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Background Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. Methods We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient’s medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon’s rank test was used to look at the correlation between two subgroups upon admission and discharge. Results On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant ( p  = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. Conclusions Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission.

This descriptive research study focused on nursing preceptorship programs and the verbal interactions which took place as inexperienced Registered Nurses were hired and oriented into the hospital environment. The study's purpose was to identify and describe those verbal interactions, the patterns that evolved during the orientation process, and any exemplary interactions which took place. The subjects for this study included thirteen pairs of nurses. Each group consisted of one preceptor (experienced Registered Nurse) and one preceptee (inexperienced Registered Nurse). The setting was a large, community-based hospital in Massachusetts. Participants audiotaped each of four weekly review sessions. Forty-three audiotaped sessions were transcribed according to a version of the \"Teacher Talk Cribsheet\" developed by Gower, Campbell and Saphier (1995), adapted to nursing by this Researcher. Nurses' verbal interactions were examined to identify patterns and skills (e.g. sharing, active listening, and encouraging). Thirty-seven types of skills were identified. Patterns of verbal interactions were depicted on pathway charts. Analysis helped identify exemplary skills employed, and why some preceptorship relationships are more productive. One major finding was that the first step taken by preceptors was to develop a peer relationship with their preceptees. They employed many sharing, listening and encouraging skills in the sessions. Another major finding was that the complexity and quality of the skilled behavior was directly related to the time preceptors had been Registered Nurses. Those preceptors who had the most experience most often employed highly skilled and exemplary interactions. This study promoted an awareness of the necessity for effective interactions and productive conversations. Nurses develop philosophies and methods of practice through practical education, experience, and through their participation in conversations with other nurses and the perceptions that result. It is important to improve the quality of conversations between nurses in order to further their professional growth. Nurses need to understand talk and effectively manage their conversations with other nurses, and with members of the health care community. This research effort discovered what can be done to enhance the quality of those interactions and thus help to stimulate an awareness of the necessity for effective and productive verbal interactions between nurses. A more positive preceptorship experience and a more meaningful orientation for the preceptee should result. The ultimate goal of this endeavor was to help improve the quality of nursing care to patients and thus improve patient care outcomes.

The risk for depression markedly rises during the 5-6 years leading up to the cessation of menstruation, known as the menopause transition. Exposure to extreme estradiol levels may help explain this increase but few studies have examined individual sensitivity to estradiol in predicting perimenopausal depression. The current study recruited 101 perimenopausal women. During Phase 1, we quantified each woman's sensitivity to changes in estradiol using 12 weekly measures of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, and concurrent depressive symptoms. The weekly cortisol awakening response was measured to examine the hypothalamic-pituitary-adrenal (HPA) axis in mediating mood sensitivity to estradiol. In Phase 2, depressive symptoms and major depression diagnoses were assessed monthly for 9 months. The relationship between Phase 1 E1G sensitivity and Phase 2 depressive symptoms and major depressive episodes was examined. Several baseline characteristics were examined as potential moderators of this relationship. The within-person correlation between weekly E1G and mood varied greatly from woman to woman, both in strength and direction. Phase 1 E1G mood sensitivity predicted the occurrence of clinically significant depressive symptoms in Phase 2 among certain subsets of women: those without a prior history of depression, reporting a low number of baseline stressful life events, and reporting fewer months since their last menstrual period. HPA axis sensitivity to estradiol fluctuation did not predict Phase 2 outcomes. Mood sensitivity to estradiol predicts risk for perimenopausal depression, particularly among women who are otherwise at low risk and among those who are early in the transition.

There is great interest in repurposing the commonly prescribed anti-diabetic drug metformin for cancer therapy. Intracellular uptake and retention of metformin is affected by the expression of organic cation transporters (OCT) 1-3 and by multidrug and toxic compound extrusion (MATE) 1-2. Inside cells, metformin inhibits mitochondrial function, which leads to reduced oxygen consumption and inhibition of proliferation. Reduced oxygen consumption can lead to improved tumor oxygenation and radiation response. Here we sought to determine if there is an association between the effects of metformin on inhibiting oxygen consumption, proliferation and expression of OCTs and MATEs in a panel of 19 cancer cell lines. There was relatively large variability in the anti-proliferative response of different cell lines to metformin, with a subset of cell lines being very resistant. In contrast, all cell lines demonstrated sensitivity to the inhibition of oxygen consumption by metformin, with relatively small variation. The expression of OCT1 correlated with expression of both OCT2 and OCT3. OCT1 and OCT2 were relatively uniformly expressed, whereas expression of OCT3, MATE1 and MATE2 showed substantial variation across lines. There were statistically significant associations between resistance to inhibition of proliferation and MATE2 expression, as well as between sensitivity to inhibition of oxygen consumption and OCT3 expression. One cell line (LNCaP) with high OCT3 and low MATE2 expression in concert, had substantially higher intracellular metformin concentration than other cell lines, and was exquisitely sensitive to both anti-proliferative and anti-respiratory effects. In all other cell lines, the concentration of metformin required to inhibit oxygen consumption acutely in vitro was substantially higher than that achieved in the plasma of diabetic patients. However, administering anti-diabetic doses of metformin to tumor-bearing mice resulted in intratumoral accumulation of metformin and reduced hypoxic tumor fractions. All cancer cells are susceptible to inhibition of oxygen consumption by metformin, which results in reduced hypoxic tumor fractions beneficial for the response to radiotherapy. High MATE2 expression may result in resistance to the anti-proliferative effect of metformin and should be considered as a negative predictive biomarker in clinical trials.

Background The menopause transition is associated with an increased risk of depression. While the mechanisms behind this increased risk are not well understood, the changing perimenopausal hormonal environment has been hypothesized to play a role. The current study examined the potential influence of testosterone and the ratio of testosterone to estradiol as a potential contributor to depressed mood in the menopause transition. Methods Fifty non-depressed perimenopausal women ages 45–55 were recruited for this study. Once every 3 weeks, for a total of four times, the women completed the Centre for Epidemiological Studies-Depression (CES-D) scale for the measurement of depressive symptoms and provided a first-morning urine sample for the measurement of urinary testosterone as well as estrone-3-glucuronide (E1G), a urinary metabolite of estradiol. The week-to-week and mean effects of testosterone, E1G, and the testosterone/E1G ratio on CES-D score were examined. Self-reported sleep quality and vasomotor symptoms were also assessed at each of the four time points. Results Testosterone levels rose with increasing months since last menstrual period associated with testosterone levels ( β (SE) = 175.3(63.2), p = .006), though this effect was moderated by body mass index ( p for the interaction = .001) such that overweight women showed a less pronounced increase over time. Past and current smokers also had higher testosterone levels compared to never smokers. Week-to-week testosterone/E1G ratio was positively associated with CES-D score ( β (SE) = 1.57(0.76), p = .041) but not sleep quality or vasomotor symptoms ( p s > .05). Mean testosterone/E1G ratio was also positively associated with vasomotor symptom bother ( β (SE) = 0.14(0.06), p = .018) and poorer sleep quality ( β (SE) = − 0.34(0.09), p = .0001). Conclusion These results suggest that, within the context of the menopause transition, times that are characterized by a higher testosterone-to-estradiol ratio may be associated with higher depressive symptoms. Perimenopausal women with a higher average ratio of testosterone relative to estradiol may also experience more sleep difficulties and vasomotor symptom bother.

A disintegrin and metalloprotease 10 (ADAM10) is essential for embryonic development and impacts on diseases such as cancer, Alzheimer's and inflammatory diseases. ADAM10 is a molecular scissor that proteolytically cleaves the extracellular region from over 100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors and chemokines. ADAM10 was recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six regulatory tetraspanins, termed TspanC8s. However, it remains unclear to what degree ADAM10 function is critically dependent on a TspanC8 partner. To address this, we generated the first monoclonal antibodies to Tspan15 as a model TspanC8. These were used to show that ADAM10 is the principal Tspan15-interacting protein, that Tspan15 expression requires ADAM10 in cell lines and primary cells, and that a synthetic ADAM10/Tspan15 fusion protein is a functional scissor. Together these findings suggest that ADAM10 exists as an intimate ADAM10/TspanC8 scissor complex.