Utility of urine and serum lateral flow assays to determine the prevalence and predictors of cryptococcal antigenemia in HIV-positive outpatients beginning antiretroviral therapy in Mwanza,Tanzania

Background

Detection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV-positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre-emptively. Recently developed point-of-care cryptococcal antigen tests may be useful for screening, particularly in resource-limiting settings, but few studies have assessed their utility.

Methodology

The objectives of this study were to determine the prevalence and factors associated with cryptococcal antigenemia in HIV-positive patients with CD4⁺ T-cell counts ≤200 cells/µL who were initiating ART, and also to evaluate the utility of the point-of-care urine lateral flow assay (LFA) cryptococcal antigen test using two different diluents, compared to gold standard serum antigen testing, as a screening tool. Urine and serum of outpatients initiating antiretroviral therapy at two hospitals in Mwanza were tested for cryptococcal antigen, and demographic and clinical characteristics were obtained using structured questionnaires and patients’ files. Patients with asymptomatic cryptococcal antigenemia received oral fluconazole in accordance with World Health Organization recommendations.

Results

Among 140 patients screened, 10 (7.1%) had asymptomatic cryptococcal antigenemia with a positive serum cryptococcal antigen. Four of these ten patients had CD4 counts between 100 and 200 cells/µL. The prevalence of cryptococcal antigen detected in urine using a standard (older) and a test (newer) diluent were 44 (31.4%) and 19 (13.6%), with Kappa coefficients compared to serum of 0.28 and 0.51 (p<0.001 for both). Compared to the new LFA diluent for urine cryptococcal antigen, the standard diluent had higher sensitivity (100% versus 80%) but lower specificity (74% versus 92%) using serum cryptococcal antigen as a gold standard.

Conclusions

Our findings suggest that HIV-positive outpatients with CD4 counts <200 cells/µL, rather than 100, should be screened for asymptomatic cryptococcal antigenemia given its association with mortality if untreated. Agreement of the urine LFA with the serum LFA was not sufficient to recommend routine screening with urine LFA.     

Vesical calculus formation on non-absorbable sutures used for open inguinal hernia repair

INTRODUCTION

Iatrogenic injuries to the urogenital tract are rare, with the bladder being the organ most affected. We describe a case of a vesical calculus that formed on non-absorbable sutures that were used to repair an inguinal hernia.

PRESENTATION OF CASE

A 45-year-old male presented with frank haematuria and dysuria 2 years following an open left inguinal hernia repair. A CT urography showed a vesical calculus adherent to the left anterio-lateral wall of the bladder. Cystoscopy revealed that the calculus formed on non-absorbable sutures. Cystolapaxy was performed followed by cystoscopic excision of the sutures. The patient''s post-operative course was uneventful.

DISCUSSION

Foreign bodies in the urinary bladder always act as a nidus for formation of a calculus. Iatrogenic bladder injuries are common during hernia repair. It is however rare for sutures used to repair an inguinal hernia to involve the urinary bladder wall. The patient most likely had a full bladder at the time of hernia repair or the bladder was part of the contents of the hernia sac.

CONCLUSION

This case illustrates the need to ensure that the bladder is empty prior to pelvic surgery and for surgeons to have a good understanding of inguinal anatomy to avoid injuring the contents of the hernia sac.     

An Analysis of Sodium,Total Fat and Saturated Fat Contents of Packaged Food Products Advertised in Bronx-Based Supermarket Circulars

Americans’ consumption of sodium, fat, and saturated fat exceed federally recommended limits for these nutrients and has been identified as a preventable leading cause of hypertension and cardiovascular disease. More than 40 % of the Bronx population comprises African–Americans, who have increased risk and earlier onset of hypertension and are also genetically predisposed to salt-sensitive hypertension. This study analyzed nutrition information for packaged foods advertised in Bronx-based supermarket circulars. Federally recommended limits for sodium, saturated fat and total fat contents were used to identify foods that were high in these nutrients. The proportion of these products with respect to the total number of packaged foods was calculated. More than a third (35 %) and almost a quarter (24 %) of the 898 advertised packaged foods were high in saturated fat and sodium respectively. Such foods predominantly included processed meat and fish products, fast foods, meals, entrees and side dishes. Dairy and egg products were the greatest contributors of high saturated fat. Pork and beef products, fast foods, meals, entrees and side dishes had the highest median values for sodium, total fat and saturated fat content. The high proportion of packaged foods that are high in sodium and/or saturated fat promoted through supermarket circulars highlights the need for nutrition education among consumers as well as collaborative public health measures by the food industry, community and government agencies to reduce the amounts of sodium and saturated fat in these products and limit the promotion of foods that are high in these nutrients.     

Tanzanian Adolescent Boys’ Transitions Through Puberty: The Importance of Context

We explored the masculinity norms shaping transitions through puberty in rural and urban Tanzania and how these norms and their social-ecological context contribute to high-risk health behaviors. We conducted a qualitative case study of adolescent boys in and out of school in 2011 and 2012. Tanzania’s social and economic development is reshaping the transition into young manhood. Adolescent boys are losing traditional mechanisms of pubertal guidance, and new meanings of manhood are arising from globalization. Traditional masculinity norms, including pressures to demonstrate virility and fertility, remain strong. Adolescent boys in modernizing Tanzania receive inadequate guidance on their burgeoning sexuality. Contradictory masculinity norms from family and society are shaping their sexual expectations, with implications for their engagement in unsafe sexual behaviors.Inadequate attention has been paid to adolescent boys’ transitions through puberty in the context of the rapidly changing social norms and contexts of many sub-Saharan African countries, including Tanzania.1,2 Significant attention and resources have focused on adolescent girls aged 15 years and older because of their increased vulnerability to HIV and other sexually transmitted infections, unplanned pregnancy, and gender-based violence. Adolescent boys have their own unique health needs and challenges,3 such as increased risks of injury; engagement in violence; abuse of alcohol, tobacco, and other drugs; and risky sexual behaviors.1,4 Adolescent boys’ and young men’s behaviors may also significantly affect the sexual and reproductive health of adolescent girls and young women.Tanzania, like other sub-Saharan African countries, has undergone significant social upheaval in recent decades. Participation in traditional practices, such as puberty rites and ceremonies, has declined; extended-family structures have changed because of migration to cities and the devastatingly high mortality toll of HIV/AIDS5; and globalization and modernization have brought an influx of new ideas and images. These factors are reshaping the contexts in which adolescent Tanzanian boys transition into young adulthood.6,7 It is important to understand how such changes influence boys’ growing-up experiences, including the masculinity norms shaping their perceptions of manhood and sexuality, to develop effective interventions that promote healthy transitions into adulthood and reduce unsafe sexual behaviors.In many sub-Saharan African countries, girls reaching puberty experience new controls imposed on their burgeoning sexuality.8,9 One reason is their perceived vulnerability to pregnancy and its implications for their marriageability and for family honor.10 By contrast, postpubescent boys are likely to be encouraged, or even expected, to demonstrate their virility (not necessarily through safe sex practices).11 The expression of any qualities that can be interpreted as feminine may be verbally if not physically suppressed.12 Heteronormativity, at least in public, is often the strongly reinforced and desired sign of manhood, and it frequently encompasses engagement in sexual relations and dominance over girls and women.13Growing evidence suggests that early adolescence may be an important window of opportunity for health interventions affecting the transition into young manhood.14,15 This is partially because of the increased intensity of gendered norms focused on young people during puberty (as compared with younger children) and the perceived possibility of reshaping norms that may play a role in high-risk health behaviors.16 Little is known about the masculinity norms and other contextual influences shaping adolescent boys’ perceptions of becoming a man in a modernizing society such as Tanzania, but these may contribute to risky behaviors that endanger health. We have even less evidence on the perspectives of adolescent boys themselves about the influences shaping their participation in and decision-making about safe or unsafe sexual behaviors.Tanzania is a large East African country with an estimated population of 48 million, of whom almost 65% are younger than 24 years.17 More than 120 ethnic groups reside in the country, and Christianity and Islam are the predominant religions. Overall, 2.0% of adolescents and young men and women (aged 15–24 years) are HIV positive, with the likelihood of infection with HIV increasing with age: among persons aged 23 to 24 years, young women are more than twice as likely as young men to be infected (6.6% vs 2.8%).18,19 The increasing prevalence rates with age emphasize the importance of improving prevention efforts with adolescents. The few prevention initiatives that have included adolescent boys have also relied on limited evidence about young people''s sexual maturation experiences in a changing society.We conducted an in-depth study with adolescent boys in rural and urban Tanzania. We sought to explore, from the perspectives of adolescent boys themselves, their experiences of puberty and their interpretations of manhood in their changing social context. We (1) compared an urban to a rural context, which was important because of expected differences in traditional practices regarding puberty; (2) examined the predominant and alternative local masculinity norms being shaped simultaneously by tradition and modernization; and (3) assessed the globalizing influences shaping adolescent boys’ perceptions of manhood and sexuality, such as mass media, the Internet, and global marketing (e.g., alcohol companies). We hypothesized that influences from globalization and modernization create experiences of adolescence that conflict with traditional expectations of young manhood, particularly in urban contexts.We used an ecological framework of adolescent health20 to assess the multiple levels of influence shaping Tanzanian adolescent boys’ transitions through puberty today, particularly those that affect high-risk behaviors.21 We examined historical and cultural norms related to manhood at the societal level, along with adolescent boys'' interpersonal interactions and individual-level experiences. The conceptual framework guided an exploration of adolescent boys'' emotional and physical experiences among their families and peers, in school and in the larger community, along with the norms shaping their perceptions of manhood. We applied the theory of the social construction of gender to better understand the ways adolescent boys’ gendered experiences within their own identities, and among their peers, families, and communities, shaped their perceptions and experiences of young manhood.22,23     

Stat3 mediates LIF‐induced protection of astrocytes against toxic ROS by upregulating the UPC2 mRNA pool

Reactive oxygen species (ROS) have been implicated in various types of CNS damage, including stroke. We used a cultured astrocyte model to explore mechanisms of survival of CNS cells following ROS damage. We found that pretreatment with leukemia inhibitory factor (LIF) preserves astrocytes exposed to toxic levels of t‐BHP by inhibiting an increase in intracellular ROS following t‐BHP treatment. Astrocytes lacking functional Stat3 did not benefit from the pro‐survival or antioxidant effects of LIF. Inhibition of mitochondrial uncoupling protein 2 (UCP2) using a chemical inhibitor or siRNA abrogates the prosurvival effects of LIF, indicating a critical role for UCP2 in modulation of mitochondrial ROS production in survival following ROS exposure. LIF treatment of astrocytes results in increased UCP2 mRNA that is accompanied by an increase in Stat3 binding to the UCP2 promoter region. Although treatment with LIF alone did not increase UCP2 protein, a combination of LIF treatment and ROS stress led to increased UCP2 protein levels. We conclude that LIF protects astrocytes from ROS‐induced death by increasing UCP2 mRNA, allowing cells to respond to ROS stress by rapidly producing UCP2 protein that ultimately decreases endogenous mitochondrial ROS production. GLIA 2014;62:159–170     

Traumatic events and their relative PTSD burden in Northern Ireland: a consideration of the impact of the ‘Troubles’

Purpose

Over a 30-year period in its recent history, daily life in Northern Ireland (NI) was characterised by civil violence, colloquially termed as the ‘Troubles’. The current report examines exposure to 29 traumatic event types and the associated conditional prevalence of post-traumatic stress disorder (PTSD) among the Northern Ireland population, with a focus on the impact of traumatic events that were characteristic of the NI ‘Troubles’.

Method

Results presented are based on analysis of data from the Northern Ireland Study of Health and Stress (NISHS). The NISHS is a representative epidemiological study of mental health among the NI adult population (N = 4,340) and part of the World Mental Health Survey Initiative.

Results

Perpetration of violence, physical assault by a spouse or partner and private events were the event types associated with the highest conditional prevalence of PTSD. Despite this elevated risk, collectively these events accounted for just 16.8 % of the overall public burden of PTSD, given their low prevalence among the general population. Events that were characteristic of civil conflict, including unexpected death of a loved one, witnessing death or a dead body or someone seriously injured and being mugged or threatened with a weapon accounted for the highest proportion of the overall public health burden of PTSD (18.6, 9.4 and 7.8 %, respectively). These findings are a feature of the higher prevalence of these events among the general population coupled with their moderate to above average risk of PTSD.

Conclusions

Despite the formal end to conflict in NI in 1999, a substantial proportion of the adult population continue to suffer the adverse mental health effects of chronic trauma exposure. Given rates of recovery of PTSD in the absence of evidence-based treatments, it is likely that the legacy of mental ill health associated with conflict, if not adequately addressed, will endure for many years.     

Contribution of the motor system to the perception of reachable space: an fMRI study

The present functional magnetic resonance imaging (fMRI) study investigates the neural correlates of reachability judgements. In a block design experiment, 14 healthy participants judged whether a visual target presented at different distances in a virtual environment display was reachable or not with the right hand. In two control tasks, they judged the colour or the relative position of the visual target according to flankers. Contrasting the activations registered in the reachability judgement task and in the control tasks, we found activations in the frontal structures, and in the bilateral inferior and superior parietal lobe, including the precuneus, and the bilateral cerebellum. This fronto‐parietal network including the cerebellum overlaps with the brain network usually activated during actual motor production and motor imagery. In a following event‐related design experiment, we contrasted brain activations when targets were rated as ‘reachable’ with those when they were rated as ‘unreachable’. We found activations in the left premotor cortex, the bilateral frontal structures, and the left middle temporal gyrus. At a lower threshold, we also found activations in the left motor cortex, and in the bilateral cerebellum. Given that reaction time increased with target distance in reachable space, we performed a subsequent parametric analysis that revealed a related increase of activity in the fronto‐parietal network including the cerebellum. Unreachable targets did not show similar activation, and particularly in regions associated to motor production and motor imagery. Taken together, these results suggest that dynamical motor representations used to determine what is reachable are also part of the perceptual process leading to the distinct representation of peripersonal and extrapersonal spaces.     

Founder effect and ancestral origin of the spinocerebellar ataxia type 7 (SCA7) mutation in Mexican families

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disease characterized by progressive cerebellar ataxia and macular degeneration causing progressive blindness. It accounts for 1 to 11.6 % of spinocerebellar ataxias (SCAs) cases worldwide and for 7.4 % of SCA7 cases in Mexico. We identified a cluster of SCA7 families who resided in a circumscribed area of Veracruz and investigated whether the high incidence of the disease in this region was due to a founder effect. A total of 181 individuals from 20 families were studied. Four microsatellite markers and one SNP flanking the ATNX7 gene were genotyped and the ancestral origin and local ancestry analysis of the SCA7 mutation were evaluated. Ninety individuals from 19 families had the SCA7 mutation; all were found to share a common haplotype, suggesting that the mutation in these families originated from a common ancestor. Ancestral origin and local ancestry analysis of SCA7 showed that the chromosomal segment containing the mutation was of European origin. We here present evidence strongly suggesting that the high frequency of SCA7 in Veracruz is due to a founder effect and that the mutation is most likely of European origin with greatest resemblance to the Finnish population.     

Laser tongue debridement for oral malodor—A novel approach to halitosis

Study objectiveMalodor is a multifactorial condition with oral pathology representing the main culprit and the tongue being the first to second contributor to the malodor. Bacterial load can represent a quantifiable measure regardless of the original pathology. We hypothesize that reduction in malodor can be represented by tongue changes both in appearance, bacterial and biofilm load reduction (measured by CFU and volatile gases measurement), organoleptic measurement and subjective improvement.MethodsA randomized controlled prospective study under IRB approval. Diagnostic criteria for enrollment and follow up were organoleptic test by 2 judges, Halimeter reading, tongue colors changes HALT questionnaire and direct aerobic and anaerobic tongue cultures measured by CFU. Patients were treated with laser tongue debridement (LTD) with an Er,Cr:YSGG solid state laser has been shown to be effective in biofilm reduction.Results54 patients recruited with 35 available for follow up. Improvement was observed on all objective and QOL subjective parameters. Treatment was tolerated well with minimal discomfort.ConclusionsThe tongue is proven to be a major contributor to oral malodor and must be addressed in treatment protocol. LTD significantly reduces malodor by subjective and objective criteria. While impossible to determine whether the tongue serves as a bacterial reservoir or is the origin for oral bacteria it is clear that LTD improves oral hygiene and reduces malodor. LTD is safe and easy to perform. We encourage LTD to be a crucial part of any oral malodor treatment protocol.Trial registration: clinical trials, NCT04120948. Registered 25 September 2019 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S00098SX&selectaction=Edit&uid=U0000W0Y&ts=51&cx=-elnx7e