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We investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36–0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32–0.74), and (HR 0.51, 95% Cl 0.35–0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D. [ABSTRACT FROM AUTHOR]

Next-generation sequencing-based microbiological analysis is a complex way to profile vaginal microbiome samples since each step affects the results gained. Methodologies for sample collection lack golden standards. We compared Puritan DNA/RNA swab (PS) and Copan FLOQ swab (CS) and provided consistent and reliable microbiome profiles analyzed by 16S rRNA gene sequencing. We collected two consecutive vaginal samples utilizing PS with room temperature storing and CS with instant freezing from 26 women. Variable region 4 of bacterial 16S rRNA gene was amplified with single PCR by custom-designed dual-indexed primers and sequenced with Illumina MiSeq system. Read quality control, operational taxonomic unit tables, and alpha and beta diversities analysis were performed, and community richness, diversity, and evenness were evaluated and compared between the two samplings and tests. Nineteen sample pairs produced detectable, intact DNA during the extraction protocol and/or further microbial profiles. Alpha bacterial diversity indices were independent on the collection protocol. No significant statistical differences were found in the measured beta diversity metrics between the collection methods. Of the women, 43% had Lactobacillus-dominated vaginal microbiome profile despite of collection method. Previously reported important vaginal microbiome phyla Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria were present in the sample set although their relative abundances varied among individuals. PS and CS enable constant vaginal microbiota sampling. The PS method with no need for instant freezing is suitable for on-site collections at clinics. Furthermore, it seems to be possible to take two samples instead of one with constant microbiological results. [ABSTRACT FROM AUTHOR]

Background: Uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer (HLRCC) patients are driven by fumarate hydratase (FH) inactivation or occasionally by mediator complex subunit 12 (MED12) mutations. The aim of this study was to analyse whether MED12 mutations and FH inactivation are mutually exclusive and to determine the contribution of MED12 mutations on HLRCC patients' myomagenesis.Methods: MED12 exons 1 and 2 mutation screening and 2SC immunohistochemistry indicative for FH deficiency was performed on a comprehensive series of HLRCC patients' (122 specimens) and sporadic (66 specimens) tumours. Gene expression analysis was performed using Affymetrix GeneChip Human Exon Arrays (Affymetrix, Santa Clara, CA, USA).Results: Nine tumours from HLRCC patients harboured a somatic MED12 mutation and were negative for 2SC immunohistochemistry. All remaining successfully analysed lesions (107/116) were deficient for FH. Of sporadic tumours, 35/64 were MED12 mutation positive and none displayed a FH defect. In global gene expression analysis FH-deficient tumours clustered together, whereas HLRCC patients' MED12 mutation-positive tumours clustered together with sporadic MED12 mutation-positive tumours.Conclusions: Somatic MED12 mutations and biallelic FH inactivation are mutually exclusive in both HLRCC syndrome-associated and sporadic uterine leiomyomas. The great majority of HLRCC patients' uterine leiomyomas are caused by FH inactivation, but incidental tumours driven by somatic MED12 mutations also occur. These MED12 mutation-positive tumours display similar expressional profiles with their sporadic counterparts and are clearly separate from FH-deficient tumours. [ABSTRACT FROM AUTHOR]

Acute downhill running has been shown to activate matrix metalloproteinase- (MMP-) 2 and to change type IV collagen concentration in some muscle types. In order to study the influence of more intense exercise on total collagen and type IV collagen concentrations, molecules regulating their synthesis and degradation were investigated after forced lengthening contractions in rat skeletal muscle. Tibialis anterior (TA) muscle of 24 male Wistar rats was subjected to 240 forced lengthening contractions. TA muscle was excised at consecutive time points (0 and 6 h, 2, 4, and 7 days) after stimulation. With immunohistochemistry, types I, III and IV collagen were located in the swollen, necrotic and regenerated fibres in a similar manner as in intact undamaged skeletal muscle fibre. An increase in the activity of prolyl 4-hydroxylase was indicative of an overall elevated collagen biosynthesis. No change was demonstrated in total collagen concentration, whereas type IV collagen concentration increased after exercise. MMP-2 and MMP-9, which are the proteins that degrade type IV collagen, elevated after exercise. In conclusion, the increase in type IV collagen concentration seems to be the result of an increase in both the synthesis and activation of degrading enzymes and their inhibitors during recovery after forced lengthening contractions. [ABSTRACT FROM AUTHOR]