Receptors implicated in cough hypersensitivity are transient receptor potential vanilloid 1 (TRPV1), transient receptor potential cation channel, Subfamily A, Member 1 (TRPA1) and acid sensing ion ...channel receptor 3 (ASIC3). Respiratory viruses, such as respiratory syncytial virus (RSV) and measles virus (MV) may interact directly and/or indirectly with these receptors on sensory nerves and epithelial cells in the airways. We used in vitro models of sensory neurones (SHSY5Y or differentiated IMR-32 cells) and human bronchial epithelium (BEAS-2B cells) as well as primary human bronchial epithelial cells (PBEC) to study the effect of MV and RSV infection on receptor expression. Receptor mRNA and protein levels were examined by qPCR and flow cytometry, respectively, following infection or treatment with UV inactivated virus, virus-induced soluble factors or pelleted virus. Concentrations of a range of cytokines in resultant BEAS-2B and PBEC supernatants were determined by ELISA. Up-regulation of TRPV1, TRPA1 and ASICS3 expression occurred by 12 hours post-infection in each cell type. This was independent of replicating virus, within the same cell, as virus-induced soluble factors alone were sufficient to increase channel expression. IL-8 and IL-6 increased in infected cell supernatants. Antibodies against these factors inhibited TRP receptor up-regulation. Capsazepine treatment inhibited virus induced up-regulation of TRPV1 indicating that these receptors are targets for treating virus-induced cough.
The association between religiosity and the construct of sexual passion was examined to see whether religiosity is associated with harmonious, inhibited, and obsessive sexual passion styles. Using ...multiple regression and checking for interactions between religiosity, gender, broad categories of religion (Catholic, other Christian, other religious, nonreligious), and the three sexual passion styles, the following associations were found: Religiosity had a significant curvilinear relationship to all three sexual passion styles, suggesting an overlap in levels of religiosity and the construct of sexual passion. Optimal sexual passion outcomes were found at both higher and lower levels of religiosity, whereas mid-level religiosity was associated with the less beneficial sexual passion outcomes. Religious men were significantly more obsessively passionate than religious women, and religious men and women were similarly high on levels of harmonious and low on inhibited sexual passion. There were no significant interactions between religiosity, broad categories of religion, and sexual passion styles. Understanding how religion and sexual passion are associated could be useful for applied researchers as well as those who work with religious individuals who want to help these individuals develop beneficial patterns of sexual passion.
To cause infection,
must withstand damage caused by host immune defenses. However, the mechanisms by which staphylococcal DNA is damaged and repaired during infection are poorly understood. Using a ...panel of transposon mutants, we identified the
operon as being important for the survival of
in whole human blood. Mutants lacking
were also attenuated for virulence in murine models of both systemic and skin infections. We then demonstrated that RexAB is a member of the AddAB family of helicase/nuclease complexes responsible for initiating the repair of DNA double-strand breaks. Using a fluorescent reporter system, we were able to show that neutrophils cause staphylococcal DNA double-strand breaks through reactive oxygen species (ROS) generated by the respiratory burst, which are repaired by RexAB, leading to the induction of the mutagenic SOS response. We found that RexAB homologues in
and
also promoted the survival of these pathogens in human blood, suggesting that DNA double-strand break repair is required for Gram-positive bacteria to survive in host tissues. Together, these data demonstrate that DNA is a target of host immune cells, leading to double-strand breaks, and that the repair of this damage by an AddAB-family enzyme enables the survival of Gram-positive pathogens during infection.
To cause infection, bacteria must survive attack by the host immune system. For many bacteria, including the major human pathogen
, the greatest threat is posed by neutrophils. These immune cells ingest the invading organisms and try to kill them with a cocktail of chemicals that includes reactive oxygen species (ROS). The ability of
to survive this attack is crucial for the progression of infection. However, it was not clear how the ROS damaged
and how the bacterium repaired this damage. In this work, we show that ROS cause breaks in the staphylococcal DNA, which must be repaired by a two-protein complex known as RexAB; otherwise, the bacterium is killed, and it cannot sustain infection. This provides information on the type of damage that neutrophils cause
and the mechanism by which this damage is repaired, enabling infection.
The number and complexity of patients being admitted to hospitals is rising and some patients may not receive a full clinical pharmacy review or be reviewed as regularly as needed during their ...inpatient stay. This is a risk factor for medication errors. Clinical prioritisation identifies patients who are high-risk and most in need of a pharmacist review, targeting finite pharmacy resources to patients who will benefit the most.
Assess and enhance clinical prioritisation within a hospital pharmacy department.
The study was conducted in a large urban academic teaching hospital. A cross-sectional survey of clinical pharmacists in the hospital was conducted to establish the patient clinical criteria they prioritise in their work. A clinical prioritisation tool was developed based on survey findings and was integrated into an existing electronic pharmacy care interface. A pre- and post-intervention study was conducted, consisting of data collection for five days pre- and five days post-implementation of the tool. Quantitative data were analysed using descriptive and inferential statistics. Qualitative data were analysed by thematic analysis.
Of 39 eligible pharmacists, 37 (95%) responded to the survey. The top-rated prioritisation criteria, including medicines reconciliation tasks and high-risk medicines, helped to inform the content of the clinical prioritisation tool. Post-intervention, there were more Level 1 complex patients reviewed by pharmacists and fewer Level 3 stable patients compared to pre-intervention. Tool sensitivity ranged from 51 to 88%, depending on the experience of the pharmacist using the tool. High levels of satisfaction with clinical prioritisation were reported by those using the tool.
This newly developed clinical prioritisation tool has the potential to support pharmacists in identifying and reviewing patients in a more targeted manner than practice prior to tool development. Continued development and validation of the tool is essential, with a focus on developing a fully automated tool.
Marriage is an important adult relationship, and recent research indicates that sexual mindfulness, awareness and non-judgment, may be an important tool in helping maintain relational and sexual ...well-being. Using a nationally representative U.S. sample of newly married, mixed-sex couples (women’s age
M
= 29.70 years; men’s age
M
= 31.76 years;
N
= 1473 couples), we evaluated whether the two factors of sexual mindfulness, awareness and non-judgment, were linked with relational flourishing, sexual harmony, and orgasm consistency. We utilized an actor–partner interdependence model within a structural equation modeling framework to evaluate how husbands’ and wives’ awareness and non-judgment were associated with relational flourishing, sexual harmony, and orgasm consistency. Results indicated that both wives’ and husbands’ awareness was positively associated with relational flourishing, sexual harmony, and orgasm consistency. Partner effects were found for all outcomes. However, no partner effects were found between non-judgment and orgasm consistency. Therapists, educators, and couples may consider the use of sexual mindfulness skills when addressing marriage and sexual relationships.
In laboratory exposures of bumble bees to two neonicotinoids, imidacloprid and thiamethoxam, both toxicants caused dose-dependent decreases in the rates of rewarming and in the equilibrated thoracic ...temperatures.
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•Neonicotinoid insecticides affect rates of recovery from cold-torpor in bumble bees.•Dietary neonicotinoid insecticides disrupt thermogenesis in worker bumble bees.•Imidacloprid caused low-dose stimulation of thermogenesis in bumble bees.
For bumble bees (genus Bombus), the capacity for non-flight thermogenesis is essential for two fundamental processes undertaken by adult workers, namely recovery from torpor after chilling and brood incubation. Farmland bees can be widely exposed to dietary residues of neurotoxic neonicotinoid insecticides that appear in the nectar and pollen of treated bee-attractive crops, which may harm them. An earlier study shows that dietary neonicotinoids cause complex alterations to thermoregulation in honey bees, but their effect on the thermogenic capabilities of individual bumble bees has been untested previously. We therefore conducted laboratory trials involving separate dietary exposures of bumble bees to two neonicotinoids, imidacloprid and thiamethoxam, and we measured their effects on the thoracic temperatures of bees during recovery from chilling. Specifically, we used thermal imaging to measure the rates of rewarming by individual bees after chill-induced torpor and to quantify their equilibrated thoracic temperatures post-recovery. We found that both toxicants caused dose-dependent decreases in the rates of rewarming and in the equilibrated thoracic temperatures. As previously found in honey bees, the dose–response relationship for imidacloprid exhibited a biphasic hormesis with low-dose stimulation and high-dose inhibition, for which we propose a mechanism. Our present study is among the first to detect ecologically relevant effects on bees in neonicotinoid exposures involving dietary concentrations below 5 ppb. If the effects on thoracic temperatures that we observed over a short period were sustained, they could have ecologically significant impacts on farmland bumble bees.
Knowledge of the role of melatonin, xenograft experiments, and epidemiological studies suggests that exposure to light at night (LAN) may disturb circadian rhythms, possibly increasing the risk of ...developing breast cancer.
We examined the association between residential outdoor LAN and the incidence of breast cancer: overall and subtypes classified by estrogen (ER) and progesterone (PR) receptor status.
We used data on 16,941 nurses from the Danish Nurse Cohort who were followed-up from the cohort baseline in 1993 or 1999 through 2012 in the Danish Cancer Registry for breast cancer incidence and the Danish Breast Cancer Cooperative Group for breast cancer ER and PR status. LAN exposure data were obtained from the U.S. Defense Meteorological Satellite Program (DMSP) available for 1996, 1999, 2000, 2003, 2004, 2006, and 2010 in nW/cm2/sr unit, and assigned to the study participants’ residence addresses during the follow-up. Time-varying Cox regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LAN and breast cancer, adjusting for individual characteristics, road traffic noise, and air pollution.
Of 16,941 nurses, 745 developed breast cancer in total during 320,289 person-years of follow-up. We found no association between exposure to LAN and overall breast cancer. In the fully adjusted models, HRs for the highest (65.8–446.4 nW/cm2/sr) and medium (22.0–65.7 nW/cm2/sr) LAN tertiles were 0.97 (95% CI: 0.77, 1.23) and 1.09 (95% CI: 0.90, 1.31), respectively, compared to the lowest tertile of LAN exposure (0–21.9 nW/cm2/sr). We found a suggestive association between LAN and ER-breast cancer.
This large cohort study of Danish female nurses suggests weak evidence of the association between LAN and breast cancer incidence.
•An association between light-at-night (LAN) and breast cancer incidence was investigated.•Of 16,941 Danish nurses (≥44 years), 745 developed breast cancer.•Null association between LAN and overall breast cancer.•A suggestive association between LAN and ER-breast cancer.
Optimal cord management (OCM), defined as waiting at least 60 seconds (s) before clamping the umbilical cord after birth, is an evidence-based intervention that improves outcomes for both term and ...preterm babies. All major resuscitation councils recommend OCM for well newborns.National Neonatal Audit Programme (NNAP) benchmarking data identified our tertiary neonatal unit as a negative outlier with regard to OCM practice with only 12.1% of infants receiving the recommended minimum of 60 s. This inspired a quality improvement project (QIP) to increase OCM rates of ≥ 60 s for infants <34 weeks. A multidisciplinary QIP team (Neonatal medical and nursing staff, Obstetricians, Midwives and Anaesthetic colleagues) was formed, and robust evidence-based quality improvement methodologies employed. Our aim was to increase OCM of ≥ 60 s for infants born at <34 weeks to at least 40%.The percentage of infants <34 weeks receiving OCM increased from 32.4% at baseline (June–September 2022) to 73.6% in the 9 months following QIP commencement (October 2022–June 2023). The intervention period spanned two cohorts of rotational doctors, demonstrating its sustainability. Rates of admission normothermia were maintained following the routine adoption of OCM (89.2% vs 88.5%), which is a complication described by other neonatal units.This project demonstrates the power of a multidisciplinary team approach to embedding an intervention that relies on collaboration between multiple departments. It also highlights the importance of national benchmarking data in allowing departments to focus QIP efforts to achieve long-lasting transformational service improvements.
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The global emergence of antibiotic resistance is one of the most serious challenges facing modern medicine. There is an urgent need for validation of new drug targets and the ...development of small molecules with novel mechanisms of action. We therefore sought to inhibit bacterial DNA repair mediated by the AddAB/RecBCD protein complexes as a means to sensitize bacteria to DNA damage caused by the host immune system or quinolone antibiotics. A rational, hypothesis-driven compound optimization identified IMP-1700 as a cell-active, nanomolar potency compound. IMP-1700 sensitized multidrug-resistant Staphylococcus aureus to the fluoroquinolone antibiotic ciprofloxacin, where resistance results from a point mutation in the fluoroquinolone target, DNA gyrase. Cellular reporter assays indicated IMP-1700 inhibited the bacterial SOS-response to DNA damage, and compound-functionalized Sepharose successfully pulled-down the AddAB repair complex. This work provides validation of bacterial DNA repair as a novel therapeutic target and delivers IMP-1700 as a tool molecule and starting point for therapeutic development to address the pressing challenge of antibiotic resistance.
Hip-worn triaxial accelerometers are widely used to assess physical activity in terms of energy expenditure. Methods for classification in terms of different types of activity of relevance to the ...skeleton in populations at risk of osteoporosis are not currently available. This publication aims to assess the accuracy of four machine learning models on binary (standing and walking) and tertiary (standing, walking, and jogging) classification tasks in postmenopausal women. Eighty women performed a shuttle test on an indoor track, of which thirty performed the same test on an indoor treadmill. The raw accelerometer data were pre-processed, converted into eighteen different features and then combined into nine unique feature sets. The four machine learning models were evaluated using three different validation methods. Using the leave-one-out validation method, the highest average accuracy for the binary classification model, 99.61%, was produced by a k-NN Manhattan classifier using a basic statistical feature set. For the tertiary classification model, the highest average accuracy, 94.04%, was produced by a k-NN Manhattan classifier using a feature set that included all 18 features. The methods and classifiers within this study can be applied to accelerometer data to more accurately characterize weight-bearing activity which are important to skeletal health.
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