Seasonality of the incidence of bronchiolitis in infants - Brazil, 2016-2022: An interrupted time-series analysis.

OBJECTIVE: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons. METHODS: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model. RESULTS: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak. CONCLUSIONS: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.

Placental and Neonatal Serum Leptin Levels in Premature Infants After Phototherapy: Are They Determining Factors for the Safe Indication of Passive Exercises?

Purpose: To analyze leptin levels in placental tissue and premature infants undergoing phototherapy and to evaluate the potential for prescribing passive exercise after phototherapy in this population. Patients and Methods: This analytical, longitudinal, prospective cohort study included 108 parturients and their respective premature infants. Variables examined included weight, gestational age, body mass index, sex, serum leptin levels in placental tissue, serum bilirubin levels, and reticulocyte count. Results: When comparing each group to a leptin threshold, statistically significant differences were observed at all evaluated time points for placental leptin levels (p < 0.001). Additionally, reticulocyte count decreased in relation to rebound time (p < 0.004). No correlations were found between leptin/bilirubin levels, leptin/reticulocytes, onset of nutrition, and BMI/leptin levels. Conclusion: The findings regarding leptin levels suggest that prescribing passive exercises to premature infants undergoing phototherapy may be feasible because this intervention did not increase leptin levels.

Efficient photocatalytic activity and selective adsorption of UiO-67 (Zr)/g-C3N4 composite toward a mixture of parabens.

In this study, UiO-67 (Zr)/g-C3N4 composites (U67N) were synthesized at wt.% ratios of 05:95, 15:85, and 30:70 using the solvothermal method at 80 °C for 24 h followed by calcination at 350 °C. The composites were characterized using UV-Vis diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy-energy-dispersive X-ray spectroscopy, transmission electron microscopy, and nitrogen physisorption analysis. In addition, thermal stability analysis of UiO-67 was conducted using thermogravimetric analysis. The photocatalytic performance of the composites was assessed during the degradation and mineralization of a mixture of methylparaben (MeP) and propylparaben (PrP) under simulated sunlight. The adsorption process of U67N 15:85 was characterized through kinetic studies and adsorption capacity experiments, which were modeled using pseudo-first-order and pseudo-second-order kinetics and Langmuir and Freundlich isotherms, respectively. The influence of pH levels 3, 5, and 7 on the photocatalytic degradation of the mixture was investigated, revealing enhanced degradation and mineralization at pH 3. The U67N composite exhibited dual capability in removing contaminants through adsorption and photocatalytic processes. Among the prepared composites, U67N 15:85 demonstrated the highest photocatalytic activity, achieving removal efficiencies of 96.8% for MeP, 92.5% for PrP, and 45.7% for total organic carbon in 300 kJ/m2 accumulated energy (3 h of reaction time). The detoxification of the effluent was confirmed through acute toxicity evaluation using the Vibrio fischeri method. The oxidation mechanism of the heterojunction formed between UiO-67 (Zr) and g-C3N4 was proposed based on PL analysis, photoelectrochemistry studies (including photocurrent response, Nyquist, and Mott-Schottky analyses), and scavenger assays.

Oligodendrocyte Progenitors in Glial Scar: A Bet on Remyelination.

Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar-a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial.

OBJECTIVE: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. METHODS: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. RESULTS: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. CONCLUSIONS: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.

Stress and exhaustion among medical students: a prospective longitudinal study on the impact of the assessment period on medical education.

BACKGROUND: Stress significantly affects both the physical and emotional health of individuals, particularly students in health-related fields. Medical students in Brazil face unique challenges due to the demanding nature of their studies, especially during assessment periods, which heighten academic pressure. These pressures often lead to poor coping strategies and mental health concerns. It is crucial to understand the complex dynamics of stress within medical education to develop strategies that improve student well-being and promote a healthier academic environment. This study aims to investigate the intricate relationship between assessment periods and stress levels among medical students. It seeks to understand how academic demands and sociodemographic factors contribute to stress dynamics during these periods. METHODS: An online observational, longitudinal, and prospective study was conducted from February to October 2022. Medical students were recruited through snowball sampling and participated in surveys administered via Google Forms at two timepoints: before (T1) and during (T2) assessment periods. The surveys collected sociodemographic data and stress symptoms using Lipp's Inventory of Stress Symptoms for Adults (LSSI). RESULTS: The transition from T1 to T2 was defined by a rise in the prevalence of stress from 59.6 to 84.2% (p = 0.001) and a decline in symptom-free students from 40.4 to 15.8% (p = 0.001). There was a significant increase in exhaustion, from 12.3 to 31.6% (p = 0.0001). Higher stress levels were notably more prevalent among younger students (≤ 24 years), females, those from wealthier families, students without scholarships, those without prior degrees, and those in the clinical phase of their studies. However, non significant correlations were found between these sociodemographic and academic factors and the increase in stress. CONCLUSION: The findings highlight significant concerns regarding the mental health of medical students during assessment periods, marked by increased stress and exhaustion levels. These results emphasize the need for proactive interventions to manage stress effectively in medical education, considering its profound impact on students' well-being.

Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Higher volume resistance training enhances whole-body muscle hypertrophy in postmenopausal and older females: A secondary analysis of systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: This study explored the effects of resistance training (RT) volume on muscle hypertrophy in postmenopausal and older females. METHODS: This systematic review searched randomized controlled trials (RCTs) on PubMed/MEDLINE, Scopus, Web of Science, and SciELO. Studies with postmenopausal (age ≥ 45 y) or older females (age ≥ 60 y) that compared RT (whole-body) effects on muscle hypertrophy with a control group (CG) were included. Independently reviewers selected the studies, extracted data, and performed the risk of bias of RCTs (RoB2) and certainty of the evidence (GRADE). Whole-body lean mass, free-fat mass, and skeletal muscle mass measurements were included as muscle hypertrophy outcomes. A random-effects model standardized mean difference (Hedges'g), and 95% confidence interval (95%CI) were used for meta-analysis. RESULTS: Fourteen RCTs (overall RoB2: some concerns, except one study with high risk; GRADE: low evidence) were included. RT groups were divided into low (LVRT, total volume: 445.0 au) and high-volume (HVRT, total volume: 997.3 au). Most exercises performed were arm curl, bench press or chest press, calf raise, leg curl, leg extension, leg press or squat, seated row or lat pulldown, and triceps pushdown. Both groups experienced muscle hypertrophy (HVRT = ∼1.3 kg vs. LVRT = ∼0.9 kg) when compared to CG, although HVRT demonstrated moderate effects size (HVRT = 0.52, 95%CI: 0.27, 0.77) and LVRT demonstrated small effects size (LVRT = 0.34, 95%CI: 0.14, 0.53). CONCLUSIONS: Compared to CG, results suggest that the HVRT protocol elicits superior improvements in muscle hypertrophy outcomes than LVRT in postmenopausal and older females.

[Usefulness of the Beck depression inventory in the diagnosis of depressive disorders in multiple sclerosis]. / Utilidad de la escala de depresión de Beck para el diagnóstico de los trastornos depresivos en la esclerosis múltiple.

INTRODUCTION: Depression is one of the most prevalent psychiatric conditions in adulthood, reaching figures of around 20%. The methodologies used to study depression are varied, and range from a self-administered test to structured psychiatric assessment. Several studies of patients with multiple sclerosis (MS) have been conducted in the last 20 years, and figures of around 35% have been found for depressive symptoms, while depressive disorders are less frequent, at approximately 21%. AIMS: The aim of this study is to evaluate the usefulness of patient self-reported scales such as the Beck depression inventory (BDI) for identifying depressive symptoms in patients with MS, and to analyse their correlation with the diagnosis of clinical depression or depressive disorder using the psychiatric clinical interview based on the criteria of the Diagnostic and statistical manual of mental disorders, fifth edition. PATIENTS AND METHODS: This is a multicentre descriptive cross-sectional study of patients with MS and depressive symptoms. The BDI and the Hamilton depression rating scale (HDRS) were used, and the patients with the highest scores underwent psychiatric assessment. RESULTS: A total of 191 patients were included; 81 of these (40.5%) had depressive symptomatology in the pathological range according to the BDI (cut-off point of 14), and 20 had a severe score (above 28). Nineteen patients with severe depressive symptoms according to both scales were selected and finally evaluated by a psychiatrist, who also assessed five patients who according to the neurologist had severe depressive symptoms despite a BDI score of almost 28, but did not reach that level. The suspected major depressive disorder was confirmed in only four (21%) cases with BDI scores indicative of severe symptoms. There is no correlation between the severity score as evidenced by the BDI and the psychiatric assessment. A major depressive disorder was diagnosed in 16 (66.6%) of the 24 patients with BDI > 26 evaluated by psychiatry. A score above 26 on the BDI enables identification of 75% of cases of depressive disorder without subtyping. The correlation between the HDRS and the BDI was statistically significant (r = 0.8; p < 0). CONCLUSIONS: The BDI is a useful screening test for identifying patients with depressive symptoms; in specific terms, a score above 26 is probably indicative of a depressive disorder that may benefit from psychiatric assessment.

TITLE: Utilidad de la escala de depresión de Beck para el diagnóstico de los trastornos depresivos en la esclerosis múltiple.Introducción. La depresión es una de las condiciones psiquiátricas con mayor prevalencia en la edad adulta y alcanza cifras alrededor del 20%. Las metodologías para el estudio de la depresión son varias y van del uso de un test autoadministrado a la valoración psiquiátrica estructurada. En los últimos 20 años se han realizado varios estudios en los pacientes con esclerosis múltiple (EM), y se han objetivado cifras alrededor del 35% para los síntomas depresivos, mientras que los trastornos depresivos son menos frecuentes, aproximadamente el 21%. Objetivos. El objetivo de este estudio es evaluar la utilidad de una escala autoinformada por el paciente, como la escala de depresión de Beck (BDI), para la detección de síntomas depresivos en pacientes con EM, y analizar su correlación con el diagnóstico de depresión clínica o trastorno depresivo realizado a través de la entrevista clínica psiquiátrica basada en los criterios del Manual diagnóstico y estadístico de los trastornos mentales, quinta edición. Pacientes y métodos. Es un estudio descriptivo transversal multicéntrico de pacientes con EM y síntomas depresivos. Se emplearon la BDI y la escala de valoración de la depresión de Hamilton (HDRS), y los pacientes con puntuaciones más altas se sometieron a una valoración psiquiátrica. Resultados. Se incluyó a 191 pacientes; de ellos, 81 (40,5%) presentaron sintomatología depresiva en el rango patológico de acuerdo con la BDI (punto de corte en 14), y 20, puntuación grave (superior a 28). Se ha seleccionado a 19 pacientes con síntomas depresivos graves según ambas escalas que finalmente han sido evaluados por un psiquiatra, que además ha valorado a cinco pacientes que según el neurólogo presentaban síntomas depresivos graves a pesar de una puntuación en la BDI cercana, pero inferior, a 28. Sólo en cuatro (21%) casos con puntuación indicativa de síntomas graves en la BDI se ha confirmado la sospecha de trastorno depresivo mayor grave. No hay correlación entre la puntuación de gravedad evidenciada por la BDI y la valoración psiquiátrica. Se ha formulado el diagnóstico de trastorno depresivo mayor en 16 (66,6%) de los 24 pacientes con BDI menor que 26 evaluados por psiquiatría. Una puntuación superior a 26 en la BDI permite identificar el 75% de los casos de trastorno depresivo sin subtipificar. La correlación entre la HDRS y la BDI fue estadísticamente significativa (r = 0,8; p menor que 0). Conclusiones. La BDI es un test de cribado útil para identificar a pacientes con síntomas depresivos; en particular, una puntuación superior a 26 es indicativa con buena probabilidad de un trastorno depresivo que se podría beneficiar de una valoración psiquiátrica.

Clinical profile and parameters of patients monoinfected with HBV and infected with HDV in Western Amazon.

Background: Hepatitis Delta represents a greater risk in the progression of advanced liver disease and HCC compared with HBV. The exact mechanism that determines the spontaneous clearance of delta virus or its progression to cirrhosis remains unknown. Therefore, this study aimed to analyze the clinical profile of HBV and HBV/HDV individuals in the Western Amazon. Methods: The study was carried out at the Specialized Outpatient Clinic for Viral Hepatitis belonging to the Centro de Pesquisa em Medicina Tropical de Rondônia/CEPEM. 100 individuals were included, stratified into two groups: 50 with hepatitis B virus and 50 with hepatitis Delta virus. Results: The overall mean age was 48 years. For the HBV and HDV groups, 66 % (33/50) and 54 % (27/50) were men and 56 % (28/50) and 58 % (29/50) were on antiviral treatment, respectively. Patients with detectable HDV-RNA demonstrated high levels of ALT and AST compared to individuals with undetectable HDV-RNA. Comparative analysis between HBV carriers and infected with HDV shows significant differences in terms of age, HBV-DNA levels, albumin, hepatomegaly and splenomegaly. Conclusion: Several markers were important for differentiating HBV and HDV infections. HDV-RNA detectable showed significant changes in biomarkers compared to undetectable patients, suggesting a possible worse prognostic effect in this group.

Potential availability of metals in anaerobic mono- and co-digestion of pig manure and maize.

This study aims to analyse the potential availability of essential metals including as Co, Fe, Ni, Zn, Mn, and Cu and non-essential metals such as Pb, Cr, and Cd within anaerobic mono- and co-digestion of pig manure and maize. The metals partitioning was determined using the Modified BCR (European Community Bureau of Reference) sequential extraction at defined intervals over a 45-days period, correlating changes in metals speciation with key digestion variables. The findings revealed that Cr, Cu, Fe, and Pb were predominantly associated with the oxidisable fraction, while Zn, Mn, and Cd were potentially available in both processes. Notably, NH4+-N and the VFAs, except propionic acid, correlated significantly with the available fractions of Co, Mn, Ni, Zn, Cr, and Pb during mono-digestion of pig manure. The wider pH range and the chemical properties of the feedstock in co-digestion resulted in varied correlations between the metals availability and the digestion variables.

Bromelain as a natural anti-inflammatory drug: a systematic review.

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1ß, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

Functional activation of dorsal striatum astrocytes improves movement deficits in hemi-parkinsonian mice.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source of striatal network modulation. However, it remains unknown how dopamine loss affects striatal astrocyte activity and whether astrocyte activity regulates behavioral deficits in PD. We addressed these questions by performing astrocyte-specific calcium recordings and manipulations using in vivo fiber photometry and chemogenetics. We find that locomotion elicits astrocyte calcium activity over a slower timescale than neurons. Unilateral dopamine depletion reduced locomotion-related astrocyte responses. Chemogenetic activation facilitated astrocyte activity, and improved asymmetrical motor deficits and open field exploratory behavior in dopamine lesioned mice. Together, our results establish a novel role for functional striatal astrocyte signaling in modulating motor function in PD and highlight non-neuronal targets for potential PD therapeutics.

Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Application of nanoformulations as a strategy to optimize chemotherapeutic treatment of glioblastoma: a systematic review.

The aim of this review was to explore the advances of nanoformulations as a strategy to optimize glioblastoma treatment, specifically focusing on targeting and controlling drug delivery systems to the tumor. This review followed the PRISMA recommendations. The studies were selected through a literature search conducted in the electronic databases PubMed Central, Science Direct, Scopus and Web of Science, in April 2023, using the equation descriptors: (nanocapsule OR nanoformulation) AND (glioblastoma). Forty-seven investigations included were published between 2011 and 2023 to assess the application of different nanoformulations to optimize delivery of chemotherapies including temozolomide, carmustine, vincristine or cisplatin previously employed in brain tumor therapy, as well as investigating another 10 drugs. Data demonstrated the possible application of different matrices employed as nanocarriers and utilization of functionalizing agents to improve internalization of chemotherapeutics. Functionalization was developed with the application of peptides, micronutrients/vitamins, antibodies and siRNAs. Finally, this review demonstrated the practical and clinical application of nanocarriers to deliver multiple drugs in glioblastoma models. These nanomodels might ideally be developed using functionalizing ligand agents that preferably act synergistically with the drug these agents carry. The findings showed promising results, making nanoformulations one of the best prospects for innovation and improvement of glioblastoma treatment.

Proteomic Analysis of a Rat Streptozotocin Model Shows Dysregulated Biological Pathways Implicated in Alzheimer's Disease.

Alzheimer's Disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracerebroventricular (ICV) injection of low to moderate doses of streptozotocin (STZ) in adult male Wistar rats can reproduce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, knowledge regarding the molecular aspects of the ICV-STZ model is still incipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on mass spectrometry (MS). To achieve that, samples from the pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differential protein abundance, pathway, and network analysis were performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in the early stages of late-onset Alzheimer's disease (LOAD), based on differentially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further investigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.

Enhancing oral bioavailability of an antifungal thiazolylhydrazone derivative: Development and characterization of a self-emulsifying drug delivery system.

RN104 (2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole) is a thiazolylhydrazone derivative with prominent antifungal activity. This work aimed to develop a self-emulsifying drug delivery system (SEDDS) loaded with RN104 to improve its biopharmaceutical properties and enhance its oral bioavailability. Medium chain triglycerides, sorbitan monooleate, and polysorbate 80 were selected as components for the SEDDS formulation based on solubility determination and a pseudo-ternary phase diagram. The formulation was optimized using the central composite design in response surface methodology. The optimized condition consisted of medium chain triglycerides, sorbitan monooleate, and polysorbate 80 in a mass ratio of 65.5:23.0:11.5, achieving maximum drug loading (10 mg/mL) and minimum particle size (118.4 ± 0.7 nm). The developed RN104-SEDDS was fully characterized using dynamic light scattering, in vitro release studies, stability assessments, polarized light microscopy, and transmission electron microscopy. In vivo pharmacokinetic studies in mice demonstrated that RN104-SEDDS significantly improved oral bioavailability compared to free RN104 (the relative bioavailability was 2133 %). These results clearly indicated the successful application of SEDDS to improve the pharmacokinetic profile and to enhance the oral bioavailability of RN104, substantiating its potential as a promising antifungal drug candidate.