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Agitation is a common complication of Alzheimer’s dementia (Agit-AD) associated with substantial morbidity, high healthcare service utilization, and adverse emotional and physical impact on care partners. There are currently no FDA-approved pharmacological treatments for Agit-AD. We present the study design and baseline data for an ongoing multisite, three-week, double-blind, placebo-controlled, randomized clinical trial of dronabinol (synthetic tetrahydrocannabinol [THC]), titrated to a dose of 10 mg daily, in 80 participants to examine the safety and efficacy of dronabinol as an adjunctive treatment for Agit-AD. Preliminary findings for 44 participants enrolled thus far show a predominately female, white sample with advanced cognitive impairment (Mini Mental Status Examination mean 7.8) and agitation (Neuropsychiatric Inventory-Clinician Agitation subscale mean 14.1). Adjustments to study design in light of the COVID-19 pandemic are described. Findings from this study will provide guidance for the clinical utility of dronabinol for Agit-AD. ClinicalTrials.gov Identifier: NCT02792257.
Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is an amphetamine derivative that is used recreationally and is now being tested in clinical trials for treatment of posttraumatic stress disorder. Ecstasy can damage serotonin neurones in brain of experimental animals; however, relevance of these findings to the human is debated.
To measure by positron emission tomography (PET) levels of binding to the serotonin transporter (SERT), a marker of serotonin neurones, in brain of chronic ecstasy users and in matched controls.
An estimate of brain SERT levels was obtained, using the PET tracer 11C-DASB, in 50 chronic (confirmed by drug hair testing) ecstasy users (mean age, 26 years; mean duration of drug use, 3.9 years; median drug withdrawal time, 38 days) and 50 (drug-hair negative) control subjects (mean age 26 years).
SERT binding levels in the ecstasy group were significantly decreased by 22 to 46% in frontal, temporal, cingulate, insular and occipital cortices, and by 23% in hippocampus. However, concentrations were distinctly normal in the SERT-rich caudate, putamen, ventral striatum and thalamus.
Our imaging data suggest that cerebral cortical SERT concentration is below normal in some ecstasy users for at least one month after last use of the drug. However, it remains to be established whether low SERT might have preceded drug use, reflects actual loss of brain serotonin neurones, or is causally related to any functional impairment in the ecstasy users. (Supported by US NIH NIDA DA017301).
Starting university is an important time with respect to dietary changes. This study reports a novel approach to assessing student diet by utilising student-level food transaction data to explore dietary patterns. First-year students living in catered accommodation at the University of Leeds (UK) received pre-credited food cards for use in university catering facilities. Food card transaction data were obtained for semester 1, 2016 and linked with student age and sex. k-Means cluster analysis was applied to the transaction data to identify clusters of food purchasing behaviours. Differences in demographic and behavioural characteristics across clusters were examined using χ2 tests. The semester was divided into three time periods to explore longitudinal changes in purchasing patterns. Seven dietary clusters were identified: ‘Vegetarian’, ‘Omnivores’, ‘Dieters’, ‘Dish of the Day’, ‘Grab-and-Go’, ‘Carb Lovers’ and ‘Snackers’. There were statistically significant differences in sex (P < 0·001), with women dominating the Vegetarian and Dieters, age (P = 0·003), with over 20s representing a high proportion of the Omnivores and time of day of transactions (P < 0·001), with Dieters and Snackers purchasing least at breakfast. Many students (n 474, 60·4 %) changed dietary cluster across the semester. This study demonstrates that transactional data present a feasible method for dietary assessment, collecting detailed dietary information over time and at scale, while eliminating participant burden and possible bias from self-selection, observation and attrition. It revealed that student diets are complex and that simplistic measures of diet, focusing on narrow food groups in isolation, are unlikely to adequately capture dietary behaviours.
Gender equality is considered paramount to the success of the Sustainable Development Goals and incorporated into global health programming and delivery, but there is great gender disparity within global health leadership and an absence of women at the highest levels of decision making. This perspective piece outlines the current gaps and challenges, highlighting the lack of data and unanswered questions regarding possible solutions, as well as the activity of Women in Global Health and efforts to directly address the inequity and lack of female leaders. We conclude with an agenda and tangible next steps of action for promoting women's leadership in health as a means to promote the global goals of achieving gender equality and catalyzing change.
Gender equity is imperative to the attainment of healthy lives and wellbeing of all, and promoting gender equity in leadership in the health sector is an important part of this endeavour. This empirical research examines gender and leadership in the health sector, pooling learning from three complementary data sources: literature review, quantitative analysis of gender and leadership positions in global health organisations and qualitative life histories with health workers in Cambodia, Kenya and Zimbabwe. The findings highlight gender biases in leadership in global health, with women underrepresented. Gender roles, relations, norms and expectations shape progression and leadership at multiple levels. Increasing women's leadership within global health is an opportunity to further health system resilience and system responsiveness. We conclude with an agenda and tangible next steps of action for promoting women's leadership in health as a means to promote the global goals of achieving gender equity.
We present results from our ongoing monitoring programs aimed at identifying and understanding Active Galactic Nuclei (AGN) in extreme flux and spectral states. Observations of AGN in extreme states can reveal the nature of the inner accretion flow, the physics of matter under strong gravity, and they provide insight on the properties of ionized absorbers and outflows launched near supermassive black holes (SMBHs). We present new results from our long-term monitoring of IC 3599, WPVS007, and Mrk 335, multi-wavelength follow-ups of the newly identified changing-look AGN HE 1136–2304, and UV–X-ray follow-ups of the binary SMBH candidate OJ 287 after its 2015 optical maximum, now in a new optical-X-ray–high-state.
Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1β, IL-12p70 and IL-10 in human macrophages.
This paper is a report from the Extreme Events Working Party. The paper considers some of the difficulties in calculating capital buffers to cover potential losses. This paper considers the reasons why a purely mechanical approach to calculating capital buffers may bot be possible or justified. A range of tools and techniques is presented to help address some of the difficulties identified.
We sought to estimate mortality and associated factors in HIV-hepatitis co-infected individuals in Michigan using a retrospective cohort study. For the study period of 1 January 2006 to 31 December 2009, all HIV-infected individuals were matched to hepatitis B and C cases. In the final Cox proportional hazards regression model, individuals of other [hazard ratio (HR) 2·2, 95% confidence interval (CI) 1·4–3·2] and black (HR 1·3, 95% CI 1·1–1·6) race had decreased survival compared to white race. Similarly, injecting drug users (IDUs) (HR 2·1, 95% CI 1·6–2·6), men who have sex with men (MSM)/IDUs (HR 1·5, 95% CI 1·1–2·2), individuals with undetermined risk (HR 1·5, 95% CI 1·2–1·9) and heterosexual practices (HR 1·4, 95% CI 1·1–1·8) had decreased survival compared to MSM. Additionally, an interaction was found between current HIV status and co-infection. Mortality in HIV-hepatitis co-infected individuals remains a continuing problem. Our study can help in planning interventions to reduce mortality in HIV-infected individuals.
Military trainees are at high risk for skin and soft-tissue infections (SSTIs), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). A multicomponent hygiene-based SSTI prevention strategy was implemented at a military training center. After implementation, we observed 30% and 64% reductions in overall and MRSA-associated SSTI rates, respectively.
A retrospective cohort study was conducted from 1 January 2006 to 31 December 2009 in Michigan to estimate the prevalence of HIV and hepatitis co-infection and identify associated factors. The prevalence of co-infection was 4·1% [95% confidence interval (CI) 3·8–4·5]. Multivariable logistic regression analysis revealed a significant association between co-infection and being male and: of Black race [odds ratio (OR) 2·0, 95% CI 1·2–3·6] and of Other race (OR 3·5, 95% CI 1·7–7·0) compared to Hispanic race. A significant association was found between co-infection and risk categories of blood products (OR 11·1, 95% CI 6·2–20·2), injecting drug user (IDU) (OR 3·6, 95% CI 2·7–4·8) and men who have sex with men/IDU (OR 3·4, 95% CI 2·4–4·9) in addition to two interactions; one between sex and current HIV status and the other between current HIV status and age at HIV diagnosis. Our results document the changing epidemiology of HIV–hepatitis co-infection which can guide preventive measures and interventions to reduce the prevalence of hepatitis co-infection.
Cpefat/fat mice have a point mutation in carboxypeptidase E (Cpe), an exopeptidase that removes C-terminal basic amino acids from intermediates to produce bioactive peptides. The mutation renders the enzyme inactive and unstable. The absence of Cpe activity in these mutants leads to abnormal processing of many peptides, with elevated levels of intermediates and greatly reduced levels of the mature peptides. Cpefat/fat mice develop obesity, diabetes and infertility in adulthood. We examined whether anxiety- and/or depressive-like behaviours are also present. Anxiety-like responses are not evident in young Cpefat/fat mice (∼60 d), but appear in older animals (>90 d). These behaviours are reversed by acute treatment with diazepam or fluoxetine. In contrast, increased immobilities in forced swim and tail suspension are evident in all age groups examined. These behaviours are reversed by acute administration of reboxetine. In comparison acute treatments with fluoxetine or bupropion are ineffective; however, immobility times are normalized with 2 wk treatment. These data demonstrate that Cpefat/fat mice display depressive-like responses aged ∼60 d, whereas anxiety-like behaviours emerge ∼1 month later. In tail suspension, the reboxetine findings show that noradrenergic actions of antidepressants are intact in Cpefat/fat mice. The ability of acute fluoxetine treatment to rescue anxiety-like while leaving depressive-like responses unaffected suggests that serotonin mechanisms underlying these behaviours are different. Since depressive-like responses in the Cpefat/fat mice are rescued by 2 wk, but not acute, treatment with fluoxetine or bupropion, these mice may serve as a useful model that resembles human depression.
The objective of the present study was to explore the consistency of dietary choices made by children as they grow up. The dietary habits of 342 healthy children were reported annually from 5 to 13 years on a forty-five-item FFQ and analysed by factor analysis. The same two principal dietary patterns – ‘Healthy’ and ‘Unhealthy’ – emerged each year, and their consistency was assessed using Tucker's congruence coefficient (φ). Individual dietary z-scores for both of these patterns were then calculated every year for each child, and their consistency was measured by Pearson's correlation coefficient (r). Linear mixed-effects modelling was used to investigate individual trends and to quantify reliability of the individual dietary z-scores. Dietary patterns were moderately consistent and systematic over time (0·65 ≤ φHealthy ≤ 0·76; 0·62 ≤ φUnhealthy ≤ 0·78). Individual choices were also consistent year-on-year (0·64 ≤ rHealthy ≤ 0·71; 0·57 ≤ rUnhealthy ≤ 0·68). Reliability rose from 70 % with a single measure to over 90 % with four consecutive measures. The quality of diet diminished over time in 29 % of the children and improved in only 14 %. Dietary habits appear to be set early and seldom improve spontaneously.
Of the radiation types, alpha-(α) particles are of particular interest as they are an environmental concern, predominately due to inhalation of radon and its daughter progeny. Furthermore, α-particle emitters like Americium-241, Plutonium-238 and Polonium-210 have been identified as probable isotopes to be used in radiological dispersal devices. Thus, the identification of potential biomarkers to α-particle radiation exposure would be useful for the development of field deployable bioassays which could be used for human risk assessment and public health protection. Human lung cells were exposed to α-particle radiation and assessed for modulations in protein expression using two-dimensional gel electrophoresis (2D-GE). Concurrently, cell culture supernatants were analyzed for cytokine secretion using a multiplex-27 bead array assay. Cell culture supernatants assessed for cytokine secretion expressed 8 statistically significant cytokines following α-particle exposure, among which VEGF was confirmed to be dose-responsive and not modulated in X-irradiated cells. Analysis of whole cell lysates using 2-D gel electrophoresis showed 15 upregulated and 1 downregulated protein spot, of which 4 were identified by mass spectrometry. These data suggest that α-particle exposure results in the alterations in expression-levels of specific proteins which may be potential biomarkers used further for the development of fast and reliable bioassays.
A portable air purifier significantly reduced mal odour in a small room. If the atmosphere was deliberately contaminated with Serratia marcescens the unit rapidly removed this organism. However, if incorrectly sited, the purifier could disperse organisms into the atmosphere.