Mycoplasma genitalium in Singapore is associated with Chlamydia trachomatis infection and displays high macrolide and Fluoroquinolone resistance rates.

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this, M. genitalium is not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance in M. genitalium isolates. METHODS: Urine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested for C. trachomatis (CT) or N. gonorrhoeae (NG) infection and for the presence of M. genitalium. Antibiotic resistance in M. genitalium strains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance. RESULTS: We report the results of a study into M. genitalium prevalence at the national sexual health clinic in Singapore. M. genitalium was heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection. CONCLUSIONS: Our results support targeted screening of CT positive patients for M. genitalium as a cost-effective strategy to reduce the incidence of M. genitalium in the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistant M. genitalium isolates.

Industry perspective on the nonclinical safety assessment of heterobifunctional degraders.

Targeted protein degraders (TPDs), which act through the ubiquitin proteasome system (UPS), are one of the newest small-molecule drug modalities. Since the initiation of the first clinical trial in 2019, investigating the use of ARV-110 in patients with cancer, the field has rapidly expanded. Recently, some theoretical absorption, distribution, metabolism, and excretion (ADME) and safety challenges have been posed for the modality. Using these theoretical concerns as a framework, the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) Protein Degrader Working Group (WG) conducted two surveys to benchmark current preclinical practices for TPDs. Conceptually, the safety assessment of TPDs is the same as for standard small molecules; however, the techniques used, assay conditions/study endpoints, and timing of assessments might need to be modified to address differences in mode of action of the class.

How did South Africans with disabilities experience COVID-19? Results of an online survey.

Background: People with disabilities are a large, disadvantaged minority, comprising approximately 12% of the population. The South African government has ratified international and regional disability treaties but deals with disability rights within general anti-discrimination legislation. There are no specific frameworks to monitor justice for people with disabilities. The study aims to inform further development of disability inclusive mechanisms relating to crises including pandemics. Objectives: This study explored the perceptions of South Africans with disabilities, to understand their experiences during coronavirus disease 2019 (COVID-19), focussing on socioeconomic, well-being and human rights aspects. Method: An online survey tool generated quantitative and qualitative data. Widespread publicity and broad recruitment were achieved through project partners networks. Participants responded via mobile phone and/or online platforms. Results: Nearly 2000 people responded, representing different genders, impairments, races, socio-economic status, education and ages. Findings include: (1) negative economic and emotional impacts, (2) a lack of inclusive and accessible information, (3) reduced access to services, (4) uncertainty about government and non-government agencies' support and (5)exacerbation of pre-existing disadvantages. These findings echo international predictions of COVID-19 disproportionally impacting people with disabilities. Conclusion: The evidence reveals that people with disabilities in South Africa experienced many negative impacts of the pandemic. Strategies to control the virus largely ignored attending to human rights and socioeconomic well-being of this marginalised group. Contribution: The evidence will inform the development of the national monitoring framework, recognised by the South African Government and emphasised by the United Nations as necessary to ensure the realisation of the rights of people with disabilities during future crises including pandemics.

Osteological, multi-isotope and proteomic analysis of poorly-preserved human remains from a Dutch East India Company burial ground in South Africa.

Skeletal remains discovered in Simon's Town, South Africa, were hypothesised as being associated with a former Dutch East India Company (VOC) hospital. We report a novel combined osteological and biochemical approach to these poorly-preserved remains. A combined strontium (87Sr/86Sr), oxygen (δ18OVPDB) and carbon (δ13CVPDB) isotope analysis informed possible childhood origins and diet, while sex-specific amelogenin enamel peptides revealed biological sex. Osteological analyses presented evidence of residual rickets, a healed trauma, dental pathological conditions, and pipe notches. The combined isotope analyses yielded results for 43 individuals which suggested a diverse range of geological origins, including at least 16% of the population being non-local. The inclusion of δ13CVPDB had intriguing implications for three individuals who likely did not have origins in the Cape Town region nor in Europe. Peptide analysis on the dental enamel of 25 tested individuals confirmed they were all biologically male. We suggest that isolated enamel may provide crucial information about individuals' pathological conditions, geographical origins, diet, and biological sex. These data further demonstrated that a combined approach using multiple osteological and biochemical methods is advantageous for human remains which are poorly preserved and can contextualise a site with little direct evidence.

The COVID-19 pandemic reveals an unprecedented rise in hunger: The South African Government was ill-prepared to meet the challenge.

Recent research has shown increasing household food and nutrition insecurity in South Africa, indicating weaknesses in the national food system due to historical and current socioeconomic inequalities. The lack of inclusive governance and collaboration among actors and institutions to develop long-term strategies increase the problem. Such weaknesses intensify the government's ill-preparedness to provide food relief during disasters. We drew upon two rounds of the longitudinal University of Johannesburg and the Human Sciences Research Council's COVID-19 Democracy Survey to illustrate how ill-preparedness has resulted in increased hunger. The rollout of food relief was slow because the state ignored established non-governmental food relief structures. Delayed tender processes and corruption have worsened local distribution and access to food relief, increasing households' hunger. Individuals reported higher experiences of hunger above pre-COVID-19 figures of 11% attaining highs of 42% in 2020. We argue that COVID-19 has emphasised the South African food system's inequalities, particularly the state's inability to ensure integration, inclusiveness and rapidly provide emergency food relief. We focused on individual and households' experiences of hunger and economic circumstances. Challenges were evident where access to food was provided in-kind or through financial aid. The pandemic food relief interventions and the lack of food price controls were serious challenges. The state and stakeholders must prevent high transitory food insecurity levels from resulting in chronic food insecurity. The state's practices and challenges during lockdown must be examined to ensure this situation does not reoccur. Some essential foods require subsidisation and price regulation to ensure long-term access for the poor. To ensure zero hunger and increased food security, these elements of the NDP must be re-examined. Research is required on vulnerabilities in the system, ways to overcome these and the understanding of factors contributing to system-wide resilience, including at individual and household levels.

Pelvic vein embolisation of gonadal and internal iliac veins can be performed safely and with good technical results in an ambulatory vein clinic, under local anaesthetic alone - Results from two years' experience.

Objectives Pelvic vein embolisation is increasing in venous practice for the treatment of conditions associated with pelvic venous reflux. In July 2014, we introduced a local anaesthetic "walk-in walk-out" pelvic vein embolisation service situated in a vein clinic, remote from a hospital. Methods Prospective audit of all patients undergoing pelvic vein embolisation for pelvic venous reflux. All patients had serum urea and electrolytes tested before procedure. Embolisation coils used were interlock embolisation coils (Boston Scientific, USA) as they can be repositioned after deployment and before release. We noted (1) complications during or post-procedure (2) successful abolition of pelvic venous reflux on transvaginal duplex scanning (3) number of veins (territories) treated and number of coils used. Results In 24 months, 121 patients underwent pelvic vein embolisation. Three males were excluded as transvaginal duplex scanning was impossible and six females excluded due to lack of complete data. None of these nine had any complications. Of 112 females analysed, mean age 45 years (24-71), 104 were for leg varices, 48 vulval varices and 20 for pelvic congestion syndrome (some had more than one indication). There were no deaths or serious complications to 30 days. Two procedures were abandoned, one completed subsequently and one was technically successful on review. One more had transient bradycardia and one had a coil removed by snare during the procedure. The mean number of venous territories treated was 2.9 and a mean of 3.3 coils was used per territory. Conclusion Pelvic vein embolisation under local anaesthetic is safe and technically effective in a remote out-patient facility outside of a hospital.

Primary avalvular varicose anomalies are a naturally occurring phenomenon that might be misdiagnosed as neovascular tissue in recurrent varicose veins.

OBJECTIVE: The objective of this study was to report a phenomenon in patients with primary varicose veins that resembles neovascular tissue in postsurgical recurrences-primary avalvular varicose anomalies (PAVA). METHODS: Between March 2012 and July 2013, 756 patients (122 men, 634 women) with primary varicose veins (mean age, 53 years; range, 18-89 years) underwent duplex ultrasonography with retrospective analysis of their reflux patterns. We diagnose PAVA as small, refluxing vessels in legs with primary varicose veins and no history of surgery, trauma, or infection in the area that show one or more of three patterns of distribution: lymph node pattern-PAVA arising directly from groin lymph nodes; peritruncal pattern-PAVA wrapping around the great, small, or anterior accessory saphenous veins; and atypical pattern. PAVA are predominantly found within the saphenous fascia, but components have been found to emerge into the superficial and deep venous compartments. RESULTS: We analyzed results from 1398 legs (756 patients). Sixty-four legs (4.6%) in 58 patients exhibited PAVA, bilateral in six patients and unilateral in 52 patients. Lymph node involvement and peritruncal PAVA were seen in 23.4% and 70.3% of legs, respectively. The small saphenous vein was the most common truncal vein to be involved (48.9% of peritruncal cases). More than one pattern of PAVA could be observed in seven legs. Of the 48 women with PAVA, 42% had concurrent pelvic vein reflux. CONCLUSIONS: Neovascularization has been identified as a major cause of clinically recurrent varicose veins. Neovascular tissue has been described after endovenous thermoablation. We suggest that this might represent PAVA undetected preoperatively in some cases. PAVA are thin-walled, serpiginous, incompetent vessels that resemble neovascular tissue. We conclude that neovascularization should be diagnosed as a source of recurrence after endovenous surgery only if PAVA had been actively looked for, and excluded, in the preoperative diagnostic duplex ultrasound examination.