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Contamination of arsenic in drinking water is associated with several human diseases including cancer. It has been reported that oxidative stress plays a vital role in arsenic-induced biochemical and molecular alterations. The aim of the present study was to improve the understanding of arsenic-induced oxidative damage to proteins and to DNA and the role of antioxidants such as ascorbic acid and α-tocopherol in alleviating arsenic-induced damages in experimental rats. A significant increase in the levels of protein oxidation, DNA strand breaks, and DNA–protein cross-links was observed in blood, liver, and kidney of rats exposed to arsenic (100 ppm in drinking water) for 30 days. Co-administration of ascorbic acid and α-tocopherol to arsenic-exposed rats showed a substantial reduction in the levels of arsenic-induced oxidative products of protein and DNA. The results of this study support that free radical–mediated toxic manifestations of arsenic and also suggest that ascorbic acid and α-tocopherol supplementation can improve the arsenic-induced molecular alterations.

AbstractPurposeManagement of anal fistula represents a balance between curing the condition and maintaining anal continence. Recent reports of the results of the porcine anal fistula plug have demonstrated excellent fistula healing rates without reporting significant complications.MethodsThe outcome of patients who underwent treatment for anal fistula with the Surgisis® anal plug was retrospectively reviewed.ResultsTwenty patients were treated; three underwent concomitant anal advancement flap at the time of plug placement. Seventeen patients had a trans‐sphincteric fistula, and three had an anoperineal fistula. Ten patients had previously undergone failed surgical therapy to cure their fistula, including anal advancement flap in four, muscle interposition flap in two, fistulotomy in two, and cutting seton placement in two. Mean follow‐up was 7.4 months. Only 4 of 17 (24%) patients treated with the plug alone had closure of their fistula. Acute postoperative sepsis was seen in 5 of 17 (29%) patients treated with the plug alone. Four developed perianal abscesses that required incision and drainage, and one intersphincteric abscess was treated with antibiotics. Two of the patients who underwent concomitant anal advancement flaps and plug placement healed successfully.ConclusionsContrary to other published series, the use of the Surgisis® anal plug was associated with a low rate of fistula healing and a high incidence of perianal sepsis. The addition of a transanal advancement flap to the procedure may improve success rates.

OBJECTIVE—Current criteria for the diagnosis of diabetic ketoacidosis (DKA) are limited by their nonspecificity (serum bicarbonate [HCO3] and pH) and qualitative nature (the presence of ketonemia/ketonuria). The present study was undertaken to determine whether quantitative measurement of a ketone body anion could be used to diagnose DKA. RESEARCH DESIGN AND METHODS—A retrospective review of records from hospitalized diabetic patients was undertaken to determine the concentration of serum β-hydroxybutyrate (βOHB) that corresponds to a HCO3 level of 18 mEq/l, the threshold value for diagnosis in recently published consensus criteria. Simultaneous admission βOHB and HCO3 values were recorded from 466 encounters, 129 in children and 337 in adults. RESULTS—A HCO3 level of 18 mEq/l corresponded with βOHB levels of 3.0 and 3.8 mmol/l in children and adults, respectively. With the use of these threshold βOHB values to define DKA, there was substantial discordance (∼≥20%) between βOHB and conventional diagnostic criteria using HCO3, pH, and glucose. In patients with DKA, there was no correlation between HCO3 and glucose levels on admission and a significant but weak correlation between βOHB and glucose levels (P < 0.001). CONCLUSIONS—Where available, serum βOHB levels ≥3.0 and ≥3.8 mmol/l in children and adults, respectively, in the presence of uncontrolled diabetes can be used to diagnose DKA and may be superior to the serum HCO3 level for that purpose. The marked variability in the relationship between βOHB and HCO3 is probably due to the presence of other acid-base disturbances, especially hyperchloremic, nonanion gap acidosis.

Abstract Pluripotent stem cells demonstrate an inherent propensity for unrestricted multi-lineage differentiation. Translation into regenerative applications requires identification and isolation of tissue-specified progenitor cells. From a comprehensive pool of 11,272 quality-filtered genes, profiling embryonic stem cells at discrete stages of cardiopoiesis revealed 736 transcripts encoding membrane-associated proteins, where 306 were specifically upregulated with cardiogenic differentiation. Bioinformatic dissection of exposed surface biomarkers prioritized the chemokine receptor cluster as the most significantly over-represented gene receptor family during pre cardiac induction, with CXCR4 uniquely associated with mesendoderm formation. CXCR4+ progenitors were sorted from the embryonic stem cell pool into mesoderm-restricted progeny according to co-expression with the early mesoderm marker Flk-1. In contrast to CXCR4−/Flk-1− cells, the CXCR4+/Flk-1+ subpopulation demonstrated overexpressed cardiac lineage transcription factors (Mef2C, Myocardin, Nkx2.5), whereas pluripotent genes (Oct4, Fgf4, Sox2) as well as neuroectoderm (Sox1) and endoderm alpha-fetoprotein markers were all depleted. In fact, the CXCR4+/Flk-1+ biomarker combination identified embryonic stem cell progeny significantly enriched with Mesp-1, GATA-4, and Tbx5, indicative of pre cardiac mesoderm and the primary heart field. Although the CXCR4+/Flk-1+ transcriptome shared 97% identity with the CXCR4−/Flk-1− counterpart, the 818 divergent gene set represented predominantly cardiovascular developmental functions and formed a primitive cardiac network. Differentiation of CXCR4+/Flk-1+ progenitors yielded nuclear translocation of myocardial transcription factors and robust sarcomerogenesis with nascent cardiac tissue demonstrating beating activity and calcium transients. Thus, the CXCR4/Flk-1 biomarker pair predicts the emergence of cardiogenic specification within a pluripotent stem cell pool, enabling targeted selection of cardiopoietic lineage. Disclosure of potential conflicts of interest is found at the end of this article.

ABSTRACT Introduction Severe obstructive sleep apnea has been associated with sexual dysfunction; however, it is unclear whether milder forms of sleep disturbances might also be associated with sexual problems. Aim To evaluate the association between snoring and five measures of sexual dysfunction in a population-based sample of men. Methods A stratified random sample of men residing in Olmsted County, Minnesota completed a questionnaire containing questions from the Brief Male Sexual Function Inventory (BMSFI) and a sleep questionnaire. Main Outcome Measures Levels of sexual drive (libido), erectile function, ejaculatory function, sexual problem assessment, and sexual satisfaction as assessed by the BMSFI. Results Of 827 men with a regular sexual partner, subjects were divided into categories of heavy (N=95), moderate (N=573), and none/mild (N=159) snoring. Their median age was 64 years (range 51–90). The sexual satisfaction domain score was significantly lower in the heavy snoring group (P value=0.01). The odds of low sexual satisfaction was 2.3 (95% CI 1.2, 4.1) among the heavy snorers compared with the none/mild snoring group. This association remained statistically significant after adjustment for smoking, medical comorbidities, and mental health status. However, there was no significant difference in ejaculatory function, erectile function, sexual drive, and sexual problem assessment across snoring categories. Conclusions These data provide evidence of an association between snoring severity and reduced sexual satisfaction in a population of elderly community males. Snoring was not associated with biologic measures of sexual dysfunction.