Postural Tachycardia Syndrome (POTS) is a form of chronic orthostatic intolerance for which the hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a >6-month history of symptoms that are relieved by recumbence. The heart rate abnormality and orthostatic symptoms should not be caused by medications that impair autonomic regulation or by debilitating disorders that can cause tachycardia. POTS is a “final common pathway” for a number of overlapping pathophysiologies, including an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic tone, mast cell activation, deconditioning, and autoantibodies. Not only may patients be affected by more than one of these pathophysiologies, but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos Syndrome, vasovagal syncope, and inappropriate sinus tachycardia. POTS can be treated with a combination of non-pharmacological approaches, a structured exercise training program, and often some pharmacological support.

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The data document influence of a common genetic variant on susceptibility to endothelial dysfunction and its response to sildenafil treatment.

Context Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired vascular function. GH-releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion. Objective We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS. Methods Eighteen women with PCOS participated in a double-blind, crossover study. They received sitagliptin either 100 mg or placebo daily for 1 month, with crossover treatments separated by an 8-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT) and assessments of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm. Results During OGTT, sitagliptin increased glucagon-like peptide-1 (P < 0.001), early insulin secretion (from mean [± SD] insulinogenic index 1.9 ± 1.2 to 3.2 ± 3.1; P = 0.02), and decreased peak glucose (mean −17.2 mg/dL [95% CI, −27.7 to −6.6]; P < 0.01). At 1 month, sitagliptin decreased VAT (from 1141.9 ± 700.7 to 1055.1 ± 710.1 g; P = 0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9 ± 3.6 to 17.0 ± 6.8 min, N = 16; P = 0.04) and interpulse interval (from 53.2 ± 20.0 to 77.3 ± 38.2 min, N = 16; P < 0.05) but did not increase mean overnight GH (P = 0.92 vs placebo). Conclusions Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval. Clinical Trial Registration This study was registered at www.clinicaltrials.gov as NCT02122380 prior to enrollment of the first participant.

Objective-The objective of this study was to evaluate whether mandatory fortification of grain products with folic acid in the USA is associated with changes in DNA methyltransferase (Dnmt) 1 expression in cells involved in cervical carcinogenesis.Methods-Archived specimens of cervical intraepithelial neoplasia (CIN) diagnosed before and after mandatory folic acid fortification (2000-02) were used to examine the expression of Dnmt 1 in specific lesions involved in cervical carcinogenesis by immunohistochemistry. The total number of lesions examined was 101 in the pre-fortification period and 96 in the postfortification period. Immunohistochemical staining for Dnmt 1, its assessment and data entry were blinded with regard to the fortification status.Results-Age-and race-adjusted mean percentage of cells positive for Dnmt 1 or the Dnmt 1 score was significantly higher in all lesion types (i.e., normal cervical epithelium, reactive cervical epithelium, metaplastic cervical epithelium, CIN or carcinoma in situ) detected in the postfortification period compared to pre-fortification period (P < 0.05, all comparisons). The degree of Dnmt 1 was significantly higher (P < 0.0001) in ≥ CIN 2 lesions compared to ≤ CIN 1 lesions, regardless of the fortification group. Conclusions-These results suggest that mandatory fortification with folic acid in the UnitedStates seem to have resulted in a change in the degree of expression of Dnmt 1 in cells involved in cervical carcinogenesis. Because the approach we have taken to demonstrate these differences have limitations inherent to a study of this nature and this is the first study to report a folate fortification associated change in Dnmt 1, validating these results in other study populations and or with other techniques of assessing Dnmt 1 will increase the scientific credibility of these findings.