Rapid, minimally invasive adult voluntary male circumcision: A randomised trial

Background. Voluntary medical male circumcision (VMMC) is a priority HIV preventive intervention. To facilitate male circumcision scale- up, the World Health Organization is actively seeking circumcision techniques that are quicker, easier, and safer than open surgical methods. Objective. To compare conventional open surgical circumcision with suturing with a minimally invasive technique using the Gomco circumcision clamp plus tissue adhesive.Methods. We conducted a non-blinded randomised controlled trial comprising 200 male volunteers >18 years of age, seen at the outpatient university teaching clinic of the Catholic University of Mozambique. We compared two interventions – open surgical circumcision with suturing v. Gomco instrument plus tissue adhesive. Our primary outcome was intraoperative time and our secondary outcomes included: ease of performance, post-operative pain, adverse events, time to healing, patient satisfaction and cosmetic result. Results. The intraoperative time was less with the Gomco/tissue adhesive technique (mean 12.8 min v. 22.5 min; p<0.001). Adverse events were similar except that wound disruption was greater in the Gomco/tissue adhesive group, with no difference in wound healing at 4 weeks. Levels of satisfaction were high in both groups. The cosmetic result was superior in the Gomco/tissue adhesive group.Conclusions. This study has important implications for the scale-up of VMMC services. Removing the foreskin with the Gomco instrument and sealing the wound with cyanoacrylate tissue adhesive in adults is quicker, is an easier technique to learn, and is potentially safer than open surgical VMMC. A disposable plastic, Gomco-like device should be produced and evaluated for use in resource-limited settings.

Covalent attachment of active enzymes to upconversion phosphors allows ratiometric detection of substrates

Upconverting phosphors (UCPs) convert multiple low energy photons into higher energy emission via the process of photon upconversion and offer an attractive alternative to organic fluorophores for use as luminescent probes. Here, UCPs were capped with functionalized silica in order to provide a surface to covalently conjugate proteins with surface?accessible cysteines. Variants of green fluorescent protein (GFP) and the flavoenzyme pentaerythritol tetranitrate reductase (PETNR) were then attached via maleimide?thiol coupling in order to allow energy transfer from the UCP to the GFP or flavin cofactor of PETNR, respectively. PETNR retains its activity when coupled to the UCPs, which allows reversible detection of enzyme substrates via ratiometric sensing of the enzyme redox state

Hippurate: the natural history of a mammalian-microbial co-metabolite

Hippurate, the glycine conjugate of benzoic acid, is a normal constituent of the endogenous urinary metabolite profile and has long been associated with the microbial degradation of certain dietary components, hepatic function and toluene exposure, and is also commonly used as a measure of renal clearance. Here we discuss the potential relevance of hippurate excretion with regards to normal endogenous metabolism and trends in excretion relating to gender, age, and the intestinal microbiota. Additionally, the significance of hippurate excretion with regards to disease states including obesity, diabetes, gastrointestinal diseases, impaired renal function, psychological disorders and autism, as well as toxicity and parasitic infection, are considered

A Single Bout of Breast Milk Expression Does Not Increase Resting Metabolic Rate

Introduction: Breastfeeding women have elevated resting metabolic rate (RMR); however, whether a single bout of lactation increases RMR is unknown. This study aimed to determine if a single bout of lactation acutely increased RMR. Methods: Twenty-two lactating women (age: 31 ± 0.9 year, body mass index: 27.3 ± 1.2 kg/m2) were recruited. RMR was assessed at baseline and at 1- and 2-h following breast milk expression. Results: RMR was unchanged in lactating women following a single bout of lactation (baseline: 1437 ± 39; 1 h: 1425 ± 37 2 h: 1440 ± 31 kcal/day) (p \u3e .05). RMR was not correlated to daily milk produced (r = 0.05, p \u3e .05), but was correlated to body mass (r = 0.74, p \u3c .001), fat-free mass (kg) (r = 0.61, p \u3c .01), and fat mass (kg) (r = 0.71, p \u3c .01). Conclusion: RMR in lactating women appears to be more related to body mass or composition in the postpartum period rather than lactation

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized

Accelerometry cut points for physical activity in underserved African Americans

Background: Despite their increased use, no studies have examined the validity of Actical accelerometry cut points for moderate physical activity (PA) in underserved (low-income, high-crime), minority populations. The high rates of chronic disease and physical inactivity in these populations likely impact the measurement of PA. There is growing concern that traditionally defined cut points may be too high for older or inactive adults. The present study aimed to determine the self-selected pace associated with instructions to walk for exercise and the corresponding accelerometry estimates (e.g. Actical counts/minute) for underserved, African American adults. Method: Fifty one participants (61% women) had a mean age of 60.1 (SD=9.9) and a mean body mass index of 30.5 kg/m2 (SD=60). They performed one seated task, on standing task, and three walking tasks: strolling ; walking for exercise ; and walking in an emergency. Results: The average pace for strolling, walking for exercise, and walking in an emergency were 1.62 miles per hour (mph; SD=.51), 2.51 mph (SD=.53), and 2.86 mph (SD=.58), respectively. Regression analyses showed that the predicted counts/minute for a pace of 2.0 mph (which is used as the criterion for moderate exercise in this study) was 1075 counts/minute (SEM=73). Conclusions: The cut point associated with subjectively determined moderate PA is similar to those previously published for older adults and extends to the use of adjusted cut points to African American populations. These results indicate that accurate cut points can be obtained using this innovative methodology

Deceleration of one-dimensional mixing by discontinuous mappings

We present a computational study of a simple one-dimensional map with dynamics composed of stretching, permutations of equal sized cells, and diffusion. We observe that the combination of the aforementioned dynamics results in eigenmodes with long-time exponential decay rates. The decay rate of the eigenmodes is shown to be dependent on the choice of permutation and changes non-monotonically with the diffusion coefficient for many of the permutations. The global mixing rate of the map M in the limit of vanishing diffusivity approximates well the decay rates of the eigenmodes for small diffusivity, however this global mixing rate does not bound the rates for all values of the diffusion coefficient. This counter-intuitively predicts a deceleration in the asymptotic mixing rate with increasing diffusivity rate. The implication of the results on finite time mixing are discussed