Frog hepatic health and metal pollution: An assemblage-level approach in a hotspot in southeastern Brazil.

Chemical pollutants include the harmful effects of various substances on soils, water bodies, and biodiversity. Amphibians are one of the most endangered groups of vertebrates and are impacted by chemical pollutants in various ways due to their complex life cycles. Since trace pollutant concentrations vary across environments, different frog ecomorphs (classified by their microhabitat use) may have different exposures. We aimed to determine the association between frog ecomorphs and the occurrence of histopathological hepatic lesions (HHLs) as an indicator of contaminant exposure. We focused on small forest streams near a large urban region in Brazil, heavily polluted in the 1980s. We examined 104 frog specimens from various families. All specimens exhibited HHLs, with melanomacrophages being the most common (n = 99). Arboreal frogs exhibited more vascular congestion, while terrestrial frogs showed structural hepatic damage. Higher cobalt levels were linked to increased liver necrosis in arboreal frogs and structural issues in both arboreal and terrestrial frogs. Cadmium was associated with hepatitis in terrestrial frogs. Although metal levels had no significant effects on rheophilic frogs, the prevalence of hepatitis and necrosis indicated complex exposure pathways. Iron and aluminum were linked to fewer lesions in rheophilic frogs, suggesting resilience. The high prevalence of HHLs signals an ongoing issue, with variations among ecomorphs suggesting differential exposure to pollutants and posing a complex challenge for community conservation.

A web step-based digital solution's impact on physical, cognitive and psychosocial functioning of community-dwelling older adults: A mixed methods randomized and controlled trial.

Background: As the population ages, innovative responses are urgently needed to promote physical activity at scale. Thus, this study investigated whether a step-based activity mediated by a digital solution impacts the physical functioning of community-dwelling older adults. The secondary aims were to assess whether the same activity impacts cognitive and psychosocial functioning and explore participants' views towards the activity. Methods: A mixed method, randomized, and controlled study with one group performing a step-based activity using DanceMove (recommended dosage: twice a week for 20 to 30 min for eight weeks) and the other their usual activities. DanceMove was used at the individuals' homes without any direct supervision. Clinical tests and questionnaires administered in person were used to assess participants at baseline, post-intervention, and three-month follow-up. The primary outcome of interest was gait velocity. Secondary outcomes were balance, pain intensity, cognitive functioning, self-efficacy, social support, loneliness, and quality of life. Also, at the end of the intervention, a semi-structured individual interview was conducted with participants in the experimental group. Results: Seventy participants were randomized to the control (n = 37) and experimental (n = 33) groups. Of the 33 participants in the experimental group, four did not use the DanceMove at all and two used it for only 3 min. The remaining 26 participants used it for a total time over the eight weeks that varied between 15 and 991 min (mean ± SD = 306.55 ± 258.83 min). The step-based activity was not more effective than usual activities for any of the variables assessed (P > .05). Difficulties, positive and negative aspects regarding the digital solution, and reasons for not using it were identified in the interviews. Conclusions: Eight weeks of a step-based activity mediated by a digital solution did not impact the physical, cognitive, and psychosocial functioning of community-dwelling healthy older adults. However, the activity was enjoyable and safe to be performed at home without direct supervision. Further studies are needed to explore aspects that could modulate the impact of this type of technology-mediated activity. Trial registration: The study was registered at clinialtrials.gov (NCT05460039) before the enrolment of the first participant.

Angiotensin-(1-7) infusion in COVID-19 patients admitted to the ICU: a seamless phase 1-2 randomized clinical trial.

BACKGROUND: The coronavirus-related disease (COVID-19) is mainly characterized by a respiratory involvement. The renin-angiotensin system (RAS) has a relevant role in the pathogenesis of COVID-19, as the virus enters host's cells via the angiotensin-converting enzyme 2 (ACE2). METHODS: This investigator-initiated, seamless phase 1-2 randomized clinical trial was conceived to test the safety and efficacy of continuous short-term (up to 7 days) intravenous administration of Angiotensin-(1-7) in COVID-19 patients admitted to two intensive care units (ICU). In addition to standard of care, intravenous administration of Angiotensin-(1-7) was started at 5 mcg/Kg day and increased to 10 mcg/Kg day after 24 h (Phase 1; open label trial) or given at 10 mcg/Kg day and continued for a maximum of 7 days or until ICU discharge (Phase 2; double-blind randomized controlled trial). The rate of serious adverse events (SAEs) served as the primary outcome of the study for Phase 1, and the number of oxygen free days (OFDs) by day 28 for Phase 2. RESULTS: Between August 2020 and July 2021, when the study was prematurely stopped due to low recruitment rate, 28 patients were included in Phase 1 and 79 patients in Phase 2. Of those, 78 were included in the intention to treat analysis, and the primary outcome was available for 77 patients. During Phase 1, one SAE (i.e., bradycardia) was considered possibly related to the infusion, justifying its discontinuation. In Phase 2, OFDs did not differ between groups (median 19 [0-21] vs. 14 [0-18] days; p = 0.15). When patients from both phases were analyzed in a pooled intention to treat approach (Phase 1-2 trial), OFDs were significantly higher in treated patients, when compared to controls (19 [0-21] vs. 14 [0-18] days; absolute difference -5 days, 95% CI [0-7] p = 0.04). CONCLUSIONS: The main findings of our study indicate that continuous intravenous infusion of Angiotensin-(1-7) at 10 mcg/Kg day in COVID-19 patients admitted to the ICU with severe pneumonia is safe. In Phase II intention to treat analysis, there was no significant difference in OFD between groups. Trial Registration ClinicalTrials.gov Identifier: NCT04633772-Registro Brasileiro de Ensaios Clínicos, UTN number: U1111-1255-7167.

The association between anxiety and depression symptoms and clinical and pain characteristics in patients with hip and knee osteoarthritis.

OBJECTIVES: This study aimed to estimate the prevalence of anxiety and depression symptoms and explore the association between these symptoms and clinical and pain characteristics in patients with chronic pain (CP) due to hip and knee osteoarthritis (OA). METHODS: In this cross-sectional study, adult patients with CP and knee and/or hip OA were included. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Visual analogue scale, Western Ontario and McMaster Universities Arthritis Index (WOMAC) and PainDetect Questionnaire assessed pain characteristics and Health Assessment Questionnaire (HAQ) evaluated functional disability. Correlation coefficients were used to explore the associations between anxiety and depression symptoms and clinical and pain characteristics. RESULTS: A total of 61 patients (age 66.2±9.4 years, 67.2% female) were included. Most patients (70.5%) had clinically significant anxiety and/or depression symptoms. Patients with anxiety and/or depression symptoms had higher pain severity (p=0.032) and disability (p=0.014). Depression symptoms had a moderate positive correlation with WOMAC physical function subscale (r=0.520), WOMAC total (r=0.511) and HAQ (r=0.405). CONCLUSIONS: Anxiety and depression symptoms are prevalent in knee or hip OA patients with CP and were associated with higher pain severity and functional disability. These findings support the screening of anxiety and depression symptoms in OA patients, in order to develop more effective multidisciplinary treatments.

Vat-based photopolymerization 3D printing: From materials to topical and transdermal applications.

Three-dimensional (3D) printing is an innovative manufacturing method with the potential to revolutionize topical and transdermal dosage forms. Nowadays, it is established that Vat-based photopolymerization (VP) 3D printing technologies offer superior printing efficiency and versatility compared to other 3D printing technologies available on the market. However, there are some limitations that impair their full application in pharmaceutical contexts, such as the lack of a range of biocompatible materials for topical and transdermal applications. This review article explores all types of VP-based 3D printing and discusses the relevance of implementing this kind of technology. We start with a detailed description of the printing process, focusing on the commercial materials available and lab-made resins proposed by different authors. We also review recent studies in this field, which mainly focus on the fabrication of transdermal devices based on microneedle arrays. In the future, it is expected that the manufacturers of 3D printers invest in modifications to the printing apparatus to allow the simultaneous printing of different resins and/or compound types, which will open frontiers to the personalization of treatment approaches.

Maple syrup urine disease diagnosis in Brazilian patients by massive parallel sequencing.

Biallelic pathogenic variants cause maple syrup urine disease (MSUD) in one of the branched-chain α-keto acid dehydrogenase (BCKDH) complex genes (BCKDHA, BCKDHB, DBT, DLD, and PPM1K) leading to the accumulation of leucine, isoleucine, and valine. This study aimed to perform a molecular diagnosis of Brazilian patients with MSUD using gene panels and massive parallel sequencing. Eighteen Brazilian patients with a biochemical diagnosis of MSUD were analyzed by massive parallel sequencing in the Ion PGM Torrent Server using a gene panel with the BCKDHA, BCKDHB, and DBT genes. The American College of Medical Genetics and Genomics guidelines were used to determine variant pathogenicity. Thirteen patients had both variants found by massive parallel sequencing, whereas 3 patients had only one variant found. In 2 patients, the variants were not found by this analysis. These 5 patients required additional Sanger sequencing to confirm their genotype. Twenty-five pathogenic variants were identified in the 3 MSUD-related genes (BCKDHA, BCKDHB, and DBT). Most variants were present in the BCKDHB gene, and no common variants were found. Nine novel variants were observed: c.922 A > G, c.964C > A, and c.1237 T > C in the BCKDHA gene; and c.80_90dup, c.384delA, c.478 A > T, c.528C > G, c.977 T > C, and c.1039-2 A > G in the BCKDHB gene. All novel variants were classified as pathogenic. Molecular modeling of the novel variants indicated that the binding of monomers was affected in the BCKDH complex tetramer, which could lead to a change in the stability and activity of the enzyme. Massive parallel sequencing with targeted gene panels seems to be a cost-effective method that can provide a molecular diagnosis of MSUD.

Risks of oral anticoagulants: Analysis of adverse drug reactions reported to the Portuguese National Pharmacovigilance System.

Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was "Clinically Important" (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was "Gastrointestinal disorders," with the most commonly reported Preferred Term being "Gastrointestinal hemorrhage," and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population.

A conversational agent for enhanced Self-Management after cardiothoracic surgery.

BACKGROUND: Enhanced self-management is crucial for long-term survival following cardiothoracic surgery. OBJECTIVES: This study aimed to develop a conversational agent to enhance patient self-management after cardiothoracic surgery. METHODOLOGY: The solution was designed and implemented following the Design Science Research Methodology. A pilot study was conducted at the hospital to assess the feasibility, usability, and perceived effectiveness of the solution. Feedback was gathered to inform further interactions. Additionally, a focus group with clinicians was conducted to evaluate the acceptability of the solution, integrating insights from the pilot study. RESULTS: The conversational agent, implemented using a rule-based model, was successfully tested with patients in the cardiothoracic surgery unit (n = 4). Patients received one month of text messages reinforcing clinical team recommendations on a healthy diet and regular physical activity. The system received a high usability score, and two patients suggested adding a feature to answer user prompts for future improvements. The focus group feedback indicated that while the solution met the initial requirements, further testing with a larger patient cohort is necessary to establish personalized profiles. Moreover, clinicians recommended that future iterations prioritize enhanced personalization and interoperability with other hospital platforms. Additionally, while the use of artificial generative intelligence was seen as relevant for content personalization, clinicians expressed concerns regarding content safety, highlighting the necessity for rigorous testing. CONCLUSIONS: This study marks a significant step towards enhancing post-cardiothoracic surgery care through conversational agents. The integration of a diversity of stakeholder knowledge enriches the solution, grants ownership and ensures its sustainability. Future research should focus on automating message generation and delivery based on patient data and environmental factors. While the integration of artificial generative intelligence holds promise for enhancing patient interaction, ensuring the safety of its content is essential.

Aminocarb Exposure Induces Cytotoxicity and Endoplasmic Reticulum Stress-Mediated Apoptosis in Mouse Sustentacular Sertoli Cells: Implications for Male Infertility and Environmental Health.

Exposure to pesticides, poses a significant threat to male fertility by compromising crucial cells involved in spermatogenesis. Aminocarb, is a widely used carbamate insecticide, although its detrimental effects on the male reproductive system, especially on sustentacular Sertoli cells, pivotal for spermatogenesis, remains poorly understood. In this study, we investigated the effects of escalating concentrations of aminocarb on a mouse Sertoli cell line, TM4. Assessments included cytotoxic analysis, mitochondrial biogenesis and membrane potential, expression of apoptotic proteins, caspase-3 activity, and oxidative stress evaluation. Our findings revealed a dose-dependent reduction in the proliferation and viability of TM4 cells following exposure to increasing concentrations of aminocarb. Notably, exposure to 5 µM of aminocarb induced depolarization of mitochondria membrane potential, and a significant decrease in the ratio of phosphorylated eIF2α to total eIF2α, suggesting heightened endoplasmic reticulum stress via the activation of the eIF2α pathway. Moreover, the same aminocarb concentration was demonstrated to increase both caspase-3 protein levels and activity, indicating an apoptotic induction. Collectively, our results demonstrate that aminocarb serves as an apoptotic inducer for mouse sustentacular Sertoli cells in vitro, suggesting its potential to modulate independent pathways of the apoptotic cascade. These findings underscore the deleterious impact of aminocarb on spermatogenic performance and male fertility, highlighting the urgent need for further investigation into its mechanisms of action and mitigation strategies to safeguard male fertility.

Adjunctive photobiomodulation to Basic Periodontal therapy using different low-power laser application techniques: a systematic review and meta-analysis.

To review current literature and synthesize clinical outcomes related to different low-level laser techniques as a complement to basic periodontal therapy (BPT). Electronic searches were conducted in PubMed, Cochrane, and Scopus, and clinical trials published from January 2013 to August 2023 using photobiomodulation as a complement to basic periodontal therapy, with a clear description of the laser technique, were included. The risk of bias was assessed using the Joanna Briggs Institute Critical Assessment Checklist. Estimates of interest were calculated using random effects meta-analyses. A total of 947 references were retrieved, and 22 studies were included for qualitative synthesis. Ten studies used intrasulcular laser techniques, with 89% using infrared wavelength, and 12 studies used transgingival techniques, with 61.5% using red wavelength. The frequency of photobiomodulation after BPT ranged from 1 to 9 sessions, with follow-up periods ranging from 5 days to 12 months. Risk of bias was considered low in 16 studies and moderate in six studies. Meta-analysis of 13 studies showed that BPT reduced probing depth at 4-, 12- and 24-weeks post-treatment, and improved clinical level attachment at 6-, 12- and 24-weeks post-treatment. Studies suggest that photobiomodulation may be a valuable complement in the treatment of periodontitis, especially using transgingival application technique.

Can we predict the risk factors for switching due to ineffectiveness in the first year of therapy with bDMARD in patients with rheumatoid arthritis?

INTRODUCTION: Biological disease-modifying antirheumatic drugs (bDMARD) have improved the clinical course and quality of life of patients with rheumatoid arthritis (RA). However, some patients failed to respond or have an insufficient response to bDMARD early in the course of the treatment. OBJECTIVES: To determine the percentage of RA patients who need to switch due to ineffectiveness in the first year of treatment and to identify specific baseline features as possible predictors of switch due to ineffectiveness in the first year of treatment. MATERIALS AND METHODS: An observational retrospective study was conducted with patients with RA that started their first bDMARD. Demographic data, disease characteristics, disease activity data scores, laboratory parameters and treatment at baseline were collected. The proportion of patients who failed to respond and who switched to another bDMARD in the first year of treatment was calculated. RESULTS: A total of 437 (364 females, 83.3%) patients with RA were included. The majority of these patients started an anti-TNF-α agent (n=315, 72.1%). Forty-eight (11.0%) patients failed to respond to the bDMARD in the first year of treatment. There were significantly more current or former smokers (p=0.030), with a history of depression (p=0.003) and positive for RF at baseline (p=0.014) in the switch group. In the multivariate analysis, anti-TNF-α agents use (OR 8.3, 95% CI 2.4-28.8, p=0.001), tobacco exposure (OR 2.3, 95% CI 1.1-4.8, p=0.02) and history of depression (OR 3.1, 95% CI 1.3-7.7) seem to predict the need to switch in the first year of treatment due to ineffectiveness. DISCUSSION AND CONCLUSION: In our study, tobacco exposure and depression appear to be modifiable risk factors associated with early switching due to ineffectiveness. Addressing these factors in daily clinical practice is crucial to enhance the overall response to therapy and improve the well-being of patients.

Can microvascular damage predict disease severity in patients with systemic sclerosis?

INTRODUCTION: Systemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC). MATERIALS AND METHODS: A retrospective study of patients with SSc and a NVC performed within the first 6 months after diagnosis was conducted. Visceral involvement in the first 3 years of the disease and NVC findings were collected. The severity of microvascular damage was classified into four categories, according to the worsening of the NVC patterns. The severity of organ involvement was assessed by the disease severity scale of Medsger for each organ and as a global measure of disease severity, the simple summation was used. RESULTS: A total of 86 patients with SSc were included. A moderate correlation was found between the severity of microvascular damage and the global measure of disease severity (r=0.55, p<0.001), the severity of peripheral vascular involvement (r=0.43, p<0.001) and the severity of skin involvement (r=0.34, p=0.001). The presence of a late scleroderma pattern in NVC were predictive in univariate analysis of digital ulcers (OR 6.03, 95% CI 1.52-23.86, p=0.01), muscular involvement (OR 13.09, 95% CI 1.09-156.78, p=0.04), calcinosis (OR 27.22, 95% CI 5.56-133.33, p<0.001) and worse global disease severity score (OR 1.67, 95% CI 1.17-2.38, p=0.005). Multivariate analysis adjusted for disease duration and gender confirmed late pattern as an independent predictor of calcinosis (OR 42.89, 95% CI 5.53-332.85, p<0.001). DISCUSSION AND CONCLUSION: In this study, the worsening of NVC pattern in SSc was associated with the overall disease severity, the severity of peripheral vascular involvement and extension of skin involvement. This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement.

Zika virus capsid protein closed structure modulates binding to host lipid systems.

Zika virus (ZIKV), a mosquito-borne Flavivirus of international concern, causes congenital microcephaly in newborns and Guillain-Barré syndrome in adults. ZIKV capsid (C) protein, one of three key structural proteins, is essential for viral assembly and encapsidation. In dengue virus, a closely related flavivirus, the homologous C protein interacts with host lipid systems, namely intracellular lipid droplets, for successful viral replication. Here, we investigate ZIKV C interaction with host lipid systems, showing that it binds host lipid droplets but, contrary to expected, in an unspecific manner. Contrasting with other flaviviruses, ZIKV C also does not bind very-low density-lipoproteins. Comparing with other Flavivirus, capsid proteins show that ZIKV C structure is particularly thermostable and seems to be locked into an auto-inhibitory conformation due to a disordered N-terminal, hence blocking specific interactions and supporting the experimental differences observed. Such distinct structural features must be considered when targeting capsid proteins in drug development.

Long-term follow-up of treatment outcomes in Graves' disease and toxic nodular disease.

PURPOSE: Hyperthyroidism guidelines have not been updated over the past five years, despite numerous data on the subject, and recent studies providing a wide variation in treatment success rates. We aim to compare the effectiveness and safety of treatment modalities in patients with Graves' disease or toxic nodular disease. METHODS: Single center retrospective cohort study of Graves' disease and toxic nodular disease patients treated between 1983 and 2023. RESULTS: A total of 411 patients were treated for hyperthyroidism, 245 due to Graves' disease and 166 due to or toxic nodular disease, followed for a median of 7 years. In Graves' disease, 90.2% were treated with antithyroid drugs over 250 cycles, achieving 41.7% cumulative remission. Half of all relapses (50.9%) occurred in the first year, 76.3% in the first three years, and 98.3% within nine years. Treatment periods of 12-24 months showed higher remission and lower relapse rates than longer periods. I-131 was used in 103 cycles with 82.5% remission and 7.1% relapse. A total of 29 thyroidectomies resulted in 100% remission, with no relapse. In toxic nodular disease, surgery was the most frequently used treatment (54.5%), followed by I-131 (37.1%). CONCLUSION: Our findings support antithyroid drugs as the preferential first-line treatment for Graves' disease, allowing for euthyroidism with minimal adverse effects. Given the propensity for relapse, we suggest a rigorous monitoring, particularly within the first three years. In toxic nodular disease, surgery should be the preferred option, with I-131 being reserved for single adenomas and small goiters.

How hot is too hot? Thermal tolerance, performance, and preference in juvenile mangrove whiprays, Urogymnus granulatus.

Mangrove habitats can serve as nursery areas for sharks and rays. Such environments can be thermally dynamic and extreme; yet, the physiological and behavioural mechanisms sharks and rays use to exploit such habitats are understudied. This study aimed to define the thermal niche of juvenile mangrove whiprays, Urogymnus granulatus. First, temperature tolerance limits were determined via the critical thermal maximum (CTMax) and minimum (CTMin) of mangrove whiprays at summer acclimation temperatures (28 °C), which were 17.5 °C and 39.9 °C, respectively. Then, maximum and routine oxygen uptake rates (MO2max and MO2routine, respectively), post-exercise oxygen debt, and recovery were estimated at current (28 °C) and heatwave (32 °C) temperatures, revealing moderate temperature sensitivities (i.e., Q10) of 2.4 (MO2max) and 1.6 (MO2routine), but opposing effects on post-exercise oxygen uptake. Finally, body temperatures (Tb) of mangrove whiprays were recorded using external temperature loggers, and environmental temperatures (Te) were recorded using stationary temperature loggers moored in three habitat zones (mangrove, reef flat, and reef crest). As expected, environmental temperatures varied between sites depending on depth. Individual mangrove whiprays presented significantly lower Tb relative to Te during the hottest times of the day. Electivity analysis showed tagged individuals selected temperatures from 24.0 to 37.0 °C in habitats that ranged from 21.1 to 43.5 °C. These data demonstrate that mangrove whiprays employ thermotaxic behaviours and a thermally insensitive aerobic metabolism to thrive in thermally dynamic and extreme habitats. Tropical nursery areas may, therefore, offer important thermal refugia for young rays. However, these tropical nursery areas could become threatened by mangrove and coral habitat loss, and climate change.

Caffeine Consumption and Interaction with ADORA2A, CYP1A2 and NOS1 Variants Do Not Influence Age at Onset of Machado-Joseph Disease.

BACKGROUND: The age at onset (AO) of Machado-Joseph disease (SCA3/MJD), a disorder due to an expanded CAG repeat (CAGexp) in ATXN3, is quite variable and the role of environmental factors is still unknown. Caffeine was associated with protective effects against other neurodegenerative diseases, and against SCA3/MJD in transgenic mouse models. We aimed to evaluate whether caffeine consumption and its interaction with variants of caffeine signaling/metabolization genes impact the AO of this disease. METHODS: a questionnaire on caffeine consumption was applied to adult patients and unrelated controls living in Rio Grande do Sul, Brazil. AO and CAGexp were previously determined. SNPs rs5751876 (ADORA2A), rs2298383 (ADORA2A), rs762551 (CYP1A2) and rs478597 (NOS1) were genotyped. AO of subgroups were compared, adjusting the CAGexp to 75 repeats (p < 0.05). RESULTS: 171/179 cases and 98/100 controls consumed caffeine. Cases with high and low caffeine consumption (more or less than 314.5 mg of caffeine/day) had mean (SD) AO of 35.05 (11.44) and 35.43 (10.08) years (p = 0.40). The mean (SD) AO of the subgroups produced by the presence or absence of caffeine-enhancing alleles in ADORA2A (T allele at rs5751876 and rs2298383), CYP1A2 (C allele) and NOS1 (C allele) were all similar (p between 0.069 and 0.516). DISCUSSION: Caffeine consumption was not related to changes in the AO of SCA3/MJD, either alone or in interaction with protective genotypes at ADORA2A, CYP1A2 and NOS1.

Liraglutide in the management of obesity: real world data (Portugal).

BACKGROUND: Overweight and obesity are major public health issues with increasing incidence and prevalence, affecting more than 50% of the population in developed countries. Due to its complex pathophysiology and multifactorial etiology, disease understanding, diagnostic approach and management remain suboptimal. Together with a structured nutritional intervention and physical activity plan, pharmacological treatment has the potential to magnify weight loss and health related benefits. Liraglutide is one of the most effective and frequently prescribed weight loss medication. Its efficacy and safety have been demonstrated in randomized clinical trials, however, real world data in Portugal is scarce. The authors report on the experience of a University Hospital Endocrine Clinic in the management of patients with overweight and obesity with liraglutide on top of lifestyle intervention. The aim of the study was to evaluate the effectiveness of liraglutide in the management of overweight and obesity. METHODS: Retrospective, longitudinal observational study. Inclusion criteria were adult patients (>18 years old) with obesity (BMI>30 kg/m2) or overweight (≥27 kg/m2) with at least one obesity related co-morbidity (hypertension, dyslipidemia, obstructive sleep apnea, non-alcoholic fatty liver disease) with at least three months of liraglutide treatment. Diabetes diagnosis and prior bariatric surgery were exclusion criteria. Demographic and clinical variables were included and weight was recorded before and after at least 3 months of liraglutide treatment. RESULTS: One hundred forty-eight patients (85.8% females) with a mean age of 48.7±11.9 years were treated with liraglutide. Mean baseline BMI was 33.8±5.2 kg/m2 and median follow-up was 13 months. At the last appointment, 85.8% were still taking liraglutide. Among patients still taking liraglutide, mean weight loss was 7.6 kg (7.9%), with significantly greater losses in patients treated for more than 6 months (8.6kg vs. 6.2 kg, P=0.016). Patients with obesity lost significantly more weight than overweight patients (8.3 kg vs. 4.5 kg, P=0.028), despite similar treatment duration. The reasons for liraglutide withdrawal were gastrointestinal intolerance (7), medication cost (2), inefficacy (10) and physician instructions (1). CONCLUSIONS: The present study documents the long-term efficacy of liraglutide in the treatment of patients with overweight and obesity, with a low rate of drug withdrawal. Mean weight loss was significant and more evident from the 6th month of treatment on. Liraglutide, along with lifestyle intervention, is a good option for weight management in the majority of patients with obesity.

Which government policies to create sustainable food systems have the potential to simultaneously address undernutrition, obesity and environmental sustainability?

INTRODUCTION: A transformation of food systems is urgently needed, given their contribution to three ongoing and interlinked global health pandemics: (1) undernutrition and food insecurity, (2) obesity and non-communicable diseases (NCDs), and (3) climate change and biodiversity loss. As policymakers make decisions that shape food systems, this study aimed to identify and prioritise policies with double- or triple-duty potential to achieve healthier and more environmentally sustainable food systems. METHODS: This study undertook a 4-step methodological approach, including (i) a compilation of international policy recommendations, (ii) an online survey, (iii) four regional workshops with international experts and (iv) a ranking for prioritisation. Policies were identified and prioritised based on their double- or triple-duty potential, synergies and trade-offs. Using participatory and transdisciplinary approaches, policies were identified to have double- or triple-duty potential if they were deemed effective in tackling two or three of the primary outcomes of interest: (1) undernutrition, (2) obesity/NCDs and (3) environmental degradation. RESULTS: The desk review identified 291 recommendations for governments, which were merged and classified into 46 initially proposed policies. Based on the results from the online survey, 61% of those policies were perceived to have double- or triple-duty potential. During the workshops, 4 potential synergies and 31 trade-offs of these policies were identified. The final list of 44 proposed policies for healthier and more environmentally sustainable food systems created was divided into two main policy domains: 'food supply chains' and 'food environments'. The outcome with the most trade-offs identified was 'undernutrition', followed by 'environmental sustainability', and 'obesity/NCDs'. Of the top five expert-ranked food supply chain policies, two were perceived to have triple-duty potential: (a) incentives for crop diversification; (b) support for start-ups, and small- and medium-sized enterprises. For food environments, three of the top five ranked policies had perceived triple-duty potential: (a) affordability of healthier and more sustainable diets; (b) subsidies for healthier and more sustainable foods; (c) restrictions on children's exposure to marketing through all media. CONCLUSION: This study identified and prioritised a comprehensive list of double- and triple-duty government policies for creating healthier and more environmentally sustainable food systems. As some proposed policies may have trade-offs across outcomes, they should be carefully contextualised, designed, implemented and monitored.

Use and misuse of psychoactive medicines: a descriptive cross-sectional study in a densely populated region of Portugal.

Introduction: Although psychoactive medicines (PMed) are needed in several psychiatric conditions, their use and misuse bear risks. We aimed at estimating the prevalence of PMed use and misuse. Methods: Data on all PMed prescribed in 2017 and dispensed in community pharmacies of the Lisbon and Tagus Valley region of Portugal (ARSLVT) were extracted from ARSLVT medicines' dispensing database. For 21 PMed among prescription opioids, benzodiazepines and z-drugs (BZDR), antidepressants (AD) and anticonvulsants (AC), we estimated the number of users of each PMed, and assessed PMed misuse by a set of proxy indicators for studying this practice: chronic use (use of ≥180 DDD during the study period) of PMed intended for short-term treatments, concomitant use of several PMed, in particular if involving long-term (≥ 30 days) opioid analgesic (OA) use, and doctor shopping (patients consulting several physicians in order to have access to a quantity higher than intended by each prescriber). Data were analysed using descriptive statistics and hypothesis testing, and multivariate logistic regression was used to explore potential factors affecting long-term concomitant treatment of chronic OA with other PMed. Results: PMed use prevalence was 21.7%: 6.6% for OA, 12.7% for benzodiazepines (BZD), 5.3% for AD and 2.8% for AC. BZDR were mainly prescribed in primary care and OA in hospital outpatients. Chronic use of PMed was observed in 25%, especially with sertraline and buprenorphine for opioid use disorder (long-term treatment), and lorazepam (short-term treatment). About 56.6% of OA chronic users were long-term concurrent users with other PMed, mainly BZDR. Risk of abuse was low for BZDR, whilst four opioids had meaningful doctor shopping indicators - fentanyl, opioid use disorder buprenorphine, morphine and hydromorphone. Conclusions: BZD are the main PMed used in ARSLVT, often chronically, especially lorazepam. Prevalence of OA use is low, although with higher risk of misuse than BZDR. Concomitant use of several PMed is frequent.

Integrated magneto-plasmonic nanostructures-based immunoassay for galectin-3 detection.

Cardiovascular diseases remain a leading cause of global mortality, highlighting the need for accurate diagnostic tools and the detection of specific cardiac biomarkers. Surface-enhanced Raman scattering (SERS) spectroscopy has proved to be a promising alternative diagnostic tool to detect relevant biomarkers compared to traditional methods. To our knowledge, SERS methodology has never been used to detect galectin-3 (Gal-3), a crucial biomarker for cardiovascular conditions. Our study aimed to develop plasmonic and magneto-plasmonic nanoplatforms for the sensitive immunodetection of Gal-3 using SERS. Spherical gold nanoparticles (AuNPs) were synthesized and functionalized with 11-mercaptoundecanoic acid (MUDA) to enable antibody binding and 4-mercaptobenzoic acid (4MBA) that served as a Raman reporter due to its intense Raman signal. Following bioconjugation with Gal-3 antibody, the AuNPs were employed in the immunodetection of Gal-3 in phosphate-buffer saline (PBS) solution, offering a limit of detection (LOD) of 12.2 ng mL-1 and a working range up to 120 ng mL-1. Furthermore, our SERS-based immunosystem demonstrated selectivity for Gal-3 (40 ng mL-1) in the presence of other biomolecules such as α-amylase, bovine serum albumin and human C-reactive protein. As a proof of concept, we developed magneto-plasmonic nanoparticles composed of silica-coated magnetite decorated with the bioconjugated AuNPs aimed at enhancing the uptake and detection of Gal-3 via SERS coupled with Raman imaging. Our findings underscore the potential of SERS-based techniques for the sensitive and specific detection of biomarkers, holding significant implications for improved diagnosis and surveillance of cardiovascular diseases. Future research will focus on further optimizing these nanoplatforms and their translation into clinical settings.