Antibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults

Autoantibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults. Forty-seven adults with urinary tract infection (UTI), 9 with recent acute pyelonephritis and 38 with previous renal infection, were investigated for the presence of autoantibodies to Tamm-Horsfall protein (THP). All patients except 6 had or had had vesicoureteric reflux (VUR). In patients with recent acute pyelonephritis, only IgA antibodies were significantly elevated. Among the patients with previous UTI, more than 6 months before the time of testing, a graded response was found for IgG and IgM specific antibodies, with the lowest value in those with renal damage and elevated serum creatinine and the highest in those with a normal X-ray. A negative correlation was found between IgG antibodies to THP and elevated serum creatinine (r = -0.76, P < 0.02). No significant correlation was found between VUR itself and antibodies to THP. A low IgG antibody level to THP in patients with a history of previous UTI seems to be a useful indicator of renal scarring. Possible immunologic mechanisms behind the low antibody level and the renal damage are discussed.Auto-anticorps anti-protéine de Tamm-Horsfall associés à des lésions rénales et à des infections urinaires chez l'adulte Quarante-sept adultes atteints d'infection urinaire, 9 ayant une pyélonéphrite aiguë récente et 38 une infection rénale antérieure ont été étudiés pour la présence d'auto-anticorps anti-protéine de Tamm-Horsfall (THP). Tous les malades sauf six avaient ou avaient eu un reflux vésico-urétéral. Chez les malades ayant un antécédent récent de pyélonéphrite seul les anti-corps IgA étaient significativement élevés. Parmi les malades dont l'antécédent d'infection urinaire remontait à plus de six mois une réponse a été obtenue pour les anti-corps spécifiques IgG et IgM, avec la valeur la plus faible chez ceux qui étaient atteints de lésions rénales et avaient une créatininémie élevée et la valeur la plus élevée chez ceux qui étaient indemnes de lésions radiologiques. Une corrélation négative a été observée entre les anti-corps IgG anti THP et l'augmentation de la créatininémie (r = -0,76, P < 0,02). Il n'a pas été observé de corrélation significative entre le reflux par lui-même et les anti-corps anti THP. Un taux faible d'anti-corps IgG anti THP chez des malades ayant des antécédents d'infection urinaire peut être un indicateur utile de lésions rénales. Les mécanismes immunologiques qui peuvent sous tendre le taux faible d'anti-corps et les lésions rénales sont discutés

Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery

Background Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term. Methods Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery &lt;37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses. Results We found 17 human genes to be differentially expressed (false discovery rate, FDR &lt; 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR &lt; 0.05). We found 11 individual bacterial species to be differentially expressed (FDR &lt; 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups. Conclusions In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD

Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia

Peer reviewe

Seniors' experiences of living in special housing accommodation

This article presents a hermeneutic phenomenological analysis of interview material in which 12 seniors living in Special Housing Accommodation (SHA) facilities reflect on the experience of living in such facilities. Of particular interest in the analysis is living in a SHA as a phenomenon. The finding shows that the phenomenon of lived experience in a SHA seems to be a state of ambiguity regarding one's existence, which is made up of several constituents (elements of meaning). The analysis contributes to the understanding of how the phenomenon of SHA living is coming into existence as a need, due to an individual's failing health; however, the SHA is not considered to be a true home. Accordingly, this has consequences to the subject position for the seniors in that they have to navigate between existing and not existing. The seniors learn to cope with living in the SHA by lowering their expectations of life and existence while the SHA provides the prerequisites for their existence. An implication for promoting care is to support the seniors to enable a full existence of life within SHA living

Innovaatiomyönteinen sääntely : Nykytila ja hyvät käytännöt

Nopea teknologinen kehitys ja tarve löytää ratkaisuja yhteiskunnallisiin haasteisiin edellyttävät uusia sääntelyn lähestymistapoja. Viime vuosina eri maissa onkin otettu käyttöön erilaisia innovaatiomyönteisen sääntelyn käytäntöjä. Sääntelystä on tullut yhä tärkeämpi innovaatiopolitiikan väline. Aihe on kuitenkin vielä uusi ja jäsentymätön. Tässä selvityksessä on esitetty innovaatiomyönteisen sääntelyn viitekehys sekä kuvattu innovaatiomyönteisen sääntelyn nykytilaa Suomessa. Lisäksi on tunnistettu innovaatiomyönteiseen sääntelyyn liittyviä hyviä käytäntöjä Suomesta ja kansainvälisesti. Yleiskuvan lisäksi aihetta on tarkasteltu kolmen alakohtaisen esimerkin (alustatalous, kiertotalous ja terveystiedon hyödyntäminen) kautta. Selvitys suosittelee innovaatiomyönteisen sääntelyn yleisten periaatteiden ja reunaehtojen tarkempaa määrittelyä, ministeriöiden välisen poikkihallinnollisen yhteistyön vahvistamista, säädösehdotusten arvioinnin ohjeistusten täsmentämistä sekä viranomaisten ja yritysten välisen vuoropuhelua kehittämistä. Lisäksi selvitys peräänkuuluttaa sääntelyn roolin vahvistamista innovaatiopolitiikan välineenä, innovaatiomyönteisten lainsäädännön ratkaisujen (esim. kokeilujen) rohkeampaa hyödyntämistä, sääntelytarpeiden tunnistamisen ja ennakoinnin lisäämistä sekä neuvovan sääntelyn ja täytäntöönpanovaiheen käytäntöjen tehokkaampaa hyödyntämistä.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa (tietokayttoon.fi). Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations

Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.Peer reviewe

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia

Peer reviewe

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Att utveckla läsförståelse. En studie om lärares arbete med läsförståelse i årskurs tre

Syfte: Syftet med föreliggande studie har varit att undersöka hur lärare i grundskolans årskurs tre arbetar med läsförståelse, vad de anser vara mest viktigt för att elever ska utveckla sin läsförståelse, vilka didaktiska redskap de använder sig av och i vilken omfattning de uppmärksammar och följer elevers läsutveckling. Teori: Studiens teoretiska utgångspunkt är det sociokulturella perspektivets syn på människans språk-, tanke- och kunskapsutveckling, där lärande sker genom deltagande i en gemenskap och där det grundläggande i lärprocesserna är språket och kommunikationen i interaktion med andra människor. Metod: Som metod har studien en kvalitativ ansats. Det empiriska materialet utgörs av kvalitativa samtalsintervjuer med åtta lärare som genomfördes under vårterminen 2008. Resultat: Studiens resultat tyder på att samtliga lärare ansåg att det är viktigt att arbeta med att utveckla elevers läsning för att automatisera avkodningsförmågan och få läsflyt. Det visade sig däremot inte finnas något gemensamt synsätt på arbetet med läsförståelse. Lärarna använde sig inte av sig själva som modell för att hjälpa eleverna att utveckla en strategisk läskompetens, för att kunna bedöma sin egen förståelse och göra inferenser. Lärarna hade olika uppfattning om, när arbetet med läsförståelse skulle påbörjas och på vilket sätt elevgruppen kunde vara en tillgång för att skapa läsargemenskaper. Lärarna arbetade med olika former av textsamtal men överlät dock i stor utsträckning till eleverna att arbeta vidare på egen hand med hjälp av läromedel. Resultatet tyder på att långt ifrån alla lärare upplevde sig ha den kompetens som krävs för att bedöma vad som gör att en text är läsbar och har god kvalitet. I arbetet med att kartlägga och bedöma var eleverna befann sig i sin läsutveckling lade flera av lärarna stor vikt vid den egna professionella bedömningen och använde sig av olika kartläggningsmaterial. Resultatet tyder på att på de skolor de intervjuade lärarna var verksamma fanns ingen tydlig organisation på skolnivå för att systematiskt följa, analysera, utvärdera och dokumentera elevers läsutveckling