Metformin increases fasting plasma peptide tyrosine tyrosine (PYY) in women with polycystic ovarian syndrome (PCOS)

Objective The beneficial effects of metformin in patients with type 2 diabetes mellitus (T2DM) and polycystic ovarian syndrome (PCOS) are thought to be in part due to weight reduction. However, the mechanisms by which metformin causes weight loss are unclear. We sought to determine whether circulating levels of the anorectic gut hormone peptide tyrosine tyrosine (PYY) show any correlation with metformin‐induced weight loss. Design and patients We examined the acute effects of orally administrated metformin on fasting PYY levels in eight healthy normal‐weight female subjects. Subsequently, we evaluated the effects of 6 months metformin treatment on fasting PYY levels and anthropometric measurements in 20 women with PCOS. Results In normal‐weight females 10 days’ metformin treatment increased fasting PYY levels (P < 0·01). Similarly, in PCOS subjects metformin treatment increased fasting PYY concentrations (P < 0·05). In both groups a marked variation in PYY increase in response to metformin was observed. Long‐term metformin treatment was associated with improvements in weight (P < 0·05), BMI (P < 0·05), fasting glucose (P < 0·05) and menstrual frequency (P < 0·01). Interestingly, change in PYY levels were correlated with change in waist circumference (r = 0·55, P < 0·05). Conclusions Acute and chronic oral metformin administration increase fasting PYY levels and may contribute to metformin's weight loss effect. Further studies are now required to clarify whether changes in circulating PYY levels in response to metformin treatment can be used to predict which patients will subsequently lose weight long‐term and gain cycle restoration.     

Contraceptive efficacy of a depot progestin and androgen combination in men

WHO studies provided proof of concept for hormonal male contraception using a prototype androgen-alone regimen. Combined testosterone plus progestin regimens offer more practical promise, but no contraceptive efficacy studies have been completed. The objective of this study was to establish the proof of principle for depot hormonal androgen/progestin combination as a male contraceptive. We performed a contraceptive efficacy study of 55 healthy men in stable fertile relationships seeking a change in contraceptive method. Testosterone (four 200-mg implants, every 4 or 6 months) and 300 mg depot medroxyprogesterone acetate, im, every 3 months were administered. Once sperm output was suppressed (<1 million/ml for 2 consecutive months), men entered a 12-month contraceptive efficacy period, ceasing other contraception. The main outcome measure was contraceptive failure (pregnancy) rate. No pregnancies occurred in 426 person-months (35.5 person-years; 95% confidence limits for contraceptive failure rate, 0-8%/annum), superior to the first year failure rate of condoms, the only reversible male method. Sperm density fell rapidly, so 94% of men entered the efficacy phase by 3 months, with only 2 of 55 (3.6%) men not sufficiently suppressed to enter efficacy. A few men treated with testosterone implants at 6-month intervals demonstrated androgen deficiency symptoms and/or escape of gonadotropin and spermatogenic suppression between months 5 and 6; after a protocol amendment, all men receiving testosterone implants at 4-month intervals avoided androgen deficiency or loss of gonadotropin and sperm output suppression. Recovery was complete (median, 3.6 months to sperm reappearance and 5.0 months to 20 million sperm/ml) in all but one man with an incidental testicular disorder. Discontinuations were for protocol-related reasons (n = 15) or altered personal circumstances (n = 12), but there were no serious adverse effects related to drug exposure. The first male contraceptive efficacy study using a prototype depot androgen/progestin combination demonstrates high contraceptive efficacy with satisfactory short-term safety and recovery of spermatogenesis. Further studies of purpose-developed products are required to extend the overall safety and efficacy experience with depot androgen/progestin combinations, the most promising approach to hormonal male contraception.     

What Online Communities Can Tell Us About Electronic Cigarettes and Hookah Use: A Study Using Text Mining and Visualization Techniques

Background

The rise in popularity of electronic cigarettes (e-cigarettes) and hookah over recent years has been accompanied by some confusion and uncertainty regarding the development of an appropriate regulatory response towards these emerging products. Mining online discussion content can lead to insights into people’s experiences, which can in turn further our knowledge of how to address potential health implications. In this work, we take a novel approach to understanding the use and appeal of these emerging products by applying text mining techniques to compare consumer experiences across discussion forums.

Objective

This study examined content from the websites Vapor Talk, Hookah Forum, and Reddit to understand people’s experiences with different tobacco products. Our investigation involves three parts. First, we identified contextual factors that inform our understanding of tobacco use behaviors, such as setting, time, social relationships, and sensory experience, and compared the forums to identify the ones where content on these factors is most common. Second, we compared how the tobacco use experience differs with combustible cigarettes and e-cigarettes. Third, we investigated differences between e-cigarette and hookah use.

Methods

In the first part of our study, we employed a lexicon-based extraction approach to estimate prevalence of contextual factors, and then we generated a heat map based on these estimates to compare the forums. In the second and third parts of the study, we employed a text mining technique called topic modeling to identify important topics and then developed a visualization, Topic Bars, to compare topic coverage across forums.

Results

In the first part of the study, we identified two forums, Vapor Talk Health & Safety and the Stopsmoking subreddit, where discussion concerning contextual factors was particularly common. The second part showed that the discussion in Vapor Talk Health & Safety focused on symptoms and comparisons of combustible cigarettes and e-cigarettes, and the Stopsmoking subreddit focused on psychological aspects of quitting. Last, we examined the discussion content on Vapor Talk and Hookah Forum. Prominent topics included equipment, technique, experiential elements of use, and the buying and selling of equipment.

Conclusions

This study has three main contributions. Discussion forums differ in the extent to which their content may help us understand behaviors with potential health implications. Identifying dimensions of interest and using a heat map visualization to compare across forums can be helpful for identifying forums with the greatest density of health information. Additionally, our work has shown that the quitting experience can potentially be very different depending on whether or not e-cigarettes are used. Finally, e-cigarette and hookah forums are similar in that members represent a “hobbyist culture” that actively engages in information exchange. These differences have important implications for both tobacco regulation and smoking cessation intervention design.     

Now how do we get them home? Outpatient care of pediatric patients on mechanical circulatory support

The last five yr have been monumental for the pediatric heart failure community. In the US, the most notable has been the FDA approval of the first pediatric specific device (Berlin Heart EXCOR^®; Berlin Heart, Inc., Berlin, Germany). Subsequently, the field of heart failure has gained a great deal of knowledge regarding the nuances of MCS in children. Despite FDA approval in the US, the Berlin EXCOR^® is only currently indicated for in‐hospital use. Due to the limitations with discharge and the positive in‐ hospital experiences with the Berlin EXCOR^®, there has been an increased interest in the implantation of adult durable devices into children. While many institutions have focused their intial efforts on the first phase of care within the hospital, they are now ready to tackle the challenge of how to safely transition children to the community setting.     

L-fucose stimulates utilization of D-ribose by Escherichia coli MG1655 DeltafucAO and E. coli Nissle 1917 DeltafucAO mutants in the mouse intestine and in M9 minimal medium

Escherichia coli MG1655 uses several sugars for growth in the mouse intestine. To determine the roles of L-fucose and D-ribose, an E. coli MG1655 DeltafucAO mutant and an E. coli MG1655 DeltarbsK mutant were fed separately to mice along with wild-type E. coli MG1655. The E. coli MG1655 DeltafucAO mutant colonized the intestine at a level 2 orders of magnitude lower than that of the wild type, but the E. coli MG1655 DeltarbsK mutant and the wild type colonized at nearly identical levels. Surprisingly, an E. coli MG1655 DeltafucAO DeltarbsK mutant was eliminated from the intestine by either wild-type E. coli MG1655 or E. coli MG1655 DeltafucAO, suggesting that the DeltafucAO mutant switches to ribose in vivo. Indeed, in vitro growth experiments showed that L-fucose stimulated utilization of D-ribose by the E. coli MG1655 DeltafucAO mutant but not by an E. coli MG1655 DeltafucK mutant. Since the DeltafucK mutant cannot convert L-fuculose to L-fuculose-1-phosphate, whereas the DeltafucAO mutant accumulates L-fuculose-1-phosphate, the data suggest that L-fuculose-1-phosphate stimulates growth on ribose both in the intestine and in vitro. An E. coli Nissle 1917 DeltafucAO mutant, derived from a human probiotic commensal strain, acted in a manner identical to that of E. coli MG1655 DeltafucAO in vivo and in vitro. Furthermore, L-fucose at a concentration too low to support growth stimulated the utilization of ribose by the wild-type E. coli strains in vitro. Collectively, the data suggest that L-fuculose-1-phosphate plays a role in the regulation of ribose usage as a carbon source by E. coli MG1655 and E. coli Nissle 1917 in the mouse intestine.