The role of disease modifying therapies in late-onset multiple sclerosis: A Portuguese multicentric characterization study.

Introduction: Knowledge about the effect of disease modifying treatment (DMT) in late-onset multiple sclerosis (LOMS, onset ≥50 years-old) is scarce. This study aims to evaluate the association between DMT use and multiple sclerosis (MS) evolution in a LOMS cohort.

Methods: This multicentre, retrospective and observational study included LOMS patients with ≥2 years of follow-up.

Using biodiversity databases to assess vascular plant diversity in Protected Areas: a case study of Parque Estadual do Forno Grande, Brazil.

Background: The Parque Estadual do Forno Grande is a fully protected area in the southern Espírito Santo State, Brazil. It belongs to the Atlantic Forest domain, with predominantly dense, ombrophilous, seasonal semi-deciduous forests and herbaceous/shrubby vegetation on rock outcrops. The area is recognised as highly important for conservation, designated as a priority biological area for protecting the Atlantic Forest's biodiversity.

Influence of polymorphisms on the phenotype of TLR1, TLR4 and TLR9 genes and their association with cervical cancer: Bioinformatics prediction analysis and a case-control study.

Susceptibility to cervical cancer has been associated with Toll-like receptors (TLRs), which is an important component of innate immunity. According to previous studies, polymorphisms in TLRs genes can affect immune response pathways and lead to the development of cervical cancer. The present study aims to evaluate the functionality of polymorphisms in TLR1, TLR4 and TLR9 genes and their associations with cervical cancer.

A comprehensive floristic knowledge of a fragment of Semideciduous Seasonal Forest [Parque Estadual da Serra da Concórdia], Rio de Janeiro, Brazil.

Background: The "Serra da Concórdia" is part of the Atlantic Forest phytogeographical domain in the Brazilian state of Rio de Janeiro and it has a predominant phytophysiognomy of Semideciduous Seasonal Forest. This region underwent intense habitat loss and fragmentation during the 19 century, due to coffee plantations and later pastures. With the decline of these activities, the areas were abandoned, triggering secondary succession.

Neonatal factors associated with early weaning in a municipality in Bahia, Brazil: a cross-sectional study.

Objective: To analyze neonatal factors associated with early weaning.

Method: This is a cross-sectional study conducted between March and September 2023 with 180 women six months to two years postpartum, from a municipality in Bahia, Brazil. For bivariate analysis, Pearson's chi-square tests were used, considering p < 0.

Selective inhibition of HDAC6 by N-acylhydrazone derivative reduces the proliferation and induces senescence in carcinoma hepatocellular cells.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths globally. Systemic therapy is the only treatment option for HCC at an advanced stage, with limited therapeutic response. In this study, we evaluated the antitumor potential of four N-acylhydrazone (NAH) derivatives, namely LASSBio-1909, 1911, 1935, and 1936, on HCC cell lines.

Remapping the Chemical Space and the Pharmacological Space of Drugs: What Can We Expect from the Road Ahead?

This work examines the current landscape of drug discovery and development, with a particular focus on the chemical and pharmacological spaces. It emphasizes the importance of understanding these spaces to anticipate future trends in drug discovery. The use of cheminformatics and data analysis enabled in silico exploration of these spaces, allowing a perspective of drugs, approved drugs after 2020, and clinical candidates, which were extracted from the newly released ChEMBL34 (March 2024).

Cytotoxic and Antiproliferative Activity of LASSBio-2208 and the Attempts to Determine Its Drug Metabolism and Pharmacokinetics In Vitro Profile.

Inappropriate expression of histone deacetylase (HDAC-6) and deregulation of the phosphatidylinositol 3-kinase (PI3K) signalling pathway are common aberrations observed in cancers. LASSBio-2208, has been previously described as a dual inhibitor in the nanomolar range of HDAC-6 and PI3Kα and is three times more potent in inhibiting HDAC-6. In this paper we described the cytotoxic and antiproliferative potency of LASSBio-2208 on different tumour cell lines, its possible synergism effect in association with PI3K and HDAC-6 inhibitors, and its drug metabolism and pharmacokinetics (DMPK) in vitro profile.

Cell Therapy Transplant Canada (CTTC) Consensus-Based Guideline 2024 for Management and Treatment of Chronic Graft-Versus-Host Disease and Future Directions for Development.

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD.

Molecular hybridization: a powerful tool for multitarget drug discovery.

Introduction: The current drug discovery paradigm of 'one drug, multiple targets' has gained attention from both the academic medicinal chemistry community and the pharmaceutical industry. This is in response to the urgent need for effective agents to treat multifactorial chronic diseases. The molecular hybridization strategy is a useful tool that has been widely explored, particularly in the last two decades, for the design of multi-target drugs.

Natural Products and Diabetes: (-)-Epicatechin and Mechanisms Involved in the Regulation of Insulin Sensitivity.

Type 2 diabetes (T2D) is a disease that occurs when cells do not respond normally to insulin, a condition called insulin resistance, which leads to high blood glucose levels. Although it can be treated pharmacologically, dietary habits beyond carbohydrate restriction can be highly relevant in the management of T2D. Emerging evidence supports the possibility that natural products (NPs) could contribute to managing blood glucose or counteract the undesirable effects of hyperglycemia and insulin resistance.

Severe Hemolytic Anemia: Atypical Presentation of Cobalamin Deficiency.

Two severe cases of hemolytic anemia are described in different pediatric age groups, both linked to severe cobalamin deficiency from distinct causes. The first case refers to an exclusively breastfed infant with vitamin deficit secondary to maternal impaired absorption. Apart from the neurological deficits present at diagnosis, he also presented with infantile epileptic spasms syndrome a few months after treatment while having normal cobalamin serum levels.

(Poly)phenols and the regulation of NADPH oxidases.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are enzymes that generate superoxide anion (O•) and hydrogen peroxide (HO), and that are widely distributed in mammalian tissues. Many bioactives, especially plant (poly)phenols are being studied for their capacity to regulate NOXs. The modulation of these enzymes are of central relevance to maintain redox homeostasis and regulate cell signaling.

Acute Fulminant Cerebral Edema in a Child With Suspected Meningoencephalitis.

Acute fulminant cerebral edema (AFCE) is a recently identified encephalitis type associated with significant morbimortality. Described as rare, limited data exists on its early detection and treatment. This paper describes a case of AFCE that progressed to unresponsive intracranial hypertension.

Canadian real-world experience of asciminib treatment in heavily pre-treated chronic myeloid leukemia (CML) patients who failed multiple lines of tyrosine kinase inhibitor (TKI) therapy.

Background: Asciminib is a novel drug specifically targeting ABL myristoyl pocket in the ABL1 protein.

Methods: Forty one patients with chronic myeloid leukemia treated with asciminib from 2018 to 2022 were reviewed and analyzed for the efficacy and tolerability of asciminib using real-world experience data.

Results: The median age was 60 years (range 17-90) with a past history of a cardiovascular event in 21 patients (51%).

The Magic Methyl and Its Tricks in Drug Discovery and Development.

One of the key scientific aspects of small-molecule drug discovery and development is the analysis of the relationship between its chemical structure and biological activity. Understanding the effects that lead to significant changes in biological activity is of paramount importance for the rational design and optimization of bioactive molecules. The "methylation effect", or the "magic methyl" effect, is a factor that stands out due to the number of examples that demonstrate profound changes in either pharmacodynamic or pharmacokinetic properties.

Oral health of an indigenous population in northeastern Brazil: a cross-sectional Study of the Fulni-ô ethnic group.

Background: There is a lack of studies evaluating the oral health of traditional indigenous communities in Brazil.

Objectives: Thus, the objective of this study was to describe the oral health characteristics of the indigenous Fulni-ô ethnic group in Northeast Brazil.

Design And Setting: A cross-sectional observational investigation was conducted within the Project on Atherosclerosis among Indigenous Populations.

Trace Element Imbalances in Acquired Hepatocerebral Degeneration and Changes after Liver Transplant.

Brain manganese (Mn) accumulation is a key feature in patients with acquired hepatocerebral degeneration (AHD). The role of trace elements other than Mn in AHD needs to be clarified. In this study, using inductively coupled plasma mass spectrometry, we aimed to evaluate blood levels of trace elements in patients with AHD before and after liver transplantation (LT).

A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area.

Background: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S.

Management of infantile hemangiomas-experience of a tertiary hospital.

The purpose of the study is to describe the experience of a multidisciplinary team in a tertiary hospital regarding the management of Infantile Hemangiomas (IH). The method employed is a retrospective analysis of patients with IH followed in a tertiary pediatric hospital between January 2010 and May 2022. A total of 393 IH were diagnosed (56.

Imidazole: Synthesis, Functionalization and Physicochemical Properties of a Privileged Structure in Medicinal Chemistry.

Imidazole was first synthesized by Heinrich Debus in 1858 and was obtained by the reaction of glyoxal and formaldehyde in ammonia, initially called glyoxaline. The current literature provides much information about the synthesis, functionalization, physicochemical characteristics and biological role of imidazole. Imidazole is a structure that, despite being small, has a unique chemical complexity.