Fourniermoses9462

Trial registration number FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049).

Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene.

Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants.

Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%.

Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.

Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.The fatty acid composition of fats and oils is commonly determined by gas chromatography after preparing fatty acid methyl esters (FAME). Capillary columns coated with polyethylene glycol emerged as the preferred separation tool for the quantification of the polyunsaturated fatty acids contained primarily in marine oils. However, their selectivity is inadequate for measuring the trans fatty acids (TFA) contained in refined vegetable oils, dairy fats, and marine oils. Highly polar 100% poly(biscyanopropyl siloxane) capillary columns provide the necessary selectivity, but small differences in the phase polarity caused by column age, conditioning, or manufacturing variations affect the reproducibility of their separations of these complex samples. In this study, a simple procedure is described to compensate for small variations in column selectivity by adjusting the elution temperature. The balance between the dipole-induced dipole interactions and dispersive interactions was determined by measuring selectivity factors [SF(i)] corresponding to the elution of an unsaturated FAME such as 183n-3 relative to two saturated FAME such as 200 and 220. Knowing the SF(i) provided by the installed capillary column at a given elution temperature, and the SF(i) of the target separation, we propose a simple calculation to determine the necessary elution temperature adjustment to achieve (or restore) the desired separation. After determining the SF(i) which provides the optimal separation of TFA, the novel methodology was applied to the separation of refined vegetable oils, butter fats, and marine oils.

To assess the clinico-epidemiological profile of paediatric patients with Corona virus disease 2019 (COVID-19) infection during the pandemic.

Clinico-epidemiological and laboratory profile of children between 1 month and 14 years were studied between 15 May and 31 July 2020, who had positive nasopharyngeal and oropharyngeal swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by reverse transcriptase-polymerase chain reaction (RT-PCR).

A total of 30 children with median age of 10.5 years (8 months to 14 years) were included in the present study. Sixty percent were boys. Twenty-seven (90%) belonged to an urban area and all 30 children were from a containment area. All were belonging to Kuppuswamy upper lower and lower socioeconomic class. Twenty-one (70%) were asymptomatic. All children had a positive household contact. Symptomatic children had only mild symptoms of fever, dry cough and rhinitis. All were fully vaccinated as per age. Nine (30%) had anaemia. The mean leucocyte count was 7470 ± 2427 (4300-14100). Leucocytosis was seen in 3 (9%) children. C-reactive protein was found to be raised in only 4 (13%) children. We did not find alteration in sense of smell and taste. No mortality was reported.

COVID-19 in paediatric patients is usually mild. Severe acute respiratory infection is not a major manifestation of COVID 19 infection in children. All children infected by the novel Corona virus-2 in this study, have a documented household contact.

COVID-19 in paediatric patients is usually mild. Severe acute respiratory infection is not a major manifestation of COVID 19 infection in children. All children infected by the novel Corona virus-2 in this study, have a documented household contact.

G protein-coupled receptor kinase 4 (GRK4) has been reported to play an important role in hypertension, but little is known about its role in cardiomyocytes and myocardial infarction (MI). The goal of present study is to explore the role of GRK4 in the pathogenesis and progression of MI.

We studied the expression and distribution pattern of GRK4 in mouse heart after MI. GRK4 A486V transgenic mice, inducible cardiomyocyte-specific GRK4 knockout mice, were generated and subjected to MI with their control mice. Cardiac infarction, cardiac function, cardiomyocyte apoptosis, autophagic activity, and HDAC4 phosphorylation were assessed. The mRNA and protein levels of GRK4 in the heart were increased after MI. Transgenic mice with the overexpression of human GRK4 wild type (WT) or human GRK4 A486V variant had increased cardiac infarction, exaggerated cardiac dysfunction and remodelling. In contrast, the MI-induced cardiac dysfunction and remodelling were ameliorated in cardiomyocyte-specific GRK4 knockout mice. GRK4 overexpression in cardiomyocytes aggravated apoptosis, repressed autophagy, and decreased beclin-1 expression, which were partially rescued by the autophagy agonist rapamycin. MI also induced the nuclear translocation of GRK4, which inhibited autophagy by increasing HDAC4 phosphorylation and decreasing its binding to the beclin-1 promoter. HDAC4 S632A mutation partially restored the GRK4-induced inhibition of autophagy. MI caused greater impairment of cardiac function in patients carrying the GRK4 A486V variant than in WT carriers.

GRK4 increases cardiomyocyte injury during MI by inhibiting autophagy and promoting cardiomyocyte apoptosis. These effects are mediated by the phosphorylation of HDAC4 and a decrease in beclin-1 expression.

GRK4 increases cardiomyocyte injury during MI by inhibiting autophagy and promoting cardiomyocyte apoptosis. These effects are mediated by the phosphorylation of HDAC4 and a decrease in beclin-1 expression.

Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population.

An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria.

We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Brequinar Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age.

Sjögren syndroarch including creation of paediatric-specific classification criteria.

Cardiac biomarkers elevation is common after revascularization, even in absence of periprocedural myocardial infarction (PMI) detection by imaging methods. Thus, late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) may be useful on PMI diagnosis and prognosis. We sought to evaluate long-term prognostic value of PMI and new LGE after revascularization.

Two hundred and two patients with multivessel coronary disease and preserved ventricular function who underwent elective revascularization were included, of whom 136 (67.3%) underwent coronary artery bypass grafting and 66 (32.7%) percutaneous coronary intervention. The median follow-up was 5 years (4.8-5.8 years). Cardiac biomarkers measurement and LGE-CMR were performed before and after procedures. The Society for Cardiovascular Angiography and Interventions definition was used to assess PMI. Primary endpoint was composed of death, infarction, additional revascularization, or cardiac hospitalization. Primary endpoint was observed in 29 (14.3%) patients, of whom 13 (14.9%) had PMI and 16 (13.9%) did not (P = 0.93). Thirty-six (17.8%) patients had new LGE. Twenty (12.0%) events occurred in patients without new LGE and 9 (25.2%) in patients with it (P = 0.045). LGE was also associated to increased mortality, with 4 (2.4%) and 4 (11.1%) deaths in subjects without and with it (P = 0.02). LGE was the only independent predictor of primary endpoint and mortality (P = 0.03 and P = 0.02). Median LGE mass was estimated at 4.6 g. Patients with new LGE had a greater biomarkers release (median troponin 8.9 ng/mL vs. 1.8 ng/mL and median creatine kinase-MB 38.0 ng/mL vs. 12.3 ng/mL; P < 0.001 in both comparisons).

New LGE was shown to be better prognostic predictor than biomarker-only PMI definition after uncomplicated revascularization. Furthermore, new LGE was the only independent predictor of cardiovascular events and mortality.

http//www.controlled-trials.com/ISRCTN09454308.

http//www.controlled-trials.com/ISRCTN09454308.

Blood stream infections are considered as a major cause of morbidity and mortality in neonates. Recent trend shows increasing resistance to commonly used antibiotics.

The aim of this study is to find the antibiotic susceptibility pattern of various bacteria from blood samples in neonates and associated risk factors.

All consecutive cases of intramural neonatal sepsis were enrolled for >12 months. Before starting or changing antibiotic, blood sample under all aseptic precautions was taken for culture. Clinical and demographic details were recorded to analyze risk factors for sepsis. Antibiotic sensitivity tests were done as per CLSI 2019 guidelines.

Of the 898 participants, 107 showed culture positivity. Klebsiella pneumoniae (25.2%) and Coagulase-negative Staphylococcus (23.3%). The blood culture positivity rate was 11.9%. Approximately 79% of isolates were multidrug-resistant extended-spectrum beta-lactamase 90%, carbapenemase-resistant Enterobacteriaceae 27.7% and MRSA 43%. The risk factors found to be associated with sepsis were period of gestation ≤37 weeks, meconium-stained liquor, birth weight <1500 g, mechanical ventilation, partial exchange transfusion, duration of antibiotics for >10 days and duration of both NICU stay and hospital stay for >10 days.