Leishmania infantum infection after visiting southern Spain in patients on biological treatment; an observational, longitudinal, cohort study

Background: Reports of leishmaniasis in immunosuppressed patients after visiting the Mediterranean Basin are becoming increasingly common. Still, awareness of the risk of infection and its clinical manifestations may be insufficient among healthcare professionals in the travellers' home countries. Methods: This observational, longitudinal study included 47 patients from Sweden with rheumatic disease and ongoing immunomodulatory treatment, who visited a rehabilitation centre in southern Spain where leishmaniasis is endemic. Patients were evaluated for clinical signs of leishmaniasis at baseline and after three years. Patients with leishmaniasis were followed for 4-5 years. The treatment outcome was assessed by clinical evaluation and determination of the cell-mediated immunological response to Leishmania by a whole blood cytokine release assay. Results: Seven patients (15%) were diagnosed with leishmaniasis. The median time from exposure to the onset of symptoms was 3 [1-17] months. The median delay between the onset of symptoms and treatment start was 9 [1-12] months. All patients with leishmaniasis responded well to treatment. Only one patient had a relapse, which occurred within the first year. Conclusion: Healthcare professionals need to be aware of the increased risk of leishmaniasis for travellers who are immunosuppressed. Knowledge of the symptoms is crucial for a timely diagnosis and early treatment.S

Коллективистско-индивидуалистические компоненты в учебно-познавательной деятельности белорусских студентов

(В статье исследуются коллективистско-индивидуалистические компоненты в учеоно-познавательной деятельности белорусских, студентов. Подчеркивается необходимость определения роли личности, личностные ценностей и роли коллектива в высшей школе. Отмечены тенденции ослабления идеи коллективизма и усиления личностно-индивидуалькых ценностей. Выявлены особенности ментальных характеристик современных белорусов, выраженные в «неиндивидуальном трудолюбии». Определена значимость коллективистско-индивидуалистических ценностей через соотношение одной из важейших ментальных характеристик "стремление к личной свободе, независимости", что позволило дать оптимальную оценку индивидуализма и коллективизма

Genomic basis for RNA alterations in cancer.

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer

Predictors for prolonged hospital stay solely to complete intravenous antifungal treatment in patients with candidemia: Results from the ECMM candida III multinational European observational cohort study

Background To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). Methods Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. Findings Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 – 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 – 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 – 0.45; p < 0.03). Interpretation Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis

Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study

© 2022 Elsevier Ltd. All rights reserved.[Background] The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes.[Methods] In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines.[Findings] 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04–1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05–1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4–30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals.[Interpretation] Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay.Scynexis.Peer reviewe

High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Vems röst går först? En kvalitativ litteraturstudie om hur barnperspektivet i BBIC tillämpas i praktiken vid barnavårdsutredningar hos socialtjänsten.

Syftet med denna undersökning har varit att se hur barnperspektivet inom BBIC tillämpas i praktiken vid socialtjänstens arbete med barnavårdsutredningar. För att besvara vårt syfte har vi använt oss av följande underfrågor; hur kommer barnperspektivet och barnens behov till uttryck i våra valda publikationer, samt vilken hänsyn tas till barnets ålder och mognad utifrån deras möjlighet till deltagande? Vi har gjort en kvalitativ litteraturstudie där vi analyserat ett urval av tidigare forskning vilka tar upp frågor som ligger i linje med vårt syfte och som publicerats mellan åren 2001­2014. I vårt analysarbete har en tematisk innehållsanalys gjorts av publikationerna utifrån en socialkonstruktionistisk ansats, med de teoretiska utgångspunkterna utvecklingsekologisk teori samt objekt­ respektive aktörsperspektiv. Våra slutsatser är att det finns ett flertal faktorer som är viktiga för hur barnperspektivet inom BBIC framkommer i barnutredningar, och hur barnen därmed ges möjlighet till delaktighet. Barnets ålder, dess vilja att delta och hur vuxna tolkar denna vilja är några sådana faktorer. Även relationen mellan barnet och socialsekreteraren samt samarbetet mellan barnets föräldrar och socialtjänsten är av vikt. Vi fann att barn i stor utsträckning vill vara delaktiga men att det många gånger är vuxna som sätter ramarna för deltagandet. Vårt resultat visar att vuxna i många fall företräder barnen, och att de vuxnas röster om barnets behov och dess bästa tillskrivs större betydelse i utredningarna än barnens egen uppfattning om sina behov. Vår analys visar att dokumentationen av barnets röst i utredningarna förefaller vara av högst varierande grad, barnets perspektiv förefaller hamna i skymundan till fördel för de vuxnas barnperspektiv

Kompensatoriska strategier för ordmobiliseringssvårigheter vid Alzheimers sjukdom : En fallstudie med enspråkiga och flerspråkiga personer

Sweden is getting an aging population and with this comes an increase in neurodegenerative diseases such as Alzheimer’s disease (AD). Bilingualism is also on the rise and this may result in an increase of bilingual people suffering from AD. Due to the linguistic deterioration associated with the illness people with AD, bilingual and monolingual, will be an increasing patient group with speech and language pathologists (SLPs). Word retrieval difficulty is an early symptom of the disease and several strategies to compensate for this have been observed (e.g. fillers, circumlocutions and semantic parafasias). The effectiveness of these strategies has not yet been established. With this background this study attempts to investigate which strategies are used by monolingual and bilingual people with AD to compensate for word retrieval difficulties. A case study was performed on four participants with AD, two of which were monolingual and two were bilingual. Spontaneous speech was collected by means of a semi-structured conversation and a short story was produced with picture support. The results showed that there were individual differences in terms of the compensatory strategies. The results indicated that the strategies’ effectiveness depended on the progression of the disease in each individual. No differences between the bilingual participants’ first and second language were observed with exception to the usage of code switching. The picture support seemed to be of some help for the participants to achieve better fluency of speech since word retrieval difficulties seemed to decrease. The conclusion is that SLPs could make their patients aware of several different strategies to compensate for word retrieval difficulties to discover what is the most effective for each individual; furthermore pictures can be used to help clients’ narratives.Sverige får en allt äldre befolkning. Detta för med sig ökande antal personer med Alzheimers sjukdom (AD). Då sjukdomen innebär stor språklig påverkan kan denna patientgrupp förväntas öka inom den logopediska vården. Även andelen flerspråkiga i samhället växer, vilket gör att logopeder kommer att ta emot allt fler flerspråkiga äldre patienter. Ordmobiliseringssvårigheter har setts vara ett tidigt symtom vid sjukdomen både hos enspråkiga och flerspråkiga personer. Tidigare forskning har visat att ett flertal kompensatoriska strategier (t.ex. utfyllnader, omskrivningar och utbyten) används för att hantera dessa svårigheter men det är inte klarlagt hur väl dessa strategier fungerar. Därför undersöks i denna studie vilka kompensatoriska strategier som förekommer både hos enspråkiga och flerspråkiga personer med AD. En fallstudie genomfördes på fyra deltagare med AD, varav två enspråkiga och två flerspråkiga. Spontantal samlades in genom ett semistrukturerat samtal och en kortare berättelse genomfördes med hjälp av bildstöd. Resultaten visade att effektiviteten i de använda strategierna skiljer sig mellan individer. Hur långt deltagarna kommit i sjukdomsförloppet verkade dock ha betydelse. Ingen större skillnad mellan de flerspråkiga deltagarnas båda språk observerades förutom gällande användning av kodväxling. Deltagarna verkade i viss mån vara hjälpta av bildstöd för att uppnå bättre talflyt eftersom ordmobiliseringsproblematiken tycktes minska. Slutsatser som drogs är att logopeder kan medvetandegöra patienter och närstående om ett flertal olika strategier för att hitta den strategi som fungerar bäst för den individuella patienten samt att bildstöd kan användas för att underlätta berättande