Decision-Making for HIV AIDS Prevention: Altruism and the Moral Norm.

The purpose of this enquiry was to understand how gay men form and maintain their attitudes toward HIV transmission preventative behaviors. Autobiographical life histories of sixteen gay men showed that once they acquired knowledge of preventative behavior they consistently adhered to that behavior. They adhered because of fear of HIV infection and because they held a moral norm that obligated them to behave altruistically (Schwartz, 1977) to protect not only themselves, but also their sex partners, loved ones, and their positive self-evaluation.

Frugal Innovation: Enabling Mechanical Ventilation During Coronavirus Disease 2019 Pandemic in Resource-Limited Settings.

ICUs worldwide are facing resource shortages including increased need for provision of invasive mechanical ventilation during the current coronavirus disease 2019 pandemic. Fearing shortage of ventilators, many private companies and public institutions have focused on building new inexpensive, open-source ventilators. However, designing and building new ventilators is not sufficient for addressing invasive mechanical ventilation needs in resource-limited settings.

An Integrated Circuit for Chip-Based Analysis of Enzyme Kinetics and Metabolite Quantification.

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim.

Lymphadenopathy: defining a palpable lymph node.

Background: The threshold size required to detect lymphadenopathy via palpation has never been formally determined. The purpose of this study was to determine the threshold, sensitivity, and error of node palpation and how this changes with experience.

Methods: Lymphadenopathy models were created using polyvinyl alcohol cryogel (PVA-C) to mimic tissue tactility.

Smooth muscle phenotypic modulation--a personal experience.

The idea that smooth muscle cells can exist in multiple phenotypic states depending on the functional demands placed upon them has been around for >5 decades. However, much of the literature today refers to only recent articles, giving the impression that it is a new idea. At the same time, the current trend is to delve deeper and deeper into transcriptional regulation of smooth muscle genes, and much of the work describing the change in biology of the cells in the different phenotypic states does not appear to be known.

Development of a tissue-mimicking neck model for medical education.

Background: The ability to palpate neck masses and lymph nodes and appreciate qualities such as size, location, and consistency is critical for patient care and an important clinical skill for all physicians. Medical students currently learn neck palpation by practicing on healthy, standardized patients; however, studies of similar procedures have shown that educational models with simulated pathology help improve technique and confidence.

Objective: Our goal was to create a tissue-mimicking neck model with palpable masses.

Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids.

Antagonism of the CRTH2 receptor represents a very attractive target for a variety of allergic diseases. Most CRTH2 antagonists known to date possess a carboxylic acid moiety, which is essential for binding. However, potential acid metabolites O-acyl glucuronides might be linked to idiosynchratic toxicity in humans.

Optimization of the Central Core of Indolinone-Acetic Acid-Based CRTH2 (DP2) Receptor Antagonists.

New spiroindolinone antagonists of CRTH2 are described. Following identification of insufficient stability in human plasma as an important liability of the lead compounds, replacement of the spirosuccinimide core with a spirohydantoin or spiropyrrolidinone structure has yielded a compound that is fully stable in human plasma and with good potency in a human whole blood assay (IC50 = 69 nM) but shows a much lower oral bioavailability (6-9% in rodents) than the earlier compounds. Successive optimization aimed at restoring an acceptable oral bioavailability has yielded compound (S)-17a, which exhibits both stability in human plasma and a good oral bioavailability in rat (37%) and mouse (39%).

Contribution of inter-subunit interactions to the thermostability of Pyrococcus furiosus citrate synthase.

Using citrate synthase from the hyperthermophile Pyrococcus furiosus (PfCS) as our test molecule, we show through guanidine hydrochloride-induced unfolding that the dimer separates into folded, but inactive, monomers before individual subunit unfolding takes place. Given that forces across the dimer interface are vital for thermostability, a robust computational method was derived that uses the University of Houston Brownian Dynamics (UHBD) program to calculate both the hydrophobic and electrostatic contribution to the dimerisation energy at 100°C. The results from computational and experimental determination of the lowered stability of interface mutants were correlated, being both of the same order of magnitude and placing the mutant proteins in the same order of stability.

Transcription factors expressed in olfactory bulb local progenitor cells revealed by genome-wide transcriptome profiling.

The local progenitor population in the olfactory bulb (OB) gives rise to mitral and tufted projection neurons during embryonic development. In contrast, OB interneurons are derived from sources outside the bulb where neurogenesis continues throughout life. While many of the genes involved in OB interneuron development have been characterized, the genetic pathways driving local progenitor cell differentiation in this tissue are largely unknown.

A constrained reconstruction technique of hyperelasticity parameters for breast cancer assessment.

In breast elastography, breast tissue usually undergoes large compression resulting in significant geometric and structural changes. This implies that breast elastography is associated with tissue nonlinear behavior. In this study, an elastography technique is presented and an inverse problem formulation is proposed to reconstruct parameters characterizing tissue hyperelasticity.

Virtual fragment screening for novel inhibitors of 6-phosphogluconate dehydrogenase.

The enzyme 6-phosphogluconate dehydrogenase is a potential drug target for the parasitic protozoan Trypanosoma brucei, the causative organism of human African trypanosomiasis. This enzyme has a polar active site to accommodate the phosphate, hydroxyl and carboxylate groups of the substrate, 6-phosphogluconate. A virtual fragment screen was undertaken of the enzyme to discover starting points for the development of inhibitors which are likely to have appropriate physicochemical properties for an orally bioavailable compound.

Cellular plasticity of inflammatory myeloid cells in the peritoneal foreign body response.

Implantation of sterile foreign objects in the peritoneal cavity of an animal initiates an inflammatory response and results in encapsulation of the objects by bone marrow-derived cells. Over time, a multilayered tissue capsule develops with abundant myofibroblasts embedded in extracellular matrix. The present study used the transgenic MacGreen mouse to characterize the time-dependent accumulation of monocyte subsets and neutrophilic granulocytes in the inflammatory infiltrate and within the tissue capsule by their differential expression of the csf1r-EGFP transgene, F4/80, and Ly6C.

The peritoneal cavity as a bioreactor for tissue engineering visceral organs: bladder, uterus and vas deferens.

Our objective was to produce avascular, myofibroblast-rich tissue capsules for use as autologous grafts for hollow, smooth muscle-walled visceral organs-bladder, uterus and vas deferens. To produce tissue for grafting, templates of the appropriate shape were implanted in the peritoneal cavities of rats or rabbits. After 2-3 weeks, the templates were removed, the encapsulating myofibroblast-rich tissue harvested and grafted to replace resected segments of bladder, vas deferens or uterus of the same animals in which the tissue was grown.

Engineering tissue tubes using novel multilayered scaffolds in the rat peritoneal cavity.

Our aim was to develop novel scaffolds to engineer tissue tubes of smooth muscle-like cells for autologous grafting. Small diameter tubular poly(lactic acid) scaffolds with randomly distributed, interconnected pores up to 100 mum were produced using a thermally induced phase separation method. The scaffolds were surface modified using various biomolecules via a layer-by-layer deposition technique, and implanted in the peritoneal cavities of rats.

Development of a composite material phantom mimicking the magnetic resonance parameters of the neonatal brain at 3.0 Tesla.

Objective: Development of a composite material phantom, comprised of polyvinyl alcohol cryogel (PVA-C) and an agarose additive, to effectively mimic the magnetic resonance relaxation times (T1 and T2) of neonatal white matter (WM) and gray matter (GM) at 3.0 T.

Materials And Methods: Samples of PVA-C with and without agarose were prepared with 1 cycle of freezing/thawing.

Abduction and external rotation in shoulder impingement: an open MR study on healthy volunteers initial experience.

Purpose: To prospectively evaluate rotator cuff contact with the glenoid in healthy volunteers placed in the unloaded and loaded abduction and external rotation (ABER) positions in an open magnetic resonance (MR) imager.

Materials And Methods: The study was institutional review board approved and HIPAA compliant, and informed consent was received. Eight male volunteers with no history of shoulder pain or pathology were imaged in a 0.

Vascular grafts and the endothelium.

This article discusses the importance of the endothelium for successful vascular grafts derived from both native arteries and synthetic materials. It also discusses the fundamental strategies to endothelialize synthetic grafts in animal experiments and in the clinic, as well as the use of endothelial progenitor cells (EPCs), bone marrow-derived cells, and mesothelium as endothelial substitutes.

CbrA is a stationary-phase regulator of cell surface physiology and legume symbiosis in Sinorhizobium meliloti.

Sinorhizobium meliloti produces an exopolysaccharide called succinoglycan that plays a critical role in promoting symbiosis with its host legume, alfalfa (Medicago sativa). We performed a transposon mutagenesis and screened for mutants with altered succinoglycan production and a defect in symbiosis. In this way, we identified a putative two-component histidine kinase associated with a PAS sensory domain, now designated CbrA (calcofluor-bright regulator A).

Sinorhizobium meliloti bluB is necessary for production of 5,6-dimethylbenzimidazole, the lower ligand of B12.

An insight into a previously unknown step in B(12) biosynthesis was unexpectedly obtained through our analysis of a mutant of the symbiotic nitrogen fixing bacterium Sinorhizobium meliloti. This mutant was identified based on its unusually bright fluorescence on plates containing the succinoglycan binding dye calcofluor. The mutant contains a Tn5 insertion in a gene that has not been characterized previously in S.

Discovery of novel and selective tertiary alcohol containing inhibitors of the norepinephrine transporter.

A novel series of tertiary alcohol containing 2-substituted benzyl morpholines have been discovered as potent and selective inhibitors of the norepinephrine transporter. Efficient synthetic routes were developed featuring a highly diastereoselective nucleophilic addition of benzyl Grignard reagents to enantiopure (4-benzylmorpholin-2-yl)phenylmethanone (11) as the key synthetic step. In vitro binding affinity for the norepinephrine, dopamine and serotonin transporters and in vivo examination of a select compound (16) in a pharmacodynamic animal model for norepinephrine reuptake inhibition are presented.

Establishment of metanephros transplantation in mice highlights contributions by both nephrectomy and pregnancy to developmental progression.

Background: It has been demonstrated that embryonic kidneys (metanephroi) xenotransplanted into the omentum of adult recipients continue to develop and display immune protection due to their more naïve immune presentation. To date, this has been achieved using rat, pig and human metanephroi, with unilateral nephrectomy (UNX) of recipient rats a requisite of renal development. The aim of this study was to adapt this approach for use in mice and examine the parameters affecting successful onward development in this species.

Vascular engineering for bypass surgery.

Since the introduction of synthetic vascular grafts in the 1960s, only two-stage endothelial cell seeding has demonstrated any significant improvement over conventional vascular grafts, and its benefits have yet to be demonstrated on a large scale. Tissue engineering is a rapidly expanding field with great potential, but efforts to construct tissue-engineered arterial grafts have, to date, yielded little clinical success. This review explores the latest approaches to the construction of a superior vascular graft, along with its potential for use in the clinic in the future.

Rho and vascular disease.

The Rho family GTPases are regulatory molecules that link surface receptors to organisation of the actin cytoskeleton and play major roles in fundamental cellular processes. In the vasculature Rho signalling pathways are intimately involved in the regulation of endothelial barrier function, inflammation and transendothelial leukocyte migration, platelet activation, thrombosis and oxidative stress, as well as smooth muscle contraction, migration, proliferation and differentiation, and are thus implicated in many of the changes associated with atherogenesis. Indeed, it is believed that many of the beneficial, non-lipid lowering effects of statins occur as a result of their ability to inhibit Rho protein activation.

Tissue-engineered blood vessels: alternative to autologous grafts?

Although vascular bypass grafting remains the mainstay for revascularization for ischemic heart disease and peripheral vascular disease, many patients do not have healthy vessels suitable for harvest. Thus, prosthetic grafts made of synthetic polymers were developed, but their use is limited to high-flow/low-resistance conditions because of poor elasticity, low compliance, and thrombogenicity of their synthetic surfaces. To fill this need, several laboratories have produced in vivo or in vitro tissue-engineered blood vessels using molds or prosthetic or biodegradable scaffolds, but each artificial graft has significant problems.