Effects of temperature on growth, development, and survival of amphibian larvae: macroecological and evolutionary patterns.

Temperature affects the rate of biochemical and physiological processes in amphibians, influencing metamorphic traits. Temperature patterns, as those observed in latitudinal and altitudinal clines, may impose different challenges on amphibians depending on how species are geographically distributed. Moreover, species' response to environmental temperatures may also be phylogenetically constrained. Here, we explore the effects of acclimation to higher temperatures on tadpole survival, development, and growth, using a meta-analytical approach. We also evaluate whether the latitude and climatic variables at each collection site can explain differences in species' response to increasing temperature and whether these responses are phylogenetically conserved. Our results show that species that develop at relatively higher temperatures reach metamorphosis faster. Furthermore, absolute latitude at each collection site may partially explain heterogeneity in larval growth rate. Phylogenetic signal of traits in response to temperature indicates a non-random process in which related species resemble each other less than expected under Brownian motion evolution (BM) in all traits, except survival. The integration of studies in a meta-analytic framework allowed us to explore macroecological and macroevolutionary patterns and provided a better understanding of the effects of climate change on amphibians.

Effect of Foraminal Enlargement on Periapical Healing in Necrotic Teeth: A Systematic Review.

Introduction: Foraminal Enlargement (FE) is a cleaning performed in the apical-most region of the tooth, in order to optimize root disinfection. This systematic review evaluated the influence of FE during root canal treatment on bacterial reduction and repair of the periapical lesion. Materials and Methods: Searches in PubMed/MEDLINE, Scopus, Cochrane Library, Web of Science, Embase, Scielo, Lilacs and OpenGrey were performed until January-2024. Ex vivo and in vivo studies evaluating the effects of FE in the bacterial reduction and repair of the periapical lesion were included, respectively, followed by risk of bias assessment (modified version of Joanna Briggs Institute's for ex vivo studies and Systematic Review Centre for Laboratory animal Experimentation's risk of bias tools for in vivo studies). The meta-analysis was not feasible and a qualitative summary for each outcome was provided. Results: Of 950 studies, 2 in vivo studies were eligible, using animal models with infected teeth. Of these two, periapical repair was evaluated with hematoxylin-eosin stain, and FE improved periapical healing. Regarding ex vivo studies, 3 were eligible, using extracted human teeth. The inoculations in ex vivo models were performed with Enterococcus (E.) faecalis, and FE reduced E. faecalis in the ex vivo models. Conclusions: Foraminal enlargement seems to increase bacterial reduction within the root canal, and provide major periapical tissue repair on the histological analysis in animal studies. However, caution is necessary when translating these results to the clinical environment.

Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.

Differential diagnosis between multiple sclerosis and leukodystrophies - A scoping review.

Multiple Sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) characterized by damage to the myelin sheaths of oligodendrocytes. Currently, there is no specific biomarker to identify the disease; however, a diagnostic criterion has been established based on patient's clinical, laboratory, and imaging characteristics, which assists in identifying this condition. The primary method for diagnosing MS is the McDonald criteria, first described in 2001 and revised in the years 2005, 2012, and 2017. These criteria have been continuously reviewed to enhance specificity and sensitivity in the diagnosis of MS, thereby reducing errors in its differential diagnosis. An important differential diagnosis that shares overlapping features with MS, mainly the progressive forms, are leukodystrophies with demyelination as underlying pathology. Leukodystrophies comprise a rare group of genetically determined disorders that lead to either demyelination or hypomyelination of the central nervous system that can result neuroimaging changes as well as clinical findings similar to those observed in MS. Thus, systematic evaluation encompassing clinical presentation, neuroimaging findings, and laboratory metrics proves indispensable for a differential diagnosis. As such, this study aimed to establish, clearly and objectively, the similarities and differences between MS and the main demyelinating leukodystrophies. The study analyzed the parameters of the McDonald criteria, including clinical, laboratory, and magnetic resonance imaging aspects, as found in patients with leukodystrophies through scoping literature review. The data were compared with the determinations of the revised 2017 McDonald criteria to facilitate the differential diagnosis of these diseases in clinical practice.

Data Base similarity (DBsimilarity) of natural products to aid compound identification on MS and NMR pipelines, similarity networking, and more.

INTRODUCTION: We developed Data Base similarity (DBsimilarity), a user-friendly tool designed to organize structure databases into similarity networks, with the goal of facilitating the visualization of information primarily for natural product chemists who may not have coding experience. METHOD: DBsimilarity, written in Jupyter Notebooks, converts Structure Data File (SDF) files into Comma-Separated Values (CSV) files, adds chemoinformatics data, constructs an MZMine custom database file and an NMRfilter candidate list of compounds for rapid dereplication of MS and 2D NMR data, calculates similarities between compounds, and constructs CSV files formatted into similarity networks for Cytoscape. RESULTS: The Lotus database was used as a source for Ginkgo biloba compounds, and DBsimilarity was used to create similarity networks including NPClassifier classification to indicate biosynthesis pathways. Subsequently, a database of validated antibiotics from natural products was combined with the G. biloba compounds to identify promising compounds. The presence of 11 compounds in both datasets points to possible antibiotic properties of G. biloba, and 122 compounds similar to these known antibiotics were highlighted. Next, DBsimilarity was used to filter the NPAtlas database (selecting only those with MIBiG reference) to identify potential antibacterial compounds using the ChEMBL database as a reference. It was possible to promptly identify five compounds found in both databases and 167 others worthy of further investigation. CONCLUSION: Chemical and biological properties are determined by molecular structures. DBsimilarity enables the creation of interactive similarity networks using Cytoscape. It is also in line with a recent review that highlights poor biological plausibility and unrealistic chromatographic behaviors as significant sources of errors in compound identification.

Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-ß oligomers (AßO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AßO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AßO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AßO (90 µM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AßO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AßO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AßO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AßO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AßO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.

Impact of the COVID-19 Pandemic on Births, Vaginal Deliveries, Cesarian Sections, and Maternal Mortality in a Brazilian Metropolitan Area: A Time-Series Cohort Study.

Purpose: The COVID-19 pandemic posed a worldwide challenge, leading to radical changes in healthcare. The primary objective of the study was to assess the impact of the COVID-19 pandemic on birth, vaginal delivery, and cesarian section (c-section) rates. The secondary objective was to compare the maternal mortality before and after the pandemic. Patients and Methods: Time-series cohort study including data of all women admitted for childbirth (vaginal delivery or c-section) at the maternities in the Public Health System of Federal District, Brazil, between March 2018 and February 2022, using data extracted from the Hospital Information System of Brazilian Ministry of Health (SIH/DATASUS) on September 30, 2022. Causal impact analysis was used to evaluate the impact of COVID-19 on birth, vaginal delivery, and c-section using the CausalImpact R package, and a propensity score matching was used to evaluate the effect on maternal mortality rate using the Easy R (EZR) software. Results: There were 150,617 births, and considering total births, the effect of the COVID-19 pandemic was not statistically significant (absolute effect per week: 5.5, 95% CI: -24.0-33.4). However, there was an increase in c-sections after COVID-19 (absolute effect per week: 18.1; 95% CI: 11.9-23.9). After propensity score matching, the COVID-19 period was associated with increased maternal mortality (OR: 3.22, 95% CI: 1.53-6.81). The e-value of the adjusted OR for the association between the post-COVID-19 period and maternal mortality was 5.89, with a 95% CI: 2.43, suggesting that unmeasured confounders were unlikely to explain the entirety of the effect. Conclusion: Our study revealed a rise in c-sections and maternal mortality during the COVID-19 pandemic, possibly due to disruptions in maternal care. These findings highlight that implementing effective strategies to protect maternal health in times of crisis and improve outcomes for mothers and newborns is crucial.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Habit-, reward- and fear-related motivations in alcohol use disorder: A one-year prospective study.

OBJECTIVE: Cross-sectional studies show that habitual use of alcohol is associated with severity of alcohol dependence reflected across a range of domains and lower number of detoxifications in multiple settings. In this study, we investigated whether alcohol use disorder (AUD) patients with greater habitual use of alcohol at baseline showed worse outcomes after one year of follow-up. METHODS: A sample of inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorder (AUD) was assessed at baseline (n = 50) and after one year (n = 30). The Habit, Reward, and Fear Scale (HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) drives for alcohol use, the Alcohol Dependence Scale (ADS) was used to assess clinical outcomes, and the Depression, Anxiety and Stress Scale (DASS-21) was used to quantify and control for associated affective symptoms. RESULTS: There was a significant reduction in the three HRFS scores at the follow-up. Regression analyses demonstrated that greater habit- and fear-related drives at baseline predicted greater decreases in the ADS scores at the endpoint. However, after controlling for age, sex and affective symptoms, only reward and fear were associated with reductions in ADS scores at the end of one year. Prescriptions of naltrexone and antidepressants/benzodiazepines did not predict decreases in reward and fear-related motivations. CONCLUSION: Although we were unable to confirm that habitual subscores at baseline predict worse long-term outcomes among inpatients with AUD, we found that a greater fear and reward motives for the use of alcohol predicted a greater magnitude of improvement in the AUD symptoms after one year. We hope that these findings will help develop new approaches toward AUD treatment and inform models of addiction research.

Efeito da manobra de recrutamento alveolar no pós-operatório imediato de cirurgia cardíaca: uma revisão sistemática / Effect of the alveolar recruitment maneuver in the immediate postoperative period of cardiac surgery: a systematic review

Introdução: as cirurgias cardíacas são as intervenções de escolha em níveis mais avançados das doenças cardiovasculares, e complicações pulmonares podem ocorrer como consequência das alterações fisiológicas causadas pela circulação extracorpórea, pela anestesia e pela incisão esterno torácica. A fisioterapia atua com o intuito de prevenir e tratar essas complicações, através da utilização de uma das técnicas de expansão pulmonar mais utilizadas na reversão de hipoxemia e atelectasias, a manobra de recrutamento alveolar, com o objetivo de abrir alvéolos colapsados e aumentar as trocas gasosas. Objetivo: revisar sistematicamente os efeitos da manobra, na relação PaO2/FiO2, SatO2, o tempo de ventilação mecânica, o tempo de internamento, a incidência de atelectasia, a pressão arterial média e a frequência cardíaca. Metodologia: revisão de ensaios clínicos controlados e randomizados nas bases de dados PubMed, Cochrane Library, LILACS e PEDro. Foram incluídos estudos que utilizaram a manobra como prevenção de complicações pulmonares, publicados em inglês e português. Resultados: foram incluídos 4 estudos, publicados entre os anos 2005 e 2017. O nível de pressão da manobra variou entre 30 cmH2O a 40 cmH2O. Os estudos mostraram que a manobra foi estatisticamente relevante na relação PaO2/FiO2, SatO2 e na redução da incidência de atelectasias, sem impacto no tempo de ventilação mecânica, no tempo de internamento, na pressão arterial média e na frequência cardíaca. Conclusão: a manobra de recrutamento pode ser considerada como uma técnica a ser utilizada na prevenção de alterações pulmonares, porém não é possível afirmar se os benefícios da manobra perduraram em longo prazo.

Introduction: Cardiac surgeries are the interventions of choice in more advanced levels of cardiovascular disease, and pulmonary complications can occur as a result of physiological changes caused by cardiopulmonary bypass, anaesthesia and the sternum thoracic incision. Physiotherapy acts with the aim of preventing and treating these complications, through the use of one of the most used lung expansion techniques in the reversal of hypoxemia and atelectasis, the alveolar recruitment maneuver, with the objective of opening collapsed alveoli and increasing gas exchanges. Objective: To systematically review the effects of the maneuver on the PaO2/FiO2 ratio, SatO2, duration of mechanical ventilation, length of hospitalization, incidence of atelectasis, mean arterial pressure and heart rate. Methodology: Review of controlled and randomized clinical trials in PubMed, Cochrane Library, LILACS and PEDro databases. Studies that used the maneuver to prevent pulmonary complications, published in English and Portuguese, were included. Results: 4 studies, published between 2005 and 2017, were included. The maneuver pressure level ranged from 30 cmH2O to 40 cmH2O. The studies showed that the maneuver was statistically relevant in relation to PaO2/FiO2, SatO2 and in reducing the incidence of atelectasis, with no impact on the duration of mechanical ventilation, length of hospitalization, mean arterial pressure and heart rate. Conclusion: The recruitment maneuver can be considered as a technique to be used in the prevention of pulmonary alterations; however, it is not possible to state whether the benefits of the maneuver lasted in the long term.

NMR as a tool for compound identification in mixtures.

INTRODUCTION: Natural products and metabolomics are intrinsically linked through efforts to analyze complex mixtures for compound annotation. Although most studies that aim for compound identification in mixtures use MS as the main analysis technique, NMR has complementary advances that are worth exploring for enhanced structural confidence. OBJECTIVE: This review aimed to showcase a portfolio of the main tools available for compound identification using NMR. MATERIALS AND METHODS: COLMAR, SMART-NMR, MADByTE, and NMRfilter are presented using examples collected from real samples from the perspective of a natural product chemist. Data are also made available through Zenodo so that readers can test each case presented here. CONCLUSION: The acquisition of 1 H NMR, HSQC, TOCSY, HSQC-TOCSY, and HMBC data for all samples and fractions from a natural products study is strongly suggested. The same is valid for MS analysis to create a bridged analysis between both techniques in a complementary manner. The use of NOAH supersequences has also been suggested and demonstrated to save NMR time.

Educational Interventions on Diabetic Foot Self-Care: A Study Protocol for a Pragmatic Randomized Controlled Trial.

Diabetic foot is one of the most serious complications of diabetes and foot ulcer recurrence has been associated with poor foot care. Educational programs may work as a vehicle for promoting knowledge and adequate foot self-care behaviors, reducing potential ulcerative complications in the diabetic foot, and promoting a better quality of life. This study protocol will analyze the impact of two different educational strategies - an instructive video (Experimental Group 1) compared to a foot care leaflet with real-time guided reading (Experimental Group 2) and standard care (Control Group) - on adherence and knowledge about diabetic foot care and patients' perception of their foot health. This study is a Pragmatic Randomized Controlled Trial of a non-pharmacological treatment. Participants need to have a diabetic foot diagnosis and attend a Diabetic Foot Multidisciplinary Consultation at two hospitals from the North of Portugal. Participants will be assessed at the first appointment of the diabetic foot consultation (T0), two weeks after (T1), and three months later, at follow-up (T2). Primary outcomes will be adherence and knowledge about diabetic foot care and general foot health. Secondary outcomes will be illness representations regarding diabetic foot. The results of this study will inform educational interventions to decrease diabetic foot ulcers, amputation rates, and the costs associated with both, contributing to foot care adherence and improve patient's quality of life.

Guided Tissue Regeneration in Class IV External Cervical Resorption: A Case Report.

External cervical resorption (ECR) is a type of dental resorption that originates from the loss of the cementum's protective layer. The direct exposure of dentin to the periodontal ligament may lead to the invasion of clastic cells through an entry point on the external root surface into the dentinal tissue, causing resorption. Depending on the extension of ECR, different treatments are proposed. Although the literature presents distinct materials and methods for restoring ECR areas, an existing gap is related to care in the treatment of the supporting periodontal tissue. Guided tissue regeneration (GTR)/guided bone regeneration includes the stimulation of bone formation in bone defects using different types of membranes (resorbable and nonresorbable), regardless of its association with bone substitutes or grafts. Despite the benefits of guided bone regeneration, the application of this method in cases of ECR is still under-explored in the literature. Thus, the present case report uses GTR with xenogenic material and polydioxanone membrane in a case of class IV ECR. The success of the present case is related to the correct diagnosis and treatment plan. Complete debridement of resorption areas and restoration with biodentine were effective in tooth repair. GTR contributed to the stabilization of supporting periodontal tissues. The association of the xenogeneic bone graft with the polydioxanone membrane proved to be a viable option for restoring the health of the periodontium.

The Effectiveness of a Journal Club for Improving Evidence-Based Medicine Skills and Confidence in Pre-clerkship Medical Students.

Introduction: Evidence-based medicine (EBM) refers to medical practice that uses current best evidence to inform decision-making. This requires several skills including (1) creating an answerable question, (2) searching literature, (3) critically appraising evidence, and (4) applying results. Journal clubs are known to be effective in improving searching and critical appraisal skills in graduate medical education. In pre-clerkship medical education, journal clubs are used less often, and students often do not have the opportunity to engage in all of the steps above. Methods: We developed a journal club for pre-clerkship students and measured its effectiveness using a pre-test, post-test design. Students attended 5 journal club sessions run by rotating student leaders and facilitated by faculty. Student groups developed searchable questions from clinical cases, searched the literature, located and critically appraised an article, and applied results to the case. We measured EBM skills and confidence using two validated questionnaires. Results: Twenty-nine students (MS-1 and MS-2) completed the study. EBM confidence significantly improved at post-test with greatest improvements in the MS-1 student cohort. Confidence in developing a searchable question from a patient case significantly improved in both cohorts. There were no changes measured on the Test of EBM Knowledge and Skills. Discussion: Participation in a faculty-mentored, student-led journal club improved confidence across all domains of EBM, primarily in MS-1 students. Journal clubs are positively received by pre-clerkship medical students and provide effective mechanisms to teach and promote all steps of EBM in pre-clerkship curricula. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01779-y.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

Relax to Heal? Perspectives of Patients with Diabetic Foot Ulcers and Health Professionals on Relaxation Sessions for Wound Healing.

OBJECTIVE: To explore patients' and healthcare professionals' (HPs') perspectives on the suitability/acceptability of a relaxation intervention, its effects on patients' well-being and diabetic foot ulcer (DFU) healing, and its incorporation into the multidisciplinary management of patients with diabetic foot. METHODS: This qualitative study was nested within a three-arm pilot randomized controlled trial. Patients with a chronic DFU received four relaxation sessions. Investigators then interviewed patients, physicians, and nurses involved with diabetic foot consultations. Interviews were audio-recorded, transcribed, and analyzed using thematic content analysis. RESULTS: Five themes emerged from patient's interviews about the suitability/acceptability of the relaxation intervention: perceptions regarding the psychological intervention, distress, the relaxation technique, changes in the patient's life, and changes in DFU/contribution to healing. Three themes emerged from interviews with HPs: perceptions regarding relaxation, changes in the patient, and changes in DFU/healing. Regarding the feasibility of the relaxation intervention, three themes emerged for both patients and HPs: suggested modifications, stressors/difficulties, and impact of COVID-19 pandemic. The utility theme emerged only in HP interviews, with subthemes of patients' distress, psychological interventions, relaxation intervention, and integration of the psychologist in the team. CONCLUSIONS: These findings provide evidence for the suitability/acceptability, feasibility, and utility of a relaxation intervention in diabetic foot consultations.

Relaxation intervention to improve diabetic foot ulcer healing: Results from a pilot randomized controlled study.

This pilot randomised controlled study (RCT) aimed to assess the feasibility and acceptability of a progressive muscle relaxation with guided imagery intervention (experimental group [EG]) compared to a neutral guided imagery placebo (active control group [ACG]) and standard care to diabetic foot ulcer [DFU] treatment (passive control group [PCG]), to decide on the need for a definitive RCT. Diabetic foot patients with one or two chronic DFU and significant levels of stress/anxiety/depression were recruited and assessed during a period of 6 months, at three moments. Primary outcomes: feasibility rates and satisfaction with relaxation sessions. Secondary outcomes: DFU healing score, DFU-related quality of life (DFUQoL), physical and mental HRQoL, stress and emotional distress, DFU representations, arterial blood pressure, and heart rate. A total of 146 patients completed the baseline (T0) assessment with 54 participants presenting significant distress being randomised into three groups. Patients were assessed 2 months post-intervention (T1) and 4 months after T1 (T2). Feasibility rates showed reduced values on eligibility, recruitment and inclusion in the study, although with an acceptable rate of refusal lower than 10%. On average, participants reported being satisfied with relaxation sessions and recommended them to other patients. Differences between groups showed that, at T1, PCG participants reported higher levels of stress than those from EG and ACG. Within-group differences showed improvements in stress, distress, DFUQoL and DFU extent over time only in EG and ACG. Only EG showed significant changes in DFU representations at T1. The results suggest that relaxation may be a promising coping strategy to deal with DFU distress and an important adjuvant therapy for DFU healing, supporting the implementation of a definitive RCT.

High concentrations of fructose cause brain damage in mice.

Excessive fructose consumption is associated with the incidence of obesity and systemic inflammation, resulting in increased oxidative damage and failure to the function of brain structures. Thus, we hypothesized that fructose consumption will significantly increase inflammation, oxidative damage, and mitochondrial dysfunction in the mouse brain and, consequently, memory damage. The effects of different fructose concentrations on inflammatory and biochemical parameters in the mouse brain were evaluated. Male Swiss mice were randomized into four groups: control, with exclusive water intake, 5%, 10%, and 20% fructose group. The 10% and 20% fructose groups showed an increase in epididymal fat, in addition to higher food consumption. Inflammatory markers were increased in epididymal fat and in some brain structures. In the evaluation of oxidative damage, it was possible to observe significant increases in the hypothalamus, prefrontal cortex, and hippocampus. In the epididymal fat and in the prefrontal cortex, there was a decrease in the activity of the mitochondrial respiratory chain complexes and an increase in the striatum. Furthermore, short memory was impaired in the 10% and 20% groups but not long memory. In conclusion, excess fructose consumption can cause fat accumulation, inflammation, oxidative damage, and mitochondrial dysfunction, which can damage brain structures and consequently memory.

Exploring Scoring Function Space: Developing Computational Models for Drug Discovery.

BACKGROUND: The idea of scoring function space established a systems-level approach to address the development of models to predict the affinity of drug molecules by those interested in drug discovery. OBJECTIVE: Our goal here is to review the concept of scoring function space and how to explore it to develop machine learning models to address protein-ligand binding affinity. METHOD: We searched the articles available in PubMed related to the scoring function space. We also utilized crystallographic structures found in the protein data bank (PDB) to represent the protein space. RESULTS: The application of systems-level approaches to address receptor-drug interactions allows us to have a holistic view of the process of drug discovery. The scoring function space adds flexibility to the process since it makes it possible to see drug discovery as a relationship involving mathematical spaces. CONCLUSION: The application of the concept of scoring function space has provided us with an integrated view of drug discovery methods. This concept is useful during drug discovery, where we see the process as a computational search of the scoring function space to find an adequate model to predict receptor-drug binding affinity.