Search Results (99)

Viral outbreaks have caused significant mortality and economic losses in aquaculture, highlighting the urgent need for effective therapies and a deeper understanding of antiviral and immune mechanisms in key species. This study investigates the constitutive and virus-induced antiviral responses in juvenile rainbow trout (Oncorhynchus mykiss) following infection with viral hemorrhagic septicemia virus (VHSV). Trout (30 g) were infected by immersion with VHSV (TCID₅₀ = 10⁵ mL⁻¹) for two hours. Samples were collected at 24, 72, and 120 h post-infection to assess hematology, innate immunity, viral load, and transcriptomic response. At 24 h post-infection, no immune response or increase in viral load was detected, suggesting the host had not yet recognized the virus and was still in the incubation phase. By 72 h, viral replication peaked, with high viral loads observed in mucosal tissues (skin and gills) and immune organs (kidney, spleen, liver), alongside strong up-regulation of antiviral genes, such as viperin. This gene maintained high expression through the final sampling point, indicating its key role in the antiviral response. At this stage, reduced immune competence was observed, marked by elevated nitric oxide and circulating thrombocytes. At 120 h, modest increases in peripheral monocyte, plasma lysozyme, and peroxidase activity were detected; however, these responses were insufficient to reduce viral load, suggesting the resolution phase had not yet begun. In summary, while a limited immune response was observed by the end of the trial, the consistent antiviral activity of viperin from peak infection to 120 h post-infection underscores its importance in the defence against VHSV in rainbow trout. Full article

Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on microbiota composition, metabolic activity, and immune markers in fecal samples from patients with anxiety on SSRIs, using the SHIME^® (Simulator of the Human Intestinal Microbial Ecosystem) model. Methods: The fecal microbiotas of four patients using sertraline or escitalopram were inoculated in SHIME^® reactors simulating the ascending colon. After stabilization, a 14-day probiotic intervention was performed. Microbial composition was assessed by 16S rRNA sequencing. Short-chain fatty acids (SCFAs), ammonia, and GABA were measured, along with the prebiotic index (PI). Intestinal barrier integrity was evaluated via transepithelial electrical resistance (TEER), and cytokine levels (IL-6, IL-8, IL-10, TNF-α) were analyzed using a Caco-2/THP-1 co-culture system. The statistical design employed in this study for the analysis of prebiotic index, metabolites, intestinal barrier integrity and cytokines levels was a repeated measures ANOVA, complemented by post hoc Tukey’s tests to assess differences across treatment groups. For the 16S rRNA sequencing data, alpha diversity was assessed using multiple metrics, including the Shannon, Simpson, and Fisher indices to evaluate species diversity, and the Chao1 and ACE indices to estimate species richness. Beta diversity, which measures microbiota similarity across groups, was analyzed using weighted and unweighted UniFrac distances. To assess significant differences in beta diversity between groups, a permutational multivariate analysis of variance (PERMANOVA) was performed using the Adonis test. Results: Probiotic supplementation increased Bifidobacterium and Lactobacillus, and decreased Klebsiella and Bacteroides. Beta diversity was significantly altered, while alpha diversity remained unchanged. SCFA levels increased after 7 days. Ammonia levels dropped, and PI values rose. TEER values indicated enhanced barrier integrity. IL-8 and TNF-α decreased, while IL-6 increased. GABA levels remained unchanged. Conclusions: The probiotic combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 modulated gut microbiota composition, metabolic activity, and inflammatory responses in samples from individuals with anxiety on SSRIs, supporting its potential as an adjunctive strategy to mitigate antidepressant-associated dysbiosis. However, limitations—including the small pooled-donor sample, the absence of a healthy control group, and a lack of significant GABA modulation—should be considered when interpreting the findings. Although the SHIME^® model is considered a gold standard for microbiota studies, further clinical trials are necessary to confirm these promising results. Full article

Technology-based strategies for the prevention and management of suicidal behavior are widely referenced for identifying vulnerable groups and for supporting clinical reasoning, decision-making, and appropriate referrals. In this study, we estimated the interface and content validity evidence of an interactive mobile application developed for managing suicidal behavior. This methodological study employed psychometric parameters to evaluate the content and interface of the mobile application, following five action phases: analysis, design, development, implementation, and evaluation. A total of 27 healthcare professionals participated, selected by convenience sampling, all working within the Psychosocial Care Network across different regions of Brazil. Data were collected using an electronic form, the Delphi technique for evaluation rounds, and a Likert scale to achieve consensus. The validity analysis was based on a Content Validity Index (CVI) equal to or greater than 0.80. The results showed that GerenciaVida, a technology developed for healthcare workers—regardless of their level of care or professional category—can be used to screen for suicide risk in the general population and indicate preventive alternatives. The app demonstrated satisfactory indicators of content validity (0.974) and interface validity (0.963), reflecting clarity (0.925), objectivity (1.00), adequacy (0.925), coherence (0.962), accuracy (0.962), and clinical relevance (1.00). The development path of this mobile application provided scientific, technological, and operational support, establishing it as an innovative care tool. It consolidates valid evidence that supports the identification, risk classification, and prevention of suicidal behavior in various healthcare contexts. Full article

The first ray plays a fundamental role in foot biomechanics, particularly in stabilizing the medial longitudinal arch and enabling efficient weight transfer during the mid-stance and propulsion phases of gait. When dorsiflexed—a condition known as metatarsus primus elevatus—especially in its flexible form, this structure disrupts load distribution, impairs propulsion, and contributes to various clinical symptoms. Despite its clinical importance, the biomechanical impact of orthotic elements placed beneath the first ray remains underexplored. This study aimed to quantify the variations in medio-lateral (Fx), antero-posterior (Fy), and vertical (Fz) force vectors generated during gait in response to different orthotic elements positioned under the first ray. A quasi-experimental, post-test design was conducted involving 22 participants (10 men and 12 women) diagnosed with flexible metatarsus primus elevatus. Each participant was evaluated using custom-made insoles incorporating various orthotic elements, while gait data were collected using a dynamometric platform during the mid-stance and propulsion phases. Significant gait-phase-dependent force alterations were observed. A cut-out (E) reduced medio-lateral forces during propulsion (p < 0.05), while a kinetic wedge (F) was correlated with late-stance stability (r = −0.526). The foot posture index (FPI)/body mass index (BMI) mediated the vertical forces. The effect sizes reached 0.45–0.42 for antero-posterior force modulation. Phase-targeted orthoses (a cut-out for propulsion, a kinetic wedge for late stance) and patient factors (FPI/BMI) appear to promote biomechanical efficacy in metatarsus primus elevatus, enabling personalized therapeutic strategies. Full article

Hypomagnesemia is the most common electrolyte disorder in kidney transplant recipients (KTR), yet its causes remain unclear. Few studies have explored its underlying factors. This study aimed to assess its prevalence and identify risk factors in KTR. We conducted a retrospective cross-sectional study in 489 outpatient KTR. Demographic, clinical, and laboratory data were collected. Univariate and multivariate logistic regression analyses were used to identify factors associated with hypomagnesemia (≤1.7 mg/dL). Hypomagnesemia was present in 50.7% of patients. Multivariate analysis identified tacrolimus [OR 2.91 (1.62–5.22)], thiazides [OR 2.23 (1.21–4.08)], cinacalcet [OR 2.31 (1.29–4.13)], serum phosphate < 3.7 mg/dL [1.99 (1.29–3.05)], serum calcium ≤ 10 mg/dL [1.99 (1.29–3.05)] and diabetes [1.94 (1.22–3.08)] as risk factors. Protective factors included SGLT2 inhibitors (SGLT2i) [OR 0.17 (0.10–0.27)] and mTOR inhibitors (mTORi) [OR 0.62 (0.38–0.98)]. Among hypomagnesemic patients, those receiving Mg²⁺ supplements had lower Mg²⁺ levels [1.54 (0.15) vs. 1.59 (0.13) mg/dL, p = 0.005] and higher fractional Mg²⁺ excretion [8.28 (4.48)% vs. 7.36 (4.19)%, p = 0.05]. Hypomagnesemia is highly prevalent in KTR. Tacrolimus, thiazides, and cinacalcet are key risk factors and, in some patients, risks and benefits of continuing these medications should be carefully weighed. In refractory cases, SGLT2i or mTORi may offer benefit. Full article

Crop water use (ET_c) is typically estimated as the product of crop evapotranspiration (ET_o) and a crop coefficient (K_c). However, the estimation of ET_o requires various meteorological data, which are often unavailable or of poor quality, particularly in countries such as Guinea-Bissau, where the maintenance of weather stations is frequently inadequate. The present study aimed to assess alternative approaches, as outlined in the revised FAO56 guidelines, for estimating ET_o when only temperature data is available. These included the use of various predictors for the missing climatic variables, referred to as the Penman–Monteith temperature (PMT) approach. New approaches were developed, with a particular focus on optimizing the predictors at the cluster level. Furthermore, different gridded weather datasets (AgERA5 and MERRA-2 reanalysis) were evaluated for ET_o estimation to overcome the lack of ground-truth data and upscale ET_o estimates from point to regional and national levels, thereby supporting water management decision-making. The results demonstrate that the PMT is generally accurate, with RMSE not exceeding 26% of the average daily ET_o. With regard to shortwave radiation, using the temperature difference as a predictor in combination with cluster-focused multiple linear regression equations for estimating the radiation adjustment coefficient (k_Rs) yielded accurate results. ET_o estimates derived using raw (uncorrected) reanalysis data exhibit considerable bias and high RMSE (1.07–1.57 mm d⁻¹), indicating the need for bias correction. Various correction methods were tested, with the simple bias correction delivering the best overall performance, reducing RMSE to 0.99 mm d⁻¹ and 1.05 mm d⁻¹ for AgERA5 and MERRA-2, respectively, and achieving a normalized RMSE of about 22%. After implementing bias correction, the AgERA5 was found to be superior to the MERRA-2 for all the studied sites. Furthermore, the PMT outperformed the bias-corrected reanalysis in estimating ET_o. It was concluded that PMT-ET_o can be recommended for further application in countries with limited access to ground-truth meteorological data, as it requires only basic technical skills. It can also be used alongside reanalysis data, which demands more advanced expertise, particularly for data retrieval and processing. Full article

Objective: We aimed to analyze the real-world use of COMT inhibitors associated with levodopa in patients with Parkinson’s disease (PD) who present early fluctuations and to explore whether early COMT inhibition optimizes treatment outcomes. Methods: REONPARK is an ongoing 2-year prospective observational study. We included patients diagnosed with PD who presented signs of end-of-dose motor fluctuations for <2 years and started COMT inhibitors according to clinical practice. Outcomes included the clinician and patient global impression of change (CGI-C, PGI-C), the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Parkinson’s Disease Questionnaire-8 (PDQ-8), Non-Motor Symptoms Scale (NMSS), 19-Symptom Wearing-off Questionnaire (WOQ-19), and safety. We present a pre-planned interim analysis (cut-off date 3 July 2023) of patients who completed the first 3 months of follow-up. Results: Seventy patients were analyzed (mean levodopa dose at inclusion 484.8 mg; duration of motor fluctuations 0.6 years). In all cases, COMT inhibition was initiated with opicapone, and 81% maintained a stable levodopa dose at 3 months. After 3 months of treatment with opicapone, 73.5% and 62.8% of patients improved on CGI-C and PGI-C, respectively. MDS-UPDRS scores improved significantly with a mean change from baseline of −3.3 ± 7.7 (p < 0.001) for Part III and −1.3 ± 1.7 (p < 0.001) for Part IV. The mean OFF time decreased from 3.7 ± 2.6 h at baseline to 2.2 ± 2.3 h, and 20.6% of patients no longer experienced OFF periods. Patients experiencing no impact of fluctuations increased from 10% to 45.6%. Conclusions: In PD patients with early fluctuations, three months of opicapone reduced the OFF time and improved functional outcomes, suggesting potential benefits in the early stages. Full article

Upadacitinib has demonstrated efficacy in psoriatic arthritis in clinical trials, but its real-world performance in difficult-to-treat PsA remains underexplored. This observational, multicenter, open-label study evaluated the efficacy and safety of upadacitinib in 134 patients with psoriatic arthritis (97 women, mean age 51.8 ± 11.2 years, mean disease duration 9.94 ± 7.72 years) who showed inadequate response to advanced therapies. Most patients (74.6%) had received at least two biological/targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action. Upadacitinib was initiated at 15 mg daily, and within one month, significant improvements were observed: DAS28-ESR decreased from 4.7 to 3.77 (p < 0.001), DAPSA from 25 to 17 (p < 0.001), and CRP from 2.90 to 1.50 mg/L (p = 0.001). These reductions persisted throughout the study. Prednisone dosage decreased significantly (p = 0.049). Adverse events led to upadacitinib discontinuation in 8.2% of patients, but no serious adverse events were reported. Compared to the SELECT-PsA 2 trial, our cohort had a higher proportion of females and greater prior exposure to biologic agents but showed comparable efficacy and safety outcomes. These findings suggest that upadacitinib is a rapid, effective, and relatively safe therapeutic option for difficult-to-treat psoriatic arthritis under real-world conditions, supporting its use despite differing patient characteristics from clinical trial populations. Full article

mTORopathies represent a group of neurodevelopmental disorders linked to dysregulated mTOR signaling, resulting in conditions such as tuberous sclerosis complex, focal cortical dysplasia, hemimegalencephaly, and Smith–Kingsmore Syndrome. These disorders often manifest with epilepsy, cognitive impairments, and, in some cases, structural brain anomalies. The mTOR pathway, a central regulator of cell growth and metabolism, plays a crucial role in brain development, where its hyperactivation leads to abnormal neuroplasticity, tumor formation, and heightened neuronal excitability. Current treatments primarily rely on mTOR inhibitors, such as rapamycin, which reduce seizure frequency and tumor size but fail to address underlying genetic causes. Advances in gene editing, particularly via CRISPR/Cas9, offer promising avenues for precision therapies targeting the genetic mutations driving mTORopathies. New delivery systems, including viral and non-viral vectors, aim to enhance the specificity and efficacy of these therapies, potentially transforming the management of these disorders. While gene editing holds curative potential, challenges remain concerning delivery, long-term safety, and ethical considerations. Continued research into mTOR mechanisms and innovative gene therapies may pave the way for transformative, personalized treatments for patients affected by these complex neurodevelopmental conditions. Full article

The objective of this study was to evaluate the biaxial flexural strength of zirconia-reinforced lithium silicate (ZLS, eMax CAD, Ivoclar Vivadent) and lithium disilicate (LDS, Suprinity, VITA)) discs after abrasion with a diamond tip, before or after crystallization of the ceramic. Discs of 1.2 × 15 mm dimensions were fabricated. The samples were separated into two groups: AC—abrasion with a diamond tip before material crystallization, and CA—material crystallization and subsequent abrasion with a diamond tip (n = 15). The initial roughness was measured before abrasion/crystallization, and final measurement was performed after abrasion/crystallization/polishing. The abraded surface was placed downward during the biaxial flexural strength test, and the data were recorded. The final roughness was significantly higher compared to the initial roughness in all groups. The ZLS-AC and LDS-AC groups (both materials with abrasion prior to material crystallization) showed higher biaxial flexural strength values than groups that underwent abrasion before crystallization. This study concluded that the clinical adjustment performed by abrasion with the diamond tip of glass ceramics lithium disilicate and zirconia-reinforced lithium silicate carried out prior to crystallization favored the resistance of the ceramics. Full article

Background: Ductal carcinoma in situ (DCIS) is a precursor of invasive breast cancer and its early diagnosis and treatment are essential to prevent progression and recurrences. Risk stratification guidelines, such as the Van Nuys Prognostic Index (VNPI) and those by the National Comprehensive Cancer Network (NCCN), help guide appropriate treatment. This study compares VNPI recommendations for DCIS patients treated at Hospital do Servidor Público Estadual de São Paulo (HSPE) with NCCN guidelines, focusing on treatment conducted and recurrence rates. Methods: This retrospective, cross-sectional study reviewed medical records of 145 patients treated for DCIS at HSPE between January 1996 and June 2022, with a mean follow-up of 60.3 months. Results: Based on VNPI, 38.8% were low risk, 53.2% intermediate risk, and 7.8% high risk. NCCN guidelines classified only 12.9% as low risk and 87.1% as high risk. Treatment included breast-conserving surgery (BCS) with radiotherapy (43.1%), BCS alone (38.8%), and mastectomy (18.1%). There were 18 recurrences (15.5%): 5.2% as DCIS and 10.3% as invasive cancer. Of these recurrences, 5.6% occurred in patients who, according to NCCN, would have received BCS with radiotherapy or mastectomy. Conclusion: By integrating the VNPI with NCCN treatment guidelines, the NCCN’s recommendations could potentially reduce local recurrence rates by 5.6%. However, further studies are necessary to evaluate the long-term impact of these guidelines on overall survival outcomes. Full article

Background: Digital technologies are increasingly being used to promote effective health interventions in the older adult population. This study aimed to develop and validate instant messages with educational content related to glycemic control, delivered via an instant messaging application, as a type 2 DM control strategy for older adults. Methods: This was a methodological study that developed instant messages containing text and images. The validation process was conducted by a panel of experts composed of nursing, nutrition, and physical education professionals. SPSS version 25.0 was used for the statistical analysis. A CVI was used to measure the experts’ agreement regarding the validity of the content of the educational messages. An exact test of binomial distribution with p > 0.05, indicating statistical significance, and a 0.95 proportion of agreement was used to estimate the statistical reliability of the CVI. Results: Sixty-one text messages were prepared with illustrations as support, and were divided into three themes. The educational messages were validated by experts, with an average CVI score above 0.80 for all indicators. Conclusions: The educational messages developed in this study were considered relevant and clear for older adults and could be applied in the digital environment, with the objective of helping older adults manage type 2 DM. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder marked by motor deficits and non-motor symptoms, such as depression, which are associated with dopaminergic loss and α-synuclein aggregation in the brain. Objectives: This study investigated the neuroprotective effects of a hydroalcoholic extract of the purple fruit of Eugenia uniflora (PFEU) on motor ability and depressive-like behaviors in a PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in female Wistar rats. Methods: Rats received intranasal administration of MPTP or vehicle, followed by 14 days of oral administration of PFEU (300 or 2000 mg/kg, administered once daily) or vehicle. Depressive-like behavior was assessed using the splash and forced swimming tests, while motor ability was evaluated using the rotarod and open field tests. On day 15, hippocampal tissue was collected for immunoreactivity analysis. Results: MPTP treatment induced depressive-like behavior, which was significantly reversed by PFEU, as evidenced by increased grooming and decreased immobility. No motor coordination or locomotion deficits were observed. Furthermore, PFEU treatment prevented the MPTP-induced increase in hippocampal α-synuclein, p-p53, and Bax while restoring Bcl-2 levels, suggesting neuroprotective effects through the modulation of apoptotic pathways and α-synuclein. Conclusions: These findings support PFEU’s potential as a neuroprotective agent for MPTP-induced depressive-like behavior in female rats, highlighting its molecular mechanisms. Full article

This study aimed to enhance the properties and compostability of active poly(lactic acid) (PLA) films by incorporating β-cyclodextrin (β-CD) inclusion complexes with allyl isothiocyanate (AITC). Films were prepared using melt extrusion and characterized based on their structural, chemical, morphological, thermal, and barrier properties. These inclusion complexes improved the thermal stability and moisture absorption of films, enhancing disintegration under composting conditions. The release of AITC in the vapor phase was responsive to relative humidity, maintaining the antimicrobial functionality at low values and releasing effectively at higher humidity levels, with a maximum release at 100%. Incorporating 5% and 10% β-CD:AITC complexes accelerated disintegration under composting conditions, reducing the time by 5 days for disintegration compared to pure PLA, achieving up to 90% in 23 days. These results, with a general improvement in functional properties, suggest that PLA films with β-CD:AITC are promising for developing sustainable, biodegradable antimicrobial packaging solutions for food applications. Full article

Background and objective: Staging Parkinson’s disease (PD) with a novel simple classification called MNCD, based on four axes (Motor; Non-motor; Cognition; Dependency) and five stages, correlated with disease severity, patients’ quality of life and caregivers’ strain and burden. Our aim was to apply the MNCD classification in advanced PD patients treated with device-aided therapy (DAT). Patients and Methods: A multicenter observational retrospective study of the first patients to start the levodopa-entacapone-carbidopa intestinal gel (LECIG) in Spain was performed (LECIPARK study). The MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) were collected by the neurologist at V0 (before starting LECIG) and V2 (follow-up visit). Wilcoxon’s signed rank and Marginal Homogeneity tests were applied to compare changes from V0 to V2. Results: Sixty-seven PD patients (58.2% males; 69.9 ± 9.3 years old) with a mean disease duration of 14.4 ± 6.5 years were included. The mean treatment duration (V2) was 172.9 ± 105.2 days. At V0, patients were classified as in stage 2 (35.8%), 3 (46.3%) or 4 (17.9%). The frequency of patients in stage 4 decreased to 9% at V2 (p = 0.001). The MNCD total score decreased from 6.27 ± 1.94 at V0 to 5.21 ± 2.23 (p < 0.0001). From V0 to V2, the motor (M; p < 0.0001) and non-motor symptom (N; p < 0.0001) burden decreased, and autonomy for the activities of daily living (D; p = 0.005) improved. Conclusions: The MNCD classification could be useful to classify advanced PD patients and to monitor the response to a DAT. Full article