Prevention of vertical transmission of HIV in Khayelitsha, South Africa: A contemporary review of services after 20 years.

BACKGROUND: The first vertical transmission of HIV prevention (VTP) programme in South Africa was launched in 1999 in Khayelitsha, Western Cape Province (WC). Since then, VTP guidelines have expanded in complexity and scope. OBJECTIVES: To describe contemporary VTP uptake in Khayelitsha and quantify vertical transmission (VT) risk factors based on linked routine electronic health data. METHODS: In the WC, all patients at public health facilities have a unique identifier allowing linkage across electronic health platforms through a health information exchange hosted within the WC Department of Health. We conducted a cohort analysis of mother-infant pairs where the mother was living with HIV and attended any obstetric care in Khayelitsha in 2017. Descriptive statistics assessed VTP coverage along the care cascade, including maternal viral load (VL) testing and early infant diagnosis (EID). Logistic regression analysis quantified a priori-defined risk factors associated with VT. RESULTS: Antenatal HIV prevalence in the cohort was 31.3%, and VT was 1.8% by 12 months. Of women living with HIV, 88.3% knew of their positive status at the first antenatal visit and 77.9% were already receiving antiretroviral therapy (ART). Most women diagnosed prior to delivery (94.5%) were initiated on ART; 85.0% received an antenatal VL test, of whom 88.0% were virologically suppressed. Women who were not virally suppressed had a five-fold (adjusted odds ratio (aOR) 5.3; 95% confidence interval (CI) 2.5 - 12.3) increased VT risk compared with those who were suppressed. Women who attended no antenatal care were at higher risk of VT (aOR 1.6; 95% CI 0.7 - 3.6) than those who did attend. EID coverage was suboptimal: a birth HIV polymerase chain reaction (PCR) test was available for 79.2% of infants, and a low proportion with a negative birth test had a repeat test around 10 weeks (57.9%). Data linkage identified an additional 15 infants living with HIV who were not detected by HIV-PCR testing alone. CONCLUSION: Although most women presented to care already knowing their HIV status, ART initiation was suboptimal prior to the first antenatal visit but improved over the course of pregnancy. The VT rate based on laboratory HIV-PCR testing alone underestimated HIV transmission: linked data from multiple sources suggested higher VT than programme-reported rates based on HIV-PCR testing alone.

Too stressed to eat: Investigating factors associated with appetite loss in subordinate rainbow trout.

Juvenile rainbow trout (Oncorhynchus mykiss) form dominance hierarchies in which subordinates experience chronic social stress and suppression of food intake. Here we tested the hypothesis that inhibition of food intake reflects increased expression of anorexigenic (appetite inhibiting) signals and decreased expression of orexigenic (appetite stimulating) signals. Trout were confined in pairs for 1 or 4 days, or were confined in pairs for 4 days and then allowed to recover from social interactions for 2 or 4 days; sham fish were handled identically but held alone. Subordinates did not feed during social interaction and had lower food intake than dominants or shams during recovery. In parallel, plasma cortisol (∼18-26x) and liver leptin (lep-a1) transcript abundance (∼10-14x) were elevated in subordinates during social interaction but not recovery, suggesting that these factors contributed to the suppression of food intake. Fish deemed likely to become subordinate based on inhibition of food intake in response to a mild stressor also showed elevated liver lep-a1 transcript abundance (∼5x). The moderate response in these fish coupled with a correlation between liver lep-a1 and cortisol suggest that stress-induced elevation of cortisol increased liver lep-a1 transcript abundance in subordinate trout, contributing to stress-induced suppression of food intake.

Bovine dopamine type-2 receptor SNP has no effect on growth, semen characteristics and prolactin concentrations in beef bulls treated with a dopamine agonist.

A dopamine type-2 receptor (DRD2) SNP, previously found to be correlated with serum prolactin (PRL) concentrations in cattle, was evaluated for impact on growth traits, serum prolactin concentration, and semen quality. Over a four-year period, yearling beef bulls were allowed diets containing or lacking ergot alkaloids (EA). Every 21 or 28 d semen was collected for semen motility and morphology assessment and blood samples were collected to measure serum PRL concentrations. In addition, body condition score and scrotal circumference were evaluated. Serum PRL concentrations were assessed using a radioimmunoassay. In the first year, all bulls were sacrificed at the end of a 126-day study. Testicles and epididymis were collected at the end of the study or 60 days after removal from treatment. Immunohistochemistry was performed on testis, epididymis, and sperm cells, incubated with or without a primary antibody for DRD2 and counterstained with DAPI. Isolation of DNA was performed on sperm pellets using DNAzol (Thermo Fisher Scientific, Waltham, MA, USA) methods. Polymerase chain reaction was performed to amplify the region of the DRD2 gene containing the SNP of interest. The products were subjected to restriction fragment length polymorphism analysis. Further, all samples were subjected to genotyping using a custom Taqman genotyping assay (Applied Biosystems, Foster city, CA, USA). The presence of DRD2 was detected in the testis, epididymis, and sperm cells. The DRD2 genotype was not associated with semen quality, serum PRL, or growth traits. Consumption of EA resulted in lesser PRL serum concentrations but had no effect on values for other variable examined.

Progression and stop organization reveals conservation of movement organization during dark exploration across rats and mice.

Spatial orientation is a ubiquitous feature of animal behavior. Environmental and self-movement cues are sources of information used to maintain spatial orientation. The literature has typically focused on differences between mice and rats using environmental cues to guide movement. The current study uses the organization of exploratory behavior under dark conditions to investigate species differences in self-movement cue processing. Mouse and rat exploratory behavior was recorded under dark conditions on a circular table without walls. The resulting movements were segmented in progressions (movement ≥ 3 cm/s) and stops (movement < 3 cm/s). Mice exhibited longer travel distances, faster progression peak speeds, and weaker tendency to scale progression peak speeds to Euclidean distances relative to rats. In contrast, similar levels of performance were observed on measures (progression path circuity, change in heading, stability of stopping behavior) sensitive to vestibular pathology. These results are consistent with species differences in a variety of performance variables; however, self-movement cue based spatial orientation did not differentiate between mice and rats. This work establishes a translational foundation for future work investigating the neurobiology of self-movement cue processing using species-unique neuroscience techniques.

Gonadotrophin-inhibitory hormone and its mammalian orthologue RFamide-related peptide-3: Discovery and functional implications for reproduction and stress.

At the turn of the millennium, a neuropeptide with pronounced inhibitory actions on avian pituitary gonadotrophin secretion was identified and named gonadotrophin-inhibitory hormone (GnIH). Across bird species, GnIH acts at the level of the pituitary and the gonadotrophin-releasing hormone (GnRH) neuronal system to inhibit reproduction. Subsequent to this initial discovery, orthologues of GnIH have been identified and characterised across a broad range of species. In many vertebrates, the actions of GnIH and its orthologues serve functional roles analogous to those seen in birds. In other cases, GnIH and its orthologues exhibit more diverse actions dependent on sex, species, season and reproductive condition. The present review highlights the discovery and functional implications of GnIH across species, focusing on research domains in which the significance of this neuropeptide has been explored most.

Post-Laryngectomy stricture and pharyngocutaneous fistula: Review of techniques in primary pharyngeal reconstruction in laryngectomy.

OBJECTIVE: The purpose of this study was to find a correlation between closure technique in pharyngeal closure and outcomes of both pharyngocutaneous fistula and post-laryngectomy stricture after laryngectomy. STUDY DESIGN: Retrospective Chart Review. METHODS: We retrospectively reviewed a total of 151 patients over a 20-year period from January 1994 to December of 2013 who underwent primary pharyngeal reconstruction after total laryngectomy specifically looking at the closure technique in relation to pharyngo-cutaneous fistula (PCF) and post-laryngectomy stricture postoperatively. Patients were excluded based on secondary pharyngeal closure. Using logistic regression modelling, we performed univariate and multivariate analyses of our data. RESULTS: The overall PCF and post-laryngectomy stricture rates were 19.1% and 15.8%. When salvage laryngectomy was excluded, t-type closure had a significantly lower risk of fistula rate (P=.038) compared to vertical closure. In multivariate analysis, this statistical significance was lost (P=.23); however, non-salvage t-type closure remained significantly better than both salvage laryngectomy groups (t-type, P=.033, vertical, P=.037), while non-salvage vertical closure had no significant difference from other groups. There was no difference in stricture rate between the two closure techniques (P=.63). CONCLUSION: Our study supports the role of t-type closure decreasing fistula rates in primary pharyngeal reconstruction. Orientation of the pharyngeal closure does not appear to change the risk of post-laryngectomy stricture formation after total laryngectomy. Salvage laryngectomy with primary pharyngeal reconstruction remains an independent risk factor for fistula formation.

Role of Google Glass in improving patient satisfaction for otolaryngology residents: a pilot study.

OBJECTIVES: To demonstrate the feasibility and efficacy of the Google Glass as a tool to improve patient satisfaction and patient-physician communication for otolaryngology residents in the outpatient clinic setting. The primary outcome of the study was to improve patient satisfaction scores based on physician communication-related questions from Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys. STUDY DESIGN: Prospective randomised trial. SETTING: Tertiary care hospital. SUBJECT AND METHODS: To evaluate the effect on patient satisfaction, five residents were recorded using the Google Glass in an outpatient clinic setting by 50 randomised patients. Modified surveys based on the CG-CAHPS survey were completed by patients at the conclusion of each clinic encounter. The recorded videos were evaluated by two independent faculties. Summarised data and video were distributed to each resident for review as the intervention. The residents were recorded again by 45 additional patients with evaluation by patients and faculties. RESULTS: After intervention, the scores from faculty surveys regarding patient satisfaction including the subject of better explanations (P > 0.001), listening carefully (P > 0.001), addressing patient questions (P > 0.001), displaying respect (P > 0.001) and spending adequate time (P = 0.0005) all significantly improved, as well as overall performance (P = 0.014). The scores from patient surveys did significantly improve. CONCLUSION: This study demonstrates the improvements in patient satisfaction and patient-physician communication can be achieved with the use of Google Glass as a first-person recording device in the outpatient otolaryngology clinic setting.

Emtonjeni-A Structural Intervention to Integrate Sexual and Reproductive Health into Public Sector HIV Care in Cape Town, South Africa: Results of a Phase II Study.

Integration of sexual and reproductive health within HIV care services is a promising strategy for increasing access to family planning and STI services and reducing unwanted pregnancies, perinatal HIV transmission and maternal and infant mortality among people living with HIV and their partners. We conducted a Phase II randomized futility trial of a multi-level intervention to increase adherence to safer sex guidelines among those wishing to avoid pregnancy and adherence to safer conception guidelines among those seeking conception in newly-diagnosed HIV-positive persons in four public-sector HIV clinics in Cape Town. Clinics were pair-matched and the two clinics within each pair were randomized to either a three-session provider-delivered enhanced intervention (EI) (onsite contraceptive services and brief milieu intervention for staff) or standard-of-care (SOC) provider-delivered intervention. The futility analysis showed that we cannot rule out the possibility that the EI intervention has a 10 % point or greater success rate in improving adherence to safer sex/safer conception guidelines than does SOC (p = 0.573), indicating that the intervention holds merit, and a larger-scale confirmatory study showing whether the EI is superior to SOC has merit.

An integrated community TB-HIV adherence model provides an alternative to DOT for tuberculosis patients in Cape Town.

SETTING: Cape Town, South Africa. OBJECTIVE: To evaluate anti-tuberculosis treatment outcomes and rate of antiretroviral therapy (ART) initiation using weekly community-based adherence support compared to daily directly observed therapy (DOT). METHODS: This was a retrospective analysis comparing two cohorts treated for tuberculosis (TB) in 70 TB clinics during 6-month periods before and after the introduction of a new adherence model comprising treatment literacy sessions during 2 weeks of DOT, followed by weekly home visits by community care workers to eligible patients managing their own treatment. Odds ratios (ORs) of treatment success and ART initiation were calculated using multivariable random effects logistic regression models. Hazard ratios (HRs) of default and death were calculated using multivariable random effects Cox regression models. RESULTS: The pre-intervention cohort comprised 11 896 patients with TB and the post-intervention cohort 11 314. There was no difference in pre- and post-intervention anti-tuberculosis treatment success rates (respectively 82.8% and 82.5%, adjusted OR [aOR] 1.02, 95%CI 0.89-1.17, P = 0.76) nor an increased hazard of death (adjusted HR [aHR] 0.98, 95%CI 0.80-1.21, P = 0.87) or default (aHR 0.97, 95%CI 0.81-1.15, P = 0.69). The ART initiation rate increased from 67% to 74% (aOR 1.43; 95%CI 1.01-1.85, P < 0.01). CONCLUSION: Weekly community-based adherence support was a viable alternative to daily DOT, with no deterioration in anti-tuberculosis treatment outcomes and an increase in ART initiation.

Integration of TB and ART services fails to improve TB treatment outcomes: comparison of ART/TB primary healthcare services in Cape Town, South Africa.

BACKGROUND: The combined tuberculosis (TB) and HIV epidemics in South Africa (SA) have created enormous operational challenges for a health service that has traditionally run vertical programmes for TB treatment and antiretroviral therapy (ART) in separate facilities. This is particularly problematic for TB/HIV co-infected patients who need to access both services. OBJECTIVE: To determine whether integrated TB facilities had better TB treatment outcomes than single-service facilities in Cape Town, SA. METHODS: TB treatment outcomes were determined for newly registered, adult TB patients (aged > or = 18 years) at 13 integrated ART/TB primary healthcare (PHC) facilities and four single-service PHC facilities from 1 January 2009 to 30 June 2010. A chi2 test adjusted for a cluster sample design was used to compare outcomes by type of facility. RESULTS: Of 13,542 newly registered patients, 10,030 received TB treatment in integrated facilities and 3,512 in single-service facilities. There was no difference in baseline characteristics between the two groups with HIV status determined for 9,351 (93.2%) and 3,227 (91.9%) patients, of whom 6 649 (66.3%) and 2,213 (63%) were HIV-positive in integrated facilities and single-service facilities, respectively. The median CD4+ count of HIV-positive patients was 152 cells/microl (interquartile range (IQR) 71-277) for integrated facilities and 148 cells/microl (IQR 67-260) for single-service facilities. There was no statistical difference in the TB treatment outcome profile between integrated and single-service facilities for all TB patients (p = 0.56) or for the sub-set of HIV-positive TB patients (p = 0.58) CONCLUSION: This study did not demonstrate improved TB treatment outcomes in integrated PHC facilities and showed that the provision of ART in the same facility as TB services was not associated with lower TB death and default rates.

Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle.

Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups (P < 0.05). However, the ingestion of the protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein (P < 0.05). Postexercise myofibrillar protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein.

Isotopic decay of urinary or plasma 3-methylhistidine as a potential biomarker of pathologic skeletal muscle loss.

BACKGROUND: Skeletal muscle loss accompanying aging or cancer is associated with reduced physical function and predicts morbidity and mortality. 3-Methylhistidine (3MH) has been proposed as a biomarker of myofibrillar proteolysis, which may contribute to skeletal muscle loss. METHODS: We hypothesized that the terminal portion of the isotope decay curve following an oral dose of isotopically labeled 3MH can be measured non-invasively from timed spot urine samples. We investigated the feasibility of this approach by determining isotope enrichment in spot urine samples and corresponding plasma samples and whether meat intake up to the time of dosing influences the isotope decay. RESULTS: Isotope decay constants (k) were similar in plasma and urine, regardless of diet. Post hoc comparison of hourly sampling over 10 h with three samples distributed over 10 or fewer hours suggests that three distributed samples over 5-6 h of plasma or urine sampling yield decay constants similar to those obtained over 10 h of hourly sampling. CONCLUSION: The findings from this study suggest that an index of 3MH production can be obtained from an easily administered test involving oral administration of a stable isotope tracer of 3MH followed by three plasma or urine samples collected over 5-6 h the next day.

Tuberculosis cases missed in primary health care facilities: should we redefine case finding?

SETTING: This study was conducted in Cape Town in two primary health care facilities in a sub-district with a high prevalence of bacteriologically confirmed pulmonary tuberculosis (TB). OBJECTIVE: To determine the proportion of adults with respiratory symptoms who attend health care facilities but are not examined for nor diagnosed with TB in facilities where routine TB diagnosis depends on passive case finding. DESIGN: A total of 423 adults with respiratory symptoms exiting primary health care services were consecutively enrolled during April-July 2011. RESULTS: Twenty-one (5%) participants were diagnosed with culture-positive TB. None had sought care at the facility for their respiratory symptoms, none were asked about respiratory symptoms during their visit and none were asked to produce a sputum sample. Nine cases had attended the facility for reasons regarding their own health, while 12 cases were accompanying someone else attending the facility, or for another reason. CONCLUSION: Patients with infectious TB attend primary health care facilities, but are not recognised and diagnosed as cases. Health care staff should search actively within facilities for cases who attend the health care services to ensure that cases are not missed. Intensified case finding should start within the facility, and should not be limited to patients who report respiratory symptoms or who are human immunodeficiency virus positive.

Gender differences in binge eating and behavioral correlates among college students.

PURPOSE: The purpose of this study was to investigate gender differences in binge eating and associated behavioral correlates in college students. METHODS: A webbased survey was conducted with 2073 students (mean age 19.8 yr; range 18-23 yr). Multiple logistic regression was used to calculate odds ratios and 95% confidence intervals for the factors associated with binge eating. RESULTS: Twenty-nine percent of students reported recent bingeing. Factors associated with binge eating included being female, having a higher body mass index, current tobacco use, and exercising to lose weight. Women were more likely to binge eat (73.8%; χ(2)=32.3; p≤0.001), report loss of control (45%; χ(2)=16.3; p≤0.001), self induced vomiting (20.7%; χ(2)=15.9; p≤0.001), and laxative use (6.7%; χ(2)=8.93; p≤0.001). CONCLUSIONS: Results generated from this study suggest that gender-disparate behaviors are potential targets for future tailored interventions.

Mice overexpressing the 5-hydroxytryptamine transporter show no alterations in feeding behaviour and increased non-feeding responses to fenfluramine.

RATIONALE: The 5-HT transporter (5-HTT) is implicated in the regulation of appetite. Expression of the 5-HTT varies in the human population, and this variation may determine both individual differences in feeding and abnormal feeding behaviours such as eating disorders. OBJECTIVES: The effects of 5-HTT expression on feeding and satiety were examined in a transgenic mouse model of 5-HTT overexpression. MATERIALS AND METHODS: We measured free-feeding food intake and observed the behavioural satiety sequence (BSS) after food deprivation in mice at baseline and after administration of the anorectic drug fenfluramine. RESULTS: 5-HTT overexpressing mice were both lighter and shorter than their wildtype littermates. Despite this size difference, food intake by transgenic and wildtype mice did not differ. There was no effect of genotype on the BSS or on food intake during the test at baseline. Increasing doses of fenfluramine reduced food intake in a similar manner in both transgenic and wildtype mice. After 0.3 and 1 mg/kg fenfluramine, the temporal pattern of the BSS was the same for both groups, whereas 3 and 10 mg/kg fenfluramine disrupted the BSS. In transgenic mice, this disruption was evident at the 3 mg/kg dose, while in wildtypes, it emerged only at the 10-mg/kg dose. CONCLUSION: These data suggest that overexpression of the 5-HTT does not lead to alterations in feeding or satiety in food-deprived mice but does increase the occurrence of other non-feeding behaviours in response to the 5-HT releasing agent fenfluramine.

Evidence that genetic variation in 5-HT transporter expression is linked to changes in 5-HT2A receptor function.

Variability in expression of the 5-HT transporter (5-HTT) gene in the human population has been associated with a range of behavioural phenotypes. The underlying mechanisms are unclear but may involve changes in 5-HT receptor levels and/or signalling. The present study used a novel 5-HTT overexpressing transgenic mouse to test the hypothesis that variability in 5-HTT expression may alter 5-HT(2A) receptor function. In wildtype mice, the 5-HT(2) receptor agonist DOI increased regional brain mRNA expression of two immediate early genes (c-fos and Arc), and induced head twitches, and both effects were abolished by pre-treatment with the 5-HT(2A) receptor antagonist MDL 100907. In 5-HTT overexpressing mice, DOI induced a greater increase in both c-fos and Arc mRNA expression in cortical brain regions, and more head twitches, compared to wildtype mice. Autoradiographic and in situ hybridisation experiments showed that 5-HT(2A) receptor binding sites and 5-HT(2A) receptor mRNA did not differ between transgenic and wildtype mice. Finally, the transgenic mice had lower regional brain 5-HT levels compared to wildtype mice. This depletion of 5-HT may underpin the increase in 5-HT(2A) receptor function because in wildtype mice 5-HT depletion using the 5-HT synthesis inhibitor, p-chlorophenylalanine, enhanced the head twitch response to DOI. These data demonstrate that elevated 5-HTT expression is accompanied by increased 5-HT(2A) receptor function, an effect possibly mediated by decreased availability of synaptic 5-HT. Variation in levels of 5-HTT expression may therefore be a source of variability in 5-HT(2A) receptor function, which may be an important modifier of 5-HTT-linked phenotypes.

Hospital volume of throughput and periprocedural and medium-term adverse events after percutaneous coronary intervention: retrospective cohort study of all 17,417 procedures undertaken in Scotland, 1997-2003.

OBJECTIVE: To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium-term events, and whether any associations are independent of differences in case mix. DESIGN: Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six-year period. METHODS: All PCIs in Scotland during 1997-2003 were examined. Linkage to administrative databases identified events over two years' follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. RESULTS: Of the 17,417 PCIs, 4900 (28%) were in low-volume hospitals and 3242 (19%) in high-volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high-volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p = 0.002). Over two years, patients in high-volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p = 0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. CONCLUSION: Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high-volume hospitals. Over two years, patients treated in high-volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery.