Unveiling the potential of intranasal delivery of renin-angiotensin system drugs: Insights on the pharmacokinetics of irbesartan.

The therapeutic interest of renin-angiotensin system (RAS) drugs for the treatment of neuroinflammation has been recently acknowledged. Nevertheless, most of them display limited passage across the blood-brain barrier (BBB). Therefore, this study investigated the potential of intranasal (IN) delivery of six RAS drugs to circumvent the BBB and attain the brain, envisioning its future use in central nervous system (CNS) neuroinflammatory diseases, such as Alzheimer's disease (AD).

The potential of exosomes as a new therapeutic strategy for glioblastoma.

Glioblastoma (GBM) stands for the most common and aggressive type of brain tumour in adults. It is highly invasive, which explains its short rate of survival. Little is known about its risk factors, and current therapy is still ineffective.

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity.

Antimicrobial resistance presents a substantial threat to global public health, demanding urgent attention and action. This study focuses on lanthipeptides, ribosomally encoded peptides that display significant structural diversity and hold promising potential as antibiotics. Genome mining was employed to locate biosynthetic gene clusters (BGCs) containing class II lanthipeptide synthetases encoded by genes.

Intranasal irbesartan reverts cognitive decline and activates the PI3K/AKT pathway in an LPS-induced neuroinflammation mice model.

Background: New strategies are urgently needed to manage and delay the development of Alzheimer's disease (AD). Neuroinflammation is a significant contributor to cognitive decline in neurodegenerative diseases, including AD. Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) protect hypertensive patients against AD, but the cellular and molecular mechanisms underlying these effects remain unknown.

Lack of Methylation Changes in and Non-coding Regions of Cochlear Implant Patients with Sensorineural Hearing Loss.

Objective: Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in and another in in Filipino patients with SNHL compared to hearing control individuals.

Methods: We investigated an promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure.

Clinical Spectrum of Tuberculosis Otitis Media (TBOM) and Management Outcomes.

Objectives: To determine the initial clinical diagnoses of patients with tuberculous otitis media (TBOM), to determine the value of PCR test, biopsy, and ancillary diagnostic procedures in detecting middle ear TB infection, and to establish the differences in treatment outcomes.

Methods: The clinical records of twenty-eight patients identified with middle ear TB infection by PCR test and biopsy, from January 2010 to December 2016, were reviewed to determine their initial clinical diagnoses. The positivity rates of PCR test and biopsy were compared.

Design of a Blended Learning Course for Training Community Healthcare Providers on eHealth-enabled Newborn Hearing Screening.

Objectives: We present in this article the design and evaluation of a blended learning approach for training community healthcare providers in performing newborn hearing screening (NHS).

Methods: We developed a blended learning course for training community healthcare providers on eHealth-enabled NHS, following Bloom's revised taxonomy of educational objectives. The training involved three components: computer-based training (CBT), face-to-face (FTF) training, and on-site coaching.

Pilot Implementation of a Computer-based Training Course on Newborn Hearing Screening and Teleaudiology among Primary Healthcare Providers in Low Resource Settings.

Objective: Newborn hearing screening (NHS) in the Philippines has been mandated by law since 2009. However, lack of awareness and knowledge about NHS remains a challenge, especially among healthcare providers. This paper describes the pilot implementation of a computer-based training (CBT) course on NHS and teleaudiology among primary healthcare providers (PHCPs) in rural Philippines.

Audiologic Measures in an Indigenous Community with and Related Otitis Media.

Many indigenous peoples are at elevated risk for otitis media, however there is limited information on hearing loss due to OM in these communities. An Indigenous Filipino community that has previously been described with an elevated prevalence of OM that is due to rare variants and a common variant underwent additional phenological testing. In this study, we describe the audiologic profiles in - and -related otitis media and the validity of otoscopy and genotyping for and variants in screening for otitis media and hearing loss.

An ultra-sensitive electrochemical biosensor using the Spike protein for capturing antibodies against SARS-CoV-2 in point-of-care.

This work presents an innovative ultra-sensitive biosensor having the Spike protein on carbon-based screen-printed electrodes (SPEs), for monitoring in point-of-care antibodies against SARS-CoV-2, a very important tool for epidemiological monitoring of COVID-19 infection and establishing vaccination schemes. In an innovative and simple approach, a highly conductive support is combined with the direct adsorption of Spike protein to enable an extensive antibody capture. The high conductivity was ensured by using carboxylated carbon nanotubes on the carbon electrode, by means of a simple and quick approach, which also increased the surface area.

Improvement of Glycaemia and Endothelial Function by a New Low-Dose Curcuminoid in an Animal Model of Type 2 Diabetes.

Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays.

Otologic and vestibular symptoms in COVID-19: A scoping review.

Background: Otologic and vestibular symptoms have been seen in patients confirmed to have COVID-19 disease. Further discussion of these symptoms may provide insight into short- and long-term management for these patients.

Objective: The aim of this review was to describe the otologic and vestibular symptoms that present in patients with COVID-19.

Targeting brain Renin-Angiotensin System for the prevention and treatment of Alzheimer's disease: Past, present and future.

Alzheimer's disease (AD) is a well-known neurodegenerative disease characterized by the presence of two main hallmarks - Tau hyperphosphorylation and Aβ deposits. Notwithstanding, in the last few years the scientific evidence about the drivers of AD have been changing and nowadays age-related vascular alterations and several cardiovascular risk factors have been shown to trigger the development of AD. In this context, drugs targeting the Renin Angiotensin System (RAS), commonly used for the treatment of hypertension, are evidencing a high potential to delay AD development due to their action on brain RAS.

Elemental Chemometrics as Tools to Depict Stalked Barnacle () Harvest Locations and Food Safety.

The stalked barnacle is an abundant species on the very exposed rocky shore habitats of the Spanish and Portuguese coasts, constituting also an important economical resource, as a seafood item with high commercial value. Twenty-four elements were measured by untargeted total reflection X-ray fluorescence spectroscopy (TXRF) in the edible peduncle of stalked barnacles sampled in six sites along the Portuguese western coast, comprising a total of 90 individuals. The elemental profile of 90 individuals originated from several geographical sites ( = 15 per site), were analysed using several chemometric multivariate approaches (variable in importance partial least square discriminant analysis (VIP-PLS-DA), stepwise linear discriminant analysis (S-LDA), linear discriminant analysis (LDA), random forests (RF) and canonical analysis of principal components (CAP)), to evaluate the ability of each approach to trace the geographical origin of the animals collected.

Establishing a governance threshold in small-scale fisheries to achieve sustainability.

The lack of effective governance is a major concern in small-scale fisheries. The implementation of governance that encompasses the three pillars of sustainability (social, economic, and ecological) is still a worldwide challenge. We examined nine stalked barnacle fisheries (Pollicipes pollicipes) across Southwest Europe to better understand the relationship between governance elements and sustainability.

Antifungal and Anti-Inflammatory Potential of subsp. (Brot.) H.Wolff Essential Oil.

Fungal infections remain a major health concern with aromatic plants and their metabolites standing out as promising antifungal agents. The present study aims to assess, for the first time, the antifungal and anti-inflammatory potential of subsp. (Brot.

Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies.

Hearing loss remains an important global health problem that is potentially addressed through early identification of a genetic etiology, which helps to predict outcomes of hearing rehabilitation such as cochlear implantation and also to mitigate the long-term effects of comorbidities. The identification of variants for hearing loss and detailed descriptions of clinical phenotypes in patients from various populations are needed to improve the utility of clinical genetic screening for hearing loss. Clinical and exome data from 15 children with hearing loss were reviewed.

Exosomes as new therapeutic vectors for pancreatic cancer treatment.

Pancreatic cancer (PC) is one of the deadliest cancers with a very short rate of survival and commonly without symptoms in its early stage. This absence of symptoms can lead to a late diagnosis associated with an advanced metastasis process, for which therapy is not effective. Although with extensive research in this field, the 5-year survival rate has not increased significantly.

NLRP3 Inflammasome and Allergic Contact Dermatitis: A Connection to Demystify.

Allergic contact dermatitis is a common occupational disease that manifests as a cell-mediated hypersensitivity reaction following skin exposure to small reactive chemicals termed haptens. Haptens penetrate the stratum corneum and covalently modify proteins in the epidermis, inducing intracellular stress, which further leads to the release of damage-associated molecular patterns (DAMPs), such as uric acid, reactive oxygen species, hyaluronic acid fragments and extracellular adenosine triphosphate (ATP). These DAMPs are recognized by pattern recognition receptors (PRRs) in innate immune cells, namely dendritic cells (DCs), leading to their maturation and migration to the draining lymph nodes where they activate naïve T lymphocytes.

Otitis media susceptibility and shifts in the head and neck microbiome due to variants.

Background: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.

Methods: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity.

Is Alzheimer's disease an inflammasomopathy?

Alzheimer's disease (AD) is the most common form of dementia in the elderly and, despite the tremendous efforts researchers have put into AD research, there are no effective options for prevention and treatment of the disease. The best way to reach this goal is to clarify the mechanisms involved in the onset and progression of AD. In the last few years the views about the drivers of AD have been changing and nowadays it is believed that neuroinflammation takes center stage in disease pathogenesis.

A2ML1 and otitis media: novel variants, differential expression, and relevant pathways.

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media.

The state of the fishery, conservation and management of the stalked barnacle Pollicipes pollicipes in Portugal.

The stalked barnacle Pollicipes pollicipes is the most important intertidal economical resource in Portugal. The assessment of the state of the fishery, conservation and management of P. pollicipes in Portugal was made for the first time in three regions with different regulations regarding this fishery: two marine protected areas ("Reserva Natural das Berlengas", RNB; and "Parque Natural do Sudoeste Alentejano e Costa Vicentina", PNSACV); and the Center coast.

Loss of thermal refugia near equatorial range limits.

This study examines the importance of thermal refugia along the majority of the geographical range of a key intertidal species (Patella vulgata Linnaeus, 1758) on the Atlantic coast of Europe. We asked whether differences between sun-exposed and shaded microhabitats were responsible for differences in physiological stress and ecological performance and examined the availability of refugia near equatorial range limits. Thermal differences between sun-exposed and shaded microhabitats are consistently associated with differences in physiological performance, and the frequency of occurrence of high temperatures is most probably limiting the maximum population densities supported at any given place.

Systemic drugs inducing non-immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP-1 cells.

Contact sensitizers induce phenotypic and functional changes in dendritic cells (DC) that enhance their antigen-presenting capacity and, ultimately, modulate the T cell response. To evaluate if there is a similar effect of drugs causing T-cell-mediated cutaneous adverse drug reactions (CADR), we studied the in vitro effect of drugs on THP-1 cells, a cell line widely used to evaluate the early molecular and cellular events triggered by contact sensitizers. The effect of allopurinol, oxypurinol, ampicillin, amoxicillin, carbamazepine and sodium valproate, at EC30 concentrations, was evaluated on p38 MAPK activation, by Western Blot, and on the expression of genes coding for DC maturation markers, pro-inflammatory cytokine/chemokines and hemeoxygenase 1 (HMOX1), by real-time RT-PCR.