Compost and Legionella longbeachae : an emerging infection?

Human disease caused by Legionella species is dominated by Legionella pneumophila, the main causative agent in cases of Legionnaires’ disease. However, other species are known to cause infection, for example, Legionella longbeachae causes an equivalent number of cases of disease as L. pneumophila in Australia and New Zealand. Infection with L. longbeachae is commonly associated with exposure to composts and potting soils, and cases of infection with this organism have been increasing in Europe over the past ten years. The increase in incidence may be linked to factors such as increased awareness of clinical presentation, or due to changing formulation of growing media, although it should be noted that the presence of Legionella species in growing media does not correlate with the number of cases currently seen. This is likely due to the variables associated with infection, for example, host factors such as smoking or underlying health conditions, or difference in growing media storage or climate, especially warm humid conditions, which may affect survival and growth of these organisms in the growing media environment. There are numerous unknowns in this area and collaboration between growing media manufacturers and researchers, as well as more awareness among diagnosing clinicians, laboratory staff and the general public is necessary to reduce risk. More research is needed before definitive conclusions can be drawn: L. pneumophila research currently dominates the field and it is likely that the overreliance on diagnostic techniques such as the urinary antigen test, which is specific for L. pneumophila Sg 1, is detrimental to the diagnosis of L. longbeachae infection

Removing the societal and legal impediments to the HIV response: An evidence-based framework for 2025 and beyond.

Societal and legal impediments inhibit quality HIV prevention, care, treatment and support services and need to be removed. The political declaration adopted by UN member countries at the high-level meeting on HIV and AIDS in June 2021, included new societal enabler global targets for achievement by 2025 that will address this gap. Our paper describes how and why UNAIDS arrived at the societal enabler targets adopted. We conducted a scoping review and led a participatory process between January 2019 and June 2020 to develop an evidence-based framework for action, propose global societal enabler targets, and identify indicators for monitoring progress. A re-envisioned framework called the '3 S's of the HIV response: Society, Systems and Services' was defined. In the framework, societal enablers enhance the effectiveness of HIV programmes by removing impediments to service availability, access and uptake at the societal level, while service and system enablers improve efficiencies in and expand the reach of HIV services and systems. Investments in societal enabling approaches that remove legal barriers, shift harmful social and gender norms, reduce inequalities and improve institutional and community structures are needed to progressively realize four overarching societal enablers, the first three of which fall within the purview of the HIV sector: (i) societies with supportive legal environments and access to justice, (ii) gender equal societies, (iii) societies free from stigma and discrimination, and (iv) co-action across development sectors to reduce exclusion and poverty. Three top-line and 15 detailed targets were recommended for monitoring progress towards their achievement. The clear articulation of societal enablers in the re-envisioned framework should have a substantial impact on improving the effectiveness of core HIV programmes if implemented. Together with the new global targets, the framework will also galvanize advocacy to scale up societal enabling approaches with proven impact on HIV outcomes

Human Telomerase Reverse Transcriptase (hTERT) Q169 Is Essential for Telomerase Function In Vitro and In Vivo

BACKGROUND:Telomerase is a reverse transcriptase that maintains the telomeres of linear chromosomes and preserves genomic integrity. The core components are a catalytic protein subunit, the telomerase reverse transcriptase (TERT), and an RNA subunit, the telomerase RNA (TR). Telomerase is unique in its ability to catalyze processive DNA synthesis, which is facilitated by telomere-specific DNA-binding domains in TERT called anchor sites. A conserved glutamine residue in the TERT N-terminus is important for anchor site interactions in lower eukaryotes. The significance of this residue in higher eukaryotes, however, has not been investigated. METHODOLOGY/PRINCIPAL FINDINGS:To understand the significance of this residue in higher eukaryotes, we performed site-directed mutagenesis on human TERT (hTERT) Q169 to create neutral (Q169A), conservative (Q169N), and non-conservative (Q169D) mutant proteins. We show that these mutations severely compromise telomerase activity in vitro and in vivo. The functional defects are not due to abrogated interactions with hTR or telomeric ssDNA. However, substitution of hTERT Q169 dramatically impaired the ability of telomerase to incorporate nucleotides at the second position of the template. Furthermore, Q169 mutagenesis altered the relative strength of hTERT-telomeric ssDNA interactions, which identifies Q169 as a novel residue in hTERT required for optimal primer binding. Proteolysis experiments indicate that Q169 substitution alters the protease-sensitivity of the hTERT N-terminus, indicating that a conformational change in this region of hTERT is likely critical for catalytic function. CONCLUSIONS/SIGNIFICANCE:We provide the first detailed evidence regarding the biochemical and cellular roles of an evolutionarily-conserved Gln residue in higher eukaryotes. Collectively, our results indicate that Q169 is needed to maintain the hTERT N-terminus in a conformation that is necessary for optimal enzyme-primer interactions and nucleotide incorporation. We show that Q169 is critical for the structure and function of human telomerase, thereby identifying a novel residue in hTERT that may be amenable to therapeutic intervention

What determines violence among female sex workers in an intimate partner relationship? Findings from North Karnataka, south India.

BACKGROUND: Like other women in India, female sex workers (FSWs) frequently experience violence from their intimate partners (IPs)-a reality that increases their risk of acquiring HIV or other sexually transmitted infections. Less is known about the nature of these intimate relationships or what aspect of the relationship increases the risk of IP violence (IPV). We measured the prevalence and determinants of IPV on FSWs in the context of north Karnataka, India, characterized by high HIV-prevalence and extreme poverty. METHODS: Overall 620 FSWs with an IP participated in a baseline survey conducted for an on-going cluster-randomised controlled trial aiming to evaluate the impact of a multi-level intervention on IPV reduction. We characterize the nature of intimate relationships and explored determinants of severe physical and/or sexual IP violence using univariable and multivariable analyses. RESULTS: The median age of participants was 35 years with 10 years of duration in an intimate relationship. Though most relationships originated from a sex work encounter, 84% stated that IPs did not know they were currently practicing sex work. In past 6 months, the experience of emotional violence was 49% (95%CI:45.2-53.2), physical 33% (95%CI:29.5-37.1) and sexual violence 7% (95%CI:4.8-8.9), while 24% (95%CI:21.0-27.9) FSWs experienced recent severe physical and/or sexual violence from IPs. Factors associated with recent IPV included experience of physical and/or sexual violence from their clients in last 6 months (AOR 2.20; 95%CI: 1.29-3.75), sexual intercourse in the past 1 month when their IP was under the influence of alcohol (AOR 2.30; 95%CI: 1.47-3.59) and providing financial support to their IP (AOR 2.07; 95%CI: 1.28-3.34). CONCLUSIONS: The association between increased risk of violence and provision of financial support to an IP is indicative of gendered power dynamics as men remain dominant irrespective of their financial dependency on FSWs. Interventions are needed that address inequitable gender norms which makes FSWs tolerate violence even though she is not financially dependent on IP. Higher likelihood of violence in presence of alcohol use and FSWs' previous experience of workplace violence linked to IPV call for strengthening the crisis management systems within community-based organisations that can address all forms of violence and associated risk factors. TRIAL REGISTRATION: Clinical Trials NCT02807259

Violence against female sex workers in Karnataka state, south India: impact on health, and reductions in violence following an intervention program

<p>Abstract</p> <p>Background</p> <p>Violence against female sex workers (FSWs) can impede HIV prevention efforts and contravenes their human rights. We developed a multi-layered violence intervention targeting policy makers, secondary stakeholders (police, lawyers, media), and primary stakeholders (FSWs), as part of wider HIV prevention programming involving >60,000 FSWs in Karnataka state. This study examined if violence against FSWs is associated with reduced condom use and increased STI/HIV risk, and if addressing violence against FSWs within a large-scale HIV prevention program can reduce levels of violence against them.</p> <p>Methods</p> <p>FSWs were randomly selected to participate in polling booth surveys (PBS 2006-2008; short behavioural questionnaires administered anonymously) and integrated behavioural-biological assessments (IBBAs 2005-2009; administered face-to-face).</p> <p>Results</p> <p>3,852 FSWs participated in the IBBAs and 7,638 FSWs participated in the PBS. Overall, 11.0% of FSWs in the IBBAs and 26.4% of FSWs in the PBS reported being beaten or raped in the past year. FSWs who reported violence in the past year were significantly less likely to report condom use with clients (zero unprotected sex acts in previous month, 55.4% vs. 75.5%, adjusted odds ratio (AOR) 0.4, 95% confidence interval (CI) 0.3 to 0.5, p < 0.001); to have accessed the HIV intervention program (ever contacted by peer educator, 84.9% vs. 89.6%, AOR 0.7, 95% CI 0.4 to 1.0, p = 0.04); or to have ever visited the project sexual health clinic (59.0% vs. 68.1%, AOR 0.7, 95% CI 0.6 to 1.0, p = 0.02); and were significantly more likely to be infected with gonorrhea (5.0% vs. 2.6%, AOR 1.9, 95% CI 1.1 to 3.3, p = 0.02). By the follow-up surveys, significant reductions were seen in the proportions of FSWs reporting violence compared with baseline (IBBA 13.0% vs. 9.0%, AOR 0.7, 95% CI 0.5 to 0.9 p = 0.01; PBS 27.3% vs. 18.9%, crude OR 0.5, 95% CI 0.4 to 0.5, p < 0.001).</p> <p>Conclusions</p> <p>This program demonstrates that a structural approach to addressing violence can be effectively delivered at scale. Addressing violence against FSWs is important for the success of HIV prevention programs, and for protecting their basic human rights.</p

Conditional consent and sexual offences: revisiting the Sexual Offences Act 2003 after Lawrance

Critically examines the law relating to sexual consent in cases of deception/mistake, and the developing judicial approach to s74 Sexual Offences Act (SOA) 2003. Reflects on the significance of the most recent Court of Appeal judgment in Lawrance as authority for a restrictive approach to which unfulfilled premises can vitiate a complainant’s consent. Contends that this marks a legal wrong turn. The Court of Appeal’s approval and application of the CPS’s ‘closely connected’ test is based on dubious foundations: it is the result of a chain of misinterpretations of previous case law, and, most troublingly, of the effect of s74. On this basis, suggests that Lawrance ought to be reconsidered. Sets out an argument as to the doctrinally-correct interpretation of the post-2003 law – an ‘expansive’ approach to choice and sexual consent. This approach leaves open the factors on which an individual can base their sexual consent in law. Argues that this reflects the enacted and underlying intention of Parliament in the SOA, and until Lawrance, the relevant case law. This is supported via an original analysis of s74, its place in the SOA, and key values underlying the reform process – sexual autonomy and choice. Considers the consequences of these arguments for the future direction of the law