Anticholinergic burden has been associated with adverse outcomes such as falls. To date, no gold standard measure has been identified to assess anticholinergic burden, and no conclusion has been ...drawn on which of the different measure algorithms best predicts falls in older patients from general practice. This study compared the ability of five measures of anticholinergic burden to predict falls. To account for patients' individual susceptibility to medications, the added predictive value of typical anticholinergic symptoms was further quantified in this context.
To predict falls, models were developed and validated based on logistic regression models created using data from two German cluster-randomized controlled trials. The outcome was defined as "≥ 1 fall" vs. "no fall" within a 6-month follow-up period. Data from the RIME study (n = 1,197) were used in model development, and from PRIMUM (n = 502) for external validation. The models were developed step-wise in order to quantify the predictive ability of anticholinergic burden measures, and anticholinergic symptoms. In the development set, 1,015 patients had complete data and 188 (18.5%) experienced ≥ 1 fall within the 6-month follow-up period. The overall predictive value of the five anticholinergic measures was limited, with neither the employed anticholinergic variable (binary / count / burden), nor dose-dependent or dose-independent measures differing significantly in their ability to predict falls. The highest c-statistic was obtained using the German Anticholinergic Burden Score (0.73), whereby the optimism-corrected c-statistic was 0.71 after interval validation using bootstrapping and 0.63 in the external validation. Previous falls and dizziness / vertigo had the strongest prognostic value in all models.
The ability of anticholinergic burden measures to predict falls does not appear to differ significantly, and the added value they contribute to risk classification in fall-prediction models is limited. Previous falls and dizziness / vertigo contributed most to model performance.
Background and Purpose
Mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There ...are no disease‐modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate–glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high‐dose oral glutamine supplementation could reduce the increase in glutamate levels.
Method
This open‐label, single‐cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12 weeks of oral glutamine supplementation.
Results
Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8 ± 3.2 years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77 ± 1.21 vs. 18.48 ± 1.34 μmol/l, p < 0.001) and CSF glutamine levels were significantly increased (433.66 ± 15.31 vs. 336.31 ± 12.92 μmol/l, p = 0.002). A side effect observed in four of nine patients was a mild sensation of satiety. One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke‐like episode.
Discussion
This study demonstrates that high‐dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients.
Trial Registration Information
ClinicalTrials.gov Identifier: NCT04948138. Initial release 24 June 2021, first patient enrolled 1 July 2021. https://clinicaltrials.gov/ct2/show/NCT04948138.
High‐dose oral glutamine supplementation for 12 weeks significantly reduces cerebrospinal fluid (CSF) glutamate and increases CSF glutamine levels in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes (MELAS) syndrome. This decrease in CSF glutamate levels could reduce glutamate‐mediated excitotoxicity. These findings may have potential therapeutic implications in patients with MELAS syndrome.
IntroductionAtherosclerotic cardiovascular disease (ASCVD) was the main cause of death in Germany in 2021, with major risk factors (ie, hypertension, diabetes, dyslipidaemia, obesity and certain ...lifestyle factors) being highly prevalent. Preventing ASCVD by assessment and modification of these risk factors is an important challenge for general practitioners. This study aims to systematically review and synthesise recent recommendations of national and international guidelines regarding the primary prevention of ASCVD in adults in primary care.Methods and analysisWe will conduct a systematic review of clinical practice guidelines (CPGs) to evaluate primary prevention strategies for ASCVD. CPGs will be retrieved from MEDLINE and the Turning Research Into Practice database, guideline-specific databases and websites of guidelines-producing societies, with searches limited to publications from 2016 onwards. We will include CPGs in English, Spanish, German or Dutch languages that provide evidence-based recommendations for ASCVD prevention. The study population will include adults without diagnosed ASCVD. Two independent reviewers will assess guideline eligibility and quality by means of the mini-checklist MiChe, and extract study characteristics and relevant recommendations for further consistency analysis. A third reviewer will resolve disagreements. Findings will be presented as a narrative synthesis and in tabular form.Ethics and disseminationThis review does not require ethical approval. Our systematic review will inform the CPG of the German College of General Practitioners and Family Physicians on the primary prevention of ASCVD. The review results will also be disseminated through publications in peer-reviewed journals and presentations at local, national and international conferences.PROSPERO registration numberCRD42023394605.
A considerable amount of literature has been published claiming the cardiovascular benefits of moderate (red) wine drinking, which has been considered a distinguishing trait of the Mediterranean ...diet. Indeed, red wine contains relevant amounts of polyphenols, for which evidence of their biological activity and positive health effects are abundant; however, it is also well-known that alcohol, even at a low level of intake, may have severe consequences for health. Among others, it is directly related to a number of non-communicable diseases, like liver cirrhosis or diverse types of cancer. The IARC classifies alcohol as a Group 1 carcinogen, causally associated with the development of cancers of the upper digestive tract and liver, and, with sufficient evidence, can be positively associated with colorectum and female breast cancer. In these circumstances, it is tricky, if not irresponsible, to spread any message on the benefits of moderate wine drinking, about which no actual consensus exists. It should be further considered that other hallmarks of the Mediterranean diet are the richness in virgin olive oil, fruits, grains, and vegetables, which are also good sources of polyphenols and other phytochemicals, and lack the risks of wine. All of these aspects are reviewed in this article.
To examine negative police encounters and police avoidance as mediators of incarceration history and depressive symptoms among US Black men and to assess the role of unemployment as a moderator of ...these associations.
Data were derived from the quantitative phase of Menhood, a 2015-2016 study based in Washington, DC. Participants were 891 Black men, 18 to 44 years of age, who completed computer surveys. We used moderated mediation to test the study's conceptual model.
The results showed significant indirect effects of incarceration history on depressive symptoms via negative police encounters and police avoidance. Unemployment moderated the indirect effect via police avoidance. Participants with a history of incarceration who were unemployed reported significantly higher police avoidance and, in turn, higher depressive symptoms. Moderation of unemployment on the indirect effect via negative police encounters was not significant.
There is a critical need to broaden research on the health impact of mass incarceration to include other aspects of criminal justice involvement (e.g., negative police encounters and police avoidance) that negatively affect Black men's mental health.
Over the last few decades, polyphenols, and flavonoids in particular, have attracted the interest of researchers, as they have been associated with the health-promoting effects derived from diets ...rich in vegetables and fruits, including moderate wine consumption. Recent scientific evidence suggests that wine polyphenols exert their effects through interactions with the gut microbiota, as they seem to modulate microbiota and, at the same time, are metabolized by intestinal bacteria into specific bioavailable metabolites. Microbial metabolites are better absorbed than their precursors and may be responsible for positive health activities in the digestive system (local effects) and, after being absorbed, in tissues and organs (systemic effects). Differences in gut microbiota composition and functionality among individuals can affect polyphenol activity and, therefore, their health effects. The aim of this review is to integrate the understanding of the metabolism and mechanisms of action of wine polyphenols at both local and systemic levels, underlining their impact on the gut microbiome and the inter-individual variability associated with polyphenols' metabolism and further physiological effects. The advent of promising dietary approaches linked to wine polyphenols beyond the gut microbiota community and metabolism are also discussed.
To develop and validate a prognostic model to predict deterioration in health-related quality of life (dHRQoL) in older general practice patients with at least one chronic condition and one chronic ...prescription.
We used individual participant data from five cluster-randomized trials conducted in the Netherlands and Germany to predict dHRQoL, defined as a decrease in EQ-5D-3 L index score of ≥5% after 6-month follow-up in logistic regression models with stratified intercepts to account for between-study heterogeneity. The model was validated internally and by using internal–external cross-validation (IECV).
In 3,582 patients with complete data, of whom 1,046 (29.2%) showed deterioration in HRQoL, and 12/87 variables were selected that were related to single (chronic) conditions, inappropriate medication, medication underuse, functional status, well-being, and HRQoL. Bootstrap internal validation showed a C-statistic of 0.71 (0.69 to 0.72) and a calibration slope of 0.88 (0.78 to 0.98). In the IECV loop, the model provided a pooled C-statistic of 0.68 (0.65 to 0.70) and calibration-in-the-large of 0 (−0.13 to 0.13). HRQoL/functionality had the strongest prognostic value.
The model performed well in terms of discrimination, calibration, and generalizability and might help clinicians identify older patients at high risk of dHRQoL.
PROSPERO ID: CRD42018088129.
•Multimorbidity and polypharmacy increase the risk of deterioration in quality of life.•First IPD-based quality of life prognostic model for older multimorbid patients.•Model performed well in terms of discrimination, calibration, and generalizability.•Baseline quality of life and functional status have the strongest prognostic power.•Quality of life/functionality appraisal might help identify high-risk patients.
The bioactive compounds in myrtle berries, such as phenolic compounds and anthocyanins, have shown a potentially positive effect on human health. Efficient extraction methods are to be used to obtain ...maximum amounts of such beneficial compounds from myrtle. For that reason, this study evaluates the effectiveness of a rapid ultrasound-assisted method (UAE) to extract anthocyanins and phenolic compounds from myrtle berries. The influence of solvent composition, as well as pH, temperature, ultrasound amplitude, cycle and solvent-sample ratio on the total phenolic compounds and anthocyanins content in the extracts obtained were evaluated. The response variables were optimized by means of a Box-Behnken design. It was found that the double interaction of the methanol composition and the cycle, the interaction between methanol composition and temperature, and the interaction between the cycle and solvent-sample ratio were the most influential variables on the extraction of total phenolic compounds (92.8% methanol in water, 0.2 s of cycle, 60 °C and 10:0.5 mL:g). The methanol composition and the interaction between methanol composition and pH were the most influential variables on the extraction of anthocyanins (74.1% methanol in water at pH 7). The methods that have been developed presented high repeatability and intermediate precision (RSD < 5%) and the bioactive compounds show a high recovery with short extraction times. Both methods were used to analyze the composition of the bioactive compounds in myrtle berries collected from different locations in the province of Cadiz (Spain). The results obtained by UAE were compared to those achieved in a previous study where microwave-assisted extraction (MAE) methods were employed. Similar extraction yields were obtained for phenolic compounds and anthocyanins by MAE and UAE under optimal conditions. However, UAE presents the advantage of using milder conditions for the extraction of anthocyanins from myrtle, which makes of this a more suitable method for the extraction of these degradable compounds.
Climate change and pollution are two of the main environmental problems living organisms currently face. Temperature can modify a toxicant's effects and the organism's response to it. Global warming ...is expected to increase the temperature of freshwater ecosystems. In this work, we analyzed the effect of a mild temperature increase on the acute response of the aquatic larvae Chironomus riparius to the ultraviolet filter benzophenone-3 (BP3). This substance is commonly used in sunscreens and other commercial products and can reach the environment in different ways. We exposed larvae to BP3 at 18.5 or 23 °C for 8 or 24 h and analyzed the acute response at the molecular level. By quantitative real-time polymerase chain reaction (q-PCR), we studied altered messenger RNA (mRNA) levels of genes related to the endocrine system (EcR, InR and Met), detoxification mechanisms (Cyp4d2, Cyp6b7, GST d6, GST o1 and MRP-1) and stress response (Hsp22, Hsp27, Hsp70, HYOU and Gp93). Moreover, enzyme activity was evaluated, with a focus on glutathione-S-transferase (GST), phenoloxidase (PO) and acetylcholinesterase (AChE). Results showed that temperature affected the acute response of this organism by modifying the expression of EcR, Cyp6b7, GST d6, GST o1, MRP-1, Hsp22, Hsp27 and Hsp70 genes. These results suggest that even mild temperature change can affect the response of this organism to BP3 influencing short-term progress of the population. Although longer exposures are required to determine the ability of C. riparius to manage the pollutants in this novel environmental conditions, in order to know the possible mechanisms of detoxification or adaptation that may develop. This research represents a first step in the analysis of multi-stress response in this animal, and opens new possibilities in the toxicity evaluation of this organism in line with the real scenario that organisms face today.
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•Mild increase of temperature affects survival in presence of BP3.•Multi-stress alters expression of detoxification genes and EcR.•Cellular ability to eliminate BP3 is affected by the mild increase of temperature.•Hsp22, Hsp27 and Hsp70 alteration shows fast stress response at these conditions.•PO and AchE responses suggest that immunity and nervous system are compromised by BP-3 and temperature.
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