Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management.

Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS.

Effect of early vs. delayed extubation on functional outcome among patients with acute ischemic stroke treated with endovascular thrombectomy under general anesthesia: the prospective, randomized controlled EDESTROKE trial study protocol.

Background: Recent meta-analyses and randomized studies have shown that among patients with acute ischemic stroke undergoing endovascular thrombectomy, general anesthesia with mechanical ventilation is associated with better functional status compared to local anesthesia and sedation, and they recommend its use. But once the procedure is completed, when is the optimal moment for extubation? Currently, there are no guidelines recommending the optimal moment for extubation. Prolonged mechanical ventilation time could potentially be linked to increased complications such as pneumonia or disturbances in cerebral blood flow due to the vasodilatation produced by most anesthetic drugs.

Family Planning in Fertile-Age Patients With Multiple Sclerosis (MS) (ConPlanEM Study): Delphi Consensus Statements.

Family planning is essential for establishing Multiple Sclerosis (MS) prognosis, treatment decision, and disease monitoring. We aimed to generate an expert consensus addressing recommendations for family planning in MS patients of childbearing age. Initially, a committee comprising seven neurologists, experts in the MS field, identified the topics to be addressed.

Efficacy of heat-inactivated vaccine delivered to European badgers () through edible bait.

Badgers () are a major tuberculosis (TB) reservoir in Europe, with the potential to transmit infection to cattle. Here we assessed whether a recently described oral tuberculosis vaccine based on heat-inactivated (HIMB) delivered as edible baits, can protect badgers from infection. Eight badgers were given individually five baits, each one consisting of a ball of peanut butter, natural peanut and oat flakes including a dose of the vaccine containing 5 × 10 colony-forming units.

Dietary Supplementation with Yerba Mate () Infusion Increases IRS-1 and PI3K mRNA Levels and Enhances Insulin Sensitivity and Secretion in Rat Pancreatic Islets.

"Yerba mate" (YM), an aqueous extract of Ilex paraguariensis, has antioxidant, diuretic, cardio-protective and hypoglycaemic properties. Since its effect on the pancreatic islets remains unclear, we evaluated insulin sensitivity and glucose-stimulated insulin secretion (GSIS) in rats consuming YM or tap water (C) for 21 days. Glucose tolerance, glycemia, triglyceridemia, insulinemia, TBARS and FRAP serum levels were evaluated.

In Vitro Pro-Apoptotic and Anti-Migratory Effects of (syn. ) Extracts on Human Prostate Cancer Cell Lines: Bioguided Isolation of 5-Henicosene-1-yl-resorcinol.

This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Blume Kuntze plant extracts on prostate cancer cells, identify the active compound/s, and characterize their mechanism of action. The crude methanolic extract was partitioned into -hexane (MPh), chloroform (MPc), and aqueous (MPa) extracts. Antiproliferative fractions (IC50 < 30 μg/mL based on SRB staining of LNCaP and PC3 cell lines) were further fractionated.

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia.

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions.

Discrimination of foreign bodies in quinoa Willd.) grains using convolutional neural networks with a transfer learning approach.

The rising interest in quinoa ( Willd.) is due to its high protein content and gluten-free condition; nonetheless, the presence of foreign bodies in quinoa processing facilities is an issue that must be addressed. As a result, convolutional neural networks have been adopted, mostly because of their data extraction capabilities, which had not been utilized before for this purpose.

effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity.

Many medicinal plants species from European -such as - as well as Latin American traditions -such as , and are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 μg/ml) of their infusions for ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR).

Herbal supplements in Jordan: a cross-sectional survey of pharmacists' perspectives and knowledge.

Objectives: Pharmacists are ideal partners for engaging with the needs and expectations of patients. They can play a vital role by providing information and supplying herbal medicines. In some community settings, pharmacists are also the main first point of care.

Anti-Inflammatory and Antioxidant Chinese Herbal Medicines: Links between Traditional Characters and the Skin Lipoperoxidation "Western" Model.

The relationship between lipid peroxidation and inflammation has been accepted as a paradigm in the field of topical inflammation. The underlying biochemical mechanisms may be summarised as unspecific oxidative damage followed by specific oxidative processes as the physio pathological response in skin tissues. In this experimental review we hypothesise that the characteristics attributed by Traditional Chinese Medicine (TCM) to herbal drugs can be linked to their biomolecular activities within the framework of the above paradigm.

In Vitro Effects of Selective COX and LOX Inhibitors and Their Combinations with Antineoplastic Drugs in the Mouse Melanoma Cell Line B16F10.

The constitutive expression or overactivation of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes results in aberrant metabolism of arachidonic acid and poor prognosis in melanoma. Our aim is to compare the in vitro effects of selective COX-1 (acetylsalicylic acid), COX-2 (meloxicam), 5-LOX (MK-886 and AA-861), 12-LOX (baicalein) and 15-LOX (PD-146176) inhibition in terms of proliferation (SRB assay), mitochondrial viability (MTT assay), caspase 3-7 activity (chemiluminescent assay), 2D antimigratory (scratch assay) and synthesis of eicosanoids (EIA) in the B16F10 cell line (single treatments). We also explore their combinatorial pharmacological space with dacarbazine and temozolomide (median effect method).

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab.

We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.

Effects of Selected Nigerian Medicinal Plants on the Viability, Mobility, and Multidrug-Resistant Mechanisms in Liver, Colon, and Skin Cancer Cell Lines.

Medicinal plants indicated for chronic diseases usually have good safety margins as they are intended for lifelong treatments. We hypothesized that they may provide patients with baseline protection to cancers and multidrug resistance-reversing phytochemicals resulting in successful prevention and/or adjuvant treatment of chemotherapy-resistant cancers. We selected 27 popular herbal infusions widely used in Nigeria for diabetes and studied their effects on a panel of liver (HepG2), colon (Caco2), and skin (B16-F10) cancer cells.

Differential Anti-Proliferative and Anti-Migratory Activities of Ursolic Acid, 3--Acetylursolic Acid and Their Combination Treatments with Quercetin on Melanoma Cells.

We evaluate how 3-acetylation modulates the in vitro activity of ursolic acid in melanoma cells alone or in combination treatments with quercetin. Anti-proliferative studies on A375 cells and adult human dermal fibroblasts included analyses on cell cycle distribution, caspase activity, phosphatidylserine translocation, cell morphology and Bax/Bcl-2 protein expression. Then, 2D and 3D migration of B16F10 cells were studied using scratch and Transwell assays, respectively.

The Broad Concept of "Spasticity-Plus Syndrome" in Multiple Sclerosis: A Possible New Concept in the Management of Multiple Sclerosis Symptoms.

Multiple sclerosis (MS) pathology progressively affects multiple central nervous system (CNS) areas. Due to this fact, MS produces a wide array of symptoms. Symptomatic therapy of one MS symptom can cause or worsen other unwanted symptoms (anticholinergics used for bladder dysfunction produce impairment of cognition, many MS drugs produce erectile dysfunction, etc.

Protective Effect of Oral BCG and Inactivated Vaccines in European Badgers () Experimentally Infected With .

In Europe, badgers () are recognized as major tuberculosis (TB) reservoir hosts with the potential to transmit infection to associated cattle herds. Recent studies in Spain have demonstrated that vaccination with a heat-inactivated vaccine (HIMB) successfully protects captive wild boar and red deer against progressive disease. The aim of this study was to evaluate the efficacy of two oral vaccines against TB in a badger model: the live-attenuated bacillus Calmette-Guérin BCG vaccine (Danish strain) and a HIMB vaccine.

In Vitro Modulation of Glibenclamide Transport by P-glycoprotein Inhibitory Antidiabetic African Plant Extracts.

The rise of diabetes incidence in Nigeria enhances the use of popular remedies that may interact with conventional therapies. The aqueous extracts of 27 popular Nigerian "antidiabetic" plants were tested for their effects on glutathione levels within HepG2 cells, P-glycoprotein (P-gp)-mediated Rh-123 efflux activity in Caco-2 vincristine-resistant cells, and modulation of glibenclamide transport in Caco-2 monolayers. The extract from significantly depleted intracellular glutathione at 100 µg/mL similarly to the reference buthionine sulphoximine (p < 0.

Natural Cytotoxic Diterpenoids, a Potential Source of Drug Leads for Melanoma Therapy.

Diterpenes present complex structure and due to their unique carbon skeleton and interesting biological activities, have been the focus of continuous studies for the development of new anticancer agents. Phorbol esters have been known for their activity against skin malignancies since ancient times. Taxol was first studied in melanoma cells, and recently, ingenol mebutate has been approved for the chemoprevention of melanoma in actinic keratosis patients.

Pro-apoptotic and Anti-migratory Effects of L. Plant Extracts on the Human Prostate Cancer Cell Lines PC3.

This study aims to evaluate the cytotoxic and anti-migratory effects of L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var.

Differential modulation of Bax/Bcl-2 ratio and onset of caspase-3/7 activation induced by derivatives of Justicidin B in human melanoma cells A375.

Diphyllin and its derivatives are well known cytotoxic natural products structurally related to the anti-cancer drug podophyllotoxin. We here study their structure-activity relationship upon human melanoma cells for first time. To this end, human melanoma A375 cells were incubated with Justicidin B and its 4-methoxylated or 4-glycosylated derivatives to evaluate their selective cytotoxicity and study their effects on cell cycle distribution, caspase activation, apoptosis induction using Annexin V-FITC/PI staining, cell morphology and western blot analysis.

In vitro Effects of Four Native Brazilian Medicinal Plants in CYP3A4 mRNA Gene Expression, Glutathione Levels, and P-Glycoprotein Activity.

Erythrina mulungu Benth. (Fabaceae), Cordia verbenacea A. DC.

Assessment of Potential Herb-Drug Interactions among Nigerian Adults with Type-2 Diabetes.

It is becoming increasingly evident that patients with diabetes do not rely only on prescription drugs for their disease management. The use of herbal medicines is one of the self-management practices adopted by these patients, often without the knowledge of their healthcare practitioners. This study assessed the potential for pharmacokinetic herb-drug interactions (HDIs) amongst Nigerian adult diabetic patients.

Borrelia burgdorferi sensu lato prevalence and diversity in ticks and small mammals in a Lyme borreliosis endemic Nature Reserve in North-Western Spain. Incidence in surrounding human populations.

To determine the prevalence and diversity of Borrelia burgdorferi sensu lato (s.l.) in an endemic Nature Reserve (Sierra del Sueve) in North-Western Spain, and the risk of human exposure to infected ticks in Asturias, 1013 questing ticks and 70 small mammals were collected between 2012 and 2014.