The association of non-severe COVID-19 infection and progression to frailty among robust older veterans.

Background: Studies have shown that frailty was increased in hospitalized COVID-19 patients. However, it is not clear whether non-severe COVID-19 increases the risk for pre-frailty and frailty development. Our study aimed to determine the risk of developing frailty and pre-frailty in robust veterans who contracted non-severe COVID-19.

Frailty training among healthcare professionals.

As the population ages worldwide, frailty becomes more prevalent, leading to a higher risk of poor outcomes. Therefore, there is an increased need to educate healthcare providers in the areas of frailty screening, assessment, and treatment. In our review of the current state of frailty education worldwide we showed that, with the exception of a few European countries, education of clinicians on frailty screening, assessment, and treatment is inadequate.

Vaccination and Nutritional Outcomes of Hemodialysis Patients Infected With SARS-CoV-2.

Background: Patients on hemodialysis are particularly vulnerable to COVID-19 and may have a reduced response to vaccination because of a decreased immune response. The nutritional status before or during the infection could also impact on the clinical effectiveness of vaccination.

Objectives: We aim to describe the evolution of clinical and nutritional biomarkers of hemodialysis patients infected with SARS-CoV-2 and to assess their association with vaccination status.

Frailty as a risk factor for post-acute sequelae of COVID-19 among US veterans during the Delta and Omicron waves.

Background: Older populations have suffered the highest rates of SARS-CoV-2 infection and associated complications, including Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Frailty is a geriatric syndrome that often coexists with COVID-19 infection. The vulnerability to stressors caused by multisystemic dysfunction that characterizes frailty may predispose older adults to develop PASC.

Association of Frailty and Cardiopulmonary Resuscitation Outcomes in Older U.S. Veterans.

Determine the association between frailty and immediate survival of cardiopulmonary resuscitation (CPR) in older Veterans. Secondary outcomes: compare in-hospital mortality, duration of resuscitation efforts, hospital and intensive care unit (ICU) length of stay, neurologic outcomes, and discharge disposition between frail and non-frail Veterans. Retrospective cohort study including Veterans 50 years and older, who were "Full Code" and had in-hospital cardiac arrest between 7/1/2017 and 6/30/2020, at the Miami VAMC.

Frailty Reduces Vaccine Effectiveness Against SARS-CoV-2 Infection: A Test-Negative Case Control Study Using National VA Data.

Objectives: To assess the variation of vaccine effectiveness against SARS-CoV-2 infection during the Delta wave according to frailty status among U.S. veterans.

COVID-19 mRNA vaccine effectiveness against hospitalisation and death in veterans according to frailty status during the SARS-CoV-2 delta (B.1.617.2) variant surge in the USA: a retrospective cohort study.

Background: Studies have shown that COVID-19 vaccination is effective at preventing infection and death in older populations. However, whether vaccination effectiveness is reduced in patients with frailty is unclear. We aimed to compare vaccine effectiveness against hospitalisation and death after COVID-19 during the surge of the delta (B.

Long Liquid Crystal Elastomer Fibers with Large Reversible Actuation Strains for Smart Textiles and Artificial Muscles.

A method for fabricating long, soft, and reversibly actuatable liquid crystal elastomer (LCE) fibers by using direct ink write (DIW) printing was developed. Here, the LCE was produced based on a two-stage thermal-photo curing reaction between a difunctional acrylate monomer and thiol. The LCE ink, mixed with nanoclay to increase the viscosity, was extruded through a nozzle onto a rotating mandrel to obtain a long fiber.

Rab5 is critical for SNAP23 regulated granule-granule fusion during compound exocytosis.

Compound exocytosis is considered the most massive mode of exocytosis, during which the membranes of secretory granules (SGs) fuse with each other to form a channel through which the entire contents of their granules is released. The underlying mechanisms of compound exocytosis remain largely unresolved. Here we show that the small GTPase Rab5, a known regulator of endocytosis, is pivotal for compound exocytosis in mast cells.

Different activation signals induce distinct mast cell degranulation strategies.

Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules.

The econobiology of pancreatic acinar cells granule inventory and the stealthy nano-machine behind it.

The pancreatic gland secretes most of the enzymes and many other macromolecules needed for food digestion in the gastrointestinal tract. These molecules play an important role in digestion, host defense and lubrication. The secretion of pancreatic proteins ensures the availability of the correct mix of proteins when needed.

Function Suggests Nano-Structure: Quantitative Structural Support for SNARE-Mediated Pore Formation.

Granule secretory content is released in either basal or calcium-activated complete exocytosis mode. A vital element in these processes is the establishment of a fusion pore between the granule membrane and the plasma membrane, initiated by the formation of a circular rosette docking arrangement of SNARE protein complexes. The controversially disputed number of SNARE complexes needed for granule priming leading to the formation of the fusion pore, is granule-size dependent and varies between secretion modes.

Quantitative microscopy of mole rat eosinophil granule morphology.

Mole rat bone marrow cells and peritoneal eosinophils are used to study granule morphological maturation by quantitative microscopy. The bulk eosinophil granule content is pre-stored in unique granular structures known as crystalloid or secondary granules. Mole rat eosinophil granules exhibit the basic structure of an electron-dense crystalloid core surrounded by a lighter, homogeneous matrix.

Quantal Basis of Secretory Granule Biogenesis and Inventory Maintenance: the Surreptitious Nano-machine Behind It.

Proteins are molecular machines with the capacity to perform diverse physical work as response to signals from the environment. Proteins may be found as monomers or polymers, two states that represent an important subset of protein interactions and generate considerable functional diversity, leading to regulatory mechanisms closely akin to decision-making in service systems. Polymerization is not unique to proteins.

Characterization of mast cell secretory granules and their cell biology.

Exocytosis and secretion of secretory granule (SG) contained inflammatory mediators is the primary mechanism by which mast cells exert their protective immune responses in host defense, as well as their pathological functions in allergic reactions and anaphylaxis. Despite their central role in mast cell function, the molecular mechanisms underlying the biogenesis and secretion of mast cell SGs remain largely unresolved. Early studies have established the lysosomal nature of the mast cell SGs and implicated SG homotypic fusion as an important step occurring during both their biogenesis and compound secretion.

Rab5 is a novel regulator of mast cell secretory granules: impact on size, cargo, and exocytosis.

Secretion of inflammatory mediators prestored in mast cells secretory granules (SGs) enhances immune responses such as in allergy and host defense. However, the mechanisms underlying the biogenesis of the SGs remain largely unresolved. By combining high-resolution live cell imaging and quantitative morphometric analyses, we show that the small GTPase Rab5 controls the SG size and cargo composition by a VAMP8-dependent fusion mechanism.

The stealthy nano-machine behind mast cell granule size distribution.

The classical model of mast cell secretory granule formation suggests that newly synthesized secretory mediators, transported from the rough endoplasmic reticulum to the Golgi complex, undergo post-transitional modification and are packaged for secretion by condensation within membrane-bound granules of unit size. These unit granules may fuse with other granules to form larger granules that reside in the cytoplasm until secreted. A novel stochastic model for mast cell granule growth and elimination (G&E) as well as inventory management is presented.

Statistical analysis of the quantal basis of secretory granule formation.

The size distribution of vesicles exocytosed from secretory cells displays quantal nature, vesicle volume is periodic multi-modal, suggesting that these heterogeneous vesicles are aggregate sums of a variable number of homogeneous basic granules. Whether heterogeneity is a lumping-together artifact of the measurement or an inherent intra-cell feature of the vesicles is an unresolved question. Recent empirical evidence will be provided for the quantal nature of intra-cell vesicle volume, supporting the controversial paradigm of homotypic fusion: basic cytoplasmic granules fuse with each other to create heterogeneously sized vesicles.

Function suggests nano-structure: towards a unified theory for secretion rate, a statistical mechanics approach.

The inventory of secretory granules along the plasma membrane can be viewed as maintained in two restricted compartments. The release-ready pool represents docked granules available for an initial stage of fast, immediate secretion, followed by a second stage of granule set-aside secretion pool, with significantly slower rate. Transmission electron microscopy ultra-structural investigations correlated with electrophysiological techniques and mathematical modelling have allowed the categorization of these secretory vesicle compartments, in which vesicles can be in various states of secretory competence.

Function suggests nano-structure: electrophysiology supports that granule membranes play dice.

Cellular communication depends on membrane fusion mechanisms. SNARE proteins play a fundamental role in all intracellular fusion reactions associated with the life cycle of secretory vesicles, such as vesicle-vesicle and vesicle plasma membrane fusion at the porosome base in the cell plasma membrane. We present growth and elimination (G&E), a birth and death model for the investigation of granule growth, its evoked and spontaneous secretion and their information content.

VAMP8/endobrevin is a critical factor for the homotypic granule growth in pancreatic acinar cells.

The delivery of newly-formed secretory content to the granule inventory occurs through direct fusion of recently formed granules and mature granules. The introduction of knockout mice allowed us to investigate the characteristics of the delivery process and to determine the core protein machinery required for granule growth. The SNARE machinery mediates membrane fusion and is essential for the granule lifecycle.

Combining an EGFR directed tyrosine kinase inhibitor with autophagy-inducing drugs: a beneficial strategy to combat non-small cell lung cancer.

The potential therapeutic value of combinatorial regimens based on an EGF receptor tyrosine kinase inhibitor (TKI) and autophagy inducing drugs was evaluated by comparing their molecular impacts on H1299 and A549 non-small cell lung cancer (NSCLC) cells, which overexpress wild type EGF receptor, but are either deficient or have wild type p53 alleles, respectively. We show that H1299 cells display a considerably lower sensitivity to erlotinib treatment, which can be restored by combining erlotinib with rapamycin or with imatinib, though to a lesser extent. Cytotoxicity was associated with increased autophagy and hyperpolarization of the mitochondrial membrane potential.

Quantal basis of vesicle growth and information content, a unified approach.

Secretory vesicles express a periodic multimodal size distribution. The successive modes are integral multiples of the smallest mode (G(1)). The vesicle content ranges from macromolecules (proteins, mucopolysaccharides and hormones) to low molecular weight molecules (neurotransmitters).

Regulation of secretory granule size by the precise generation and fusion of unit granules.

Morphometric evidence derived from studies of mast cells, pancreatic acinar cells and other cell types supports a model in which the post-Golgi processes that generate mature secretory granules can be resolved into three steps: (1) fusion of small, Golgi-derived progranules to produce immature secretory granules which have a highly constrained volume; (2) transformation of such immature granules into mature secretory granules, a process often associated with a reduction in the maturing granule's volume, as well as changes in the appearance of its content and (3) fusion of secretory granules of the smallest size, termed 'unit granules', forming granules whose volumes are multiples of the unit granule's volume. Mutations which perturb this process can cause significant pathology. For example, Chediak-Higashi syndrome / lysosomal trafficking regulator (CHS)/(Lyst) mutations result in giant secretory granules in a number of cell types in human beings with the Chediak-Higashi syndrome and in 'beige' (Lyst(bg)/Lyst(bg)) mice.