Relaxation intervention to improve diabetic foot ulcer healing: protocol for a pilot study with a nested qualitative study.

OBJECTIVE: A mixed-methods approach nested in a pilot three-arm randomised controlled trial (RCT) was conducted to evaluate the feasibility and acceptability of an intervention of progressive muscle relaxation with guided imagery (experimental group) compared to a neutral guided imagery placebo (active control group) and a group that did not receive any psychological intervention (passive control group). The purpose was to inform a future definitive RCT that will test its effectiveness. Qualitatively, this study examined patients and health professionals' perspectives regarding the relaxation intervention, in order to assess the acceptability and applicability of relaxation as an adjuvant therapy. METHOD: Participants must have had a diagnosis of diabetes and diabetic foot disease; one or two active hard-to-heal ulcers at the time of the assessment; and clinical levels of stress or anxiety or depression. Participants were randomised and assessed at three timepoints after the first hospital consultation for hard-to-heal diabetic foot ulcer (DFU). RESULTS: Rates of eligibility, recruitment, refusal, adherence to study protocol, participation in follow-up and dropout, and patients' satisfaction with the relaxation intervention were assessed as primary outcomes. Secondary outcomes were DFU healing; patients' DFU-related quality of life; physical and mental quality of life; perceived stress; emotional distress; adherence to DFU care; perceptions of DFU; as well as arterial systolic/diastolic pressure and heart rate. CONCLUSION: The results of this pilot study contributed to clarification and better elucidation of the benefits of relaxation techniques regarding patients' HRQoL and DFU healing. DECLARATION OF INTEREST: Funding: This study was conducted at the Psychology Research Centre (CIPsi/UM) School of Psychology, University of Minho, Portugal and supported by the Foundation for Science and Technology (FCT) through the Portuguese State Budget (UIDB/01662/2020) and by a PhD fellowship from FCT assigned to GF (SFRH/BD/131780/2017) and an FCT grant (PTDC/PSI-GER/28163/2017) assigned to MGP. The authors have no conflicts of interest to declare.

Experience of living with psoriasis in Brazil: a Global Psoriasis Atlas online survey.

BACKGROUND: Psoriasis significantly burdens patients' lives, but there is limited data on this in Brazil. METHODS: Between May 2022 and January 2023, we conducted a cross-sectional online survey of 563 Brazilian residents aged ≥18 years who had been diagnosed with psoriasis. Spearman's correlation (r) was used to test the correlation between self-assessed disease severity (Simplified Psoriasis Index [saSPI] extent score; range 0 [clear/minor] to 40 [widespread/severe]) and health-related quality of life (QoL, score of 1 means perfect health) and capability (ICECAP-A: score of 1 means full capability) measures. Multivariable linear regression was used to identify predictors of QoL and capability. A thematic analysis examined the free-text responses and identified common themes. RESULTS: The mean age of participants was 42.1 ± 12.4 years, and over half had at least one other long-term condition. The mean QoL score was 0.59 ± 0.25, and the mean capability score was 0.71 ± 0.21. At the time of survey completion, over 80% of respondents reported some level of pain and/or discomfort, and 86% reported feeling anxious and/or depressed. The mean self-assessed saSPI was 7.8 ± 8.6, which negatively correlated with health-related QoL (r = -0.49, P < 0.05) and capability (r = -0.44, P < 0.05). Significant predictors of poorer QoL and reduced capability included high saSPI, number of psoriasis flares and comorbidities, female gender, Black ethnicity, and employment status (unemployed, long-term sick). Frequently reported areas that impacted patients were social stigma/prejudice, powerlessness, lack of education and public awareness, and difficulty obtaining appropriate care/treatment. CONCLUSIONS: We found that the clinical manifestations, severity, and associated comorbidities of psoriasis negatively impacted health-related QoL and capability, along with feelings of stigmatization and barriers to specialist treatment. This highlights the need for better access to care and awareness of the disease to improve the lives of people living with psoriasis in Brazil.

A network meta-analysis of non-invasive brain stimulation interventions for autism spectrum disorder: Evidence from randomized controlled trials.

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95 % confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3 + ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = - 1.40, 95 %CIs = - 2.67 to - 0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.

Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis "Nutra NMA SCZ".

Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference = SMD) in total symptomatology and acceptability (Risk Ratio = RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. The systematic review included 49 records documenting 50 studies (n = 2384) documenting 22 interventions. Citicoline (SMD =-1.05,95%CI = -1.85; -0.24), L-lysine (SMD = -1.04,95%CI = -1.84; -0.25), N-acetylcysteine (SMD = -0.87, 95%CI = -1.27; -0.47) and sarcosine (SMD = -0.5,95%CI = -0.87-0.13) outperformed placebo for total symptomatology. High heterogeneity (tau2 = 0.10, I2 = 55.9%) and global inconsistency (Q = 40.79, df = 18, p = 0.002) emerged without publication bias (Egger's test, p = 0.42). Sarcosine improved negative symptoms (SMD = -0.65, 95%CI = -1.10; -0.19). N-acetylcysteine improved negative symptoms (SMD = -0.90, 95%CI = -1.42; -0.39)/general psychopathology (SMD = -0.76, 95%CI = -1.39; -0.13). No compound improved total symptomatology within acute phase studies (k = 7, n = 422). Sarcosine (SMD = -1.26,95%CI = -1.91; -0.60), citicoline (SMD = -1.05,95%CI = -1.65;-0.44), and N-acetylcysteine (SMD = -0.55,95%CI = -0.92,-0.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD = -1.10, 95%CI = -1.75,-0.45), L-lysine (SMD = -1.05,95%CI = -1.55, -0.19), omega-3 fatty acids (SMD = -0.83,95%CI = -1.31, -0.34) and withania somnifera (SMD = -0.71,95%CI = -1.21,-0.22). Citicoline (SMD = -1.05,95%CI = -1.86,-0.23), L-lysine (SMD = -1.04,95%CI = -1.84,-0.24), N-acetylcysteine (SMD = -0.89,95%CI = -1.35,-0.43) and sarcosine (SMD = -0.61,95%CI = -1.02,-0.21) outperformed placebo augmentation of TAU ("any phase"). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU. Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted.

Structural and Functional Characterization of New Lipid Transfer Proteins with Chitin-Binding Properties: Insights from Protein Structure Prediction, Molecular Docking, and Antifungal Activity.

Faced with the emergence of multiresistant microorganisms that affect human health, microbial agents have become a serious global threat, affecting human health and plant crops. Antimicrobial peptides have attracted significant attention in research for the development of new microbial control agents. This work's goal was the structural characterization and analysis of antifungal activity of chitin-binding peptides from Capsicum baccatum and Capsicum frutescens seeds on the growth of Candida and Fusarium species. Proteins were initially submitted to extraction in phosphate buffer pH 5.4 and subjected to chitin column chromatography. Posteriorly, two fractions were obtained for each species, Cb-F1 and Cf-F1 and Cb-F2 and Cf-F2, respectively. The Cb-F1 (C. baccatum) and Cf-F1 (C. frutescens) fractions did not bind to the chitin column. The electrophoresis results obtained after chromatography showed two major protein bands between 3.4 and 14.2 kDa for Cb-F2. For Cf-F2, three major bands were identified between 6.5 and 14.2 kDa. One band from each species was subjected to mass spectrometry, and both bands showed similarity to nonspecific lipid transfer protein. Candida albicans and Candida tropicalis had their growth inhibited by Cb-F2. Cf-F2 inhibited the development of C. albicans but did not inhibit the growth of C. tropicalis. Both fractions were unable to inhibit the growth of Fusarium species. The toxicity of the fractions was tested in vivo on Galleria mellonella larvae, and both showed a low toxicity rate at high concentrations. As a result, the fractions have enormous promise for the creation of novel antifungal compounds.

Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.

BioPrediction-RPI: Democratizing the prediction of interaction between non-coding RNA and protein with end-to-end machine learning.

Machine Learning (ML) algorithms have been important tools for the extraction of useful knowledge from biological sequences, particularly in healthcare, agriculture, and the environment. However, the categorical and unstructured nature of these sequences requiring usually additional feature engineering steps, before an ML algorithm can be efficiently applied. The addition of these steps to the ML algorithm creates a processing pipeline, known as end-to-end ML. Despite the excellent results obtained by applying end-to-end ML to biotechnology problems, the performance obtained depends on the expertise of the user in the components of the pipeline. In this work, we propose an end-to-end ML-based framework called BioPrediction-RPI, which can identify implicit interactions between sequences, such as pairs of non-coding RNA and proteins, without the need for specialized expertise in end-to-end ML. This framework applies feature engineering to represent each sequence by structural and topological features. These features are divided into feature groups and used to train partial models, whose partial decisions are combined into a final decision, which, provides insights to the user by giving an interpretability report. In our experiments, the developed framework was competitive when compared with various expert-created models. We assessed BioPrediction-RPI with 12 datasets when it presented equal or better performance than all tools in 40% to 100% of cases, depending on the experiment. Finally, BioPrediction-RPI can fine-tune models based on new data and perform at the same level as ML experts, democratizing end-to-end ML and increasing its access to those working in biological sciences.

Protocol for the development of a reporting guideline for umbrella reviews on epidemiological associations using cross-sectional, case-control and cohort studies: the Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC).

INTRODUCTION: Observational studies are fraught with several biases including reverse causation and residual confounding. Overview of reviews of observational studies (ie, umbrella reviews) synthesise systematic reviews with or without meta-analyses of cross-sectional, case-control and cohort studies, and may also aid in the grading of the credibility of reported associations. The number of published umbrella reviews has been increasing. Recently, a reporting guideline for overviews of reviews of healthcare interventions (Preferred Reporting Items for Overviews of Reviews (PRIOR)) was published, but the field lacks reporting guidelines for umbrella reviews of observational studies. Our aim is to develop a reporting guideline for umbrella reviews on cross-sectional, case-control and cohort studies assessing epidemiological associations. METHODS AND ANALYSIS: We will adhere to established guidance and prepare a PRIOR extension for systematic reviews of cross-sectional, case-control and cohort studies testing epidemiological associations between an exposure and an outcome, namely Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC). Step 1 will be the project launch to identify stakeholders. Step 2 will be a literature review of available guidance to conduct umbrella reviews. Step 3 will be an online Delphi study sampling 100 participants among authors and editors of umbrella reviews. Step 4 will encompass the finalisation of PRIUR-CCC statement, including a checklist, a flow diagram, explanation and elaboration document. Deliverables will be (i) identifying stakeholders to involve according to relevant expertise and end-user groups, with an equity, diversity and inclusion lens; (ii) completing a narrative review of methodological guidance on how to conduct umbrella reviews, a narrative review of methodology and reporting in published umbrella reviews and preparing an initial PRIUR-CCC checklist for Delphi study round 1; (iii) preparing a PRIUR-CCC checklist with guidance after Delphi study; (iv) publishing and disseminating PRIUR-CCC statement. ETHICS AND DISSEMINATION: PRIUR-CCC has been approved by The Ottawa Health Science Network Research Ethics Board and has obtained consent (20220639-01H). Participants to step 3 will give informed consent. PRIUR-CCC steps will be published in a peer-reviewed journal and will guide reporting of umbrella reviews on epidemiological associations.

Artificial intelligence and radiomics in the diagnosis of intraosseous lesions of the gnathic bones: A systematic review.

BACKGROUND: The purpose of this systematic review (SR) is to gather evidence on the use of machine learning (ML) models in the diagnosis of intraosseous lesions in gnathic bones and to analyze the reliability, impact, and usefulness of such models. This SR was performed in accordance with the PRISMA 2022 guidelines and was registered in the PROSPERO database (CRD42022379298). METHODS: The acronym PICOS was used to structure the inquiry-focused review question "Is Artificial Intelligence reliable for the diagnosis of intraosseous lesions in gnathic bones?" The literature search was conducted in various electronic databases, including PubMed, Embase, Scopus, Cochrane Library, Web of Science, Lilacs, IEEE Xplore, and Gray Literature (Google Scholar and ProQuest). Risk of bias assessment was performed using PROBAST, and the results were synthesized by considering the task and sampling strategy of the dataset. RESULTS: Twenty-six studies were included (21 146 radiographic images). Ameloblastomas, odontogenic keratocysts, dentigerous cysts, and periapical cysts were the most frequently investigated lesions. According to TRIPOD, most studies were classified as type 2 (randomly divided). The F1 score was presented in only 13 studies, which provided the metrics for 20 trials, with a mean of 0.71 (±0.25). CONCLUSION: There is no conclusive evidence to support the usefulness of ML-based models in the detection, segmentation, and classification of intraosseous lesions in gnathic bones for routine clinical application. The lack of detail about data sampling, the lack of a comprehensive set of metrics for training and validation, and the absence of external testing limit experiments and hinder proper evaluation of model performance.

Understanding the mechanism of action of protease inhibitors in controlling the growth of the Candida Genus: potential candidates for development of new antifungal molecules.

There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance.

The dose-effect relationship of six stimulation parameters with rTMS over left DLPFC on treatment-resistant depression: A systematic review and meta-analysis.

This study aimed to evaluate the association of the six parameters, namely stimulation intensity, stimulation frequency, pulses per session, treatment duration, number of sessions, and total number of pulses with the efficacy of conventional transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex for patients with treatment-resistant depression (TRD). A random-effects dose-response meta-analysis of blinded randomized controlled trials (RCTs) involving 2391 participants were conducted to examine the dose-effect relationship of six stimulation parameters. Any of the six parameters significantly individually predicted proportion of variance in efficacy: pulses per session (R²=52.7%), treatment duration (R²=51.2%), total sessions (R²=50.9%), frequency (R²=49.6%), total pulses (R²=49.5%), and intensity (R²= 40.4%). Besides, we identified frequency as a potential parameter interacting with the other five parameters, resulting in a significant increase in variance(ΔR2) ranging from 5.0% to 16.7%. Finally, we found that RCTs using frequency > 10 Hz compared to those of 10 Hz showed better dose-effect relationships. We conclude that the six stimulation parameters significantly predict the dose-effect relationship of conventional rTMS on TRD. Besides, higher stimulation frequency, higher stimulation intensity, and adequate number of pulses were associated with treatment efficacy.

New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.

Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.

Association of chest computed tomography severity score at ICU admission and respiratory outcomes in critically ill COVID-19 patients.

OBJECTIVE: To evaluate the association of a validated chest computed tomography (Chest-CT) severity score in COVID-19 patients with their respiratory outcome in the Intensive Care Unit. METHODS: A single-center, prospective study evaluated patients with positive RT-PCR for COVID-19, who underwent Chest-CT and had a final COVID-19 clinical diagnosis needing invasive mechanical ventilation in the ICU. The admission chest-CT was evaluated according to a validated Chest-CT Severity Score in COVID-19 (Chest-CTSS) divided into low ≤50% (<14 points) and >50% high (≥14 points) lung parenchyma involvement. The association between the initial score and their pulmonary clinical outcomes was evaluated. RESULTS: 121 patients were clustered into the > 50% lung involvement group and 105 patients into the ≤ 50% lung involvement group. Patients ≤ 50% lung involvement (<14 points) group presented lower PEEP levels and FiO2 values, respectively GEE P = 0.09 and P = 0.04. The adjusted COX model found higher hazard to stay longer on invasive mechanical ventilation HR: 1.69, 95% CI, 1.02-2.80, P = 0.042 and the adjusted logistic regression model showed increased risk ventilator-associated pneumonia OR = 1.85 95% CI 1.01-3.39 for COVID-19 patients with > 50% lung involvement (≥14 points) on Chest-CT at ICU admission. CONCLUSION: COVID-19 patients with >50% lung involvement on Chest-CT admission presented higher chances to stay longer on invasive mechanical ventilation and more chances to developed ventilator-associated pneumonia.

Does pay-for-performance design matter? Evidence from Brazil.

Pay-for-performance (P4P) schemes have been shown to have mixed effects on health care outcomes. A challenge in interpreting this evidence is that P4P is often considered a homogenous intervention, when in practice schemes vary widely in their design. Our study contributes to this literature by providing a detailed depiction of incentive design across municipalities within a national P4P scheme in Brazil [Primary Care Access and Quality (PMAQ)] and exploring the association of alternative design typologies with the performance of primary health care providers. We carried out a nation-wide survey of municipal health managers to characterize the scheme design, based on the size of the bonus, the providers incentivized and the frequency of payment. Using OLS regressions and controlling for municipality characteristics, we examined whether each design feature was associated with better family health team (FHT) performance. To capture potential interactions between design features, we used cluster analysis to group municipalities into five design typologies and then examined associations with quality of care. A majority of the municipalities included in our study used some of the PMAQ funds to provide bonuses to FHT workers, while the remaining municipalities spent the funds in the traditional way using input-based budgets. Frequent bonus payments (monthly) and higher size bonus allocations (share of 20-80%) were strongly associated with better team performance, while who within a team was eligible to receive bonuses did not in isolation appear to influence performance. The cluster analysis showed what combinations of design features were associated with better performance. The PMAQ score in the 'large bonus/many workers/high-frequency' cluster was 8.44 points higher than the 'no bonus' cluster, equivalent to a difference of 21.7% in the mean PMAQ score. Evidence from our study shows how design features can potentially influence health provider performance, informing the design of more effective P4P schemes.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Comparison of Cytological Adequacy between 23- and 25-Gauge in Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules: A Single-Center Prospective Study.

INTRODUCTION: Approximately 15% of fine-needle aspiration (FNA) of thyroid nodules are considered nondiagnostic. Several factors are potentially involved, including clinical and nodule features but also the gauge (G) of the needle used. However, few studies have compared the cytological adequacy obtained with different gauge needles and the data are controversial. We aimed to evaluate cytological adequacy results using 23- or 25-G needles. METHODS: This study is an observational and prospective study of thyroid nodules submitted to ultrasound-guided FNA. The procedure was performed randomly using 23- or 25-G needles. The samples were reported by different cytopathologists who were blinded to the information of the gauge of the needle used. Statistical analysis was performed to compare cytological adequacy of FNA between the two groups. RESULTS: A total of 177 thyroid nodules were included - 98 (55.4%) using 23-G and 79 (44.6%) using 25-G needles. The 23-G group presented a higher rate of cytological adequacy (69.4% [68/98] vs. 46.8% [37/79], p = 0.002). No differences were found between the two groups regarding patient or nodule characteristics. On logistic regression, 23-G needles correlated with better cytological adequacy (unadjusted OR 2.57 [95% CI: 1.39-4.77]), even after adjusting for nodule dimension, location, and type of cytology (slides +/- additional liquid-based cytology) (adjusted OR 2.44 [95% CI: 1.23-4.84]). CONCLUSION: The gauge of the needle used was found to be an independent predictor of cytological adequacy, with 23-G needles providing more adequate samples. Further investigation is needed to confirm our results in order to stablish the optimal diagnosis technique.

Assessment of barriers to cancer screening and interventions implemented to overcome these barriers in 27 Latin American and Caribbean countries.

There is a gap in the understanding of the barriers to cancer screening participation and complying with downstream management in the Community of Latin American and Caribbean states (CELAC). Our study aimed to assess barriers across the cancer screening pathway from the health system perspective, and interventions in place to improve screening in CELAC. A standardized tool was used to collect information on the barriers across the screening pathway through engagement with the health authorities of 27 member states of CELAC. Barriers were organized in a framework adapted from the Tanahashi conceptual model and consisted of the following dimensions: availability of services, access (covering accessibility and affordability), acceptability, user-provider interaction, and effectiveness of services (which includes governance, protocols and guidelines, information system, and quality assurance). The tool also collected information of interventions in place, categorized in user-directed interventions to increase demand, user-directed interventions to increase access, provider-directed interventions, and policy and system-level interventions. All countries prioritized barriers related to the information systems, such as the population register not being accurate or complete (N = 19; 70.4%). All countries implemented some kind of intervention to improve cancer screening, group education being the most reported (N = 23; 85.2%). Training on screening delivery was the most referred provider-directed intervention (N = 19; 70.4%). The study has identified several barriers to the implementation of cancer screening in the region and interventions in place to overcome some of the barriers. Further analysis is required to evaluate the effectiveness of these interventions in achieving their objectives.

Synergistic action of synthetic peptides and amphotericin B causes disruption of the plasma membrane and cell wall in Candida albicans.

The objective of this work was to evaluate the combination of synthetic peptides based on the γ-core motif of defensin PvD1 with amphotericin B (AmB) at different concentrations against Candida albicans. We applied the checkerboard assay using different concentrations of the commercial drug AmB and the synthetic peptides γ31-45PvD1++ and γ33-41PvD1++ against C. albicans, aiming to find combinations with synergistic interactions. Between these two interactions involving γ31-45PvD1++ and AmB, an additive effect was observed. One such interaction occurred at concentrations of 0.009 µM of peptide γ31-45PvD1++ and 13.23 µM of AmB and another condition of 0.019 µM of peptide γ31-45PvD1++ and 6.61 µM of AmB. The other two concentrations of the interaction showed a synergistic effect in the combination of synthetic peptide γ31-45PvD1++ and AmB, where the concentrations were 1.40 µM peptide γ31-45PvD1++ and 0.004 µM AmB and 0.70 µM γ31-45PvD1++ peptide and 0.002 µM AmB. We proceeded with analysis of the mechanism of action involving synergistic effects. This examination unveiled a range of impactful outcomes, including the impairment of mitochondrial functionality, compromise of cell wall integrity, DNA degradation, and a consequential decline in cell viability. We also observed that both synergistic combinations were capable of causing damage to the plasma membrane and cell wall, causing leakage of intracellular components. This discovery demonstrates for the first time that the synergistic combinations found between the synthetic peptide γ31-45PvD1++ and AmB have an antifungal effect against C. albicans, acting on the integrity of the plasma membrane and cell wall.

Predictors of recurrence after total thyroidectomy in 1,611 patients with papillary thyroid carcinoma: postoperative stimulated serum thyroglobulin and ATA initial and dynamic risk assessment.

Objective: Despite a favorable prognosis, some patients with papillary thyroid carcinoma (PTC) develop recurrence. The objective of this study was to examine the impact of the combination of initial American Thyroid Association (ATA) risk stratification with serum level of postoperative stimulated thyroglobulin (s-Tg) in predicting recurrence in patients with PTC and compare the results with an assessment of response to initial therapy (dynamic risk stratification). Subjects and methods: We retrospectively analyzed 1,611 patients who had undergone total thyroidectomy for PTC, followed in most cases (87.3%) by radioactive iodine (RAI) administration. Clinicopathological features and s-Tg levels obtained 3 months postoperatively were evaluated. The patients were stratified according to ATA risk categories. Nonstimulated thyroglobulin levels and imaging studies obtained during the first year of follow-up were used to restage the patients based on response to initial therapy. Results: After a mean follow-up of 61.5 months (range 12-246 months), tumor recurrence was diagnosed in 99 (6.1%) patients. According to ATA risk, recurrence was identified in 2.3% of the low-risk, 9% of the intermediate-risk, and 25% of the high-risk patients (p < 0.001). Using a receiver operating characteristic curve approach, a postoperative s-Tg level of 10 ng/mL emerged as the ideal cutoff value, with positive and negative predictive values of 24% and 97.8%, respectively (p < 0.001). Patients with low to intermediate ATA risk with postoperative s-Tg levels < 10 ng/mL and excellent response to treatment had a very low recurrence rate (<0.8%). In contrast, higher recurrence rates were observed in intermediate-riskto high-risk patients with postoperative s-Tg > 10 ng/mL and indeterminate response (25%) and in those with incomplete response regardless of ATA category or postoperative s-Tg value (38.5-87.5%). Using proportion of variance explained (PVE), the predicted recurrence using the ATA initial risk assessment alone was 12.7% and increased to 29.9% when postoperative s-Tg was added to the logistic regression model and 49.1% with dynamic risk stratification. Conclusion: The combination of ATA staging system and postoperative s-Tg can better predict the risk of PTC recurrence. Initial risk estimates can be refined based ondynamic risk assessment following response to therapy, thus providing a useful guide for follow-up recommendations.

Unveiling a Listeria monocytogenes Outbreak in a Rabbit Farm: Clinical Manifestation, Antimicrobial Resistance, Genomic Insights and Environmental Investigation.

Listeria monocytogenes poses a threat to both human and animal health. This work describes an L. monocytogenes outbreak in a Portuguese rabbit farm, detailing the isolates' clinical manifestations, necropsy findings, and phenotypic and genomic profiles. Clinical signs, exclusively observed in does, included lethargy and reproductive signs. Post-mortem examination of does revealed splenomegaly, hepatomegaly with a reticular pattern, pulmonary congestion, and haemorrhagic lesions in the uterus, with thickening of the uterine wall and purulent greyish exudates. Positive L. monocytogenes samples were identified in fattening and maternity units across different samples, encompassing does and environmental samples. Core-genome Multi Locus Sequence Typing (cgMLST) analysis confirmed the outbreak, with the 16 sequenced isolates (lineage II, CC31, and ST325) clustering within a ≤2 allelic difference (AD) threshold. Antimicrobial susceptibility testing for five antibiotics revealed that 15 out of 19 outbreak isolates were resistant to sulfamethoxazole-trimethoprim (SXT). Concordantly, all SXT-resistant sequenced isolates were found to exclusively harbour a plasmid containing a trimethoprim-resistance gene (dfrD), along with loci linked to resistance to lincosamides (lnuG), macrolides (mphB), and polyether ionophores (NarAB operon). All sequenced outbreak isolates carried the antibiotic resistance-related genes tetM, fosX, lin, norB, lmrB, sul, and mprF. The outbreak cluster comprises isolates from does and the environment, which underscores the ubiquitous presence of L. monocytogenes and emphasizes the importance of biosecurity measures. Despite limited data on listeriosis in rabbit farming, this outbreak reveals its significant impact on animal welfare and production.