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Vincent Tran,1 Sharon E Reid,2,3 Amanda Roxburgh,1,4– 6 Carolyn A Day1,2 1Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia; 2Edith Collins Centre (Translational Research in Alcohol, Drugs and Toxicology), Sydney Local Health District, Sydney, New South Wales, Australia; 3Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia; 4Health Risks Program, Burnet Institute, Melbourne, Victoria, Australia; 5National Drug and Alcohol Research Centre, UNSW, Randwick, New South Wales, Australia; 6Monash Addiction Research Centre, Monash University, Clayton, Victoria, AustraliaCorrespondence: Carolyn A Day Tel +61 2 95191446Email carolyn.day@sydney.edu.auBackground: Drug consumption rooms (DCRs) and supervised injecting facilities (SIFs) provide a safe environment in which people who inject drugs (PWIDs) can inject under hygienic and supervised conditions. Numerous reviews have documented the benefits of these facilities; however, there is a lack of clarity surrounding their long-term effects.Purpose: To conduct, with a systematic approach, a literature review, of published peer-reviewed literature assessing the long-term impacts of DCRs/SIFs.Methods: A systematic search of the PubMed and Embase database was performed using the keywords: (“SUPERVISED” OR “SAFE*”) AND (“CONSUMPTION” OR “INJECT*” OR “SHOOTING”) AND (“FACILITY*” OR “ROOM*” OR “GALLERY*” OR “CENTRE*” OR “CENTER*” OR “SITE*”). Included studies were original articles reporting outcomes for five or more years and addressed at least one of the following client or community outcomes; (i) drug-related harms; (ii) access to substance use treatment and other health services; (iii) impact on local PWID population; (iv) impact on public drug use, drug-related crime and violence; and (v) local community attitudes to DCRs.Results: Four publications met our inclusion criteria, addressing four of the five outcomes. Long-term data suggested that while the health of PWID naturally declined over time, DCRs/SIFs helped reduce injecting-related harms. The studies showed that DCRs/SIFs facilitate drug treatment, access to health services and cessation of drug injecting. Local residents and business owners reported less public drug use and public syringe disposal following the opening of a DCR/SIF.Conclusion: Long-term evidence on DCRs/SIFs is consistent with established short-term research demonstrating the benefits of these facilities. A relative paucity of studies was identified, with most evidence originating from Sydney and Vancouver. The overall body of evidence would be improved by future studies following outcomes over longer periods and being undertaken in a variety of jurisdictions and models of DCRs/SIFs.Keywords: safe injecting facilities, intravenous, Injecting, harm reduction

In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405). [ABSTRACT FROM AUTHOR]

Young children are infected by a diverse variety of enteric pathogens in low-income, high-burden countries. Little is known about which conditions pose the greatest risk for enteric pathogen exposure and infection. Young children frequently play in residential public areas around their household, including areas contaminated by human and animal feces, suggesting these exposures are particularly hazardous. The objective of this study was to examine how the dose of six types of common enteric pathogens, and the probability of exposure to one or multiple enteric pathogens for young children playing at public play areas in Kisumu, Kenya is influenced by the type and frequency of child play behaviors that result in ingestion of soil or surface water. Additionally, we examine how pathogen doses and multi-pathogen exposure are modified by spatial variability in the number of public areas children are exposed to in their neighborhood. A Bayesian framework was employed to obtain the posterior distribution of pathogen doses for a certain number of contacts. First, a multivariate mixed effects tobit model was used to obtain the posterior distribution of pathogen concentrations, and their interdependencies, in soil and surface water, based upon empirical data of enteric pathogen contamination in three neighborhoods of Kisumu. Then, exposure doses were estimated using behavioral contact parameters from previous studies and contrasted under different exposure conditions. Pathogen presence and concentration in soil varied widely across local (< 25 meter radius area) and neighborhood-level scales, but pathogens were correlated among distinct surface water samples collected near to each other. Multi-pathogen exposure of children at public play areas was common. Pathogen doses and the probability of multi-pathogen ingestion increased with: higher frequency of environmental contact, especially for surface water; larger volume of soil or water ingested; and with play at multiple sites in the neighborhood versus single site play. Child contact with surface water and soil at public play areas in their neighborhood is an important cause of exposure to enteric pathogens in Kisumu, and behavioral, environmental, and spatial conditions are determinants of exposure.

Visceral Leishmaniasis is a deadly disease caused by Leishmania infantum, endemic in more than 98 countries across the globe. Although the most common means of transmission is via a sand fly vector, there is growing evidence that vertical transmission may be critical for maintaining L. infantum infection within the reservoir, canine, population. Vertical transmission is also an important cause of infant morbidity and mortality particularly in sub-Saharan Africa. While vertical transmission of visceralizing species of Leishmania has been reported around the globe, risk factors associated with this unique means of Leishmania transmission have not been identified therefore interventions regarding this means of transmission have been virtually non-existent. Furthermore, the basic reproductive number, (R0), or number of new L. infantum infections that one infected mother or dam can cause has not been established for vertical transmission, also hampering the ability to assess the impact of this means of transmission within reservoir of human hosts. Canine Leishmaniosis (CanL) is enzootic within a U.S. hunting dog population. CanL is transmitted within this population via transplacental transmission with no reported vector transmission, despite many repeated attempts to find infected sand flies associated with these dogs and kennels. This population with predominantly, if not solely, vertical transmission of L. infantum was used to evaluate the critical risk factors for vertical transmission of Leishmania and establish the R0 of vertical L. infantum infection. Evaluation of 124 animals born to eighteen dams diagnostically positive for infection with L. infantum showed that there was a 13.84x greater chance of being positive for L. infantum within their lifetime if the mother was also positive within her lifetime (RR: 13.84, 95% CI: 3.54-54.20, p-value:

Abstract Background Because previous studies have indicated that otitis media may be a polymicrobial disease, we prospectively analyzed middle ear effusions of children undergoing tympanostomy tube placement with multiplex polymerase chain reaction for four otopathogens. Methods Middle ear effusions from 207 children undergoing routine tympanostomy tube placement were collected and were classified by the surgeon as acute otitis media (AOM) for purulent effusions and as otitis media with effusion (OME) for non-purulent effusions. DNA was isolated from these samples and analyzed with multiplex polymerase chain reaction for Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis. Results 119 (57%) of 207 patients were PCR positive for at least one of these four organisms. 36 (30%) of the positive samples indicated the presence of more than one bacterial species. Patient samples were further separated into 2 groups based on clinical presentation at the time of surgery. Samples were categorized as acute otitis media (AOM) if pus was observed behind the tympanic membrane. If no pus was present, samples were categorized as otitis media with effusion (OME). Bacteria were identified in most of the children with AOM (87%) and half the children with OME (51%, p Haemophilus influenzae was the predominant single organism and caused 58% of all AOM in this study. Alloiococcus otitidis and Moraxella catarrhalis were more frequently identified in middle ear effusions than Streptococcus pneumoniae. Conclusions Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis were identified in the middle ear effusions of some patients with otitis media. Overall, we found AOM is predominantly a single organism infection and most commonly from Haemophilus influenzae. In contrast, OME infections had a more equal distribution of single organisms, polymicrobial entities, and non-bacterial agents.

Abstract Background Group A Streptococcus (GAS) causes acute tonsillopharyngitis in children, and approximately 20% of this population are chronic carriers of GAS. Antibacterial therapy has previously been shown to be insufficient at clearing GAS carriage. Bacterial biofilms are a surface-attached bacterial community that is encased in a matrix of extracellular polymeric substances. Biofilms have been shown to provide a protective niche against the immune response and antibiotic treatments, and are often associated with recurrent or chronic bacterial infections. The objective of this study was to test the hypothesis that GAS is present within tonsil tissue at the time of tonsillectomy. Methods Blinded immunofluorescent and histological methods were employed to evaluate palatine tonsils from children undergoing routine tonsillectomy for adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis. Results Immunofluorescence analysis using anti-GAS antibody was positive in 11/30 (37%) children who had tonsillectomy for adenotonsillar hypertrophy and in 10/30 (33%) children who had tonsillectomy for recurrent GAS pharyngitis. Fluorescent microscopy with anti-GAS and anti-cytokeratin 8 & 18 antibodies revealed GAS was localized to the tonsillar reticulated crypts. Scanning electron microscopy identified 3-dimensional communities of cocci similar in size and morphology to GAS. The characteristics of these communities are similar to GAS biofilms from in vivo animal models. Conclusion Our study revealed the presence of GAS within the tonsillar reticulated crypts of approximately one-third of children who underwent tonsillectomy for either adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis at the Wake Forest School of Medicine. Trial Registration The tissue collected was normally discarded tissue and no patient identifiers were collected. Thus, no subjects were formally enrolled.

Abstract Background Group A Streptococcus (GAS) is a human-specific pathogen responsible for a number of diseases characterized by a wide range of clinical manifestations. During host colonization GAS-cell aggregates or microcolonies are observed in tissues. GAS biofilm, which is an in vitro equivalent of tissue microcolony, has only recently been studied and little is known about the specific surface determinants that aid biofilm formation. In this study, we demonstrate that surface-associated streptococcal collagen-like protein-1 (Scl1) plays an important role in GAS biofilm formation. Results Biofilm formation by M1-, M3-, M28-, and M41-type GAS strains, representing an intraspecies breadth, were analyzed spectrophotometrically following crystal violet staining, and characterized using confocal and field emission scanning electron microscopy. The M41-type strain formed the most robust biofilm under static conditions, followed by M28- and M1-type strains, while the M3-type strains analyzed here did not form biofilm under the same experimental conditions. Differences in architecture and cell-surface morphology were observed in biofilms formed by the M1- and M41-wild-type strains, accompanied by varying amounts of deposited extracellular matrix and differences in cell-to-cell junctions within each biofilm. Importantly, all Scl1-negative mutants examined showed significantly decreased ability to form biofilm in vitro. Furthermore, the Scl1 protein expressed on the surface of a heterologous host, Lactococcus lactis, was sufficient to induce biofilm formation by this organism. Conclusions Overall, this work (i) identifies variations in biofilm formation capacity among pathogenically different GAS strains, (ii) identifies GAS surface properties that may aid in biofilm stability and, (iii) establishes that the Scl1 surface protein is an important determinant of GAS biofilm, which is sufficient to enable biofilm formation in the heterologous host Lactococcus. In summary, the GAS surface adhesin Scl1 may have an important role in biofilm-associated pathogenicity.

Abstract Background Group A Streptococcus (GAS) is a Gram-positive human pathogen that is capable of causing a wide spectrum of human disease. Thus, the organism has evolved to colonize a number of physiologically distinct host sites. One such mechanism to aid colonization is the formation of a biofilm. We have recently shown that inactivation of the streptococcal regulator of virulence (Srv), results in a mutant strain exhibiting a significant reduction in biofilm formation. Unlike the parental strain (MGAS5005), the streptococcal cysteine protease (SpeB) is constitutively produced by the srv mutant (MGAS5005Δsrv) suggesting Srv contributes to the control of SpeB production. Given that SpeB is a potent protease, we hypothesized that the biofilm deficient phenotype of the srv mutant was due to the constitutive production of SpeB. In support of this hypothesis, we have previously demonstrated that treating cultures with E64, a commercially available chemical inhibitor of cysteine proteases, restored the ability of MGAS5005Δsrv to form biofilms. Still, it was unclear if the loss of biofilm formation by MGAS5005Δsrv was due only to the constitutive production of SpeB or to other changes inherent in the srv mutant strain. To address this question, we constructed a ΔsrvΔspeB double mutant through allelic replacement (MGAS5005ΔsrvΔspeB) and tested its ability to form biofilms in vitro. Findings Allelic replacement of speB in the srv mutant background restored the ability of this strain to form biofilms under static and continuous flow conditions. Furthermore, addition of purified SpeB to actively growing wild-type cultures significantly inhibited biofilm formation. Conclusions The constitutive production of SpeB by the srv mutant strain is responsible for the significant reduction of biofilm formation previously observed. The double mutant supports a model by which Srv contributes to biofilm formation and/or dispersal through regulation of speB/SpeB.

Topic Importance: Lung cancer screening (LCS) has the potential to decrease mortality from lung cancer by 20%. Yet, more than a decade since LCS was established as an evidence-based practice, < 20% of the eligible population in the United States has been screened. This review focuses on critically appraising interventions that have been designed to increase the initial uptake of LCS, including how they address known barriers to LCS and their effectiveness in overcoming these barriers., Review Findings: Studies were categorized based on the primary barriers that they addressed: (1) identifying eligible patients (including enhancing awareness through smoking history collection, outreach, and education), (2) shared decision-making-related interventions, and (3) patient navigation interventions. Four of the studies included multicomponent interventions, which often included patient navigation as one of the components. Overall, the effectiveness of the studies reviewed at improving LCS uptake generally was modest and was limited by the multilevel barriers that need to be overcome. Multicomponent interventions generally were more effective at improving LCS uptake, but most studies still had relatively low completion of screening., Summary: Improving uptake of LCS requires learning from prior interventions to design multilevel interventions that address barriers to LCS at key steps and identifying which components of these interventions are effective and generalizable., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. All rights reserved.)

Background: People in correctional settings are a key population for HIV epidemic control. We sought to demonstrate scale-up of universal test and treat in correctional facilities in South Africa and Zambia through a virtual cross-sectional analysis., Methods: We used routine data on 2 dates: At the start of universal test and treat implementation (time 1, T1) and 1 year later (time 2, T2). We obtained correctional facility census lists for the selected dates and matched HIV testing and treatment data to generate virtual cross-sections of HIV care continuum indicators., Results: In the South African site, there were 4193 and 3868 people in the facility at times T1 and T2; 43% and 36% were matched with HIV testing or treatment data, respectively. At T1 and T2, respectively, 1803 (43%) and 1386 (36%) had known HIV status, 804 (19%) and 845 (21%) were known to be living with HIV, and 60% and 56% of those with known HIV were receiving antiretroviral therapy (ART). In the Zambian site, there were 1467 and 1366 people in the facility at times T1 and T2; 58% and 92% were matched with HIV testing or treatment data, respectively. At T1 and T2, respectively, 857 (59%) and 1263 (92%) had known HIV status, 277 (19%) and 647 (47%) were known to be living with HIV, and 68% and 68% of those with known HIV were receiving ART., Conclusions: This virtual cross-sectional analysis identified gaps in HIV testing coverage, and ART initiation that was not clearly demonstrated by prior cohort-based studies., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In the central nervous system (CNS), COX-2 is implicated in neurodegenerative and psychiatric disorders as a potential therapeutic target and biomarker. However, clinical studies with COX-2 have yielded inconsistent results, partly due to limited mechanistic understanding of how COX-2 activity relates to CNS pathology. Therefore, developing COX-2 positron emission tomography (PET) radiotracers for human neuroimaging is of interest. This study introduces [ 11 C]BRD1158, which is a potent and uniquely fast-binding, selective COX-2 PET radiotracer. [ 11 C]BRD1158 was developed by prioritizing potency at COX-2, isoform selectivity over COX-1, fast binding kinetics, and free fraction in the brain. Evaluated through in vivo PET neuroimaging in rodent models with human COX-2 overexpression, [ 11 C]BRD1158 demonstrated high brain uptake, fast target-engagement, functional reversibility, and excellent specific binding, which is advantageous for human imaging applications. Lastly, post-mortem samples from Huntington's disease (HD) patients and preclinical HD mouse models showed that COX-2 levels were elevated specifically in disease-affected brain regions, primarily from increased expression in microglia. These findings indicate that COX-2 holds promise as a novel clinical marker of HD onset and progression, one of many potential applications of [ 11 C]BRD1158 human PET., Competing Interests: The authors declare the following competing financial interest(s): Dr. Jacob Hooker discloses the following relationships: Massachusetts Institute of Technology Consultant; American Chemical Society (ACS), ACS Publications, ACS Chemical Neuroscience Editorial Role; Eikonizo Therapeutics Co-Founder, Advisor; Sensorium Therapeutics Co-Founder, Advisor; Psy Therapeutics Consultant; Delix Therapeutics Advisor; Fuzionaire Diagnostics Advisor; Arclight Therapeutics Advisor; Proximity Therapeutics Advisor; Human Health Advisor, Rocket Science Health Advisor; Atai Life Sciences Sponsored research, training grant/gift. Dr. Beth Stevens discloses the following relationships: Beth Stevens serves on the scientific advisory board of Annexon Biosciences and is a minor shareholder of this company., (© 2024 The Authors. Published by American Chemical Society.)

Advanced breast cancers represent a major therapeutic challenge due to their refractoriness to treatment. Cancer-associated fibroblasts (CAFs) are the most abundant constituents of the tumor microenvironment and have been linked to most hallmarks of cancer. However, the influence of CAFs on therapeutic outcome remains largely unchartered. Here, we reveal that spatial coincidence of abundant CAF infiltration with malignant cells was associated with reduced estrogen receptor (ER)-α expression and activity in luminal breast tumors. Notably, CAFs mediated estrogen-independent tumor growth by selectively regulating ER-α signaling. Whereas most prototypical estrogen-responsive genes were suppressed, CAFs maintained gene expression related to therapeutic resistance, basal-like differentiation, and invasion. A functional drug screen in co-cultures identified effector pathways involved in the CAF-induced regulation of ER-α signaling. Among these, the Transforming Growth Factor-β and the Janus kinase signaling cascades were validated as actionable targets to counteract the CAF-induced modulation of ER-α activity. Finally, genes that were downregulated in cancer cells by CAFs were predictive of poor response to endocrine treatment. In conclusion, our work reveals that CAFs directly control the luminal breast cancer phenotype by selectively modulating ER-α expression and transcriptional function, and further proposes novel targets to disrupt the crosstalk between CAFs and tumor cells to reinstate treatment response to endocrine therapy in patients., (© 2024. The Author(s).)

Background: Women experiencing substance use disorders face barriers to treatment, including childcare, stigma and lack of gender/trauma-informed programming. Several non-government organizations in New South Wales run women-only treatment services to address these needs., Objectives: We aim to assess characteristics of women entering treatment in these services., Design: Data on client characteristics from six women-only non-government organization substance use disorder treatment services in New South Wales between 2014 and 2018 were extracted from a database containing demographics, drug use and treatment characteristics and psychological distress (Kessler-10 scale) of women entering the services. Logistic regression models were used to estimate unadjusted odds ratio and adjusted odds ratio for treatment completion and different drugs on entry., Results: Data were available for 1357 women. Most (91%) episodes were for residential treatment. Women's mean age was 35.4 years (standard deviation = 9.8; range = 17-67). Residential clients tended to be younger than non-residential clients (35.1 vs 38.5 years, p < 0.001). Methamphetamine (43%) and alcohol (32%) were the most reported principal drug of concern. Women (89%) reported high levels of psychological distress (median Kessler-10 scale score = 27.5, range = 10-50), highest for women reporting alcohol as their principal drug. Overall, 43% of episodes resulted in treatment completion, most commonly for women entering residential treatment (45% vs 22%, p < 0.001) and for alcohol treatment (adjusted odds ratio = 1.42; confidence interval = 1.07-1.90; p < 0.001). Women with Kessler-10 scale scores indicating anxiety or depression at treatment entry were less likely to complete treatment than those with lower scores (adjusted odds ratio = 0.56; confidence interval = 0.38-0.80; p < 0.001)., Conclusion: Women entering women-only residential treatment tend to be younger and report methamphetamine as principal drug of concern. Women enter treatment with high degrees of psychological distress. Women's services need to ensure their programmes can respond to diverse needs of younger women presenting with methamphetamine use disorder and older women with alcohol use disorder experiencing high levels of psychological distress.

Voltage-gated sodium channels (Na v s) play a crucial electrical signaling role in neurons. Na v -isoforms present in peripheral sensory neurons and dorsal root ganglia of the spinal cord are critically involved in pain perception and transmission. While these isoforms, particularly Na v 1.7, are implicated in neuropathic pain disorders, changes in the functional state and expression levels of these channels have not been extensively studied in vivo. Radiocaine, a fluorine-18 radiotracer based on the local anesthetic lidocaine, a non-selective Na v blocker, has previously been used for cardiac Na v 1.5 imaging using positron-emission tomography (PET). In the present study, we used Radiocaine to visualize changes in neuronal Na v expression after neuropathic injury. In rats that underwent unilateral spinal nerve ligation, PET/MR imaging demonstrated significantly higher uptake of Radiocaine into the injured sciatic nerve, as compared to the uninjured sciatic nerve, for up to 32 days post-surgery. Radiocaine, due to its high translational potential, may serve as a novel diagnostic tool for neuropathic pain conditions using PET imaging.

During autophagy, the ATG8 family proteins have several well-characterized roles in facilitating early, mid, and late steps of autophagy, including autophagosome expansion, cargo recruitment and autophagosome-lysosome fusion. Their discovery has importantly allowed for precise experimental monitoring of the pathway, bringing about a huge expansion of research in the field over the last decades. In this review, we discuss both canonical and non-canonical roles of the autophagic lipidation machinery, with particular focus on the ATG8 proteins, their post-translational modifications and their increasingly uncovered alternative roles mediated through their anchoring at different membranes. These include endosomes, macropinosomes, phagosomes and the plasma membrane, to which ATG8 proteins can bind through canonical or alternative lipidation. Beyond new ATG8 binding partners and cargo types, we also explore several open questions related to alternative outcomes of autophagic machinery engagement beyond degradation. These include their roles in plasma membrane repair and secretion of selected substrates as well as the physiological implications hereof in health and disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Reid, Kolapalli, Nielsen and Frankel.)

Background: Despite the global scale-up of antiretroviral therapy (ART), incarcerated people have not benefited equally from test-and-treat recommendations for HIV. To improve access to ART for incarcerated people with HIV, we introduced a universal test-and-treat (UTT) intervention in correctional facilities in South Africa and Zambia, and aimed to assess UTT feasibility and clinical outcomes., Methods: Treatment as Prevention (TasP) was a multisite, mixed methods, implementation research study done at three correctional complexes in South Africa (Johnannesburg and Breede River) and Zambia (Lusaka). Here, we report the clinical outcomes for a prospective cohort of incarcerated individuals who were offered the TasP UTT intervention. Incarcerated individuals were eligible for inclusion if they were aged 18 years or older, with new or previously diagnosed HIV, not yet on ART, and were expected to remain incarcerated for 30 days or longer. To enable the implementation of UTT at the included correctional facilities, we first strengthened on-site HIV service delivery. All participants were offered same-day ART initiation, and had two study-specific follow-up visits scheduled to coincide with routine clinic visits at 6 and 12 months. The main outcomes were ART uptake, time from cohort enrolment to ART initiation, and retention in care and viral suppression at 6 and 12 months. We estimated the association between baseline demographic characteristics and time to ART initiation using Cox proportional hazard models, and, in a post-hoc analysis, we used logistic regression models to assess the association between demographic and clinical variables, including time to ART initiation, and the proportion of participants with a composite poor outcome (defined as viral load >50 copies per mL, or for participants with a missing viral load, lack of retention in care in the on-site ART programme) at 6 months. This study is registered at ClinicalTrials.gov, NCT02946762., Findings: Between June 23, 2016, and Dec 31, 2017, we identified 1562 incarcerated people with HIV, of whom 1389 (89%) were screened, 1021 (74%) met eligibility criteria, and 975 (95%) were enrolled and followed up to March 31, 2018. At the end of follow-up, 835 (86%) of 975 participants had started ART. Median time from enrolment to ART initiation was 0 days (IQR 0-8). Of 346 participants who remained incarcerated at 6 months, 327 (95%) were retained in care and 269 (78%) had a documented viral load, of whom 262 (97%) achieved viral suppression (<1000 copies per mL). The mortality rate among the 835 participants who had initiated ART was 1·9 per 100 person-years (95% CI 0·9-3·9). No statistically significant associations were identified between any baseline characteristics and time to ART initiation or composite poor outcome., Interpretation: UTT implementation is feasible in correctional settings, and can achieve levels of same-day ART uptake, retention in care, and viral suppression among incarcerated people with HIV that are comparable to those observed in community settings., Funding: UK Department for International Development, Swedish International Development Cooperation Agency, Norwegian Agency for Development Cooperation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To assess the feasibility and acceptability of integrating a contraception clinic within an opioid agonist treatment (OAT) service to improve access to contraception, especially long-acting reversible methods of contraception (LARC), for women receiving OAT, who have increased risk of unplanned pregnancies and adverse pregnancy outcomes., Methods: A contraception clinic was established at a Sydney OAT service. Forty-eight female OAT clients were surveyed regarding their contraception knowledge and needs. Interested and eligible women were referred to the contraception clinic., Results: Women were aged a median of 39 years (range 24-54 years). Most women (83%) agreed it was acceptable for their OAT clinician to discuss contraception with them. Eight women reported current LARC use and 21 reported they would consider using LARC. Twenty-three women were eligible for contraception (sexually active, aged <50 years, not using contraception, wishing to avoid pregnancy). Six months post-survey two women had presented to the clinic and two reported an unintended pregnancy., Conclusion: Uptake of an on-site contraception service within OAT clinic was low, despite participants' expressed willingness to use the service. Access is therefore not the only driver of low contraception uptake for this group. Implications for public health: Other issues besides access to contraception warrant investigation to improve contraception uptake for women receiving OAT., (© 2020 The Authors.)

Background: Previous literature has explored the underrepresentation of women in surgery. However, this research has often been quantitative or limited by considering only the perspectives and experiences of women at more advanced career stages. Here, we use a qualitative methodology and a sample of women and men across the career continuum to identify the role that gender plays in the decision to pursue a surgical career., Methods: We audio-recorded and transcribed semi-structured interviews conducted with 12 women and 12 men ranging in their level of medical training from medical students to residents to staff surgeons. We used Braun and Clarke's six-step approach to thematic analysis to analyze the data, maintaining trustworthiness and credibility by employing strategies including reflexivity and participant input., Results: Our findings suggested that the characteristics of surgery and early exposure to the profession served as important factors in participants' decisions to pursue a surgical career. Although not explicitly mentioned by participants, each of these areas may implicitly be gendered. Gender-based factors explicitly mentioned by participants included the surgical lifestyle and experiences with gender discrimination, including sexual harassment. These factors were perceived as challenges that disproportionately affected women and needed to be overcome when pursuing a surgical career., Conclusions: Our findings suggest that gender is more likely to act as a barrier to a career in surgery than as a motivator, especially among women. This suggests a need for early experiences in the operating room and mentorship. Policy change promoting work-life integration and education to target gender discrimination is also recommended., Competing Interests: Conflicts of interest: None to declare., (© 2020 Acai, Mahetaji, Reid, Sonnadara; licensee Synergies Partners.)

Background: Sub-Saharan African correctional facilities concentrate large numbers of people who are living with HIV or at risk for HIV infection. Universal test and treat (UTT) is widely recognized as a promising approach to improve the health of individuals and a population health strategy to reduce new HIV infections. In this study, we explored the feasibility and sustainability of implementing UTT in correctional facilities in Zambia and South Africa., Methods: Nested within a UTT implementation research study, our qualitative evaluation of feasibility and sustainability used a case-comparison design based on data from 1 Zambian and 3 South African correctional facilities. Primary data from in-depth interviews with incarcerated individuals, correctional managers, health care providers, and policy makers were supplemented by public policy documents, study documentation, and implementation memos in both countries. Thematic analysis was informed by an empirically established conceptual framework for health system analysis., Results: Despite different institutional profiles, we were able to successfully introduce UTT in the South Africa and Zambian correctional facilities participating in the study. A supportive policy backdrop was important to UTT implementation and establishment in both countries. However, sustainability of UTT, defined as relevant government departments' capacity to independently plan, resource, and administer quality UTT, differed. South Africa's correctional facilities had existing systems to deliver and monitor chronic HIV care and treatment, forming a "scaffolding" for sustained UTT despite some human resources shortages and poorly integrated health information systems. Notwithstanding recent improvements, Zambia's correctional health system demonstrated insufficient material and technical capacity to independently deliver quality UTT. In the correctional facilities of both countries, inmate population dynamics and their impact on HIV-related stigma were important factors in UTT service uptake., Conclusion: Findings demonstrate the critical role of policy directives, health service delivery systems, adequate resourcing, and population dynamics on the feasibility and likely sustainability of UTT in corrections in Zambia and South Africa., (© Topp et al.)

Purpose of Review: To advance a re-conceptualized prevention, treatment, and care continuum (PTCC) for HIV-associated tuberculosis (TB) in prisons, and to make recommendations for strengthening prison health systems and reducing HIV-associated TB morbidity and mortality throughout the cycle of pretrial detention, incarceration, and release., Recent Findings: Despite evidence of increased HIV-associated TB burden in prisons compared to the general population, prisoners face entrenched barriers to accessing anti-TB therapy, antiretroviral therapy, and evidence-based HIV and TB prevention. New approaches, suitable for the complexities of healthcare delivery in prisons, have emerged that may address these barriers, and include: novel TB diagnostics, universal test and treat for HIV, medication-assisted treatment for opioid dependence, comprehensive transitional case management, and peer navigation, among others., Summary: Realizing ambitious international HIV and TB targets in prisons will only be possible by first addressing the root causes of the TB/HIV syndemic, which are deeply intertwined with human rights violations and weaknesses in prison health systems, and, second, fundamentally re-organizing HIV and TB services around a coordinated PTCC. Taking these steps can help ensure universal access to comprehensive, good-quality, free and voluntary TB/HIV prevention, treatment, and care, and advance efforts to strengthen health resourcing, staffing, information management, and primary care access within prisons.

Background: Patients with HIV-associated tuberculosis (TB) often have their TB and HIV managed in separate vertical programs that offer care for each disease with little coordination. Such "siloed" approaches are associated with diagnostic and treatment delays, which contribute to unnecessary morbidity and mortality. To improve TB/HIV care coordination and early ART initiation, we integrated HIV care and treatment into two busy TB clinics in Zambia. We report here the effects of our intervention on outcomes of linkage to HIV care, early ART uptake, and TB treatment success for patients with HIV-associated TB in Lusaka, Zambia., Methods: We provided integrated HIV treatment and care using a "one-stop shop" model intervention. All new or relapse HIV-positive TB patients were offered immediate HIV program enrolment and ART within 8 weeks of anti-TB therapy (ATT) initiation. We used a quasi-experimental design, review of routine program data, and survival analysis and logistic regression methods to estimate study outcomes before (June 1, 2010-January 31, 2011) and after (August 1, 2011-March 31, 2012) our intervention among 473 patients with HIV-associated TB categorized into pre- (n = 248) and post-intervention (n = 225) cohorts., Results: Patients in the pre- and post-intervention cohorts were mostly male (60.1% and 52.9%, respectively) and young (median age: 33 years). In time-to-event analyses, a significantly higher proportion of patients in the post-intervention cohort linked to HIV care by 4 weeks post-ATT initiation (53.9% vs. 43.4%, p = 0.03), with median time to care linkage being 59 and 25 days in the pre- and post-intervention cohorts, respectively. In Cox proportional hazard modelling, patients receiving the integration intervention started ART by 8 weeks post-ATT at 1.33 times the rate (HR = 1.33, 95% CI: 1.00-1.77) as patients pre-intervention. In logistic regression modelling, patients receiving the intervention were 2.02 times (95% CI: 1.11-3.67) as likely to have a successful TB treatment outcome as patients not receiving the intervention., Conclusions: Integrating HIV treatment and care services into routine TB clinics using a one-stop shop model increased linkage to HIV care, rates of early ART initiation, and TB treatment success among patients with HIV-associated TB in Lusaka, Zambia.

This article reports findings on violence, safety, and coping strategies from interviews conducted with 281 male youth incarcerated in California's Division of Juvenile Justice (DJJ). Descriptive analyses revealed that youth report that violence is a common occurrence and that some locations, such as school or housing units, were particularly dangerous. Analysis of how youth avoid violence revealed three distinct precautionary or coping strategies. These three categories highlight a range of conflict management techniques from avoidance to aggression. Those youth who were younger, sex offenders, or newer to the facility used more passive avoidance techniques while gang members and those more active in violent misconduct used more aggressive techniques. A third group, those youth proactively navigating their interactions, had spent more time in their current institution and were marginally more likely to be adult court commitments. Intervention and policy implications of this study are also discussed.

Objectives: Prisons act as infectious disease reservoirs. We aimed to explore the challenges of TB control and continuity of care in prisons in Zambia., Methods: We evaluated treatment outcomes for a cohort of inmates diagnosed with TB during a TB REACH funded screening programme initiated by the Zambia Prisons Service and the Centre for Infectious Disease Research in Zambia., Results: Between October 2010 and September 2011, 6282 inmates from six prisons were screened for TB, of whom 374 (6.0%) were diagnosed. TB treatment was initiated in 345 of 374 (92%) inmates. Of those, 66% were cured or completed treatment, 5% died and 29% were lost to follow-up. Among those lost to follow-up, 11% were released into the community and 13% were transferred to other prisons., Conclusions: Weak health systems within the Zambian prison service currently undermines continuity of care, despite intensive TB screening and case-finding interventions. To prevent TB transmission and the development of drug resistance, we need sufficient numbers of competent staff for health care, reliable health information systems including electronic record keeping for prison facilities, and standard operating procedures to guide surveillance, case-finding and timely treatment initiation and completion., (© 2017 John Wiley & Sons Ltd.)

Summary: Attitudes toward women in surgery appear to be shifting in a positive direction. Why, then, do women still represent only 27% of surgeons in Canada? The answer may, at least in part, lie in the field's inability to adequately accommodate caregiving duties, which are still disproportionately "women's responsibilities" in our society. Although most Canadian academic centres now have paid maternity leave policies for trainees and faculty, these do not necessarily apply to surgeons working in the community, nor do they always reflect what occurs in practice. The perceived inability of the field to accommodate both personal and professional duties is often a significant deterrent to young women considering a career in surgery. In this commentary, we explore the need to address the "caregiver problem" as an important step toward achieving gender equity in surgery.

Objectives: Seasonal variations in tuberculosis diagnoses have been attributed to seasonal climatic changes and indoor crowding during colder winter months. We investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral therapy (ART) programmes in Southern Africa., Setting: Five ART programmes participating in the International Epidemiology Database to Evaluate AIDS in South Africa, Zambia and Zimbabwe., Participants: We analysed data of 331 634 HIV-positive adults (>15 years), who initiated ART between January 2004 and December 2014., Primary Outcome Measure: We calculated aggregated averages in monthly counts of PTB diagnoses and ART initiations. To account for time trends, we compared deviations of monthly event counts to yearly averages, and calculated correlation coefficients. We used multivariable regressions to assess associations between deviations of monthly ART initiation and PTB diagnosis counts from yearly averages, adjusted for monthly air temperatures and geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary tuberculosis (EPTB) diagnoses., Results: All programmes showed monthly variations in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent patterns across 2004-2014. The strongest drops in PTB diagnoses occurred in December, followed by April-May in Zimbabwe and South Africa. This corresponded to holiday seasons, when clinical activities are reduced. We observed little monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation coefficients supported parallel trends in ART initiations and PTB diagnoses (correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly temperatures and latitude did not substantially change regression coefficients between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB diagnoses similarly followed changes in ART initiations throughout the year., Conclusions: Monthly variations in PTB diagnosis at ART programmes in Southern Africa likely occurred regardless of seasonal variations in temperatures or latitude and reflected fluctuations in clinical activities and changes in health-seeking behaviour throughout the year, rather than climatic factors., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Setting: Enhanced tuberculosis (TB) case finding using detection rats in Tanzania., Objectives: To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients., Design: A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert., Results: Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone., Conclusion: Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.

The increased stiffness of a tumor triggers a multitude of responses that aid cancer cell dissemination. Stiffness-induced expression of CCN1 mediates autocrine signaling in the endothelium to upregulate N-Cadherin levels. This permits more stable interactions with cancer cells and increases their ability to spread into the circulation.

Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis., (© 2017 Cancer Research UK Beatson Institute. Published under the terms of the CC BY 4.0 license.)

Competing Interests: C.M. and G.M. are full-time employees of APOPO. S.E.R. is on the APOPO Scientific Advisory Committee.

The present study examines both the patterns of friendship networks and how these network characteristics relate to the risk factors of institutional misconduct for incarcerated youth. Using friendship networks collected from males incarcerated with California's Division of Juvenile Justice (DJJ), latent profile analysis was utilized to create homogeneous groups of friendship patterns based on alter attributes and network structure. The incarcerated youth provided 144 egocentric networks reporting 558 social network relationships. Latent profile analysis identified three network profiles: expected group (67%), new breed group (20%), and model citizen group (13%). The three network profiles were integrated into a multiple group analysis framework to examine the relative influence of individual-level risk factors on their rate of institutional misconduct. The analysis finds variation in predictors of institutional misconduct across profile types. These findings suggest that the close friendships of incarcerated youth are patterned across the individual characteristics of the youth's friends and that the friendship network can act as a moderator for individual risk factors for institutional misconduct.

The prevalence of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis are higher in prisons than in the general population in most countries worldwide. Prisons have emerged as a risk environment for these infections to be further concentrated, amplified, and then transmitted to the community after prisoners are released. In the absence of alternatives to incarceration, prisons and detention facilities could be leveraged to promote primary and secondary prevention strategies for these infections to improve prisoners health and reduce risk throughout incarceration and on release. Effective treatment of opioid use disorders with opioid agonist therapies (eg, methadone and buprenorphine) prevents blood-borne infections via reductions in injection in prison and after release. However, large gaps exist in the implementation of these strategies across all regions. Collaboration between the criminal justice and public health systems will be required for successful implementation of these strategies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Setting: Tuberculosis (TB) remains a leading cause of morbidity and mortality in sub-Saharan Africa. In Zambia, smear microscopy and chest radiography (CXR) are the primary TB diagnostic tools, and most cases are not bacteriologically confirmed., Objective: We implemented enhanced screening to determine the TB burden among new human immunodeficiency virus (HIV) clinic enrollees., Design: Consecutive adult HIV clinic enrollees were screened, regardless of symptoms. All underwent microscopy (Ziehl-Neelsen/fluorescence microscopy) on three sputum specimens, physical examination, and digital CXR. Sputum, blood and urine specimens were cultured. Xpert(®) MTB/RIF testing was performed retrospectively., Results: From July 2011 to April 2012, 399 patients were enrolled. The median age was 34.4 years; body mass index was 20.8 kg/m(2), CD4 count was 202 cells/μl and 86% were symptomatic. Culture-confirmed TB was diagnosed in 72/399 (18%) patients; an additional 31/399 (8%) were culture-negative but diagnosed clinically. Symptom screening for any cough, fever, weight loss or night sweats had high sensitivity (95%) but low specificity (14%) for detecting culture-confirmed cases. Among culture-confirmed cases, 35/72 (49%) were missed clinically and detected only by culture. Xpert was 64% sensitive and 98% specific., Conclusions: High TB prevalence was found in Zambians newly enrolled into HIV care. Screening with sensitive diagnostics should be considered with culture when feasible in this population.

Background: In Zambia the vast majority of chest radiographs (CXR) are read by clinical officers who have limited training and varied interpretation experience, meaning lower inter-rater reliability and limiting the usefulness of CXR as a diagnostic tool. In 2010-11, the Zambian Prison Service and Ministry of Health established TB and HIV screening programs in six prisons; screening included digital radiography for all participants. Using front-line clinicians we evaluated sensitivity, specificity and inter-rater agreement for digital CXR interpretation using the Chest Radiograph Reading and Recording System (CRRS)., Methods: Digital radiographs were selected from HIV-infected and uninfected inmates who participated in a TB and HIV screening program at two Zambian prisons. Two medical officers (MOs) and two clinical officers (COs) independently interpreted all CXRs. We calculated sensitivity and specificity of CXR interpretations compared to culture as the gold standard and evaluated inter-rater reliability using percent agreement and kappa coefficients., Results: 571 CXRs were included in analyses. Sensitivity of the interpretation "any abnormality" ranged from 50-70 % depending on the reader and the patients' HIV status. In general, MO's had higher specificities than COs. Kappa coefficients for the ratings of "abnormalities consistent with TB" and "any abnormality" showed good agreement between MOs on HIV-uninfected CXRs and moderate agreement on HIV-infected CXRs whereas the COs demonstrated fair agreement in both categories, regardless of HIV status., Conclusions: Sensitivity, specificity and inter-rater agreement varied substantially between readers with different experience and training, however the medical officers who underwent formal CRRS training had more consistent interpretations.

Objective: To improve the Zambia Prisons Service's implementation of tuberculosis screening and human immunodeficiency virus (HIV) testing., Methods: For both tuberculosis and HIV, we implemented mass screening of inmates and community-based screening of those residing in encampments adjacent to prisons. We also established routine systems – with inmates as peer educators – for the screening of newly entered or symptomatic inmates. We improved infection control measures, increased diagnostic capacity and promoted awareness of tuberculosis in Zambia's prisons., Findings: In a period of 9 months, we screened 7638 individuals and diagnosed 409 new patients with tuberculosis. We tested 4879 individuals for HIV and diagnosed 564 cases of infection. An additional 625 individuals had previously been found to be HIV-positive. Including those already on tuberculosis treatment at the time of screening, the prevalence of tuberculosis recorded in the prisons and adjacent encampments – 6.4% (6428/100,000) – is 18 times the national prevalence estimate of 0.35%. Overall, 22.9% of the inmates and 13.8% of the encampment residents were HIV-positive., Conclusion: Both tuberculosis and HIV infection are common within Zambian prisons. We enhanced tuberculosis screening and improved the detection of tuberculosis and HIV in this setting. Our observations should be useful in the development of prison-based programmes for tuberculosis and HIV elsewhere.

Setting: Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia., Objective: To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings., Design: Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence., Results: All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive., Conclusion: There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.

Setting: Lusaka Central Prison, Zambia., Objective: To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program., Design: We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values., Results: The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden., Conclusion: Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.

Background: Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison., Methods: Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed., Results: A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%., Conclusion: Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required.

The process of new blood vessel formation from pre-existing ones is called angiogenesis. Beyond playing a critical role in the physiological development of the vascular system, angiogenesis is a well-recognised hallmark of cancer. Unbiased system-wide approaches are required to complement the current knowledge, and intimately understand the molecular mechanisms regulating this process in physiological and pathological conditions. In this review we describe the cellular and molecular dynamics regulating the physiological growth of vessels and their deregulation in cancer, survey in vitro and in vivo models currently exploited to investigate various aspects of angiogenesis and describe state-of-the-art and most widespread methods and technologies in MS shotgun proteomics. Finally, we focus on current applications of MS to better understand endothelial cell behaviour and propose how modern proteomics can impact on angiogenesis research., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Integration of HIV treatment with other primary care services has been argued to potentially improve effectiveness, efficiency and equity. However, outside the field of reproductive health, there is limited empirical evidence regarding the scope or depth of integrated HIV programmes or their relative benefits. Moreover, the body of work describing operational models of integrated service-delivery in context remains thin. Between 2008 and 2011, the Lusaka District Health Management Team piloted and scaled-up a model of integrated HIV and general outpatient department (OPD) services in 12 primary health care clinics. This paper examines the effect of the integrated model on the organization of clinic services, and explores service providers' perceptions of the integrated model., Methods: We used a mixed methods approach incorporating facility surveys and key informant interviews with clinic managers and district officials. On-site facility surveys were carried out in 12 integrated facilities to collect data on the scope of integrated services, and 15 semi-structured interviews were carried out with 12 clinic managers and three district officials to explore strengths and weaknesses of the model. Quantitative and qualitative data were triangulated to inform overall analysis., Findings: Implementation of the integrated model substantially changed the organization of service delivery across a range of clinic systems. Organizational and managerial advantages were identified, including more efficient use of staff time and clinic space, improved teamwork and accountability, and more equitable delivery of care to HIV and non-HIV patients. However, integration did not solve ongoing human resource shortages or inadequate infrastructure, which limited the efficacy of the model and were perceived to undermine service delivery., Conclusion: While resource and allocative efficiencies are associated with this model of integration, a more important finding was the model's demonstrated potential for strengthening organizational culture and staff relationships, in turn facilitating more collaborative and motivated service delivery in chronically under-resourced primary healthcare clinics.

Objectives: To investigate the incidence of selected opportunistic infections (OIs) and cancers and the role of a history of tuberculosis (TB) as a risk factor for developing these conditions in HIV-infected patients starting antiretroviral treatment (ART) in Southern Africa., Methods: Five ART programmes from Zimbabwe, Zambia and South Africa participated. Outcomes were extrapulmonary cryptococcal disease (CM), pneumonia due to Pneumocystis jirovecii (PCP), Kaposi's sarcoma and Non-Hodgkin lymphoma. A history of TB was defined as a TB diagnosis before or at the start of ART. We used Cox models adjusted for age, sex, CD4 cell count at ART start and treatment site, presenting results as adjusted hazard ratios (aHR) with 95% confidence intervals (CI)., Results: We analysed data from 175,212 patients enrolled between 2000 and 2010 and identified 702 patients with incident CM (including 205 with a TB history) and 487 with incident PCP (including 179 with a TB history). The incidence per 100 person-years over the first year of ART was 0.48 (95% CI 0.44-0.52) for CM, 0.35 (95% CI 0.32-0.38) for PCP, 0.31 (95% CI 0.29-0.35) for Kaposi's sarcoma and 0.02 (95% CI 0.01-0.03) for Non-Hodgkin lymphoma. A history of TB was associated with cryptococcal disease (aHR 1.28, 95% CI 1.05-1.55) and Pneumocystis jirovecii pneumonia (aHR 1.61, 95% CI 1.27-2.04), but not with Non-Hodgkin lymphoma (aHR 1.09, 95% CI 0.45-2.65) or Kaposi's sarcoma (aHR 1.02, 95% CI 0.81-1.27)., Conclusions: Our study suggests that there may be interactions between different OIs in HIV-infected patients., (© 2012 Blackwell Publishing Ltd.)

Injecting drug users (IDUs), the key risk population for hepatitis C virus (HCV) infection, constitute just a small proportion of HCV treatment clients. This study describes an HCV treatment assessment model developed by an inner-city IDU-targeted primary healthcare (PHC) facility and, using a retrospective clinical audit, documents predictors of successful referrals to a tertiary liver clinic. Between July 2006-December 2010, 479 clients attended the PHC, of whom 353 (74%) were screened for HCV antibody. Sixty percent (212/353) tested positive, of whom 93% (197/212) were screened for HCV-RNA with 73% (143/197) positive. Referrals to a tertiary liver clinic were provided to 96 clients, of whom 68 (71%) attended. Eleven clients commenced antiviral therapy (AVT), with seven achieving sustained virological responses by December 2010. Clients who had not recently injected drugs and those with elevated ALT levels were more likely to attend the referrals, while those not prescribed psychiatric medications were more likely to commence AVT. The relatively high uptake of referrals, the number of individuals commencing AVT and final treatment outcomes are reasonably encouraging, highlighting the potential of targeted PHC services to facilitate reductions in liver disease burden among IDUs., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Building on earlier works demonstrating the effectiveness and acceptability of provider-initiated counselling and testing (PITC) services in integrated outpatient departments of urban primary healthcare clinics (PHCs), this study seeks to understand the relative utility of PITC services for identifying clients with early-stage HIV-related disease compared to traditional voluntary testing and counselling (VCT) services. We additionally seek to determine whether there are any significant differences in the clinical and demographic profile of PITC and VCT clients., Methods: Routinely collected, de-identified data were collated from two cohorts of HIV-positive patients referred for HIV treatment, either from PITC or VCT in seven urban-integrated PHCs. Univariate and multivariate analyses were conducted to compare the two cohorts across demographic and clinical characteristics at enrolment., Results: Forty-five per cent of clients diagnosed via PITC had CD4 < 200, and more than 70% (i.e. two thirds) had CD4 < 350 at enrollment, with significantly lower CD4 counts than that of VCT clients (p < 0.001). PITC clients were more likely to be male (p = 0.0005) and less likely to have secondary or tertiary education (p < 0.0001). Among those who were initiated on antiretroviral therapy (ART), PITC clients had lower odds of initiating treatment within four weeks of enrollment into HIV care (adjusted odds ratio, or AOR: 0.86; 95% confidence interval, or CI: 0.75-0.99; p = 0.035) and significantly lower odds of retention in care at six months (AOR: 0.84; CI: 0.77-0.99; p = 0.004)., Conclusions: In Lusaka, Zambia, large numbers of individuals with late-stage HIV are being incidentally diagnosed in outpatient settings. Our findings suggest that PITC in this setting does not facilitate more timely diagnosis and referral to care but rather act as a "safety net" for individuals who are unwilling or unable to seek testing independently. Further work is needed to document the way provision of clinic-based services can be strengthened and linked to community-based interventions and to address socio-cultural norms and socio-economic status that underpin healthcare-seeking behaviour.

Tuberculosis is one of the fastest-growing epidemics in prison populations in sub-Saharan Africa (SSA), constituting a threat to both inmates and the wider community. Various factors have contributed to the breakdown of tuberculosis control in prison facilities in SSA, including slow and insensitive diagnostics, failing prison infrastructure, inadequate funding, and weak prevention and treatment interventions for human immunodeficiency virus (HIV). In this article, we describe the challenges inherent in current approaches to tuberculosis control in prisons and consider the alternatives. We argue that although improved implementation of conventional tuberculosis control activities is necessary, considerable investment in a broader range of public health interventions, including infrastructure and staffing upgrades, cutting-edge tuberculosis diagnostics, and combination prevention for HIV, will be equally critical. This combination response to tuberculosis in prisons will be essential for tackling existing and nascent prison tuberculosis epidemics and will require high-level political support and financing.

Acyclovir pharmacokinetics was evaluated in 68 HIV-seronegative, herpes simplex virus 2 (HSV-2)-seropositive African women, who received a single oral 400-mg dose of acyclovir, with plasma acyclovir concentrations measured over 8 h. Geometric mean peak concentration and area under the concentration-time curve were 0.31 μg/ml and 1.59 h · μg/ml, respectively, 54% and 52% lower than values from non-Africans. Lower acyclovir concentrations may partly explain the reduced acyclovir suppression of HSV-2 genital ulcer recurrence in HPTN 039 African women participants.