Tackling persistent neurological symptoms in patients following acute COVID-19 infection: an update of the literature.

Introduction: The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered.

Innovative Dual Combination Cospray-Dried Rock Inhibitor/l-Carnitine Inhalable Dry Powder Aerosols.

This study introduces novel cospray-dried (Co-SD) formulations of simvastatin, a Nrf2 activator ROCK inhibitor, with l-carnitine as molecular mixtures in various molar ratios for targeted pulmonary inhalation aerosol delivery in pulmonary hypertension, optimized for excipient-free dry powder inhalers (DPIs). The two components were spray-dried at various molar ratios by using different starting feed solution concentrations and process parameters. In addition to comprehensive physicochemical characterization, in vitro aerosol dispersion performance as DPIs using two FDA-approved DPI devices with different shear stress properties, in vitro viability as a function of dose on 2D human pulmonary cellular monolayers and on 3D small airway epithelia human primary cultures at the air-liquid interface (ALI), and in vitro transepithelial electrical resistance (TEER) at the ALI were conducted.

HIV-1 Tat Protein and Cigarette Smoke Mediated ADAM17 Upregulation Can Lead to Impaired Mucociliary Clearance.

Human immunodeficiency virus type-1 (HIV-1) associated comorbidities account for the majority of poor health outcomes in people living with HIV (PLWH) in the era of antiretroviral therapy. Lung-related comorbidities such as chronic obstructive pulmonary disease (COPD) and bacterial pneumonia are primarily responsible for increased morbidity and mortality in PLWH, even when compensated for smoking. Smokers and COPD patients demonstrate cilia shortening, attenuated ciliary beat frequency (CBF), dysfunctional ciliated cells along with goblet cell hyperplasia, and mucus hypersecretion.

Differential predictive value of resident memory CD8T cell subpopulations in patients with non-small-cell lung cancer treated by immunotherapy.

Background: A high density of resident memory T cells (T) in tumors correlates with improved clinical outcomes in immunotherapy-treated patients. In most clinical studies, T are defined by the CD103 marker. However, it is clearly established that not all T express CD103, but can be defined by other markers (CD49a, CD69, etc).

Advanced Spray-Dried Inhalable Microparticles/Nanoparticles of an Innovative Mitophagy Activator for Targeted Lung Delivery: Design, Comprehensive Characterization, Human Lung Cell Culture, and In Vitro Aerosol Dispersion Performance.

Urolithin A (UA) has demonstrated the ability to stimulate mitophagy and enhance mitochondrial and cellular health in skeletal muscles in humans after oral administration. It is hypothesized that targeted delivery of UA as inhaled dry powders to the lungs will enhance mitochondrial health through mitochondrial biogenesis. This study aimed to engineer inhalable excipient-free powders of UA as dry powder inhalers (DPIs) for targeted pulmonary delivery.

Diagnosis of human envenoming by terrestrial venomous animals: Routine, advances, and perspectives.

Despite the development of new and advanced diagnostic approaches, monitoring the clinical evolution of accidents caused by venomous animals is still a challenge for science. In this review, we present the state of the art of laboratory tests that are routinely used for the diagnosis and monitoring of envenomings by venomous animals, as well as the use of new tools for more accurate and specific diagnoses. While a comprehensive range of tools is outlined, comprising hematological, biochemical, immunoassays, and diagnostic imaging tools, it is important to acknowledge their limitations in predicting the onset of clinical complications, since they provide an overview of organic damage after its development.

Immune Response in Traumatic Brain Injury.

Purpose Of Review: This review aims to comprehensively examine the immune response following traumatic brain injury (TBI) and how its disruption can impact healing and recovery.

Recent Findings: The immune response is now considered a key element in the pathophysiology of TBI, with consequences far beyond the acute phase after injury. A delicate equilibrium is crucial for a healthy recovery.

Inhalable Advanced Co-Spray Dried Microparticles/Nanoparticles of a Novel RhoA/Rho Kinase Inhibitor with Lung Surfactant Biomimetic Phospholipids for Targeted Lung Delivery.

Co-spray dried inhalable powder formulations of fasudil monohydrochloride salt (FMCS) and inhalable lung surfactant-based nanocarriers composed of synthetic phospholipids, zwitterionic DPPC (1,2-palmitoyl--glycero-3-phosphocholine) and anionic DPPG (1,2-dipalmitoyl--glycero-3-[phosphor-rac-1-glycerol]) sodium salt, were designed and optimized using organic solution advanced spray drying. FMCS can potentially be used for the treatment of various complex pulmonary diseases with this current work focusing on pulmonary arterial hypertension. Comprehensive physicochemical characterization, electron and optical microscopy imaging, thermal analysis, molecular fingerprinting spectroscopy, in vitro aerosol dispersion performance with human dry powder inhaler (DPI) devices, in vitro membrane permeation and drug release, and in vitro human cellular studies were conducted.

ProDiVis: a method to normalize fluorescence signal localization in 3D specimens.

A common problem in confocal microscopy is the decrease in intensity of excitation light and emission signal from fluorophores as they travel through 3D specimens, resulting in decreased signal detected as a function of depth. Here, we report a visualization program compatible with widely used fluorophores in cell biology to facilitate image interpretation of differential protein disposition in 3D specimens. Glioblastoma cell clusters were fluorescently labeled for mitochondrial complex I (COXI), P2X7 receptor (P2X7R), β-Actin, Ki-67, and DAPI.

The mitochondrial redistribution of ENOS is regulated by AKT1 and dimer status.

Previously, we have shown that endothelial nitric-oxide synthase (eNOS) dimer levels directly correlate with the interaction of eNOS with hsp90 (heat shock protein 90). Further, the disruption of eNOS dimerization correlates with its redistribution to the mitochondria. However, the causal link between these events has yet to be investigated and was the focus of this study.

The unique metabolic and lipid profiles of patients with severe COVID-19 compared to severe community-acquired pneumonia: a potential prognostic and therapeutic target.

Background: Compare the changes and differences in metabolome and lipidome profiles among severe COVID-19 and CAP patients with ARF to identify biomarkers that could be used for personalized diagnosis, prognosis, and treatment.

Research Design And Methods: Plasma samples were taken at hospital admission (baseline) and on the 5 day of hospitalization (follow-up) and examined by RP-LC-QTOF-MS and HILIC-LC-QTOF-MS.

Results: 127 patients, 17 with CAP and 110 with COVID-19, were included.

Design and comprehensive characterization of dry powder inhalation aerosols of simvastatin DPPC/DPPG lung surfactant-mimic nanoparticles/microparticles for pulmonary nanomedicine.

The Rho Kinase (ROCK) pathway is recognized to be involved in changes that lead to remodeling in pulmonary hypertension (PH), particularly cellular processes including signaling, contraction, migration, proliferation, differentiation, and apoptosis. Simvastatin (Sim) has a potent anti-proliferative and pro-apoptotic effect on vasculature smooth muscle cells through the inhibition of the synthesis of isoprenoids intermediates which are essential for the post-translational isoprenylation of Rho, Rac, and Ras family GTPases. Sim targets the underlying mechanism in vascular remodeling.

Thermal inkjet makes label-free single-cell proteomics accessible and easy.

In this study, we adapted an HP D100 Single Cell Dispenser - a novel low-cost thermal inkjet (TIJ) platform with impedance-based single cell detection - for dispensing of individual cells and one-pot sample preparation. We repeatedly achieved label-free identification of up to 1,300 proteins from a single cell in a single run using an Orbitrap Fusion Lumos Mass Spectrometer coupled to either an Acquity UPLC M-class system or a Vanquish Neo UHPLC system. The developed sample processing workflow is highly reproducible, robust, and applicable to standardized 384- and 1536-well microplates, as well as glass LC vials.

Inflammatory response to SARS-CoV 2 and other respiratory viruses.

Introduction: Lower respiratory tract infections (LRTI) remain a significant global cause of mortality and disability. Viruses constitute a substantial proportion of LRTI cases, with their pandemic potential posing a latent threat. After the SARS-CoV-2 pandemic, the resurgence of other respiratory viruses, including Influenza and Respiratory Syncytial Virus responsible for LRTI has been observed especially in susceptible populations.

Comparison of performances between risk scores for predicting mortality at 30 days in patients with community acquired pneumonia.

Background: Risk scores facilitate the assessment of mortality risk in patients with community-acquired pneumonia (CAP). Despite their utilities, there is a scarcity of evidence comparing the various RS simultaneously. This study aims to evaluate and compare multiple risk scores reported in the literature for predicting 30-day mortality in adult patients with CAP.

Novel mechanism of cyclic nucleotide crosstalk mediated by PKG-dependent proteasomal degradation of the Hsp90 client protein phosphodiesterase 3A.

Endothelial cAMP-specific phosphodiesterase PDE3A is one of the major negative regulators of the endothelial barrier function in acute lung injury models. However, the mechanisms underlying its regulation still need to be fully resolved. We show here that the PDE3A is a newly described client of the molecular chaperone heat shock protein 90 (hsp90).

Altered Host microRNAomics in HIV Infections: Therapeutic Potentials and Limitations.

microRNAs have emerged as essential regulators of health and disease, attracting significant attention from researchers across diverse disciplines. Following their identification as noncoding oligonucleotides intricately involved in post-transcriptional regulation of protein expression, extensive efforts were devoted to elucidating and validating their roles in fundamental metabolic pathways and multiple pathologies. Viral infections are significant modifiers of the host microRNAome.

MicroRNA mediated suppression of airway lactoperoxidase by TGF-β1 and cigarette smoke promotes airway inflammation.

Transforming Growth Factor Beta1 (TGF-β1) signaling is upregulated in Chronic Obstructive Pulmonary disease (COPD), smokers, and people living with HIV. Cigarette smoking and HIV are also independent risk factors for COPD. Chronic inflammation is a hallmark of COPD.

Performance of upper limb entry item to predict forced vital capacity in dysferlin-deficient limb girdle muscular dystrophy.

Dysferlin-deficient limb girdle muscular dystrophy (LGMD R2), also referred to as dysferlinopathy, can be associated with respiratory muscle weakness as the disease progresses. Clinical practice guidelines recommend biennial lung function assessments in patients with dysferlinopathy to screen for respiratory impairment. However, lack of universal access to spirometry equipment and trained specialists makes regular monitoring challenging.

Adherence to low tidal volume in the transition to spontaneous ventilation in patients with acute respiratory failure in intensive care units in Latin America (SPIRAL): a study protocol.

Objective: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes.