.001 and P = 0.030, respectively). The interaction term between outpatient clinical care unit and CSII treatment was statistically significant for some care units, with some care units demonstrating a benefit from CSII and others demonstrating a detriment.Patients with high HbA1c levels have a greater probability of improved HbA1c after initiating pump therapy, but effects remain relatively modest even for patients with poor control. Factors predicting successful insulin pump use need further study.

Continuous glucose monitoring (CGM) is a tool widely used in the treatment of patients with type 1 diabetes. The purpose of the current study was to evaluate whether accuracy and patient treatment satisfaction differ between the Enlite™ (Medtronic MiniMed, Inc., Northridge, CA) and Dexcom(®) (San Diego, CA) G4 PLATINUM CGM sensors.Thirty-eight ambulatory patients with type 1 diabetes used the Dexcom G4 and Enlite sensors simultaneously for a minimum of 4 and maximum of 6 days. Patients measured capillary glucose levels with a HemoCue(®) (Ängelholm, Sweden) system six to 10 times a day. In addition, two inpatient studies were performed between Days 1-3 and 4-6.The mean absolute relative difference (MARD) in blood glucose for the Dexcom G4 was significantly lower (13.9%) than for the Enlite sensor (17.8%) (P0.0001). The corresponding MARDs for Days 1-3 were 15.0% versus 19.4% (P=0.0027) and 13.6% versus 15.9% (P=0.026) for Days 4-6. For glucose levels in the hypoglycemic range (4.0 mmol/L), the MARD for the Dexcom G4 was 20.0% compared with 34.7% for the Enlite (P=0.0041). On a visual analog scale (VAS) (0-100), patients rated the Dexcom G4 more favorably than the Enlite in 12 out of the 13 user experience questions. For example, more patients rated their experience with the Dexcom G4 as positive (VAS, 79.7 vs. 46.6; P0.0001) and preferred to use it in their daily lives (VAS, 79.1 vs. 42.1; P0.0001).The Dexcom G4 sensor was associated with greater overall accuracy than the Enlite sensor during initial (Days 1-3) and later (Days 4-6) use and for glucose levels in the hypoglycemic range. Patients reported a significantly more positive experience using the Dexcom G4 than the Enlite.

The excess risk of major coronary events (acute myocardial infarction (AMI) or death from coronary heart disease (CHD)) in individuals with type 1 diabetes (T1D) in relation to glycaemic control and renal complications is not known.Individuals with T1D in the Swedish National Diabetes Registry after 1 January 1998, without a previous MI (n=33 170) and 1 64 698 controls matched on age, sex and county were followed with respect to non-fatal AMI or death from CHD. Data were censored at death due to any cause until 31 December 2011.During median follow-up of 8.3 and 8.9 years for individuals with T1D and controls, respectively, 1500 (4.5%) and 1925 (1.2%), experienced non-fatal AMI or died from CHD, adjusted HR 4.07 (95% CI 3.79 to 4.36). This excess risk increased with younger age, female sex, worse glycaemic control and severity of renal complications.The adjusted HR in men with T1D with updated mean haemoglobin A1c (HbA1c)6.9% (52 mmol/mol) and normoalbuminuria was 1.30 (95% CI 0.90 to 1.88) and in women 3.16 (95% CI 2.14 to 4.65). HRs increased to 10.7 (95% CI 8.0 to 14.3) and 31.8 (95% CI 23.6 to 42.8) in men and women, respectively, with HbA1c9.7% and renal complications.The excess risk of AMI in T1D is substantially lower with good glycaemic control, absence of renal complications and men compared with women. In women, the excess risk of AMI or CHD death persists even among patients with good glycaemic control and no renal complications.

Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM. Methods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples. Results: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P < .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P < .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P < .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82. Conclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.

Dataset of the group of ethnic Lithuanian population (LITGEN project). (PDF 138Â kb)

The aim of this paper is to analyze and systematize different approaches to corporate reputation and its support, highlighting the value of corporate reputation, assessing the problem of stakeholder heterogeneous perception of corporate reputation and identifying key dimensions of supporting a high corporate reputation. In this paper we have revealed that there is worth to support a high reputation because of the economic value, the relationship value and the value related to competitive advantage. To support a high reputation, an organization must define this construct and understand how it can be perceived by various stakeholders. We propose a definition which compounds the support of high corporate reputation. Nevertheless, this paper reviews that reputation can be supported with regard to key dimensions of corporate reputation, treating them as basic tools and considering communication as the most important one. The paper proposes an integrated view to corporate reputation and highlights new insights to communication while supporting a high corporate reputation.

Quality parameters and description of all mutations analyzed with Illumina VeraCode GoldenGate assay. (DOCX 69 kb)

Dataset of the group of affected individuals (DEAFGEN project). (PDF 191Â kb)

The conditions for PCR amplification of GJB2 and GJB6 genes coding sequences (primer sequences, annealing temperature, lengths of the amplicons). (PDF 8Â kb)

Cleft lip with or without cleft palate (CL/P) is one of the mostcommonhumanbirthdefects.CL/Pmayoccuraspartofacomplexmalformation syndrome or, as is more commonly the case, as anonsyndromic malformation. In European populations non-syndromic cleft lip with or without cleft palate (NSCL/P) has abirth prevalence of 1/700–1/1,000. NSCL/P has a multifactorialetiology resulting from interactions between multiple genetic andenvironmentalfactors.Nonsyndromiccleftpalateonly(NSCPO)isthe second most common form of nonsyndromic clefting, with aprevalence of 1/2,000 in most European populations. AlthoughNSCL/P and NSCPO are generally considered to be develop-mentally and genetically distinct entities, there is evidence thatthey may have an etiological overlap [Kondo et al., 2002; Sivertsenet al., 2008].The identification of susceptibility genes for NSCL/P has beenthe subject of extensive research. Of the many candidate genesinvestigated, however, only the IRF6 gene has shown a convincingdegreeofconsistencyacrossstudies[Zuccheroetal.,2004;Rahimovet al., 2008]. The first genome-wide association scan (GWAS)recently reported a new major susceptibility locus at chromosome8q24.21,with the strongestassociationsignal having been observedfor rs987525 (P¼3.34 10

Aim: Guidelines for the treatment of type 1 diabetes generally recommend quarterly or more frequent Haemoglobin A1c (HbA1c) assessment in patients with inadequate glycaemic control. The purpose of the current study was to evaluate to what extent these guidelines are followed in clinical practice in Sweden. Method: We studied 5989 patients with type 1 diabetes from 10 outpatient diabetes clinics in Sweden from 1 January 2005 to 31 December 2009. Data on HbA1c measurement frequency were obtained from the Diab-Base electronic medical records database, where HbA1c measurements are recorded together with other patient characteristics, including treatment and other general risk factors for diabetic complications. The frequency of HbA1c measurements was obtained for all patients by calendar year, care unit, and during time periods where glucose was classified as well controlled (HbA1c7% was performed within 4 months. The probability of a subsequent assessment in the 4 months following an HbA1c value>7.0% increase in patients treated with continuous subcutaneous insulin infusion (CSII), OR=1.57 (1.46-1.69). Differences were also noted by care unit, age, gender, glycaemic control, calendar year, and weight and diabetes duration. Conclusion: In patients with type 1 diabetes, HbA1c is measured less frequently in clinical practice in Sweden than guidelines recommend, although patients with CSII and treated in certain care units receive more frequent assessments.

This paper investigates the impact of shocking advertising to consumer buying behavior. Scientists proved that shock tactics in advertising influences consumer buying behavior. The paper analyses the main components of shocking advertising, which cause positive or negative attitude to shocking advertising, influencing consumer buying behavior. Theoretical research studies confirmed that positive or negative consumer attitudes to shocking advertising is influenced by socio-demographic and cultural-social factors - religiosity, moral principles, age, gender, individualism-collectivism, high-low context language. Developed theoretical model of the link among the socio-demographic and cultural-social factors, consumer perception of shocking advertising and consumer buying behavior, which can be used for further practical studies. DOI: http://dx.doi.org/10.5755/j01.em.18.1.3643