New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Красноуральский рабочий. 2017. № 22

<em>According to the WHO, giardiasis incidence rate in children in the world is 15 to 20%. In Russia, over 130,000 cases of giardiasis are registered annually, of which children under 14 years account for more than 70%. The study of 124 children with giardiasis conducted by the authors has shown that giardiasis in children always triggers development of chronic duodenitis, in 55% of cases that coupled with lymphostasis, in 45% — that with atrophy of duodenum mucous lining. In 40% of cases, chronic duodenitis with giardiasis is accompanied with duodenogastric reflux, in 88% — with development of lactase deficiency, in 81% — by functional biliary system distress and in all cases with intestinal tract microbiocenosis distress. Along with clinical manifestations of the disease, the researchers have studied immunological modifications in children with giardiasis, and have evaluated the information content of various diagnostic techniques, efficiency of medication. The authors have demonstrated that mono therapy with any of anti giardiasis drugs (metronidazole, nifuratel, albendozole) has low efficiency. Saccharomyces boulardii have a powerful comprehensive effect on many links of giardiasis pathogenesis.</em><br /><strong><em>Key words: giardiasis, infestation, scatoscopy, Saccharomyces boulardii.</em></strong

Эозинофильные поражения желудка и кишечника: клиника, диагностика, лечение

Eosinophilic gastrointestinal disorders (EGID) are a kind of pathology which has not been well studied and has a trend to an increase during the last years that raises concern. They may have highly variable clinical manifestations; therefore, their differential diagnosis is not infrequently challenging. The article presents a review of scientific data on EGID and three clinical cases of various eosinophilic lesions of the stomach and gut in children. Clinical manifestations of EGID depend on their location and on the depth of the lesions. The first clinical case presented with repeated gastrointestinal bleedings in a child with hemorrhagic eosinophilic gastritis. The second clinical case was eosinophilic colitis with Crohnlike clinical and endoscopic manifestations, and the third one was eosinophilic ileocolitis with ascites. All these children had a background of sensitization to various food allergens. However, there were no high specific IgE in blood in any of the cases, although IgE were identified in the biopsy sample of intestinal mucosa and in duodenal aspirates. The results of the mast cell degranulation test with corresponding allergens correlated with the efficacy of their elimination. Elimination diet was recommended to all the patients; in two patients it was combined with a short course of glucocorticosteroids and in one case with subsequent montelucast treatment. All three patients achieved complete recovery, confirmed by their follow-up and repeated endoscopic and histological examinations.Эозинофильные заболевания желудочно-кишечного тракта (ЖКТ) – недостаточно  изученная патология, тенденция к росту которой, наблюдающаяся  в  последние  годы, вызывает тревогу. Они могут иметь весьма вариабельные клинические  проявления, поэтому  дифференциальный диагноз нередко  представляет  большие сложности. В статье дан обзор научных данных по проблеме эозинофильных заболеваний ЖКТ и приведены  3 клинических примера различных эозинофильных поражений желудка и кишечника у детей. Клиническая манифестация эозинофильных  заболеваний  ЖКТ зависит от локализации  и глубины поражения.  В  первом клиническом  примере  описан  случай повторных желудочных кровотечений у ребенка с геморрагическим эозинофильным  гастритом, во втором – эозинофильного колита с клинической и эндоскопической  картиной, напоминающей болезнь Крона, и в третьем – случай асцита на фоне  эозинофильного илеоколита. Все наблюдаемые нами дети имели в основе  заболевания сенсибилизацию  к различным  пищевым аллергенам, но ни в одном случае в крови  не было повышения специфических IgE, однако IgE обнаружены  в  биоптате  слизистой  оболочки кишечника, в дуоденальном  аспирате. Тест дегрануляции тучных клеток с соответствующими аллергенами  коррелировал с эффективностью их элиминации.  Элиминационная  диета  была назначена всем больным, в двух случаях – в сочетании  с коротким  курсом глюкокортикостероидов, в  одном  – продолжена   назначением монтелукаста. У всех трех пациентов достигнуто полное  выздоровление, которое  подтверждено динамическим  наблюдением, повторным эндоскопическим  и гистологическим  исследованием

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛЯМБЛИОЗА У ДЕТЕЙ

According to the WHO, giardiasis incidence rate in children in the world is 15 to 20%. In Russia, over 130,000 cases of giardiasis are registered annually, of which children under 14 years account for more than 70%. The study of 124 children with giardiasis conducted by the authors has shown that giardiasis in children always triggers development of chronic duodenitis, in 55% of cases that coupled with lymphostasis, in 45% — that with atrophy of duodenum mucous lining. In 40% of cases, chronic duodenitis with giardiasis is accompanied with duodenogastric reflux, in 88% — with development of lactase deficiency, in 81% — by functional biliary system distress and in all cases with intestinal tract microbiocenosis distress. Along with clinical manifestations of the disease, the researchers have studied immunological modifications in children with giardiasis, and have evaluated the information content of various diagnostic techniques, efficiency of medication. The authors have demonstrated that mono therapy with any of anti giardiasis drugs (metronidazole, nifuratel, albendozole) has low efficiency. Saccharomyces boulardii have a powerful comprehensive effect on many links of giardiasis pathogenesis.Key words: giardiasis, infestation, scatoscopy, Saccharomyces boulardii.Инвазированность лямблиями среди детей в мире составляет, по данным ВОЗ, 15–20%. В России ежегодно регистрируется более 130 тыс. случаев лямблиоза, из которых более 70% составляют дети в возрасте до 14 лет. Проведенное авторами осбледование 124 детей с лямблиозом показало, что лямблиоз у детей всегда вызывает формирование хронического дуоденита, в 55% случаев с лимфостазом, в 45% — с атрофией слизистой оболочки двенадцатиперстной кишки. Хронический дуоденит при лямблиозе в 40% сопровождается дуоденогастральным рефлюксом, в 88% – развитием лактазной недостаточности, в 81% – функциональными расстройствами билиарной системы и во всех случаях – нарушением микробиоценоза кишечника. Наряду с клиническими проявлениями болезни ученые изучили иммунологические изменения у детей с лямблиозом, а также оценили информативность различных методик диагностики, эффективность медикаментозного лечения. Авторы продемонстрировали, что монотерапия любым из противо-лямблиозных препаратов (метронидазол, нифуратель, альбендазол) имеет низкую эффективность. Мощным комплексным действием на многие звенья патогенеза лямблиоза обладают Saccharomyces boulardii. Ключевые слова: лямблиоз, инвазия, копроскопия, Saccharomyces boulardii. (Педиатрическая фармакология. – 2009;6(4):40-46)

Investigation of neutron emissions from D(d,n)3^{3}He and T(d,n)4^{4} He reactions in a 10 TW picosecond laser facility SOKOL-P

Experimental results on fast neutron generation in D(d,n)$^{3}$He and T(d,n)$^{4}$He reactions in the SOKOL-P laser facility [1] are presented. Solid targets were irradiated by 1.054 ${\rm \mu}$m, s- or p-polarized laser pulses of energy 5-8 J on target and duration 0.85-2 ps. The peak laser intensity was 0.5-2$\cdot$10$^{18}$ W/cm$^{2}$. Flat deuterated plastic (CD$_{2})_{\rm n}$ targets and Ti D$_{\rm \alpha }$T$_{\rm \beta}$ targets were used in experiments. Some experiments were carried out with additional targets placed in front of and behind the laser target. The used (TOF) time-of-flight technique helped identify neutrons from D(d,n)$^{3}$He and T(d,n)$^{4}$He reactions. Yields up to 10$^{6 }$ DD-neutrons and 10$^{7}$ DT-neutrons were measured. Interaction of the fast ion beam with the target can explain the observed yield

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)