Stress hormones have been shown to be important mediators in driving malignant growth and reducing treatment efficacy in breast cancer. Glucocorticoids can induce DNA damage through an inducible ...nitric oxide synthase (iNOS) mediated pathway to increase levels of nitric oxide (NO). Using an immune competent mouse breast cancer model and 66CL4 breast cancer cells we identified a novel role of NOS inhibition to reduce stress-induced breast cancer metastasis. On a mechanistic level we show that the glucocorticoid cortisol induces expression of keys genes associated with angiogenesis, as well as pro-tumourigenic immunomodulation. Transcriptomics analysis confirmed that in the lungs of tumour-bearing mice, stress significantly enriched pathways associated with tumourigenesis, some of which could be regulated with NOS inhibition. These results demonstrate the detrimental involvement of NOS in stress hormone signalling, and the potential future benefits of NOS inhibition in highly stressed patients.
•Cortisol increases production of reactive nitrogen species an induces DNA damage through a nitric oxide synthase mediated mechanism in breast cancer cells.•Psychological stress promotes metastatic spread, and this in reversed by inhibition of NOS in vivo.•Stress induces expression of genes associated with tumourigenesis in the lungs of tumour bearing-mice.•Cortisol promotes the release of pro-tumourigenic monocyte chemoattractants.
Attending the veterinary clinic is an integral part of the physical welfare of every companion dog. However, some dogs experience their veterinary visits negatively, which poses a risk of injury to ...the veterinary staff, their guardian (owner) and themselves. It may also influence the regularity of non-urgent veterinary appointments. To date there have been conflicting reports relating to the proportion of dogs that show fear during their veterinary visits. In this study, we explored the risk factors associated with fear during veterinary examination and in novel situations (including first time at the veterinary clinic) from 26,555 responses in the Canine Behavioral Assessment and Research Questionnaire database. According to their guardians, 41% of companion dogs displayed mild to moderate fearful behaviour when examined by a veterinarian, and 14% exhibited severe or extreme fear. A similar trend was observed with dogs responding fearfully when in unfamiliar situations, including the dog's first time at the veterinary clinic. Chi-squared tests showed every bivariate relationship between fear and the environmental and demographic factors measured was significant (p < 0.05). The most important predictors of fear in a veterinary examination were, in order: the dog's breed group (27.1%), their history of roles or activities (16.7%), where they were sourced (15.2%), their weight (12%), the age of other dogs in the household (9.5%) and dog owner experience (6.3%). However, combined these risk factors only explain a total of 7% of variance of fear observed during veterinary examination. This suggests that fear exhibited during veterinary visits is common in dogs, but that the environment or human-animal interactions are likely to contribute more to prevalence and severity of this problem than the demographic factors measured here. We conclude by highlighting opportunities for future research aimed at facilitating less stressful veterinary visits for dogs and their guardians.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation ...to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with WAZ while Bifidobacterium bifidum and Bifidobacterium breve abundances were negatively associated with age. The lipopolysaccharide biosynthesis pathway was upregulated in stunted (n = 16) and wasted (n = 8) children. Findings from this study indicate that child sex may be a critical modifier of the role of gut microbiota on childhood growth.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction. Most studies lump Black immigrants (BIs) and African Americans (AAs) as “Black/African American” during investigation. Such categorization assumes that the sociocultural determinants ...that influence BIs are the same as for AAs. This study attempts to disentangle the AA and BI subgroups to recognize the differences in cancer-related psychosocial characteristics and health behaviors. Methods. Merged data from the Health Information National Survey (2011–2017) were used. Two groups were created: those who identified as AA and those who identified as AA but were born outside the United States (BI). Between-group differences were assessed with Mann–Whitney U and chi-square tests. Results. Positive communication patterns with health care providers were significantly higher among AAs (M mean = 3.41, SD standard deviation = 0.68) compared with BIs (M = 3.28, SD = 0.71) (p = .004). A greater proportion of BIs indicated that their health was excellent (14.2%), compared with AAs (7.9%). AAs reported higher cancer family history (75.1%) than BIs (46.5%). More AAs had smoked at least 100 cigarettes in their lifetime (41.5%) than BIs (16.7%). BIs consumed significantly more fruits each day (M = 2.77, SD = 1.43) than AAs (M = 2.40, SD = 1.44) (p < .001). BIs also reported more physical activity (M = 2.62, SD = 2.15) than AAs (M = 2.37, SD = 2.18) (p = .030). AA women were more likely to have had a pap smear test (M = 2.07, SD = 1.44) compared with BI women (M = 1.73, SD = 1.21) (p = .002). Discussion. Evidence suggests the need to disentangle the “Black/African American” ethnic grouping. Lumping the BI populations together with the AAs, who have been in the United States for generations, may limit the ability to uncover and consequently address culturally driven disease prevention efforts and promote understanding of the biological, environmental, and psychosocial risk factors within Black heterogeneous populations.
Recent evidence suggests that a lower extent of the retronasal aroma release correspond to a higher amount of ad libitum food intake. This has been regarded as one of the bases of behavioral choices ...towards food consumption in obese people. In this pilot study we investigated the hypothesis that saliva from obese individuals could be responsible for an alteration of the retro-nasal aroma release. We tested this hypothesis in vitro, by comparing the release of volatiles from a liquid food matrix (wine) after its interaction with saliva from 28 obese (O) and 28 normal-weight (N) individuals.
Amplicon sequencing of the 16S rRNA V4 region indicated that Firmicutes and Actinobacteria were more abundant in O, while Proteobacteria and Fusobacteria dominated in N. Streptococcaceae were significantly more abundant in the O subjects and constituted 34% and 19% on average of the saliva microbiota of O and N subjects, respectively. The Total Antioxidant Capacity was higher in O vs N saliva samples. A model mouth system was used to test whether the in-mouth wine aroma release differs after the interaction with O or N saliva. In O samples, a 18% to 60% significant decrease in the mean concentration of wine volatiles was detected as a result of interaction with saliva, compared with N. This suppression was linked to biochemical differences in O and N saliva composition, which include protein content.
Microbiological and biochemical differences were found in O vs N saliva samples. An impaired retronasal aroma release from white wine was detected in vitro and linked to compositional differences between saliva from obese and normal-weight subjects. Additional in vivo investigations on diverse food matrices could contribute to understanding whether a lower olfactory stimulation due to saliva composition can be a co-factor in the development/maintenance of obesity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nascent RNA profiling is growing in popularity; however, there is no standard analysis pipeline to uniformly process the data and assess quality. Here, we introduce PEPPRO, a comprehensive, scalable ...workflow for GRO-seq, PRO-seq, and ChRO-seq data. PEPPRO produces uniformly processed output files for downstream analysis and assesses adapter abundance, RNA integrity, library complexity, nascent RNA purity, and run-on efficiency. PEPPRO is restartable and fault-tolerant, records copious logs, and provides a web-based project report. PEPPRO can be run locally or using a cluster, providing a portable first step for genomic nascent RNA analysis.
Objectives
To assess coronary artery calcification (CAC) on non-contrast non-ECG-gated CT thorax (NC-NECG-CTT) and to evaluate its correlation with short-term risk of cardiovascular disease (CVD) ...events and death.
Methods
Single-institution retrospective study including all patients 40–70 years old who underwent NC-NECG-CTT over a period of 6 months. Individuals with known CVD were excluded. The presence of CAC was assessed and quantified by the Agatston score (CACS). CAC severity was defined as mild (< 100), moderate (100–400), or severe (> 400). CVD events (including CVD death, myocardial infarction, revascularisation procedures, ischaemic stroke, acute peripheral atherosclerotic ischaemia), and all-cause mortality over a median of 3.5 years were recorded. Cox proportional-hazards regression modelling was performed including CACS, age, gender and CVD risk factors (smoking, hypertension, diabetes mellitus, dyslipidaemia, and family history of CVD).
Results
Of the total 717 eligible cases, 325 (45%) had CAC. In patients without CAC, there was only one CVD event, compared to 26 CVD events including 5 deaths in patients with CAC. The presence and severity of CAC correlated with CVD events (
p
< 0.001). A CACS > 100 was significantly associated with both CVD events, hazard ratio (HR) 5.74, 95% confidence interval: 2.19–15.02;
p
< 0.001, and all-cause mortality, HR 1.7, 95% CI: 1.08–2.66;
p
= 0.02. Ever-smokers with CAC had a significantly higher risk for all-cause mortality compared to never-smokers (
p
= 0.03), but smoking status was not an independent predictor for CVD events in any subgroup category of CAC severity.
Conclusions
The presence and severity of CAC assessed on NC-NECG-CTT correlates with short-term cardiovascular events and death.
Key Points
• Patients aged 40–70 years old without known CVD but with CAC on NC-NECG-CTT have a higher risk of CVD events compared to those without CAC.
• CAC (Agatston) score above 100 confers a 5.7-fold increase in the risk of short-term CVD events in these patients.
• The presence and severity of CAC on NC-NECG-CTT may have prognostic and therapeutic implications.
The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the ...radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min(-1). Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.
Ion channels are transmembrane proteins that play ubiquitous roles in cellular homeostasis and activation. In addition to their recognized role in the regulation of ionic permeability and thus ...membrane potential, some channel proteins possess intrinsic kinase activity, directly interact with integrins or are permeable to molecules up to ≈1000 Da. The small size and anuclear nature of the platelet has often hindered progress in understanding the role of specific ion channels in hemostasis, thrombosis and other platelet‐dependent events. However, with the aid of transgenic mice and ‘surrogate’ patch clamp recordings from primary megakaryocytes, important unique contributions to platelet function have been identified for several classes of ion channel. Examples include ATP‐gated P2X1 channels, Orai1 store‐operated Ca2+ channels, voltage‐gated Kv1.3 channels, AMPA and kainate glutamate receptors and connexin gap junction channels. Furthermore, evidence exists that some ion channels, such as NMDA glutamate receptors, contribute to megakaryocyte development. This review examines the evidence for expression of a range of ion channels in the platelet and its progenitor cell, and highlights the distinct roles that these proteins may play in health and disease.
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