Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer's disease progression.

For over a century after their discovery astrocytes were regarded merely as cells located among other brain cells to hold and give support to neurons. Astrocytes activation, "astrocytosis" or A1 functional state, was considered a detrimental mechanism against neuronal survival. Recently, the scientific view on astrocytes has changed.

Prolonged incubation with Δ-tetrahydrocannabinol but not with cannabidiol induces synaptic alterations and mitochondrial impairment in immature and mature rat organotypic hippocampal slices.

Cannabis derivatives are among the most widely used psychoactive substances in the world, which leads to growing medical concerns regarding its chronic use and abuse especially among adolescents. Exposure to THC during formative years produces long-term behavioral alterations that share similarities with symptoms of psychiatric and neurodevelopmental disorders. In this study, we have analyzed the functional and molecular mechanisms that might underlie these alterations.

Dynamics of Histoplasma fungal load in people living with HIV with disseminated histoplasmosis under treatment with liposomal amphotericin B.

Objectives: Disseminated histoplasmosis (DH) is a lethal fungal disease in patients living with HIV in endemic regions of the world. Diagnosis relies mainly on microscopy, culture, and antigen detection. Our goal was to evaluate the diagnostic and prognostic role of our RT-quantitative PCR (RT-qPCR) in blood specimens allowing to quantify the whole nucleic acids (WNA) load.

Chronic administration of prebiotics and probiotics ameliorates pathophysiological hallmarks of Alzheimer's disease in a APP/PS1 transgenic mouse model.

The gut microbiota (MB), although one of the main producers of Aβ in the body, in physiological conditions contributes to the maintainance of a healthy brain. Dysbiosis, the dysbalance between Gram-negative and Gram-positive bacteria in the MB increases Aβ production, contributing to the accumulation of Aβ plaques in the brain, the main histopathological hallmark of Alzheimer's disease (AD). Administration of prebiotics and probiotics, maintaining or recovering gut-MB composition, could represent a nutraceutical strategy to prevent or reduce AD sympthomathology.

Correlation between cephalic screw positioning of Standard Gamma 3 Nail for intertrochanteric fractures and cut-out incidence.

Introduction: Lateral fractures of proximal femur are the most frequent fractures in elderly people. Internal fixation using medullary nails is the gold standard of treatment (Gamma 3 nail is the most implanted device) due to reduced incidence of complications than other devices. We report our experience in treating this kind of fractures with Gamma 3 nail, between January 2015 and December 2021.

New orphan disease therapies from the proteome of industrial plasma processing waste- a treatment for aceruloplasminemia.

Plasma-derived therapeutic proteins are produced through an industrial fractionation process where proteins are purified from individual intermediates, some of which remain unused and are discarded. Relatively few plasma-derived proteins are exploited clinically, with most of available plasma being directed towards the manufacture of immunoglobulin and albumin. Although the plasma proteome provides opportunities to develop novel protein replacement therapies, particularly for rare diseases, the high cost of plasma together with small patient populations impact negatively on the development of plasma-derived orphan drugs.

Outcomes of Long Bones Treated With Carbon-Fiber Nails for Oncologic Indications: International Multi-institutional Study.

Background: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts complicate imaging evaluation for bone healing or tumor progression and postoperative radiation planning. Carbon-fiber implants have gained popularity as an alternative, given their radiolucency and superior axial bending.

Phenomic Microglia Diversity as a Druggable Target in the Hippocampus in Neurodegenerative Diseases.

Phenomics, the complexity of microglia phenotypes and their related functions compels the continuous study of microglia in disease animal models to find druggable targets for neurodegenerative disorders. Activation of microglia was long considered detrimental for neuron survival, but more recently it has become apparent that the real scenario of microglia morphofunctional diversity is far more complex. In this review, we discuss the recent literature on the alterations in microglia phenomics in the hippocampus of animal models of normal brain aging, acute neuroinflammation, ischemia, and neurodegenerative disorders, such as AD.

Morphofunctional Investigation in a Transgenic Mouse Model of Alzheimer's Disease: Non-Reactive Astrocytes Are Involved in Aβ Load and Reactive Astrocytes in Plaque Build-Up.

The term neuroinflammation defines the reactions of astrocytes and microglia to alterations in homeostasis in the diseased central nervous system (CNS), the exacerbation of which contributes to the neurodegenerative effects of Alzheimer's disease (AD). Local environmental conditions, such as the presence of proinflammatory molecules, mechanical properties of the extracellular matrix (ECM), and local cell-cell interactions, are determinants of glial cell phenotypes. In AD, the load of the cytotoxic/proinflammatory amyloid β (Aβ) peptide is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells.

Virtual Screening-Accelerated Discovery of a Phosphodiesterase 9 Inhibitor with Neuroprotective Effects in the Kainate Toxicity In Vitro Model.

In the central nervous system, some specific phosphodiesterase (PDE) isoforms modulate pathways involved in neuronal plasticity. Accumulating evidence suggests that PDE9 may be a promising therapeutic target for neurodegenerative diseases. In the current study, computational techniques were used to identify a nature-inspired PDE9 inhibitor bearing the scaffold of an isoflavone, starting from a database of synthetic small molecules using a ligand-based approach.

The Microbiota-Gut-Brain Axis in Behaviour and Brain Disorders.

The gut, along with its microbiota (MB-gut), is the largest absorption organ and reservoir of bacteria in the human body [...

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

Background: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens.

Methods: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy.

Are γ-terpinene, 1,8-cineole, p-coumaric acid, and quercetin active against wild-type and non-wild-type Sporothrix brasiliensis to itraconazole?

The emergence of itraconazole (ITZ)-resistant Sporothrix brasiliensis in feline and canine cases in southern Brazil has hampered the clinical cure of animal sporotrichosis, encouraging the search for therapeutic alternatives. The promising use of plants extracts from Lamiaceae family is known; however, there are no studies with its major compounds, as γ-terpinene (γTER), 1,8-cineole (1,8CIN), p-coumaric acid (pCOU), and quercetin (QUER). For the first time, we evaluated the antifungal, synergistic, cytotoxic activities and action mechanism of these compounds against S.

The Protective Effect of CBD in a Model of In Vitro Ischemia May Be Mediated by Agonism on TRPV2 Channel and Microglia Activation.

Cannabinoids, used for centuries for recreational and medical purposes, have potential therapeutic value in stroke treatment. Cannabidiol (CBD), a non-psychoactive compound and partial agonist of TRPV2 channels, is efficacious in many neurological disorders. We investigated the effects of CBD or Δ9-tetrahydrocannabinol (THC) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of ischemia.

Cannabidiol inhibits microglia activation and mitigates neuronal damage induced by kainate in an in-vitro seizure model.

Background: Epilepsy is one of the most common brain disorder and, despite the possible use of several therapeutic options, many patients continue to have seizures for their entire lifespan and they need new therapeutic approaches. In the last years the interest on the non-psychoactive compounds present in Cannabis sativa has massively increased, and cannabidiol (CBD) has been shown to be effective in the treatment of different types of neurological disorders and neurodegenerative diseases such as epilepsy, ischemia, multiple sclerosis and Alzheimer's Disease.

Methods: We investigated the effects of the selected cannabinoids, Δ9-tetrahydrocannabinol (THC), CBD and cannabigerol (CBG) in rat organotypic hippocampal slices exposed to kainate, an in vitro seizure model.

Neuronal and Astrocytic Morphological Alterations Driven by Prolonged Exposure with Δ9-Tetrahydrocannabinol but Not Cannabidiol.

Cannabis derivatives are largely used in the general population for recreational and medical purposes, with the highest prevalence among adolescents, but chronic use and abuse has raised medical concerns. We investigated the prolonged effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in organotypic hippocampal slices from P7 rats cultured for 2 weeks. Cell death in the CA1 subregion of slices was quantified by propidium iodide (PI) fluorescence, pre-synaptic and post-synaptic marker proteins were analysed by Western blotting and neurodegeneration and astrocytic alterations by NeuN and GFAP by immunofluorescence and confocal laser microscopy.

Hypoxia/Ischemia-Induced Rod Microglia Phenotype in CA1 Hippocampal Slices.

The complexity of microglia phenotypes and their related functions compels the continuous study of microglia in diseases animal models. We demonstrated that oxygen-glucose deprivation (OGD) induced rapid, time- and space-dependent phenotypic microglia modifications in CA1 stratum pyramidalis (SP) and stratum radiatum (SR) of rat organotypic hippocampal slices as well as the degeneration of pyramidal neurons, especially in the outer layer of SP. Twenty-four h following OGD, many rod microglia formed trains of elongated cells spanning from the SR throughout the CA1, reaching the SP outer layer where they acquired a round-shaped amoeboid phagocytic head and phagocytosed most of the pyknotic, damaged neurons.

Neuroprotective Effects of Cannabidiol but Not Δ-Tetrahydrocannabinol in Rat Hippocampal Slices Exposed to Oxygen-Glucose Deprivation: Studies with Extracts and Selected Cannabinoids.

(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the and plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of extracts (Bedrocan, FM2) or selected cannabinoids (Δ-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia.

Effects of parity order on performance, metabolic, and hormonal parameters of grazing beef cows during pre-calving and lactation periods.

Background: Metabolic profile evaluation is a tool widely used in ruminant nutrition as metabolic cues that relate nutrition to physiology. Metabolic and hormonal traits change during pre-partum and lactation according to parity in dairy cows, but studies of beef cows under grazing are scarce. The present study aimed to evaluate how metabolic and hormonal traits change over time, their relationship to performance, and determine if these factors differ according to the parity order of grazing beef cows.

Can the essential oil of rosemary (Rosmarinus officinalis Linn.) protect rats infected with itraconazole-resistant Sporothrix brasiliensis from fungal spread?

Introduction: Itraconazole is the first-choice option to treat human and animal sporotrichosis. However, the emergence of itraconazole-resistant strains has encouraged research on new active antifungals. Among them, the essential oil of rosemary (Rosmarinus officinalis Linn.

NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia/Ischemia.

Brain photobiomodulation (PBM) is an innovative treatment for a variety of neurological conditions, including cerebral ischemia. However, the capability of PBM for ischemic stroke needs to be further explored and its mechanisms of action remain currently unclear. The aim of the present research was to identify a treatment protocol capable of inducing neuroprotection and to investigate the molecular mechanisms activated by a dual-wavelength near infrared (NIR) laser source in an organotypic hippocampal slice model of hypoxia/ischemia.

Total hip arthroplasty in hereditary multiple exostosis patients: literature review and evaluation of 10 cases.

Background: Acquired hip deformities in patients affected by hereditary multiple exostosis (HME) may incur in early hip osteoarthritis and functional limitation requiring primary total hip arthroplasty (THA). Characteristic coxo-femoral joint dysmorphisms in HME may pose a challenge for the orthopaedic surgeon. Here we report our experience in a series of patients with HME treated in our hospital with THA.