For patients recovering from severe acute illness, admission to a long-term acute care hospital (LTAC) is an increasingly common alternative to continued management in an intensive care unit (ICU). To examine the effectiveness of LTAC transfer in patients with chronic critical illness. Retrospective cohort study in United States hospitals from ...

Recent publications showed that the kinase MTOR localizes to lysosomes and its activation depends on amino acids inside the lysosomal lumen, implying that autophagic protein degradation is a positive regulator of MTOR in this setting. Since decreased MTOR activity results in autophagy induction, drug treatments that block autolysosomal degradation (a ...

Autophagosome formation is a complex cellular process, which requires major membrane rearrangements leading to the creation of a relatively large double-membrane vesicle that directs its contents to the lysosome for degradation. Although various membrane compartments have been identified as sources for autophagosomal membranes, the molecular mechanism underlying these membrane trafficking ...

Eukaryotic cells adapt their organelle composition and abundance according to environmental conditions. Analysis of the peroxisomal membrane protein Pex3 has revealed that this protein plays a crucial role in peroxisome maintenance as it is required for peroxisome formation, segregation and breakdown. Although its function in peroxisome formation and segregation was ...

The most common neurodegenerative diseases are characterized by the accumulation of misfolded proteins. Tauopathies, which include Alzheimer disease, progressive supranuclear palsy, corticobasal degeneration, Pick disease and cases of frontotemporal dementia and parkinsonism linked to chromosome 17, are characterized by the accumulation of hyperphosphorylated and filamentous MAPT/tau protein. The pathological mechanisms ...

IFNG/IFNγ plays a critical role in driving innate and acquired defenses against infectious pathogens. The death-associated protein kinase 1 (DAPK1), originally identified as an activator of IFNG-induced cell death, controls autophagy. Previously, we have shown that transcription factor CEBPB (C/EBP-β) regulates IFNG-induced expression of Dapk1 through a CRE/ATF motif in ...

L-arginine (L-Arg) deficiency results in decreased T-cell proliferation and impaired T-cell function. Here we have found that L-Arg depletion inhibited expression of different membrane antigens, including CD247 (CD3ζ), and led to an ER stress response, as well as cell cycle arrest at G 0/G 1 in both human Jurkat and ...

Although elevated expression of CAV1/caveolin 1 is associated with the malignant progression of various human cancers, the molecular mechanism underlying its oncogenic functions is largely unknown. We found that CAV1 is frequently overexpressed in advanced colorectal tumors due to aberrant promoter CpG site hypomethylation, and its elevation is implicated in ...

Lysosome-associated membrane protein type 2A (LAMP2A) is a key protein in the chaperone-mediated autophagy (CMA) pathway. LAMP2A helps in lysosomal uptake of modified and oxidatively damaged proteins directly into the lumen of lysosomes for degradation and protein turnover. Elevated expression of LAMP2A was observed in breast tumor tissues of all ...

Channel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded ΔF508-CFTR and are poorly responsive to potentiators, because ΔF508-CFTR is intrinsically ...

In autophagic processes a variety of cargos is delivered to the degradative compartment of cells. Recent progress in autophagy research has provided support for the notion that when autophagic processes are operating in selective mode, a receptor protein complex will process the cargo. Here we present a concept of receptor ...

Accidental or therapeutic exposure to ionizing radiation has severe physiological consequences and can result in cell death. We previously demonstrated that deficiency or blockade of the ubiquitously expressed receptor CD47 results in remarkable cell and tissue protection against ischemic and radiation stress. Antagonists of CD47 or its ligand THBS1/thrombospondin 1 ...

The objective of this study is to prospectively examine the independent and joint effects of alcohol consumption and cardiorespiratory fitness on the incidence of metabolic syndrome (MetS) in a cohort of men. A prospective examination was done of 3411 apparently healthy men at baseline, who came to the Cooper Clinic ...

Metastasis is the spread of cancer cells from their primary location to other parts of the body. Metastatic cancer is responsible for most cancer deaths. Increasing evidence indicates that epithelial-mesenchymal transition (EMT), a crucial developmental program, contributes to control cancer invasion and metastasis. We recently reported that death effector domain-containing ...

Macroautophagy is an important process for removing misfolded and aggregated protein in cells, the dysfunction of which has been directly linked to an increasing number of neurodegenerative disorders. However, the details of macroautophagy in prion diseases remain obscure. Here we demonstrated that in the terminal stages of scrapie strain 263K-infected ...

Autophagy is generally considered to be antipathogenic. The autophagy gene ATG16L1 has a commonly occurring mutation associated with Crohn disease (CD) and intestinal cell abnormalities. Mice hypomorphic for ATG16L1 (ATG16L1 (HM) ) recreate specific features of CD. Our recent study shows that the same ATG16L1 (HM) mice that are susceptible ...

T cells are essential for defense of the host against invading pathogens. Antigen activation of the T cell receptor (TCR) is required for generation of an adaptive immune response. Several groups have observed that blocking autophagy augments T cell activation, but the molecular basis of this finding has remained elusive. ...

Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. The mechanisms underlying ethanol-induced neurodegeneration are complex. Ethanol exposure produces reactive oxygen species (ROS) which cause oxidative stress in the brain. We hypothesized that ethanol would activate autophagy to alleviate oxidative stress and neurotoxicity. ...

The multiunit Cullin (CUL)-RING E3 ligase (CRL) controls diverse biological processes by targeting a mass of substrates for ubiquitination and degradation, whereas its dysfunction causes carcinogenesis. Post-translational neddylation of CUL, a process triggered by the NEDD8-activating enzyme E1 subunit 1 (NAE1), is required for CRL activation. Recently, MLN4924 was discovered ...

The microenvironment of solid tumors tends to be more acidic (6.5-7.0) than surrounding normal (7.2-7.4) tissue. Chaotic vasculature, oxygen limitation and major metabolic changes all contribute to the acidic microenvironment. We have previously proposed that low extracellular pH (pHe) plays a critical role in the development and progression of solid ...

Autophagy is an important cellular recycling mechanism through self-digestion in responses to cellular stress such as starvation. Studies have shown that autophagy is involved in maintaining the homeostasis of neural system during stroke. However, molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. Previously, we and others have ...

The EMS Swiss LithoBreaker is a new, portable, electrokinetic lithotripter. We compared its tip velocity and displacement characteristics with a handheld, pneumatic lithotripter LMA StoneBreaker.™ We also evaluated fragmentation efficiency using in vitro models of percutaneous and ureteroscopic stone fragmentation. Displacement and velocity profiles were measured for 1-mm and 2-mm ...

We demonstrated a unique optofluidic lab-on-a-chip device that can measure optically encoded forward scattering signals. From the design of the spatial pattern, we can measure the position and velocity of each cell in the flow and generate a 2-D cell distribution plot over the cross section of the channel. Moreover, ...

Endometrial decidualization, a process essential for blastocyst implantation in species with hemochorial placentation, is accompanied by an enormous but transient influx of natural killer (NK) cells. Mouse uterine NK (uNK) cell subsets have been defined by diameter and cytoplasmic granule number, reflecting stage of maturity, and by histochemical reactivity with ...

The pituitary gland is composed of hormone-producing cells essential for homeostasis and reproduction. Pituitary cells are sensitive to endocrine feedback in the adult and can have altered hormonal secretion from exposure to the endocrine disruptor bisphenol A (BPA). BPA is a prevalent plasticizer used in food and beverage containers, leading ...

Overactive bladder (OAB) is a common condition affecting the elderly. The mainstay of treatment for OAB is medical therapy with anticholinergics. However, adverse events have been reported with this class of drugs, including cognitive changes. Objective: The objective of this study was to investigate the effect of an anticholinergic medication, ...

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-Raf(V600E) mutant exhibits elevated ...

Both protective T-cell genotypes and natural killer (NK) cell genotypes have been associated with delayed progression to AIDS and shown to be co-inherited in HIV-1-infected individuals who limit viral replication in absence of antiretroviral therapy ('controllers'). However, a comparative analysis of the genotype and function of the innate and adaptive ...

Climate change is causing winters to become milder (less cold and shorter). Recent studies of overwintering ectotherms have suggested that warmer winters increase metabolism and decrease winter survival and subsequent fecundity. Energetic constraints (insufficient energy stores) have been hypothesized as the cause of winter mortality but have not been tested ...

Background: Early detection of chronic kidney disease (CKD) by the first line is essential. In many countries, serum creatinine measurements are reimbursed in home practice. In Lithuania however, until recently they were not. Therefore, the aim of this study was to assess the prevalence of risk factors of CKD in ...

Postoperative intra-abdominal septic complications are a serious concern with regard to postoperative morbidity and mortality in Crohn's disease. The aim of this study was to identify the clinical variables that potentially impact the risk of intra-abdominal septic complications in patients with Crohn's disease, as well al analyze the short-term prognosis ...

Every new nursing graduate is challenged to successfully transition from student to professional nurse. The stress involved in the transition can manifest as performance anxiety. This study was conducted to verify the presence and identify the level of performance anxiety in a sample of new graduate nurses. Results included a ...

: We have previously demonstrated the prognostic significance of rectal cancer pathologic response to neoadjuvant chemoradiation. Recent studies in other cancers have reported that hypoxia influences response to neoadjuvant chemoradiation. : This study aimed to 1) characterize hypoxia-related protein expression in locally advanced rectal cancer before neoadjuvant chemoradiation, 2) determine ...

Background: Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients. LC also contributes to a reduced oral calcium load compared with calcium carbonate (CaC) treatment. However, no crossover studies which compare the influence on serum calcium level ...

The association between primary hyperparathyroidism (PHPT) and acute or chronic pancreatitis is controversial. For this reason, we conducted a review of the literature over the past 30 years to explore the relationship between these 2 disorders. Ten retrospective studies each with >50 patients diagnosed with PHPT were identified. With the ...

Randomised trials exploring remote ischaemic preconditioning (RIPC) in patients undergoing coronary artery bypass graft (CABG) surgery have yielded conflicting data regarding potential cardiovascular and renal protection, and are individually flawed by small sample size. Three investigators independently searched the MEDLINE, EMBASE and Cochrane databases to identify randomised trials testing RIPC ...

With the advancement of breast cancer therapies, most women diagnosed with breast cancer in the United States are now expected to survive their disease, and management of competing comorbidities, particularly cardiovascular disease (CVD), is crucial. Recent studies have suggested that CVD is the most common cause of death for women ...

: Previous research in colorectal cancer has focused on survival, recurrence, and functional outcomes. Few have assessed the decisional needs of patients or the information patients are retaining from the informed consent process. : The aims of this study were to describe the decisional needs of adult patients with rectal ...

We report on a 12-year-old female patient with lipoprotein glomerulopathy (LPG) who was proven to be heterozygous for ApoE2 Kyoto (Arg25Cys). Her family members have the same variant but do not have obvious signs of renal function impairment. Six months of treatment with a statin caused significant clinical improvement in ...

Abstract Objective. Borderline personality disorder (BPD) is defined as a pervasive pattern of instability in emotion, mood and interpersonal relationships, with a comorbidity between PBD and depressive disorders (DD). A key competence for successful management of interpersonal relationships is emotional intelligence (EI). Given the low EI of patients suffering from ...

: Most self-expandable metallic stents for colorectal placement are uncovered because of the high migration rate of covered stents. However, the optimal stent design for colorectal use remains unclear. : The purpose of this study was to evaluate the efficacy and safety of a double-wire woven uncovered stent for definitive ...

Aims: Dense deposit disease (DDD) is a rare disease that has no universally effective treatment. Herein we explore the clinical and pathological features of DDD in Chinese patients and the therapeutic effect of Tripterygium wilfordii (TW). Materials and methods: Clinical and pathological data of 10 Chinese patients with biopsy-proved DDD ...

Malnutrition in the critically ill patient is associated with adverse outcomes such as increased morbidity, infectious processes, and length of stay. Alterations to the gastrointestinal system during critical illness can be devastating. Current evidence suggests that, in the presence of a functioning gut, initiating early enteral nutrition therapy (within 24-48 ...

Providing patient care for the unconscious population in the intensive care unit can be very challenging. Over time, some nurses may face barriers that prevent them from providing caring behaviors, such as communication. Review of the literature found the attitude of a nurse, hospital technology, and the working environment are ...

: The prevalence of a paracolostomy hernia has been reported to be from 10% to 50%, with serious impairment of the quality of life and sometimes life-threatening morbidity in some cases. Most essential in avoiding the need for further treatment of an end-sigmoid colostomy is prevention of a parastomal hernia. ...

: Chronic kidney disease, a disease entity increasing in number, may be an obstacle in various aspects of treatment for malignant neoplasm, such as perisurgical management and implementation of chemotherapy. : The aim of this study was to evaluate both short- and long-term outcomes of patients with colorectal cancer who ...

Terminal weaning of patients follows a standardized medical care protocol. However, the evidence found for optimal terminal weaning protocols may lack individualization for the patient and family. As nursing students in the critical care unit, we have designed a conceptual model that bridges the gap between cultural diversity and terminal ...

Background: Ferumoxytol is a unique intravenous (i.v.) iron therapy. This report examines factors affecting hemoglobin response to i.v. ferumoxytol, and the relationship between hematologic parameters, concomitant erythropoiesis-stimulating agents (ESA), and adverse events (AEs) in nondialysis CKD patients. Methods: A series of post-hoc efficacy and safety analyses were performed using pooled ...

Abstract Background Positive behaviour support (PBS) emphasises multi-component interventions by natural intervention agents to help people overcome challenging behaviours. This paper investigates which components are most effective and which factors might mediate effectiveness. Method Sixty-one staff working with individuals with intellectual disability and challenging behaviours completed longitudinal competency-based training in ...

Aims: We previously reported in patients with chronic kidney disease (CKD) that the circadian rhythms of blood pressure (BP) and urinary sodium excretion were both impaired into non-dipper pattern as renal function deteriorated. However, the circadian rhythm of urinary potassium excretion has not been studied in relation to renal dysfunction. ...