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05). The first pattern was, however, significantly associated with body fat mass, obesity degree percentage, waist circumference, fat mass index, and waist hip ratio (p  less then  0.05 for all). This is a retrospective study. Ethics approval (IR.TUMS.VCR.REC.1395.1597).BACKGROUND Cold, an environmental factor, induces many reproductive diseases. It is known that endothelin (ET) is a potent vasoconstrictor, and cold stress can increase the expression of ET and its receptors. The cold stress rat model was developed to examine two parameters (1) the effects of cold stress on ovarian and uterine morphology, function, and microvascular circulation and (2) possible mechanisms of ET and its receptors involved in cold stress-induced menstruation disorders. METHODS The rat cold stress model was prepared with an ice water bath. The estrous cycle was observed by methylene blue and hematoxylin and eosin (H&E) staining. Serum estradiol 2 (E2), testosterone (T), progesterone (P) were detected by radioimmunoassay. Hemorheology indices were measured. The real-time blood flow of auricle and uterine surfaces was measured. Expressions of CD34 and α-SMA in ovarian and uterine tissues were detected by immunohistochemistry. ET-1 contents in serum were tested, and expressions of ET-receptor types A and B (ET-AR and ET-BR) in ovarian tissues were detected via Western blotting. RESULTS Cold stress extended the estrous cycle, thereby causing reproductive hormone disorder, imbalance of local endothelin/nitric oxide expression, and microcirculation disturbance. Cold-stress led to up-regulation of ET-AR expression and protein and down-regulation of ET-BR expression in rats. CONCLUSIONS This study suggests that the reason for cold stress-induced dysfunction in reproductive organs may be closely related to the imbalance of ET-1 and its receptor expressions, leading to microvascular circulation disorders in local tissues.BACKGROUND A craniotomy is required to access the brain for tumor resection or epilepsy treatment, and despite precautionary measures, infectious complications occur at a frequency of 1-3%. Approximately half of craniotomy infections are caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap, which is recalcitrant to antibiotics. Our prior work in a mouse model of S. aureus craniotomy infection revealed a critical role for myeloid differentiation factor 88 (MyD88) in bacterial containment and pro-inflammatory mediator production. Since numerous receptors utilize MyD88 as a signaling adaptor, the current study examined the importance of Toll-like receptor 2 (TLR2) and TLR9 based on their ability sense S. aureus ligands, namely lipoproteins and CpG DNA motifs, respectively. We also examined the role of caspase-1 based on its known association with TLR signaling to promote IL-1β release. METHODS A mouse model of craniotomy-associated biofilm infection was used to investigate the role ors coincident with reduced pro-inflammatory mediator release, suggestive of pathway cooperativity. Treatment of caspase-1 KO mice with IL-1β microparticles significantly reduced S. aureus burden in the brain and galea compared to empty microparticles, confirming the critical role of IL-1β in limiting S. aureus outgrowth during craniotomy infection. CONCLUSIONS These results demonstrate the existence of an initial anti-bacterial response that depends on both TLR2 and caspase-1 in controlling S. aureus growth; however, neither pathway is effective at clearing infection in the WT setting, since craniotomy infection persists when both molecules are present.BACKGROUND Volunteers play a significant role in supporting hospice and palliative care in Africa, but little is known about the types of volunteers, their motivations and roles in service delivery. METHODS Palliative care experts from 30 African countries were invited to participate in an online survey, conducted in English and French, that consisted of 58 questions on socio-demographics, the activities, motivation and coordination of volunteers, and an appraisal of recent developments in volunteering. The questionnaire was pre-tested in Uganda. Quantitative data was analysed descriptively with SPSS v22; answers on open-ended questions were analysed using content analysis. RESULTS Twenty-five respondents from 21 countries replied to the questionnaire. The typical volunteer was reported to be a female aged between 30 and 50 years. Volunteer roles included, among others direct patient assistance, providing psychosocial / spiritual support, and assisting patients' families. Respondents considered altruism, civiunteer programmes are funding and the long-term motivation of volunteers.BACKGROUND Testicular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood and the majority of young survivors experience impairing, distressing, and modifiable adverse outcomes that can persist long after medical treatment. These include psychological distress, impairment in pursuit of life goals, persistent physical side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated diurnal stress hormones). However, few targeted interventions exist to assist young survivors in renegotiating life goals and regulating cancer-related emotions, and none focus on reducing the burden of morbidity via biobehavioral mechanisms. This paper describes the methodology of a randomized controlled biobehavioral trial designed to investigate the feasibility and preliminary impact of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET), aimed at improving distress symptoms, emotion regulation, goal navigation skills, and stress-sensitive biomarkers in young adult testicular cancer patients. METHODS Participants will be randomized to receive six sessions of GET or Individual Supportive Therapy (ISP) delivered over 8 weeks. In addition to indicators of intervention feasibility, we will measure primary (depressive and anxiety symptoms) and secondary (emotion regulation and goal navigation skills, career confusion) psychological outcomes prior to (T0), immediately after (T1), and 12 weeks after (T2) intervention. Additionally, identified biomarkers will be measured at baseline and at T2. DISCUSSION GET may have the potential to improve self-regulation across biobehavioral domains, improve overall cancer adjustment, and address the need for targeted supportive care interventions for young adult cancer survivors. TRIAL REGISTRATION Clinicaltrials.gov, NCT04150848. Registered on 28 October 2019.BACKGROUND Alzheimer's disease (AD) is a degenerative brain disease. A novel agent-based modelling framework was developed in NetLogo 3D to provide fundamental insights into the potential mechanisms by which a microbe (eg. Chlamydia pneumoniae) may play a role in late-onset AD. The objective of our initial model is to simulate one possible spatial and temporal pathway of bacterial propagation via the olfactory system, which may then lead to AD symptoms. The model maps the bacteria infecting cells from the nasal cavity and the olfactory epithelium, through the olfactory bulb and into the olfactory cortex and hippocampus regions of the brain. RESULTS Based on the set of biological rules, simulated randomized infection by the microbe led to the formation of beta-amyloid (Aβ) plaque and neurofibrillary (NF) tangles as well as caused immune responses. Our initial simulations demonstrated that breathing in C. pneumoniae can result in infection propagation and significant buildup of Aβ plaque and NF tangles in the olfactory cortex and hippocampus. Our model also indicated how mucosal and neural immunity can play a significant role in the pathway considered. Lower immunities, correlated with elderly individuals, had quicker and more Aβ plaque and NF tangle formation counts. In contrast, higher immunities, correlated with younger individuals, demonstrated little to no such formation. CONCLUSION The modelling framework provides an organized visual representation of how AD progression may occur via the olfactory system to better understand disease pathogenesis. The model confirms current conclusions in available research but can be easily adjusted to match future evidence and be used by researchers for their own individual purposes. The goal of our initial model is to ultimately guide further hypothesis refinement and experimental testing to better understand the dynamic system interactions present in the etiology and pathogenesis of AD.The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia.BACKGROUND Obesity has become global epidemic in the last three decades, whereas Coronary Heart Disease (CHD) still remains the most important cause of mortality in the world. The study was aimed at determining the pattern of lipid profile for the obese and CHD population in Pakistan. As obesity is a strong predisposing risk factor for CHD, we aimed to analyze the lipid parameters in both conditions and compare them with the healthy controls of the same ethnicity. METHODS Blood samples were collected from one thousand individuals (500 with CHD, 250 with obesity, 250 healthy controls). The lipid profile (total Cholesterol, triglycerides, HDL-C, LDL-C and VLDL) was measured using commercially available kits. The pattern of dyslipidemia was then studied by comparing the results in both groups with controls as well as population cutoffs. The quantitative variables were checked for normality and log transformation was done for variables where appropriate. Analysis of variance and logistic regression were done to ct can increase the predisposition to complications.BACKGROUND Primary ovarian mucinous tumors with mural nodules are very rare. The histogenesis of the mural nodules remains unclear. METHODS We investigated the clincopathological and molecular features in 3 cases with mural nodules. RESULTS Patient 1 was diagnosed as mucinous carcinoma with mural nodules of anaplastic carcinoma that was composed of CK+ and CK7+ spindled cells and polygonal cells with marked pleomorphism. Aberrant p53 staining was found in the mural nodules rather than in the mucinous components. A concordant KRAS mutation (c.35G > A p.G12A) was identified in both mucinous tumors and mural nodules. She died of disease at 44 months. The mural nodule in patient 2 was interpreted as a sarcoma, no other specified. The uniform short spindle cells were separated by abundant myxoid matrix. They were CD10 + , CCND1-, SMA-, and negative for break-apart BCOR, PHF1, and JAZF1 FISH assay. The adenocarcinomatous component harbored LOH at D18S51 and FGA loci while the sarcomatous component had LOH at D19S433.