Erectile Dysfunction Precedes Coronary Artery Endothelial Dysfunction in Rats Fed a High‐Fat,High‐Sucrose,Western Pattern Diet

IntroductionIt is suggested that erectile dysfunction (ED) may be an early risk factor for cardiovascular disease.AimThe goal of this study was to determine whether development of ED precedes the onset of coronary artery endothelial dysfunction in response to a Western diet (WD), thereby establishing whether the WD differentially impacts the endothelium in a time‐dependent manner. Additionally, a goal was to determine if diet‐induced ED is reversible with intracavernosal sepiapterin treatment.MethodsMale Sprague‐Dawley rats were fed a WD for 4, 8, or 12 weeks, or a control diet for 8 weeks. Erectile function was evaluated by measuring the mean arterial pressure (MAP) and intracavernosal pressure (ICP) in response to electrical field stimulation of the cavernosal nerve near the major pelvic ganglion, in the absence and presence of sepiapterin. Coronary artery endothelial function was evaluated ex vivo with cumulative doses of acetylcholine (ACh) applied to segments of the left anterior descending coronary artery preconstricted with serotonin.Main Outcome MeasuresErectile function was assessed as the ICP response to electrical field stimulation (EFS), normalized to MAP. Coronary artery endothelial function was assessed as the effective concentration producing 50% of a maximal response (EC₅₀) of the ACh response.ResultsThe ICP/MAP response to EFS was significantly attenuated following both 8 and 12 weeks of the WD compared with the control diet (P < 0.05). Sepiapterin treatment augmented the ICP/MAP response in all WD groups (P < 0.05). The coronary artery EC₅₀ of the ACh response was not different from control following 4 or 8 weeks but was significantly elevated following 12 weeks of the WD (P < 0.01).ConclusionsThese data suggest that erectile function is reduced prior to coronary artery endothelial function in response to the WD. Improvement of erectile function with sepiapterin in WD rats indicates that nitric oxide synthase uncoupling is a key mechanism in diet‐induced ED. La Favor JD, Anderson EJ, Hickner RC, and Wingard CJ. Erectile dysfunction precedes coronary artery endothelial dysfunction in rats fed a high‐fat, high‐sucrose, Western pattern diet. J Sex Med 2013;10:694–703.     

Effect of Lycium barbarum Polysaccharides on the expression of endothelin-1 and its receptors in an ocular hypertension model of rat glaucoma

Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells (RGCs) in a rat chronic ocular hypertension (COH) model. Here, we investigated the expression of endothelin-1 (ET-1), a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure (IOP) was induced in the right eye of SD rats using argon laser photocoagulation. (1) The expression of ET-1, ETA and ETB in normal and COH retinas was studied. (2) Some COH rats were fed daily with Lycium barbarum Polysaccharides (LBP) using 1 mg/kg or phosphate-buffered saline (PBS) for 3 weeks (started 1 week before photocoagulation). The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that (1) Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. (2) After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. (3) By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.     

Correction to: Gene Editing Rescues in Vitro T Cell Development of RAG2-Deficient Induced Pluripotent Stem Cells in an Artificial Thymic Organoid System

Journal of Clinical Immunology - A Correction to this paper has been published: https://doi.org/10.1007/s10875-021-01030-6     

The timing of drain removal—empiricism or science?

Surgical drains are commonly used in plastic surgery. Drains are subsequently removed at arbitrary volumes depending on local protocols. The rational for when to remove a drain has not been scientifically determined. We compared removal of drains at ≤30?ml/24?h vs. ≤50?ml/24?h for 158 wounds, in 90 patients. Postoperative complications, length of hospital stay and resulting cost–benefit were considered. Prospective data were collected for two consecutive similar cohorts of patients undergoing abdominoplasty, bilateral breast reduction and breast augmentation. In the first cohort, drains were removed when drainage was ≤30?ml/24?h and the second cohort when ≤50?ml/24?h. Demographics, days of drainage, surgeon grade and duration of postoperative hospital stay were recorded. Patient records were then analysed and complications recorded, including haematoma, infection, seroma, wound breakdown and fat necrosis. The median postoperative stay for all three operations for both drainage cohorts was similar with no statistically significant difference; however, the drainage time in breast augmentation was significantly less in the <50?ml/24?h group. There were no significant differences in outcome measures between the patients undergoing abdominoplasty, breast reduction or breast augmentation. Drain removal at ≤50 vs. ≤30?ml/24?h did not result in an increase in postoperative morbidity or adverse outcome in any of the three different operation types.     

The Role of Tissue Resection Length in the Determination of Post-Operative Eyelid Position for Muller’s Muscle-Conjunctival Resection Surgery

Purpose: To investigate the relationships between pre-operative marginal reflex distance (MRD), tissue resection length, phenylephrine response, and change in MRD with surgery for a cohort of individuals undergoing Muller’s muscle conjunctival resection (MMCR) surgery.

Methods: All cases of MMCR surgery performed over a 13-year period at a single institution were screened for entry. Individuals with adequate photographic documentation and follow up were included. Patients with previous or concurrent upper eyelid, orbital or eyebrow disease of surgery were excluded. Marginal reflex distance (MRD) was calculated based on photographs utilizing public domain software. Data was plotted for inspection and appropriate statistical tests were performed.

Results: During the study period 198 eyes fit criteria for analysis. A loose association between tissue resection length and change in MRD with surgery was found (r?=?0.176, p?p?=?0.367). There was a strong association between MRD change with surgery and pre-operative MRD (r?=?0.498, p?r?=??0.441, p?2?mm and pre-operative MRD as variables revealed a model with pre-operative MRD as the only significant predictor (p?Conclusion: Tissue resection length and phenylephrine response play small roles relative to pre-operative MRD in the determination of change in MRD with MMCR surgery.     

Hexamethylene diisocyanate (HDI) vapor reactivity with glutathione and subsequent transfer to human albumin

IntroductionAirway fluid glutathione (GSH) reactivity with inhaled vapors of diisocyanate, a common occupational allergen, is postulated to be a key step in exposure-induced asthma pathogenesis.MethodsA mixed (vapor/liquid) phase exposure system was used to model the in vivo reactivity of inhaled HDI vapor with GSH in the airway fluid. HDI–GSH reaction products, and their capacity to transfer HDI to human albumin, were characterized through mass spectrometry and serologic assays, using HDI-specific polyclonal rabbit serum.ResultsHDI vapor exposure of 10 mM GSH solutions resulted in primarily S-linked, bis(GSH)–HDI reaction products. In contrast, lower GSH concentrations (100 μM) resulted in mainly mono(GSH)–HDI conjugates, with varying degrees of HDI hydrolysis, dimerization and/or intra-molecular cyclization, depending upon the presence/absence of H₂PO₄^?/HPO₄^2? and Na⁺/Cl^? ions. The ion composition and GSH concentration of the fluid phase, during HDI vapor exposure, strongly influenced the transfer of HDI from GSH to albumin, as did the pH and duration of the carbamoylating reaction. When carbamoylation was performed overnight at pH 7, 25 of albumin’s lysines were identified as potential sites of conjugation with partially hydrolyzed HDI. When carbamoylation was performed at pH 9, more rapid (within 3 h) and extensive modification was observed, including additional lysine sites, intra-molecular cross-linkage with HDI, and novel HDI–GSH conjugation.ConclusionsThe data define potential mechanisms by which the levels of GSH, H₂PO₄^?/HPO₄^2?, and/or other ions (e.g. H⁺/OH^?, Na⁺, Cl^?) affect the reactivity of HDI vapor with self-molecules in solution (e.g. airway fluid), and thus, might influence the clinical response to HDI respiratory tract exposure.     

Polymorphic microsatellite loci for a neotropical leaf-litter frog (Craugastor bransfordii) characterized through Illumina sequencing

There are relatively few molecular resources for amphibians in the tropics where widespread habitat loss, disease, and contamination threaten the world’s most diverse assemblages. We used Illumina sequencing to develop microsatellite primers for a dominant amphibian species in Costa Rica that has recently experienced population declines. We characterized 12 polymorphic loci and have provided sequences for over 200 additional primers. These novel molecular resources will be useful for future studies of population genetic structure and may help explain recent declines in one of many species that are decreasing in Central America.     

What Are the Best Predictors of Opinions of Mental Illness in the Indian Population?

Mental illness affects millions of people around the world, and yet support, advocacy, and acceptance of people with psychological disabilities is lacking. The stigma of mental illness hinders those who want and need help from getting it, which only perpetuates the problem. The purpose of this study was to identify those factors that have predictive value for opinions of mental illness. Mechanical Turk was used to distribute the Opinions of Mental Illness scale along with a demographics survey. Taking part in the initial survey were 195 people (82 females) of Indian descent. Utilizing a backwards stepwise regression, we constructed a model that included the four most influential factors. Gender, political affiliation, parental nurturing, and age emerged as the best predictors of opinions of mental illness within the Indian population.