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Mollerup Daniels opublikował 1 rok, 8 miesięcy temu
Biological age is an important risk factor for chronic diseases. We examined the associations between five markers of unhealthy ageing; Growth Differentiation Factor-15 (GDF-15), N-terminal pro-brain natriuretic peptide (NT-proBNP), glycated hemoglobin A1c (HbA1C), C-Reactive Protein (CRP) and cystatin-C; with risks of cancer and cardiovascular disease (CVD). We used a case-cohort design embedded in the EPIC-Heidelberg cohort, including a subcohort of 3792 participants along with 4867 incident cases of cancer and CVD. Hazard ratios (HRs) were computed and the strongest associations were used to build weighted multi-marker combinations, and their associations with cancer and CVD risks were tested. After adjusting for common confounders, we observed direct associations of GDF-15 with lung cancer risk, NT-proBNP with breast, prostate and colorectal cancers, HbA1C with lung, colorectal, and breast cancer risks, and CRP with lung and colorectal cancer risks. An inverse association was observed for GDF-15 and prostate cancer risk. We also found direct associations of all 5 markers with myocardial infarction (MI) risk, and of GDF-15, NT-proBNP, CRP and cystatin-C with stroke risk. A combination of the independently-associated markers showed a moderately strong association with the risks of cancer and CVD (HRQ4-Q1 ranged from 1.78[1.36, 2.34] for breast cancer, when combining NT-proBNP and HbA1C, to 2.87[2.15, 3.83] for MI when combining NT-proBNP, HbA1C, CRP and cystatin-C). This analysis suggests that combinations of biomarkers related to unhealthy ageing show strong associations with cancer risk, and corroborates published evidence on CVD risk. If confirmed in other studies, using these biomarkers could be useful for the identification of individuals at higher risk of age-related diseases.
Our aim was to introduce damaged red blood cells (RBCs) as a tool for haemodynamic provocation in rats, hypothesised to cause decreased cerebral blood flow (CBF) and prolonged water capillary transfer time (CTT), and to investigate whether expected changes in CBF could be observed and if haemodynamic alterations were reflected by the CTT metric.
Damaged RBCs exhibiting a mildly reduced deformability were injected to cause aggregation of RBCs. Arterial spin labelling (ASL) magnetic resonance imaging experiments were performed at 9.4 T. Six datasets (baseline plus five datasets after injection) were acquired for each animal in a study group and a control group (13 and 10 female adult Wistar rats, respectively). For each dataset, ASL images at ten different inversion times were acquired. The CTT model was adapted to the use of a measured arterial input function, implying the use of a realistic labelling profile. Repeated measures ANOVA was used (alpha error = 0.05).
After injection, significant differences between the study group and control group were observed for relative CBF in white matter (up to 20 percentage points) and putamen (up to 18-20 percentage points) and for relative CTT in putamen (up to 35-40 percentage points).
Haemodynamic changes caused by injection of damaged RBCs were observed by ASL-based CBF and CTT measurements. Damaged RBCs can be used as a tool for test and validation of perfusion imaging modalities. CTT model fitting was challenging to stabilise at experimental signal-to-noise ratio levels, and the number of free parameters was minimised.
Haemodynamic changes caused by injection of damaged RBCs were observed by ASL-based CBF and CTT measurements. Damaged RBCs can be used as a tool for test and validation of perfusion imaging modalities. CTT model fitting was challenging to stabilise at experimental signal-to-noise ratio levels, and the number of free parameters was minimised.Increasing cancer drug chemo-resistance, especially in the treatment of breast and lung cancers, alarms the immediate need of newer and effective anticancer drugs. Until now, chemotherapeutics based on metal complexes are considered the most effective treatment modality. In the present study, we have evaluated the cytotoxic effect of two cobalt (III) Schiff base complexes based on the leads from complex combinatorial chemistry. Cobalt (III) Schiff base complexes (Complex 3 = Co(Ph-acacen)(HA)2](ClO4) and Complex 4 = [Co(Ph-acacen)(DA)2](ClO4)] (Ph-acacen, 1-phenylbutane-1,3-dione; DA, dodecyl amine; HA, heptylamine) were evaluated against human breast cancer cell MCF-7 and lung cancer cell A549 using MTT cell viability assay, cellular morphological changes studied by Acridine Orange and Ethidium Bromide (AO/EB), Dual fluorescent staining, Hoechst staining 33248, Comet assay, Annexin V-Cy3 and 6 CFDA assay, JC-1 staining, Reactive oxygen species (ROS) assay, Immunofluorescence assay, and Real-time reverse transcription-polymerase chain reaction (RT-qPCR). Treatment of cobalt (III) Schiff base complexes (Complex 3 & 4) affected the viability of the cancer cells. The cell death induced by the complexes was predominantly apoptosis, but necrosis also occurred to a certain extent. Complex 4 produced better cytotoxic effect than complex 3, and MCF-7 cell was more responsive than A549. In that order, the complexes were more selective to cancer cell than normal cell, and more effective in overall performance than the standard drug cisplatin. Therefore, we conclude that cobalt (III) Schiff base complexes, especially complex 4, have the potential to be developed as effective drugs for treatment of cancers in general, and breast and lung cancers in particular.
To detect the optimal timing of intervention based on different cervical vertebral maturation stage (CS1-2 vs. CS3-4) for the treatment of Class III malocclusion with early Class III protocol.
A total sample of 43 patients (23 females, 20 males) ranging between 7 and 13years of age with dentoskeletal Class III malocclusion treated with the modified SEC III (Splints, Elastic and Chincup) protocol divided into two groups based on the cervical vertebral maturation stages (CS1-2 and CS3-4) was included in this retrospective observational longitudinal study. Patient compliance was assessed using a 2-point Likert scale. Statistical comparisons between the two groups were performed with independent sample t tests.
No statistically significant differences for any of the cephalometric variables describing the baseline dentoskeletal features were found between the two groups except for the mandibular unit length that was significantly greater in the pubertal group (P = 0.005). The modified SEC III protocol produced favorable sagittal outcomes in both groups, whereas no statistically significant T1-T2 changes were found between the CS1-2 and CS3-4 groups for any of the angular and linear measurements. No significant differences were found in the prevalence rates of the degree of collaboration between the two groups (P = 1.000).
No significant differences between prepubertal and pubertal patients were found in the sagittal and vertical dentoskeletal changes with the modified SEC III protocol. Thus, this early Class III treatment produced similar favorable effects in growing subjects regardless of the cervical vertebral maturation stages from CS1 to CS4.
No significant differences between prepubertal and pubertal patients were found in the sagittal and vertical dentoskeletal changes with the modified SEC III protocol. Thus, this early Class III treatment produced similar favorable effects in growing subjects regardless of the cervical vertebral maturation stages from CS1 to CS4.
The aim of this study was to compare patients’ mid-term functional and quality of life (QoL) outcomes following robotic ventral mesh rectopexy (RVMR) and laparoscopic ventral mesh rectopexy (LVMR).
The data of consecutive female patients who underwent minimally invasive ventral mesh rectopexy for external or symptomatic internal rectal prolapse at 3 hospitals in Finland between January 2011 and December 2016 were retrospectively collected. Patients were matched by age and diagnosis at a 11 ratio. A disease-related symptom questionnaire was sent to all living patients at follow-up in July 2018.
After a total of 401 patients (RVMR, n = 187; LVMR, n = 214) were matched, 152 patients in each group were included in the final analyses. The median follow-up times were 3.3 (range 1.6-7.4) years and 3.0 (range 1.6-7.6) years for the RVMR and LVMR groups, respectively. The postoperative QoL measures did not differ between the groups. Compared with the LVMR group, the RVMR group had lower postoperative Wexner Incontinence Score (median 5 vs. median 8; p < 0.001), experienced significant ongoing incontinence symptoms less often (30.6% vs. 49.0%; p < 0.001) and reported less postoperative faecal incontinence discomfort evaluated with the visual analogue scale (median 11 vs. median 39; p = 0.005). RVMR patients had a shorter hospital stay (2.2days vs. 3.8days; p < 0.001) but experienced more frequent de novo pelvic pain (31.8% vs. 11.8%; p < 0.001).
RVMR and LVMR patients had equal functional and QoL outcomes. Those who underwent RVMR had lower mid-term anal incontinence symptom scores but suffered more frequent de novo pelvic pain.
RVMR and LVMR patients had equal functional and QoL outcomes. Those who underwent RVMR had lower mid-term anal incontinence symptom scores but suffered more frequent de novo pelvic pain.When normalized to volume, adipose tissue is comprised mainly of large lipid metabolizing and storing cells called adipocytes. Strikingly, the numerical representation of non-adipocytes, composed of a wide variety of cell types found in the so-called stromal vascular fraction (SVF), outnumber adipocytes by far. Besides its function in energy storage, adipose tissue has emerged as a versatile organ that regulates systemic metabolism and has therefore constituted an attractive target for the treatment of metabolic diseases. Recent high-resolution single cells/nucleus RNA seq data exemplify an intriguingly profound diversity of both adipocytes and SVF cells in all adipose depots, and the current data, while limited, demonstrate the significance of the intra-tissue cell composition in shaping the overall functionality of this tissue. Due to the complexity of adipose tissue, our understanding of the biological relevance of this heterogeneity and plasticity is fractional. Therefore, establishing atlases of adipose tissue cell heterogeneity is the first step towards generating an understanding of these functionalities. In this review, we will describe the current knowledge on adipose tissue cell composition and the heterogeneity of single-cell RNA sequencing, including the technical limitations.Survivors of domestic violence (DV) and of violence perpetrated by organized gangs (GV) face barriers to legal protection under U.S. asylum law. We abstracted data from 132 affidavits based on forensic medical evaluations of asylum seekers granted legal protection in the U.S. on the basis of DV and/or GV. We described claimants’ trauma exposures and resilience factors and used multiple logistic regression to quantify associations with Diagnostic and Statistical Manual-5 (DSM-5) diagnoses and improvement in mental health. People seeking asylum based on DV and/or GV have endured multiple types of trauma with significant impacts on their mental health. New experiences of trauma following migration to the U.S. were common and associated with DSM-5 diagnoses. Conversely, resilience factors were associated with improved mental health. Policies that aim to reduce ongoing trauma in the U.S. and to bolster resilience factors may promote asylee mental health and well-being.


