Rationale
Clozapine has proven to be superior to other antipsychotic drugs in the treatment of schizophrenia but is under-prescribed due to its potentially severe side effects. Clozapine-induced ...sialorrhea (CIS) is a frequent and extremely uncomfortable side effect, which remains understudied.
Objectives
To examine the prevalence of diurnal and nocturnal CIS in a sample of patients treated with clozapine, and to evaluate its impact on quality of life.
Methods
We conducted a cross-sectional, observational study of 130 patients with schizophrenia spectrum disorders treated with clozapine. The prevalence of CIS was evaluated via specific sialorrhea scales. None of the patients included in the study was receiving a specific treatment for hypersalivation during the study period. Possible associations between sialorrhea and clinical and quality of life variables were analyzed.
Results
Of 130 subjects, 120 (92.3%) suffered from CIS. Eighty-one (62.31%) suffered from diurnal CIS, 115 (88.56%) from nocturnal CIS, and 85 (65.38%) suffered from both. Significant positive associations between quality of life and diurnal CIS (
B
= 0.417;
p
= 2.1e − 6,
R
2
= 0.156) and nocturnal CIS (
B
= 0.411;
p
= 7.7e − 6,
R
2
= 0.139) were detected. Thirty per cent of the subjects reported a moderate to severe negative impact of sialorrhea on their quality of life.
Conclusions
The present study suggests that CIS is highly prevalent in patients with schizophrenia and has an important impact on quality of life in one-third of our sample. Therefore, the inclusion of a systematic evaluation and treatment of CIS in standard clinical practice is highly recommended.
Trial registration
Clinical Trials (
https://clinicaltrials.gov
) under reference NCT04197037.
Aliment Pharmacol Ther 2011; 33: 585–591
Summary
Background Temporal changes in the incidence of cause‐specific gastrointestinal (GI) complications may be one of the factors underlying changing ...medical practice patterns.
Aim To report temporal changes in the incidence of five major causes of specific gastrointestinal (GI) complication events.
Methodology Population‐based study of patients hospitalised due to GI bleeding and perforation from 1996 to 2005 in Spain. We report crude rates, and estimate regression coefficients of temporal trends, severity and recorded drug use for five frequent GI events. GI hospitalisation charts were validated by independent review of large random samples.
Results The incidence per 100 000 person‐years of hospitalisations due to upper GI ulcer bleeding and perforation decreased over time from 54.6 and 3.9 in 1996 (R2 = 0.944) to 25.8 and 2.9 in 2005 (R2 = 0.410) respectively. On the contrary, the incidence per 100 000 person‐years of colonic diverticular and angiodysplasia bleeding increased over time 3.3 and 0.9 in 1996 (R2 = 0.443) and 8.0 and 2.6 in 2005 (R2 = 0.715) respectively. A small increasing trend was observed for the incidence per 100 000 person‐years of intestinal perforations (from 1.5 to 2.3 events). Based on data extracted from the validation process, recent recorded drug intake showed an increased frequency of anticoagulants with colonic diverticular and angiodysplasia bleeding, whereas NSAID and low‐dose aspirin use were more prevalent in peptic ulcer bleeding and colonic diverticular bleeding respectively.
Conclusions From 1996 to 2005, hospitalisations due to peptic ulcer bleeding and perforation have decreased significantly, whereas the number of cases of colonic diverticular and angiodysplasia bleeding have increased.
The structural characteristics of the canopy are a key consideration for improving the efficiency of the spray application process for tree crops. However, obtaining accurate data in an easy, ...practical, and efficient way is an important problem to be solved. This paper describes the technical characteristics of a sprayer prototype developed for vineyards, following the principles and previous laboratory tests described in the complementary paper Variable rate sprayer. Part 1 – Orchard prototype: design, implementation and validation. This prototype can modify the sprayed volume application rate according to the target geometry by using an algorithm based on the canopy volume inspired by the tree row volume (TRV) model. Variations in canopy width along the row crop are electronically measured using several ultrasonic sensors placed on the sprayer and used to modify the emitted flow rate from the nozzles in real time; the objective during this process is to maintain the sprayed volume per unit canopy volume (Lm⁻³). Field trials carried out at different crop stages for Merlot and Cabernet Sauvignon vines (Vitis vinifera) indicated a good relationship between the applied volume and canopy characteristics. The potential pesticide savings were estimated to be 21.9% relative to the costs of a conventional application. This conclusion is in accordance with the results of similar research on automated spraying systems.
Aging is an inevitable and gradual decline in several biological functions. Mitochondrial dysfunction is one of the most important hallmarks of aging. In this context, alterations in metabolites ...associated with mitochondrial dysfunction may serve as a significant biomarker. This study aimed to investigate the existence of a relationship between the key metabolites involved in bioenergetics metabolism and aging. 53 volunteers ranged 20–85 years participated in the study. We tested the association between different tricarboxylic acid (TCA) cycle metabolites, fatty acid metabolism, and amino acid metabolism with age, sex, body composition, and proxy markers of aging such as walking speed, grip strength and chair test. We found that lactic acid negatively correlated with age while several fatty acid metabolites, such as azelaic, sebacic, and linoleic acids, showed positive correlations with age (p < 0.05). Sex-specific trends, such as glycerol, and dodecanoic acid, were also observed for certain metabolites. Furthermore, citric acid levels were found to have a significant association with physical function and body composition measures. Participants with higher citric acid levels displayed improved performance in physical tests and favorable body composition indices. Additionally, fumaric acid and adipic acid showed positive correlations with fat-free body mass, while sebacic acid was negatively associated with measures of fat mass. These findings underscore the importance of understanding the role of circulating bioenergetics metabolites with age, sex variations, and their potential implications in body composition and physical performance.
•Age and sex significantly influenced circulating TCA metabolite levels.•Elevated citric acid levels correlated positively with improved physical performance and negatively with body fat mass and visceral fat area.•The study identified key metabolites that predicts age and sex underscoring their potential as biomarkers for aging and metabolic health.
Germplasm banks are the most significant repository for plant genetic resources for food and agriculture (PGRFA) worldwide. Despite their strategic importance, national germplasm banks of tropical ...megadiverse developing countries such as Colombia have extremely limited funds. Therefore, making strategic decisions about research investment is essential. Here, we designed a data-driven approach to build an index that sorts Colombian PGRFA into three groups: high, medium, or low priority, based on four pillars of information from open-access databases and aligned with the sustainable goals of no poverty and zero hunger: Geographic origin, vulnerability status, economic benefits, and food security importance. We analyzed 345 PGRFA using the index, separating them into two groups, 275 already conserved in the Colombian germplasm bank (BGVCOL group) and 70 not currently conserved in the BGVCOL (NCB group). We used fuzzy logic to classify each PGRFA by each pillar and integrate it to obtain a priority index. Missing data for native crops were frequent in the BGVCOL group. Therefore we adopted an imputation strategy to fill the gaps and calculated the uncertainty. After applying the index, PGRFA with higher priority were 24 (8.72%) from the BGVCOL (i.e., 15 potatoes, three tomatoes, two tree tomatoes, pineapple, cocoa, papaya, and yacon) and one from NCB (i.e., coffee). We concluded that this methodology successfully prioritized PGRFA in Colombia and shows the big holes of knowledge for future research and alternatives to improve this index. The versatility of this methodology could be helpful in other genebanks with budget limitations for research investment.
The BCL6 transcriptional repressor is the most frequently involved oncogene in diffuse large B cell lymphoma (DLBCL). We combined computer-aided drug design with functional assays to identify ...low-molecular-weight compounds that bind to the corepressor binding groove of the BCL6 BTB domain. One such compound disrupted BCL6/corepressor complexes in vitro and in vivo, and was observed by X-ray crystallography and NMR to bind the critical site within the BTB groove. This compound could induce expression of BCL6 target genes and kill BCL6-positive DLBCL cell lines. In xenotransplantation experiments, the compound was nontoxic and potently suppressed DLBCL tumors in vivo. The compound also killed primary DLBCLs from human patients.
► We identified a specific BCL6 small-molecule inhibitor ► This compound targets the interaction of BCL6 with its corepressors ► This compound displayed antilymphoma activity in vitro and in vivo
SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms ...underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.
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