Лазерні технології в лікуванні ускладнених форм варикозного розширення вен нижніх кінцівок

Treatment results of complicated chronic venous disorders has been shown. The experience of using of endovenous laser ablation in complex treatment of trophic ulcers in chronic venous insufficiency is shown. The purpose of this work is to evaluate the efficiency of endovenous laser ablation (EVLA) of varicose vein disease of shins and to define the ways to optimize such treatment. The treatment of 60 patients was analyzed. In work the features of engineering of realization laser coagulation are considered. The received results lead to conclusion, that endovenous laser coagulation of affected veins is a reliable method of threatment. The causes of trophic ulcers were chronic venous insufficiency on the background of varicose veins and post-thrombotic syndrome. An ultrasound duplex vascular sean of lower limbs was made for all patients at all stages of diagnostics and treatment. The work displays tactics and features of laser technology application techniques of patients with venous trophic ulsers. All trophic ulcers heald up within one or two month after treatment. Endovenous laser ablation is the method of choice in the composition of the combined complex treatment of complicated chronic venous disorders C6s stage in CEAP. The use of laser technology reduce operative trauma and postoperative complications and also significantly reduces the time of postoperative rehabilitation.Мета роботи – поліпшення результатів лікування пацієнтів із ускладненими формами вари козного розширення вен нижніх кінцівок за допомогою використання високоенергетичного лазера. Матеріал і методи. Проліковано 60 хворих з ускладненими формами варикозного розши рення поверхневих вен нижніх кінцівок у період з 2016 по 2018 рік на базі Хірургічного цен тру стаціонарної медичної допомоги Державної наукової установи ≪Науково-практичний центр профілактичної та клінічної медицини≫ Державного управління справами (ДНУ ≪НПЦ ПКМ≫ ДУС). У роботі описано тактику та особливості техніки застосування лазерних технологій у таких пацієнтів. Результати. Причиною венозних трофічних виразок шкіри була хронічна венозна недостат ність на тлі варикозної хвороби та посттромботичного синдрому. Пацієнтам проводили уль тразвукове дуплексне сканування (УЗДС) судин нижніх кінцівок на усіх етапах діагностики та лікування, за результатами якого в поопераційний період констатовано тотальну облітера цію коагульованих вен у 58 (96,7%) пацієнтів. У 2 (3,3%) хворих у пригирловому відділі вели кої підшкірної вени (ВПВ) відзначено неспадіння ВПВ до 5 см, яке самостійно облітерувало впродовж 2 тижнів без додаткових маніпуляцій. Усі трофічні виразки загоїлись впродовж 1-2 місяців. Висновок. Ендовенозна лазерна абляція є методом вибору в складі комбінованого комплек сного лікування пацієнтів із хронічним захворюванням вен стадії С6 за класифікацією СЕАР. Застосування лазерних технологій знижує операційну травму та кількість поопераційних ускладнень, а також значно скорочує терміни поопераційного перебування хворих у стаціо нарі та їх реабілітації

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Investigation of the genetic aetiology of Lewy body diseases with and without dementia

\ua9 The Author(s) 2024.Up to 80% of Parkinson\u27s disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson\u27s disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson\u27s disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson\u27s disease and dementia with Lewy bodies/Parkinson\u27s disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson\u27s, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson\u27s Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

Targeted Dy intercalation under graphene/SiC for tuning its electronic band structure

Metal intercalation of graphene is a promising method to tune its electronic band structure and generate novel electronic and topological phases. The tuning depends critically on the ability to bond the intercalated atoms at predesigned, subsurface interlayer locations because the emerging band structure depends on metal location.We have studied Dy intercalation under single-layer graphene (SLG) on SiC using spot profile analysis–low-energy electron diffraction and scanning tunneling microscopy (STM). The experimental work is complemented with density-functional theory (DFT) analysis. Because different diffraction spots originate from different subsurface interlayer regions, it is possible to identify changes in the intercalation location by monitoring the spot intensity as a function of growth conditions. DFT calculations of the chemical potential as a function of intercalated Dy coverage support the variation of the stability of the intercalated phase at different intercalated locations. The preferred location is confirmed from STM studies showing the removal of the 6 × 6 moiré corrugation at the preferred location, observed at higher Dy coverage.This article is published as Chen, S., Y. Han, M. Kolmer, J. Hall, M. Hupalo, J. W. Evans, and M. C. Tringides. "Targeted Dy intercalation under graphene/SiC for tuning its electronic band structure." Physical Review B 107, no. 4 (2023): 045408. DOI: 10.1103/PhysRevB.107.045408. Copyright 2023 American Physical Society. Posted with permission. DOE Contract Number(s): AC02-07CH1135

Divergent pattern of genomic variation in Plasmodium falciparum and P. vivax

The two main species causing malaria in humans, Plasmodium falciparum and P. vivax, differ significantly from each other in their evolutionary response to common drugs, but the reasons for this are not clear. Here we utilized the recently available large-scale genome sequencing data from these parasites and compared the pattern of single nucleotide polymorphisms, which may be related to these differences. We found that there was a five-fold higher preference for AT nucleotides compared to GC nucleotides at synonymous single nucleotide polymorphism sites in P. vivax. The preference for AT nucleotides was also present at non-synonymous sites, which lead to amino acid changes favouring those with codons of higher AT content. The substitution bias was also present at low and moderately conserved amino acid positions, but not at highly conserved positions. No marked bias was found at synonymous and non-synonymous sites in P. falciparum. The difference in the substitution bias between P. falciparum and P. vivax found in the present study may possibly contribute to their divergent evolutionary response to similar drug pressures