Variants of the
gene have been associated with a number of primary cardiac conditions, including left ventricular noncompaction cardiomyopathy (LVNC). Most cases of
-related diseases are associated ...with such variant types as missense substitutions and in-frame indels. Thus, truncating variants in
(
tv) and associated mechanism of haploinsufficiency are usually considered not pathogenic in these disorders. However, recent large-scale studies demonstrated evidence of the significance of
tv for LVNC and gave rise to an assumption that haploinsufficiency may be the causal mechanism for LVNC. In this article, we present a family with isolated LVNC and a heterozygous splice variant of the
gene, analyze possible consequences of this variant and conclude that not all variants that are predicted truncating really act through haploinsufficiency. This study can highlight the importance of a precise assessment of
splicing variants and their participation in the development of LVNC.
Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment ...outcomes is unknown.
To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome.
We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome.
Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8).
Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes.
Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey ...among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries.
Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management.
63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited.
FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.
•The EAS FHSC is an international initiative involving a network of investigators interested in FH from around 70 countries.•Information on FH prevalence is lacking in most countries; where available, data tend to align with contemporary estimates.•FH diagnosis and management varies widely across countries, with overall suboptimal identification and under-treatment.•In most countries diagnosis primarily relies on DLCN criteria, and less frequently on Simon Broom or MEDPED.•Therapy for FH is not universally reimbursed, and criteria vary across countries. Access to PCSK9i and apheresis is limited.
The study is devoted to the defects organizational causes analysis in the machine building products production process. The companies with the small batch production were taken into consideration. ...Factors related to the time norms fulfilling percentage, the work rhythm, the consolidation of operations at one workplace, the new technologies introduction and equipment failures were chosen. A preliminary factors selection according to independence criteria allowed us to build a reliable regression model for the defects rate calculating. The main factors influencing the defects rate in small batch production are the time norms fulfilling percentage, the rate of consolidation of operations at one workplace, and the number of new technological processes introduced. This allowed us to offer recommendations on the machining sites work organization. The final operations and productswhich are made from expensive metals should be carried out at workplaces with a low rate of operations consolidation. Also, it is important that the wage system should not contribute to over-fulfillment of norms. The maintenance and repair system should prevent malfunctions during operations fulfilment.
The antibacterial resistance and virulence genotypes and phenotypes of 148 non-duplicate Klebsiella pneumoniae strains collected from 112 patients in Moscow hospitals in 2012-2016 including isolates ...from the respiratory system (57%), urine (30%), wounds (5%), cerebrospinal fluid (4%), blood (3%), and rectal swab (1%) were determined. The majority (98%) were multidrug resistant (MDR) strains carrying bla
(91%), bla
(74%), bla
(51%), bla
(38%), and bla
(1%) beta-lactamase genes, class 1 integrons (38%), and the porin protein gene ompK36 (96%). The beta-lactamase genes bla
, bla
, bla
, bla
, bla
, bla
, bla
, bla
, bla
, bla
, and bla
were detected; class 1 integron gene cassette arrays (aadA1), (dfrA7), (dfrA1-orfC), (aadB-aadA1), (dfrA17-aadA5), and (dfrA12-orfF-aadA2) were identified. Twenty-two (15%) of clinical K. pneumoniae strains had hypermucoviscous (HV) phenotype defined as string test positive. The rmpA gene associated with HV phenotype was detected in 24% of strains. The intrapersonal mutation of rmpA gene (deletion of one nucleotide at the polyG tract) was a reason for negative hypermucoviscosity phenotype and low virulence of rmpA-positive K. pneumoniae strain KPB584. Eighteen virulent for mice strains with LD
≤ 10
CFU were attributed to sequence types ST23, ST86, ST218, ST65, ST2174, and ST2280 and to capsular types K1, K2, and K57. This study is the first report about hypervirulent K. pneumoniae strain KPB2580-14 of ST23
harboring extended-spectrum beta-lactamase CTX-M-15 and carbapenemase OXA-48 genes located on pCTX-M-15-like and pOXA-48-like plasmids correspondingly.
Permian strata of northern Siberia contain a rich record of the late Paleozoic history of Siberia and surrounding fold and thrust belts (FTB). More than 850 uranium–lead (U–Pb) detrital zircon ages ...collected from the Permian strata provide vital information about sediment source areas and history of the sedimentary basins. The detrital zircon populations obtained from the Permian clastics of northern Siberia are characterized by large percentages of late Paleozoic and early Paleozoic zircons, whose ages can be correlated with magmatic events known from the Ural-Mongolian Orogen. Our data suggest that Permian clastics of northern Siberia were mainly sourced from orogens developed along the western and southwestern margins of the Siberian Craton (in present-day coordinates), with an additional sediment contribution from the reworked sedimentary cover and basement of Siberia. The contribution from Siberian sources is distinguished in the Precambrian part of the detrital zircon populations by wide distribution of ca. 1700–2000Ma and 2500–2750Ma zircons with an almost total lack of zircons ranging in age from 800 to 1700Ma. We propose that a major fluvial system, which we here term the “Paleo-Khatanga”, was the main sediment transport pathway along the western and northern margins of Siberia during the Permian. From a regional overview of detrital zircon populations in Permian deposits across the Arctic realm, we propose that the New Siberian Islands, Alexander and Farewell terranes were sourced from the western framework of the Ural-Mongolian Orogen and were located along the northern margin of Baltica during the late Paleozoic. The Arctic–Alaska–Chukotka Terrane on the other hand does not have Uralian signatures in the detrital zircon populations of the Permian sediments, and can be reconstructed adjacent to the northern margin of Laurentia. Our new data presented here help to better define the enigma of Arctic paleogeography during the Paleozoic.
•Detrital zircons point that Permian clastics of northern Siberia were sourced from framing orogens.•Existence of a major Permian fluvial system along the western and northern margins of Siberia•New data help to better define the Arctic late Paleozoic paleogeography.
Intensive mechanical milling was used to synthesize a MgH2 (50 wt.%) + TiB2 (50 wt.%) composite. Thermal stability of the composite versus H-desorption was studied employing the thermodesorption ...spectroscopy (TDS) method. The TDS data have revealed that TiB2 addition decreases the dissociation temperature of the MgH2 hydride by about 50 deg C. An X-ray photoelectron spectroscopy analysis has shown that TiB2 addition does not alter the surface chemical state of particles of the MgH2 hydride, a component of the composite under consideration. The effect of decreasing decomposition temperature of MgH2 due to addition of TiB2 has been attributed to catalytic influence of a TiB2 particle surface on processes of associative hydrogen desorption taking place on the surface of MgH2 particles, as well as to a higher degree of dispersion of magnesium dihydride provided by the presence of TiB2.
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