CAIDE Dementia Risk Score, Alzheimer and cerebrovascular pathology : a population-based autopsy study

Background. CAIDE Dementia Risk Score is a tool for estimating dementia risk in the general population. Its longitudinal associations with Alzheimer or vascular neuropathology in the oldest old are not known. Aim. To explore the relationship between CAIDE Dementia Risk Score at baseline and neuritic plaques, neurofibrillary tangles, cerebral infarcts and cerebral amyloid angiopathy (CAA) after up to 10-year follow-up in the Vantaa 85+ population. Methods. Study population included 149 participants aged 85 years, without dementia at baseline, and with available clinical and autopsy data. Methenamine silver staining was used for beta-amyloid and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brain-stem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, CAA and alpha-synuclein pathologies. The CAIDE Dementia Risk Score was calculated based on scores for age, sex, BMI, total cholesterol, systolic blood pressure, physical activity and APOE epsilon 4 carrier status (range 0-18 points). Results. A CAIDE Dementia Risk Score above 11 points was associated with more cerebral infarctions up to 10 years later: OR (95% CI) was 2.10 (1.06-4.16). No associations were found with other neuropathologies. Conclusion. In a population of elderly aged 85 years, higher CAIDE Dementia Risk Score was associated with increased risk of cerebral infarcts.Peer reviewe

Effects of Easy-to-Use Protein-Rich Energy Bar on Energy Balance, Physical Activity and Performance during 8 Days of Sustained Physical Exertion

WOS:000312384500021Peer reviewe

Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers

BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay between immune cell invasion and mutation profile in both lesions of an individual. RESULTS: The tumour pairs shared only few mutations, favouring different mutations in known CRC genes and signalling pathways and displayed variation in their signature content. Two tumour pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden. CONCLUSIONS: The study shows major diversity within SCRCs. Rather than rely on data from one tumour, our study highlights the need to evaluate both tumours of a synchronous pair for optimised targeted therapy.Peer reviewe

Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.Peer reviewe

The Glanville fritillary genome retains ancient karyotype and reveals selective chromosomal fusions in Lepidoptera

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Exome-wide somatic mutation characterization of small bowel adenocarcinoma

Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.Peer reviewe

Effects of military basic training on VO2max, body composition, muscle strength and neural responses in conscripts of different aerobic condition

Study aim: The purpose of this study was to evaluate neuromuscular adaptations in conscripts with different fitness levels (VO2max) during 8 weeks of military basic training (BT)

Effects of military basic training on VO2max, body composition, muscle strength and neural responses in conscripts of different aerobic condition

Study aim: The purpose of this study was to evaluate neuromuscular adaptations in conscripts with different fitness levels (VO2max) during 8 weeks of military basic training (BT). Material and methods: Twenty-four male conscripts (18–21 years) were divided into two groups (Good Fitness [GF] and Low fitness [LF]) based on their VO2max at the beginning of BT. Body mass (BM), fat free mass (FFM) and Fat% were measured after 2, 4, and 7 weeks of training. VO2max, maximal isometric leg press force (MVC), H-reflex (Hmax/Mmax) at rest and V-wave (V/Mmax) during maximal isometric plantarflexion were measured from the soleus muscle at the beginning, after 5, and after 8 weeks of training. Results: FFM decreased significantly in LF after 7 weeks of training (–3.0 ± 1.7%, p < 0.001), which was not observed in GF. Both GF (6.9 ± 4.6%, p < 0.01) and LF (5.7 ± 4.6%, p < 0.01) showed improved VO2max after 5 weeks, with no changes during the last 3 weeks. A main effect of training was observed in decreased leg press MVC (–7.3 ± 9.3%, F = 4.899, p < 0.05), with no between-group differences. V-wave was significantly lower in LF during 5 (–37.9%, p < 0.05) and 8 (–44.9%, p < 0.05) weeks. Conclusion: Poor development of the neuromuscular system during BT suggests that explosive and/or maximal strength training should be added to the BT protocol for all conscripts regardless of fitness level. In addition, individualized training periodization should be considered to optimize the training load.peerReviewe

Alkali activation-granulation of hazardous fluidized bed combustion fly ashes

Abstract The increasing amount of fluidized bed combustion (FBC) ash is putting pressure on researchers to invent novel methods for utilizing the ash. The low reactivity and heavy metal content constrict the use of FBC ash in the same way as coal ash from pulverized combustion. Four FBC fly ashes from different power plants were granulated with sodium silicate solution in order to produce artificial aggregates. All aggregates matched the definition for lightweight aggregate according to the EN 13055–1 standard. The strongest aggregates were produced from fly ashes that had the highest X-ray amorphous material content and the highest amount of selectively soluble SiO₂ and Al₂O₃. However, the same leaching problem (leaching of the anionic species) as with coal fly ashes was observed with the FBC fly ashes. The simultaneous high shear granulation and alkali activation of FBC ashes showed that artificial aggregates with satisfactory physical properties, such as density and strength, can be obtained even from low-reactive fly ashes that contain heavy metals