Acute effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs.

New Findings: What is the central question of this study? What are the effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity in vivo and how do carotid body chemoreceptor stimulation-mediated cardiorespiratory responses in beagle dogs compare during euglycaemia and insulin-induced hypoglycaemia? What is the main finding and its importance? Intracarotid insulin administration leads to sustained increase in carotid body chemoreceptor activity and respiratory response with significant cardiovascular effects. Insulin-induced hypoglycaemia exacerbated NaCN-mediated carotid body chemoreceptor activity and respiratory response with enhanced cardiovascular reflex response. These findings suggest that insulin-induced hypoglycaemia augments the carotid body chemoreceptors to initiate the adaptive counter-regulatory responses to restore the normoglycaemic condition.

Human-relevant near-organ neuromodulation of the immune system via the splenic nerve.

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking.

Splenic Nerve Neuromodulation Reduces Inflammation and Promotes Resolution in Chronically Implanted Pigs.

Neuromodulation of the immune system has been proposed as a novel therapeutic strategy for the treatment of inflammatory conditions. We recently demonstrated that stimulation of near-organ autonomic nerves to the spleen can be harnessed to modulate the inflammatory response in an anesthetized pig model. The development of neuromodulation therapy for the clinic requires chronic efficacy and safety testing in a large animal model.

Quantification of clinically applicable stimulation parameters for precision near-organ neuromodulation of human splenic nerves.

Neuromodulation is a new therapeutic pathway to treat inflammatory conditions by modulating the electrical signalling pattern of the autonomic connections to the spleen. However, targeting this sub-division of the nervous system presents specific challenges in translating nerve stimulation parameters. Firstly, autonomic nerves are typically embedded non-uniformly among visceral and connective tissues with complex interfacing requirements.

Feasibility of kilohertz frequency alternating current neuromodulation of carotid sinus nerve activity in the pig.

Recent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. Supressing carotid body signalling through carotid sinus nerve (CSN) modulation may offer a therapeutic approach for treating such diseases. Here we anatomically and histologically characterised the CSN in the farm pig as a recommended path to translational medicine.

Acceptability and performance of a nonwoven device for vaginal drug delivery among women and their male partners in KwaZulu-Natal, South Africa.

Multipurpose prevention technologies are needed to provide protection against HIV and sexually transmitted infections. Gel-based vaginal microbicides inserted via an applicator are prone to leakage. A novel device for vaginal drug delivery was developed to contain gel-based formulations, aiming to improve gel retention and reduce leakage.

Modeling the impact of novel male contraceptive methods on reductions in unintended pregnancies in Nigeria, South Africa, and the United States.

Objective: We modeled the potential impact of novel male contraceptive methods on averting unintended pregnancies in the United States, South Africa, and Nigeria.

Study Design: We used an established methodology for calculating the number of couple-years of protection provided by a given contraceptive method mix. We compared a "current scenario" (reflecting current use of existing methods in each country) against "future scenarios," (reflecting whether a male oral pill or a reversible vas occlusion was introduced) in order to estimate the impact on unintended pregnancies averted.

Men's Understanding of and Experiences During the Postcircumcision Abstinence Period: Results From a Field Study of ShangRing Circumcision During Routine Clinical Services in Kenya and Zambia.

Background: Men's understanding of counseling messages after voluntary medical male circumcision (VMMC) plays an important role in whether they follow them. Data on triggers for early resumption of sex may be useful as scale-up of VMMC for HIV prevention continues in sub-Saharan Africa.

Methods: Data on understanding of post-VMMC abstinence recommendations, resumption of sex, condom use, and triggers for resuming sex were collected from participants during a follow-up interview 35-42 days after ShangRing circumcision in Kenya and Zambia.

Acceptability of a nipple shield delivery system administering antiviral agents to prevent mother-to-child transmission of HIV through breastfeeding.

Background: Breastfeeding is a route of mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV). The World Health Organization recommends antiretroviral (ARV) prophylaxis as the best method to prevent mother-to-child transmission of HIV (PMTCT) during breastfeeding. The nipple shield delivery system (NSDS) is being developed as an accessible method to deliver ARVs to infants and PMTCT during breastfeeding.

Field study of adult male circumcision using the ShangRing in routine clinical settings in Kenya and Zambia.

Background: Circumcision devices can facilitate adult voluntary medical male circumcision programs for HIV prevention. The World Health Organization recommends field studies to confirm the safety of devices in local settings.

Methods: We evaluated the safety of the ShangRing device in routine service delivery by measuring adverse event (AE) rates overall and by HIV status.

Randomized controlled trial of the shang ring versus conventional surgical techniques for adult male circumcision: safety and acceptability.

Objective: To compare clinical profiles of Shang Ring versus conventional circumcisions.

Design: Parallel group open-label randomized controlled trial with one-to-one allocations in 2 sites.

Methods: We enrolled HIV-negative men aged 18-54 years in Homa Bay, Kenya, and Lusaka, Zambia and followed them at 2, 7, 14, 21, 28, 42, and 60 days after Shang Ring versus conventional circumcision.

Vitamin K deficiency bleeding and early infant male circumcision in Africa.

Background: Early infant (1-60 days of life) male circumcision is being trialed in Africa as a human immunodeficiency virus prevention strategy. Postcircumcision bleeding is particularly concerning where most infants are breastfed, and thus these infants are at increased risk of vitamin K deficiency bleeding.

Case: During a circumcision trial, one infant bled for 90 minutes postprocedure.

Criticisms of African trials fail to withstand scrutiny: male circumcision does prevent HIV infection.

A recent article in the JLM (Boyle GJ and Hill G, "Sub-Saharan African Randomised Clinical Trials into Male Circumcision and HIV Transmission: Methodological, Ethical and Legal Concerns" (2011) 19 JLM 316) criticises the large randomised controlled trials (RCTs) that scientists, clinicians and policy-makers worldwide have concluded provide compelling evidence in support of voluntary medical male circumcision (VMMC) as an effective HIV prevention strategy. The present article addresses the claims advanced by Boyle and Hill, demonstrating their reliance on outmoded evidence, outlier studies, and flawed statistical analyses. In the current authors' view, their claims portray misunderstandings of the design, execution and interpretation of findings from RCTs in general and of the epidemiology of HIV transmission in sub-Saharan Africa in particular.

Vasectomy: AUA guideline.

Purpose: The purpose of this guideline is to provide guidance to clinicians who offer vasectomy services.

Materials And Methods: A systematic review of the literature using the search dates January 1949-August 2011 was conducted to identify peer-reviewed publications relevant to vasectomy. The search identified almost 2,000 titles and abstracts.

Strengthening vasectomy services in Rwanda: introduction of thermal cautery with fascial interposition.

Background: Recent developments in vasectomy research indicate that occluding the vas using cautery combined with fascial interposition (FI) significantly lowers failure rates and is an appropriate technology for low-resource settings. We report the introduction of this technique in Ministry of Health (MOH) vasectomy services in Rwanda.

Design: In February 2010, an international vasectomy expert trained three Rwandan physicians to become trainers in no-scalpel vasectomy (NSV) with thermal cautery and FI.

Comparative efficacy of postpartum sterilisation with the titanium clip versus partial salpingectomy: a randomised controlled trial.

A multicentre trial was conducted to compare efficacy of postpartum sterilisation with clip and partial salpingectomy. Life-table estimates of pregnancy probabilities were compared through 2 years of follow up. A significantly different risk of pregnancy between the clip and partial salpingectomy groups was observed.

Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.

Background: Tenofovir gel, used vaginally before and after coitus, reduced women's acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters.

Methods: In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel.

A nipple shield delivery system for oral drug delivery to breastfeeding infants: microbicide delivery to inactivate HIV.

A new drug delivery method for infants is presented which incorporates an active pharmaceutical ingredient (API)-loaded insert into a nipple shield delivery system (NSDS). The API is released directly into milk during breastfeeding. This study investigates the feasibility of using the NSDS to deliver the microbicide sodium dodecyl sulfate (SDS), with the goal of preventing mother-to-child transmission (MTCT) of HIV during breastfeeding in low-resource settings, when there is no safer alternative for the infant but to breastfeed.

Reproductive factors in relation to ovarian cancer: a case-control study in Northern Vietnam.

Background: Ovarian cancer, one of the most common cancers in women and the most serious gynecologic cancer, is known to be influenced by reproductive factors, but these factors have not previously been examined in Vietnamese women.

Study Design: We analyzed 262 ovarian cancer patients recruited from 27 hospitals in 12 provinces and Ha Noi City from April 2001 to May 2006, plus 755 controls matched by age and residential address.

Results: The risk of ovarian cancer was significantly lower in parous women than nulliparous women.

Randomized trial of the Shang Ring for adult male circumcision with removal at one to three weeks: delayed removal leads to detachment.

Objectives: To assess healing with Shang Ring removal at different prespecified times; whether spontaneous detachment occurs with delayed removal; problems, complaints, and acceptability of wearing the device; satisfaction among participants; and acceptability of the procedure among providers.

Methods: Fifty HIV-negative men underwent a Shang Ring circumcision in Kenya. Men were randomly assigned for device removal at 7 (15 men), 14 (15 men), or 21 days (20 men).

Therapeutic ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system.

Background: Studies published in the 1970s by Mostafa S. Fahim and colleagues showed that a short treatment with ultrasound caused the depletion of germ cells and infertility. The goal of the current study was to determine if a commercially available therapeutic ultrasound generator and transducer could be used as the basis for a male contraceptive.