The Impact of Comorbid Sleep-Disordered Breathing on Hospitalization Risk Related to Diabetes and Atherosclerotic Disease: A Retrospective Cohort Analysis.

To determine the relationship between comorbid sleep-disordered breathing (SDB) and hospitalization rates related to diabetes mellitus (DM) and atherosclerotic disease (AD). This study used a retrospective cohort design from a large medical claims database with 5 years of data between 2018 and 2022. The presences of SDB, DM, and AD were identified using International Classification of Diseases (ICD-10) and relevant Current Procedural Terminology (CPT) codes.

Histone H3 K27M-mediated regulation of cancer cell stemness and differentiation in diffuse midline glioma.

Therapeutic resistance remains a major obstacle to preventing progression of H3K27M-altered Diffuse Midline Glioma (DMG). Resistance is driven in part by ALDH-positive cancer stem cells (CSC), with high ALDH1A3 expression observed in H3K27M-mutant DMG biopsies. We hypothesized that ALDH-mediated stemness and resistance may in part be driven by the oncohistone itself.

Stem cells for the treatment of glioblastoma: a 20-year perspective.

Glioblastoma, the deadliest form of primary brain tumor, remains a disease without cure. Treatment resistance is in large part attributed to limitations in the delivery and distribution of therapeutic agents. Over the last 20 years, numerous preclinical studies have demonstrated the feasibility and efficacy of stem cells as antiglioma agents, leading to the development of trials to test these therapies in the clinic.

Hyaluronic acid as a macromolecular crowding agent for production of cell-derived matrices.

Cell-derived matrices (CDMs) provide an exogenous source of human extracellular matrix (ECM), with applications as cell delivery vehicles, substrate coatings for cell attachment and differentiation, and as biomaterial scaffolds. However, commercial application of CDMs has been hindered due to the prolonged culture time required for sufficient ECM accumulation. One approach to increasing matrix deposition in vitro is macromolecular crowding (MMC), which is a biophysical phenomenon that limits the diffusion of ECM precursor proteins, resulting in increased ECM accumulation at the cell layer.

Synthesis of 3,4-dihydro-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxides and their evaluation as ligands for NMDA receptor glycine binding site.

A series of 2-substituted 3,4-dihydro-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxides were synthesized and evaluated for their affinity to the glycine binding site of the N-methyl-d-aspartate (NMDA) receptor. The binding affinity was determined by the displacement of radioligand [(3)H]MDL-105,519 from rat cortical membrane preparations. The most attractive structures in the search for prospective NMDA receptor ligands were identified to be 2-arylcarbonylmethyl substituted 3,4-dihydro-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxides.

Enhanced long-term transduction and multilineage engraftment of human hematopoietic stem cells transduced with tyrosine-modified recombinant adeno-associated virus serotype 2.

The search for the ideal stem cell gene therapy vector continues as recognized problems persist. Although recombinant adeno-associated virus serotype 2 (rAAV2) mediates gene transfer into hematopoietic stem cells, identified restrictions to transgene expression reduce overall efficiency. Studies have shown that transduction efficiencies are significantly improved by preventing early proteasomal degradation after mutation of surface-exposed tyrosine residues on the capsid to phenylalanine.

Akt regulates vitamin D3-induced leukemia cell functional differentiation via Raf/MEK/ERK MAPK signaling.

1,25-dihydroxyvitamin D3 (vitamin D3) induces differentiation of HL-60 human myeloid leukemia cells; however, the signaling mechanism governing these effects is not fully clear. Here, we show that vitamin D3 induced functional differentiation by Akt through Raf/MEK/ERK MAPK signaling. Vitamin D3 downregulated Akt, weakened Akt-Raf1 interaction, and subsequently activated the Raf/MEK/ERK MAPK pathway.

Human myeloblastic leukemia cells (HL-60) express a membrane receptor for estrogen that signals and modulates retinoic acid-induced cell differentiation.

Estrogen receptors are historically perceived as nuclear ligand activated transcription factors. An estrogen receptor has now been found localized to the plasma membrane of human myeloblastic leukemia cells (HL-60). Its expression occurs throughout the cell cycle, progressively increasing as cells mature from G(1) to S to G(2)/M.

A novel class of amino-alkylcyclohexanes as uncompetitive, fast, voltage-dependent, N-methyl-D-aspartate (NMDA) receptor antagonists--in vitro characterization.

The fact that potent NMDA receptor channel blockers produce phencyclidine-like psychotropic symptoms in man and rodents implies that uncompetitive antagonism of NMDA receptors may not be a promising therapeutic approach. However, recent data indicate that agents with moderate affinity such as memantine and neramexane (MRZ 2/579) are useful therapeutics due to their strong voltage-dependency and rapid unblocking kinetics. Merz has developed a series of novel uncompetitive NMDA receptor antagonists based on an amino-alkylcyclohexane structure.

IVM media, oocyte diameter and donor genotype at RYR1 locus in relation to the incidence of porcine diploid oocytes after maturation in vitro.

In the present study three factors were investigated that may affect the process of the first polar body extrusion in pig oocytes matured in vitro: IVM medium, oocyte diameter and donor genotype at the ryanodine receptor (RYR1) locus. In the first experiment, COCs were collected by the aspiration of slaughterhouse ovaries. Oocytes were matured in vitro at 39 degrees C, in humidified 5% CO(2) atmosphere for 44 h using the following media: (1) TCM199+hCG+eCG+follicular fluid (FF), (2) TCM199+hCG+17beta-estradiol and (3) NCSU23+hCG+eCG+FF.

Induction of competence for elicitation of defense responses in cucumber hypocotyls requires proteasome activity.

The epidermal cells of hypocotyls from etiolated cucumber seedlings are not constitutively competent for elicitation of the rapid H2O2 defense response. However, elicitor competence developed while conditioning the surface-abraded seedlings by rotating them in buffer for 4 h. Competence development was greatly potentiated by inducers of systemic acquired resistance and suppressed by specific inhibitors of proteasome activity, clastolactacystin beta-lactone (LAC) and carboxybenzoyl-L-leucyl-L-leucyl-L-leucinal (LLL).

Cucumber hypocotyls respond to cutin monomers via both an inducible and a constitutive H(2)O(2)-generating system.

Hypocotyls from etiolated cucumber (Cucumis sativa L.) seedlings were gently abraded at their surface to allow permeation of elicitors. Segments from freshly abraded hypocotyls were only barely competent for H(2)O(2) elicitation with fungal elicitor or hydroxy fatty acids (classical cutin monomers).

Lifetime health risk assessment from exposure of recreational users to polycyclic aromatic hydrocarbons.

In order to assess the lifetime risk of skin cancer for recreational users from dermal exposure to polycyclic aromatic hydrocarbons (PAHs), sediment samples were collected from beach sites along the St. Marys River near Sault Ste. Marie, Ontario, and in Hamilton Harbor and Toronto Harbor, Ontario, and analyzed for PAHs.

Cutin monomers and surface wax constituents elicit H2O2 in conditioned cucumber hypocotyl segments and enhance the activity of other H2O2 elicitors.

Hypocotyls from etiolated cucumber (Cucumis sativus L.) seedlings were gently abraded at their epidermal surface and cut segments were conditioned to develop competence for H2O2 elicitation. Alkaline hydrolysates of cutin from cucumber, tomato, and apple elicited H2O2 in such conditioned segments.

Competence for Elicitation of H2O2 in Hypocotyls of Cucumber Is Induced by Breaching the Cuticle and Is Enhanced by Salicylic Acid.

To study H2O2 production, the epidermal surfaces of hypocotyl segments from etiolated seedlings of cucumber (Cucumis sativus L.) were gently abraded. Freshly abraded segments were not constitutively competent for rapid H2O2 elicitation.

Conditioning of Parsley (Petroselinum crispum L.) Suspension Cells Increases Elicitor-Induced Incorporation of Cell Wall Phenolics.

The elicitor-induced incorporation of phenylpropanoid derivatives into the cell wall and the secretion of soluble coumarin derivatives (phytoalexins) by parsley (Petroselinum crispum L.) suspension cultures can be potentiated by pretreatment of the cultures with 2,6-dichloroisonicotinic acid or derivatives of salicylic acid. To investigate this phenomenon further, the cell walls and an extracellular soluble polymer were isolated from control cells or cells treated with an elicitor from Phytophthora megasperma f.

Late onset dementia with argyrophilic grains and subcortical tangles or atypical progressive supranuclear palsy?

Most clinically demented elderly patients are found at autopsy to have Alzheimer's disease, multi-infarct dementia, Parkinson's disease, Pick's disease, or Creutzfeldt-Jakob disease. We studied 5 patients clinically characterized by late onset dementia whose brains showed no pathological evidence of Alzheimer's disease, or any other specific neuropathological diagnosis. We found argyrophilic grains, coiled bodies, abundant Alz-50-positive and thioflavine S-negative neurofibrillary tangles, and neuropil threads in the hippocampus, entorhinal cortex, locus ceruleus, substantia nigra, subthalamic nucleus, and inferior olives.

Interpersonal skills training: evaluation in an internal medicine residency.

To determine the effectiveness of teaching interpersonal skills in a general internal medicine residency, a program was developed utilizing videotape feedback of house-staff/patient interactions, a modification of Interpersonal Process Recall (IPR). Fifty-one randomly selected house officers at different levels of training were included in a controlled, pretest-posttest study design. The major pre-post measures were three independent ratings of videotapes of actual first-visit interviews between resident and patient.