Combined targeted and untargeted high-resolution mass spectrometry analyses to investigate metabolic alterations in pompe disease.

INTRODUCTION: Pompe disease is a rare, lysosomal disorder, characterized by intra-lysosomal glycogen accumulation due to an impaired function of α-glucosidase enzyme. The laboratory testing for Pompe is usually performed by enzyme activity, genetic test, or urine glucose tetrasaccharide (Glc4) screening by HPLC. Despite being a good preliminary marker, the Glc4 is not specific for Pompe. OBJECTIVE: The purpose of the present study was to develop a simple methodology using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for targeted quantitative analysis of Glc4 combined with untargeted metabolic profiling in a single analytical run to search for complementary biomarkers in Pompe disease. METHODS: We collected 21 urine specimens from 13 Pompe disease patients and compared their metabolic signatures with 21 control specimens. RESULTS: Multivariate statistical analyses on the untargeted profiling data revealed Glc4, creatine, sorbitol/mannitol, L-phenylalanine, N-acetyl-4-aminobutanal, N-acetyl-L-aspartic acid, and 2-aminobenzoic acid as significantly altered in Pompe disease. This panel of metabolites increased sample class prediction (Pompe disease versus control) compared with a single biomarker. CONCLUSION: This study has demonstrated the potential of combined acquisition methods in LC-HRMS for Pompe disease investigation, allowing for routine determination of an established biomarker and discovery of complementary candidate biomarkers that may increase diagnostic accuracy, or improve the risk stratification of patients with disparate clinical phenotypes.

Unravelling the genetic variability of host resilience to endo- and ectoparasites in Nellore commercial herds.

BACKGROUND: Host resilience (HR) to parasites can affect the performance of animals. Therefore, the aim of this study was to present a detailed investigation of the genetic mechanisms of HR to ticks (TICK), gastrointestinal nematodes (GIN), and Eimeria spp. (EIM) in Nellore cattle that were raised under natural infestation and a prophylactic parasite control strategy. In our study, HR was defined as the slope coefficient of body weight (BW) when TICK, GIN, and EIM burdens were used as environmental gradients in random regression models. In total, 1712 animals were evaluated at five measurement events (ME) at an average age of 331, 385, 443, 498, and 555 days, which generated 7307 body weight (BW) records. Of the 1712 animals, 1075 genotyped animals were used in genome-wide association studies to identify genomic regions associated with HR. RESULTS: Posterior means of the heritability estimates for BW ranged from 0.09 to 0.54 across parasites and ME. The single nucleotide polymorphism (SNP)-derived heritability for BW at each ME ranged from a low (0.09 at ME.331) to a moderate value (0.23 at ME.555). Those estimates show that genetic progress can be achieved for BW through selection. Both genetic and genomic associations between BW and HR to TICK, GIN, and EIM confirmed that parasite infestation impacted the performance of animals. Selection for BW under an environment with a controlled parasite burden is an alternative to improve both, BW and HR. There was no impact of age of measurement on the estimates of genetic variance for HR. Five quantitative trait loci (QTL) were associated with HR to EIM but none with HR to TICK and to GIN. These QTL contain genes that were previously shown to be associated with the production of antibody modulators and chemokines that are released in the intestinal epithelium. CONCLUSIONS: Selection for BW under natural infestation and controlled parasite burden, via prophylactic parasite control, contributes to the identification of animals that are resilient to nematodes and Eimeria ssp. Although we verified that sufficient genetic variation existed for HR, we did not find any genes associated with mechanisms that could justify the expression of HR to TICK and GIN.

Preferred neoadjuvant therapy for gastric and gastroesophageal junction adenocarcinoma: a systematic review and network meta-analysis.

INTRODUCTION: Currently, the standard treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma, including distal esophagus, consists of perioperative chemotherapy (CT) according to FLOT schedule (5FU/leucovorin/oxaliplatin and docetaxel), or of concomitant chemoradiotherapy (CTRT) based on CROSS regimen. However, due to the relatively lack of direct comparisons between perioperative CT and neoadjuvant CTRT, the effectiveness of these new combinations is unknown. Therefore, we performed a network meta-analysis (NMA) to compare the efficacy of different neoadjuvant treatments for gastric and GEJ adenocarcinoma in terms of overall and disease-free survival (OS and DFS). MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane from database inception until February 1st 2022 for randomized clinical trials that enrolled adults with gastric and GEJ carcinomas and provided data about OS and/or DFS. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank (SUCRA) curve plots were produced. The primary outcome was OS, secondary endpoint DFS. RESULTS: A total of 1247 citations were screened; 14 randomized clinical trials were included. In Bayesian comparisons, FLOT-based CT ranked as one of the better regimens with a probability of 41%, both with induction CT followed by CTRT (P = 0.45). For DFS analysis, the FLOT regimen was the preferred option (P = 0.62). CONCLUSIONS: In conclusion, this NMA adds further evidence to the optimization of treatment strategies for gastric and GEJ adenocarcinomas and confirms that incorporation of perioperative triplet-based CT improved both OS and DFS compared to surgery alone and other preoperative strategies.

Nutritional interventions for heart failure patients who are malnourished or at risk of malnutrition or cachexia: a systematic review and meta-analysis.

Malnutrition is common in heart failure (HF), and it is associated with higher hospital readmission and mortality rates. This review aims to answer the question whether nutritional interventions aiming to increase protein and energy intake are effective at improving outcomes for patients with HF who are malnourished or at risk of malnutrition or cachexia. Systematic searches of four databases (Medline, Embase, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL)) were conducted on 21 June 2019. Randomized controlled trials (RCTs) or other interventional studies using protein or energy supplementation for adult HF patients who are malnourished or at risk of malnutrition or cachexia were included. Two independent reviewers assessed study eligibility and risk of bias. Five studies (four RCTs and one pilot RCT) met the inclusion criteria. The majority of studies were small and of limited quality. The pooled weighted mean difference (WMD) for body weight showed a benefit from the nutritional intervention by 3.83 kg (95% confidence interval (CI) 0.17 to 7.50, P = 0.04) from three trials with no significant benefit for triceps skinfold thickness (WMD = - 2.14 mm, 95% CI - 9.07 to 4.79, P = 0.55) from two trials. The combination of personalized nutrition intervention with conventional treatment led to a decrease in all-cause mortality and hospital readmission in one study. Findings of this review suggest that nutritional interventions could potentially improve outcomes in HF patients who are malnourished or at risk of malnutrition. However, the strength of the evidence is poor, and more robust studies with a larger number of participants are needed.

Effects of Trichoderma asperellum on Germination Indexes and Seedling Parameters of Lettuce Cultivars.

The aim of this study was to analyze the effects of Trichoderma asperellum on germination indexes and seedling parameters of lettuce cultivars. The trial was arranged in a completely randomized design with three cultivars (Cerbiata, Crespa Grand Rapids, and Mimosa), and two seed-treatment products (quality and organic) containing strain URM 5911 of Trichoderma asperellum plus a control group (untreated), with four repetitions. After seven days, six seedling characters were measured (shoot length, radicle length, total length, shoot diameter, radicle diameter, and seedling dry matter) and eight germination indexes were calculated (germination, first count, mean germination time, germination speed index, coefficient of velocity of germination, mean germination rate, Timson's germination index, and germination rate index). In general, regarding the germination indexes, the effect of the genotype factor predominated over the Trichoderma factor. The seedling characters showed significance for genotype × Trichoderma interaction for shoot length, shoot diameter, radicle diameter, and seedling dry matter. Such results demonstrate that the effects of Trichoderma asperellum on lettuce seedlings variate according to the cultivar used.

The antimicrobial effect of different ozone protocols applied in severe curved canals contaminated with Enterococcus faecalis: ex vivo study.

The aim of this study was to evaluate 3 different irrigation protocols using ozone on monoculture biofilm of Enterococcus faecalis. Fifty disto-buccal roots of maxillary first molars were instrumented up to the size 25.08, sterilized and then incubated with Enterococcus faecalis for 21 days for biofilm maturation in the root canal walls. After contamination, the initial collection (S1) was performed and the 50 samples were divided in 3 experimental groups (n = 15) and 1 positive control group (n = 5) as follows: Group1: Ozonated water (40 µg/ml); Group2: gaseous ozone (40 µg/ml); Group3: Ozonated water (40 µg/ml) under continuous ultrasonic irrigation (CUI) and, Group 4: 2.5% sodium hypochlorite (positive control). The final collection (S2) was performed using hedstroem files # 25 by scraping the root canal wall and absorbed paper cone. The collected samples were analyzed by CFU/ml count and qPCR. To compare the effect of irrigation methods and to investigate E. faecalis count data, Kruskal-Wallis and Wilcoxon nonparametric tests were used at p < 05. The values of the differences between the S1 values and the S2 values revealed that the groups did not differ significantly for either E. faecalis CFU count data (p = 0.713) or q-PCR (p = 0.185), however, it is observed that for all groups, the CFU count of E. faecalis decreased over 99%. For the q-PCR assay, the reduction was on the order of 74-95%. Only the NaOCl positive control group presented total elimination of CFU/mL bacterial counting. The ozone protocols assessed were similar in regard to Enterococcus faecalis reduction.

3-Acyltetramic acids as a novel class of inhibitors for human kallikreins 5 and 7.

Human kallikreins 5 and 7 (KLK5 and KLK7) exhibit trypsin- and chymotrypsin-like activities and are involved in pathologies related to skin desquamation process. A series of new 3-acyltetramic acids were developed as a novel class of inhibitors of KLK5, KLK7 and trypsin enzymes. The nature and length of the acyl chain is crucial to the KLK5, KLK7 and trypsin inhibition activities, and the most potent compounds (but not the most selective) 2b, 2c and 2g showed low micromolar IC50 values. While very few of the compounds were selective for KLK5, the selective inhibition of trypsin against chymotrypsin was achieved. Our molecular modelling studies revealed that the double bond in 2g provided the best fit in the binding site of KLK5, while the hydrogen bonding interactions modulated the best fit of 2c in the binding site of KLK7 due to the hydrophobicity of the cavity.

Combined Access for the Treatment of Medial Orbital Wall Fracture: Subciliary and Upper Eyelid Sulcus Incisions.

The present study presents a new surgical approach to treat medial orbital wall fractures, that is, the combined transcutaneous access through subciliary and upper eyelid sulcus incisions. The study performed the retrospective analysis of medical records belonging to 14 consecutive patients with medial orbital wall fracture, who were treated in the Plastic Surgery Division at Federal University of São Paulo, from 2005 to 2013, through the combination of subciliary and upper eyelid sulcus incisions to access the fracture foci. The mean age of the patients was 35.4 years, ranging from 8 to 66 years. Seven out of the 14 patients were women. Ten patients had fractures in the medial and inferior walls, whereas 4 patients had isolated medial wall fracture. Diplopia was found in all cases. Six patients had some type of extraocular muscle limitation. A computed tomography of the face was performed in the postoperative period to assess the orbital contour and the correct position of the grafts, whenever applicable. The patients were assessed for diplopia, enophthalmos, and scar quality. Four patients (28.6%) kept on showing diplopia at supraversion, whereas 2 patients (14.2%) evolved to enophthalmos. There was no need of reoperating the patients to reposition the grafts or the absorbable plaque. No patient evolved to ectropion or apparent scarring. The combined transcutaneous access through subciliary and upper eyelid sulcus incisions provides ample operative field, rapid exposure of the fracture foci, and adequate wall reconstruction. It can also present inconspicuous scar.

Phase Behaviour and Miscibility Studies of Collagen/Silk Fibroin Macromolecular System in Dilute Solutions and Solid State.

Miscibility is an important issue in biopolymer blends for analysis of the behavior of polymer pairs through the detection of phase separation and improvement of the mechanical and physical properties of the blend. This study presents the formulation of a stable and one-phase mixture of collagen and regenerated silk fibroin (RSF), with the highest miscibility ratio between these two macromolecules, through inducing electrostatic interactions, using salt ions. For this aim, a ternary phase diagram was experimentally built for the mixtures, based on observations of phase behavior of blend solutions with various ratios. The miscibility behavior of the blend solutions in the miscible zones of the phase diagram was confirmed quantitatively by viscosimetric measurements. Assessing the effects of biopolymer mixing ratio and salt ions, before and after dialysis of blend solutions, revealed the importance of ion-specific interactions in the formation of coacervate-based materials containing collagen and RSF blends that can be used in pharmaceutical, drug delivery, and biomedical applications. Moreover, the conformational change of silk fibroin from random coil to beta sheet, in solution and in the final solid films, was detected by circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), respectively. Scanning electron microscopy (SEM) exhibited alterations of surface morphology for the biocomposite films with different ratios. Surface contact angle measurement illustrated different hydrophobic properties for the blended film surfaces. Differential scanning calorimetry (DSC) showed that the formation of the beta sheet structure of silk fibroin enhances the thermal stability of the final blend films. Therefore, the novel method presented in this study resulted in the formation of biocomposite films whose physico-chemical properties can be tuned by silk fibroin conformational changes by applying different component mixing ratios.

Selection of performance-tested young bulls and indirect responses in commercial beef cattle herds on pasture and in feedlots.

BACKGROUND: Central testing is used to select young bulls which are likely to contribute to increased net income of the commercial beef cattle herd. We present genetic parameters for growth and reproductive traits on performance-tested young bulls and commercial animals that are raised on pasture and in feedlots. METHODS: Records on young bulls and heifers in performance tests or commercial herds were used. Genetic parameters for growth and reproductive traits were estimated. Correlated responses for commercial animals when selection was applied on performance-tested young bulls were computed. RESULTS: The 90% highest posterior density (HPD90) intervals for heritabilities of final weight (FW), average daily gain (ADG) and scrotal circumference (SC) ranged from 0.41 to 0.49, 0.23 to 0.30 and 0.47 to 0.57, respectively, for performance-tested young bulls on pasture, from 0.45 to 0.60, 0.20 to 0.32 and 0.56 to 0.70, respectively, for performance-tested young bulls in feedlots, from 0.29 to 0.33, 0.14 to 0.18 and 0.35 to 0.45, respectively, for commercial animals on pasture, and from 0.24 to 0.44, 0.13 to 0.24 and 0.35 to 0.57 respectively, for commercial animals in feedlots. The HPD90 intervals for genetic correlations of FW, ADG and SC in performance-tested young bulls on pasture (feedlots) with FW, ADG and SC in commercial animals on pasture (feedlots) ranged from 0.86 to 0.96 (0.83 to 0.94), 0.78 to 0.90 (0.40 to 0.79) and from 0.92 to 0.97 (0.50 to 0.83), respectively. Age at first calving was genetically related to ADG (HPD90 interval = -0.48 to -0.06) and SC (HPD90 interval = -0.41 to -0.05) for performance-tested young bulls on pasture, however it was not related to ADG (HPD90 interval = -0.29 to 0.10) and SC (HPD90 interval = -0.35 to 0.13) for performance-tested young bulls in feedlots. CONCLUSIONS: Heritabilities for growth and SC are higher for performance-tested young bulls than for commercial animals. Evaluating and selecting for increased growth and SC on performance-tested young bulls is efficient to improve growth, SC and age at first calving in commercial animals. Evaluating and selecting performance-tested young bulls is more efficient for young bulls on pasture than in feedlots.

Taking care of the newborn dying and their families: Nurses' experiences of neonatal intensive care.

OBJECTIVE: To understand the experiences of nurses when caring for dying newborns and their families in the NICU; and redeem their perceptions about acting before the death and grieving process. METHOD: A descriptive exploratory study with a qualitative approach, developed with nine nurses at the ICU of a hospital in São Paulo (SP), Brazil. Data was collected through semi-structured interviews and analyzed using the Collective Subject Discourse (CSD). RESULTS: Caring for newborns who are dying and their families is very difficult for nurses, due to the intense involvement. They seek strategies to deal with the situation and, before the newborn's death, despite the suffering, express the feeling of accomplishment. CONCLUSIONS: Facing death and grief triggers mechanisms that emerge life references, coming across painful issues. Learning to deal with these questions is a daily challenge for nurses of the NICU. OBJETIVO: Compreender as experiências vivenciadas por enfermeiros ao cuidar de neonatos que estão morrendo e seus familiares na UTIN; e resgatar as suas percepções sobre a atuação diante do processo de morte e luto. MÉTODO: Estudo descritivo exploratório, de abordagem qualitativa, desenvolvido com nove enfermeiras da UTIN de um hospital de São Paulo (SP), Brasil. Os dados foram coletados por meio de entrevista semi-estruturada e analisados pela técnica do Discurso de Sujeito Coletivo (DSC). RESULTADOS: Cuidar de neonatos que estão morrendo e suas famílias é muito difícil para as enfermeiras, devido ao intenso envolvimento. Buscam estratégias para lidar com a situação e, diante do óbito do neonato, apesar do sofrimento, manifestam o sentimento de dever cumprido. CONCLUSIÓN: Enfrentar a morte e o luto aciona mecanismos que afloram referências de vida, deparando-se com questões dolorosas. Aprender a lidar com essas questões é um desafio diário para os enfermeiros de UTIN.

Factors controlling the deposition of silk fibroin nanofibrils during layer-by-layer assembly.

The layer-by-layer technique has been used as a powerful method to produce multilayer thin films with tunable properties. When natural polymers are employed, complicated phenomena such as self-aggregation and fibrilogenesis can occur, making it more difficult to obtain and characterize high-quality films. The weak acid and base character of such materials provides multilayer systems that may differ from those found with synthetic polymers due to strong self-organization effects. Specifically, LbL films prepared with chitosan and silk fibroin (SF) often involve the deposition of fibroin fibrils, which can influence the assembly process, surface properties, and overall film functionality. In this case, one has the intriguing possibility of realizing multilayer thin films with aligned nanofibers. In this article, we propose a strategy to control fibroin fibril formation by adjusting the assembly partner. Aligned fibroin fibrils were formed when chitosan was used as the counterpart, whereas no fibrils were observed when poly(allylamine hydrochloride) (PAH) was used. Charge density, which is higher in PAH, apparently stabilizes SF aggregates on the nanometer scale, thereby preventing their organization into fibrils. The drying step between the deposition of each layer was also crucial for film formation, as it stabilizes the SF molecules. Preliminary cell studies with optimized multilayers indicated that cell viability of NIH-3T3 fibroblasts remained between 90 and 100% after surface seeding, showing the potential application of the films in the biomedical field, as coatings and functional surfaces.

Removal of glyphosate herbicide from water using biopolymer membranes.

Enormous amounts of pesticides are manufactured and used worldwide, some of which reach soils and aquatic systems. Glyphosate is a non-selective herbicide that is effective against all types of weeds and has been used for many years. It can therefore be found as a contaminant in water, and procedures are required for its removal. This work investigates the use of biopolymeric membranes prepared with chitosan (CS), alginate (AG), and a chitosan/alginate combination (CS/AG) for the adsorption of glyphosate present in water samples. The adsorption of glyphosate by the different membranes was investigated using the pseudo-first order and pseudo-second order kinetic models, as well as the Langmuir and Freundlich isotherm models. The membranes were characterized regarding membrane solubility, swelling, mechanical, chemical and morphological properties. The results of kinetics experiments showed that adsorption equilibrium was reached within 4 h and that the CS membrane presented the best adsorption (10.88 mg of glyphosate/g of membrane), followed by the CS/AG bilayer (8.70 mg of glyphosate/g of membrane). The AG membrane did not show any adsorption capacity for this herbicide. The pseudo-second order model provided good fits to the glyphosate adsorption data on CS and CS/AG membranes, with high correlation coefficient values. Glyphosate adsorption by the membranes could be fitted by the Freundlich isotherm model. There was a high affinity between glyphosate and the CS membrane and moderate affinity in the case of the CS/AG membrane. Physico-chemical characterization of the membranes showed low values of solubility in water, indicating that the membranes are stable and not soluble in water. The SEM and AFM analysis showed evidence of the presence of glyphosate on CS membranes and on chitosan face on CS/AG membranes. The results showed that the glyphosate herbicide can be adsorbed by chitosan membranes and the proposed membrane-based methodology was successfully used to treat a water sample contaminated with glyphosate. Biopolymer membranes therefore potentially offer a versatile method to eliminate agricultural chemicals from water supplies.

Pharmacovigilance in Brazil: The Government Monitoring of Adverse Events Reported from COVID-19 Vaccine-A Narrative Review.

BACKGROUND: Is pharmacovigilance at a moment of prominence for science, and in relation to governments' responsibilities towards their nations, as the new coronavirus pandemic has surprised everyone in a negative and lethal way? OBJECTIVE: Evaluate pharmacovigilance as a resource for controlling and understanding adverse events caused by vaccines in use. METHODS: This is a narrative review of the literature. Scientific articles available in databases, government bulletins and similar bodies were used. The search was carried out using the descriptors: "Pharmacovigilance AND COVID-19 in Brazil", "Vaccine Development AND COVID-19", "Vaccination Hesitancy AND COVID-19", "Public Health Surveillance AND COVID-19". The period from May 2021 to June 2022 was covered. RESULTS: The occurrence of some adverse events was observed, including cases of allergy, myocarditis and rheumatoid arthritis. It is important to highlight that these adverse events were identified as rare, occurring in a small percentage of the vaccinated population. Despite these adverse events, the benefits of vaccines proved to be essential for controlling the pandemic. CONCLUSIONS: The information presented highlights the importance of pharmacovigilance to continuously monitor and evaluate the safety of vaccines, identifying any potential adverse events early. This balance between risk and benefit emphasizes the need for a careful and informed approach when making decisions about vaccination policies, prioritizing public health and population safety.

Clinical and sociodemographic factors associated with time spent sitting in military police.

OBJECTIVE: To verify the association between clinical and sociodemographic factors and time spent sitting in military police. METHOD: This is a cross-sectional study, with 432 military police officers from Eastern Regional Policing Command units of the Military Police of Bahia de Feira de Santana. Data collection took place from August to December 2022 through Google Forms using the International Physical Activity Questionnaire. RESULTS: Men predominated (82.35%), race/color was black (87.04%), the head of the family had completed higher education (47.69%) and police officers with a partner (81.94%). The risk of time spent sitting ≥ 180 minutes per day was lower in males (IRR < 1). Increasing age was associated with a lower risk of time spent sitting ≥ 180 minutes per day (IRR < 1). CONCLUSION: Male police officers with more years of experience were less exposed to sedentary behavior. Specific interventions and health policies aimed at combating sedentary behavior become relevant, aiming to promote health and prevent diseases.

Differences in the Behavioral Parameters of Young Zebu and Composite Bulls Kept on Non-Forested or in Integrated Crop-Livestock-Forestry Systems.

The behavior of ruminants can influence their productive efficiency. The aim of this study was to evaluate the behavior of young zebu and composite bulls kept in pasture production systems, either in a crop-livestock-forest integration or without afforestation. The work was carried out in São Carlos, Brazil (21°57'42″ S, 47°50'28″ W), in a high-altitude tropical climate, from March to July, 2022. Forty young bulls were evaluated, being 20 Nelore (Bos indicus) (342.5 ± 36.6 kg BW; 16.9 ± 1.8 months) and 20 Canchim (5/8 Bos taurus × 3/8 Bos indicus) (338.4 ± 39.8 kg BW; 19.1 ± 1.9 months), equally distributed in full-sun (FS) and integrated crop-livestock-forestry (ICLF) production systems. Behavior was monitored uninterruptedly by an acoustic sensor and accelerometer attached to a collar, and complemented by direct visual assessment, in two one-day campaigns per month. Serum cortisol concentration was assessed monthly. Statistical analyses were conducted using a general linear model at a 5% significance level (SAS, version 9.4). The ICLF system had a milder microclimate and favored thermal comfort. Natural shading influenced grazing, resting, and rumination time. The Canchim bulls were more active when moving and grazing (p < 0.05), even at the hottest times of the day. In turn, the Nelore bulls spent more time resting at all times (p < 0.001), which was shown to be an adaptive strategy in response to environmental stimuli. The Canchim bulls had a longer rumination time than the Nelore bulls (p < 0.001), due to their longer grazing time. The frequency of water and mineral mixture intake did not differ between genotypes, regardless of the production system (p > 0.05). There was no difference in the serum cortisol concentrations of the Nelore and Canchim bulls kept in FS or ICLF (p = 0.082). Thus, young bulls of the different genotypes showed different behaviors, regardless of whether they were kept on pasture without afforestation or in an integrated crop-livestock-forestry system.

BRAF mutations and survival with surgery for colorectal liver metastases: A systematic review and meta-analysis.

INTRODUCTION: Mutations in the BRAF gene (BRAFmut) are associated with an unfavorable prognosis in patients with metastatic colorectal cancer (CRC). The aim of this meta-analysis was to evaluate the prognosis of colorectal cancer (CRC) patients with liver metastases and the potential benefits of liver resection in patients with BRAFmut CRC. MATERIAL AND METHODS: A systematic search of PubMed, Cochrane Central Controlled Trials, and Embase databases was conducted on May 31, 2023. The inclusion criteria were as follows:1) reporting of outcomes in patients with BRAFmut CRC who underwent surgery for liver metastases and/or comparison of outcomes between those who underwent and those who did not undergo resection; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. RESULTS: 34 studies were included. Median follow up was 48 months for prognostic BRAF status meta-analysis. BRAFmut status showed a significantly increased risk of mortality (hazard ratio [HR] = 2.56, 95% confidence interval [CI] 2.04-3.22; P < 0.01) and relapse (HR = 1.97, 95% CI 1.44-2.71; P < 0.01). Resection of liver metastases was associated with a survival benefit (median follow up 46 months). The HR for survival was 0.44 (95% confidence interval [CI] 0.33-0.59; P < 0.01) in favor of surgery. CONCLUSIONS: and Relevance: Our analysis indeed confirms that BRAF mutation is associated with poor survival outcomes after liver resection of CRC metastases. However, upon quantitatively assessing the survival benefit of surgical intervention in patients with BRAF-mutated CRC liver metastases, we identified a significant 56% reduction in the risk of death.

Development of cassava starch-based films incorporated with phenolic compounds produced by an Amazonian fungus.

Drug-release systems have attracted attention over the last few years since they can be used as a substitute for traditional methods of drug delivery. These have the advantage of being directly administered at the treatment site and can maintain the drug at adequate levels for a longer period, thus increasing their efficacy. Starch-based films are interesting candidates for use as matrices for drug release, especially due to starch's non-toxic properties and its biocompatibility. Endophytic fungi are an important source of bioactive molecules, including secondary metabolites such as phenolic compounds with antioxidant activity. In the present study, cassava starch-based films were developed to act as release systems of phenolic compounds with antioxidant activity. The Amazonian endophytic fungus Aspergillus niger MgF2 was cultivated in liquid media, and the fungal extract was obtained by liquid-liquid partition with ethyl acetate. The starch-based films incorporated with the fungal extract were characterized in regards to their physicochemical properties. The release kinetics of the extract from the film and its antioxidant and cytotoxic properties were also evaluated. The films incorporated with the extract presented maximum release after 25 min at 37 °C and pH 6.8. In addition, it was observed that the antioxidant compounds of the fungal extract maintain their activity after being released from the film, and were non-toxic. Therefore, considering the promising physicochemical properties of the extract-incorporated films, and their considerable antioxidant capacity, the films demonstrate great biotechnological potential with diverse applications in the pharmacological and cosmetic industries.

Initial clinical evidence on biperiden as antiepileptogenic after traumatic brain injury-a randomized clinical trial.

There is currently no efficacious intervention for preventing post-traumatic epilepsy (PTE). Preclinical studies support the potential use of anticholinergics for this condition. The purpose of this study was to evaluate the effects of biperiden as an intervention for preventing PTE. A randomized, double-blinded clinical trial was conducted at HC/FMUSP between 2018-2022. Adults with acute traumatic brain injury (TBI) were randomly assigned to receive biperiden or placebo, for 10 days. The primary outcome was the incidence of PTE while the secondary outcomes included the frequency of seizures, the frequency of any adverse events and mortality after 24 months. The study was powered at a planned enrolment of 132 patients. The trial began in January 2018 and was halted by researchers on March 2020 (and terminated in December 2022) in the face of the global COVID-19 pandemic. Overall, 123 participants were randomized and 112 contributed with data for modified mITT analysis, being that 61 (49.5%) participants completed the 24-month follow-up consult. Data analysis indicated lack of evidence of biperiden for either, the incidence of post-traumatic epilepsy (2.6, 95%CI, 0.65-10.57; p = 0.170) or the mortality rate (1.57, 95%CI, 0.73-3.38; p = 0.248). The frequency of late post-traumatic seizures was higher for biperiden group (2.03, 95%CI = 0.912-3.1597; p <0.001). The present study suggests that there was insufficient evidence regarding the effect of biperiden in preventing PTE after TBI, which underpins the need for larger studies. Clinical trial registration: ClinicalTrials.gov, identifier: NCT01048138.