COVID-19 restrictions and changing sexual behaviours in HIV-negative MSM at high risk of HIV infection in London, UK.

OBJECTIVES: The COVID-19 pandemic and its related restrictions have affected attendance to and delivery of UK sexual healthcare services (SHS). We surveyed the impact on sexual behaviour of men having sex with men (MSM) to inform future SHS provision. METHODS: We conducted a cross-sectional, anonymous, web-based survey among HIV-negative MSM at high risk of HIV infection who attended 56 Dean Street, a sexual health and HIV clinic. The survey was conducted over a 7-day period in August 2020. Data on sociodemographic characteristics, sexual behaviour and related mental well-being experienced during lockdown (defined as 23 March-30 June 2020) were extracted. Categorical and non-categorical variables were compared according to HIV pre-exposure prophylaxis (PrEP) use. RESULTS: 814 MSM completed the questionnaire: 75% were PrEP users; 76% reported they have been sexually active, of which 76% reported sex outside their household. 75% reported fewer partners than prior to lockdown. Isolation/loneliness (48%) and anxiety/stress (27%) triggered sexual activity, and 73% had discussed COVID-19 transmission risks with their sexual partners. While 46% reported no change to emotions ordinarily experienced following sex, 20% reported guilt for breaching COVID-19 restrictions. 76% implemented one or more changes to their sexual behaviour, while 58% applied one or more steps to reduce COVID-19 transmission during sex. 36% accessed SHS and 30% reported difficulties in accessing testing/treatment. Of those who accessed SHS, 28% reported an STI diagnosis. PrEP users reported higher partner number, engagement in 'chemsex' and use of SHS than non-PrEP users. CONCLUSIONS: COVID-19 restrictions had a considerable impact on sexual behaviour and mental well-being in our survey respondents. High rates of sexual activity and STI diagnoses were reported during lockdown. Changes to SHS provision for MSM must respond to high rates of psychological and STI-related morbidity and the challenges faced by this population in accessing services.

An evaluation in vitro of PARP-1 inhibitors, rucaparib and olaparib, as radiosensitisers for the treatment of neuroblastoma.

BACKGROUND: The radiopharmaceutical (131)I-meta-iodobenzylguanidine ((131)I-MIBG) is an effective treatment for neuroblastoma. However, maximal therapeutic benefit from (131)I-MIBG is likely to be obtained by its combination with chemotherapy. We previously reported enhanced antitumour efficacy of (131)I-MIBG by inhibition of the poly(ADP-ribose) polymerase-1 (PARP-1) DNA repair pathway using the phenanthridinone derivative PJ34. Recently developed alternative PARP-1 inhibitors have greater target specificity and are expected to be associated with reduced toxicity to normal tissue. Therefore, our purpose was to determine whether the more specific PARP-1 inhibitors rucaparib and olaparib enhanced the efficacy of X-radiation or (131)I-MIBG. METHODS: Radiosensitisation of SK-N-BE(2c) neuroblastoma cells or noradrenaline transporter gene-transfected glioma cells (UVW/NAT) was investigated using clonogenic assay. Propidium iodide staining and flow cytometry was used to analyse cell cycle progression. DNA damage was quantified by the phosphorylation of H2AX (γH2AX). RESULTS: By combining PARP-1 inhibition with radiation treatment, it was possible to reduce the X-radiation dose or (131)I-MIBG activity concentration required to achieve 50 % cell kill by approximately 50 %. Rucaparib and olaparib were equally effective inhibitors of PARP-1 activity. X-radiation-induced DNA damage was significantly increased 2 h after irradiation by combination with PARP-1 inhibitors (10-fold greater DNA damage compared to untreated controls; p < 0.01). Moreover, combination treatment (i) prevented the restitution of DNA, exemplified by the persistence of 3-fold greater DNA damage after 24 h, compared to untreated controls (p < 0.01) and (ii) induced greater G2/M arrest (p < 0.05) than either single agent alone. CONCLUSION: Rucaparib and olaparib sensitise cancer cells to X-radiation or (131)I-MIBG treatment. It is likely that the mechanism of radiosensitisation entails the accumulation of unrepaired radiation-induced DNA damage. Our findings suggest that the administration of PARP-1 inhibitors and (131)I-MIBG to high risk neuroblastoma patients may be beneficial.

Kinematic 3-D motion analysis of shoulder resurfacing hemiarthroplasty - An objective assessment method.

Shoulder replacement is indicated in the treatment of pain due to osteoarthritis. Few studies have objectively assessed range of motion (RoM) gains at different post-operative time points. This is a prospective 3D motion analysis study to objectively quantify RoM changes at multiple time points following shoulder resurfacing arthroplasty (SRA) for primary gleno-humeral osteoarthritis, comparing it with clinically measured RoM. Clinical assessment, Visual Analog Scale (VAS) pain score, Constant-Morley (CS) and Oxford Shoulder Score (OSS) were recorded. Motion analysis was performed for RoM and three activities of daily living tasks (ADL), pre-operatively and post-operatively at 4 and 12 months. Nineteen shoulders in fifteen patients were included. The mean age was 72 years (range 52-84). There were significant improvements in external and internal rotation, ability to place the hand behind the head and reach the fifth lumbar vertebra, at 4 months on clinical examination and kinematic analysis with no further improvements at 12 months. There was significant improvement in abduction at 4 months with further improvement at 12 months, which was significantly more than noted on clinical assessment. In contrast, kinematic analysis showed a reduction in flexion between 4 and 12 months, while clinically there appeared to be an improvement between these time periods. This is the first study to prospectively utilise objective kinematic 3-D motion analysis in addition to clinical measurements and outcome scores, to investigate the outcome of resurfacing arthroplasty at multiple time points after surgery, providing an understanding into the trends of change in these parameters.

Review: the Contribution of both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours.

Cancer is a leading cause of mortality worldwide. Cancer arises due to a series of somatic mutations that accumulate within the nucleus of a cell which enable the cell to proliferate in an unregulated manner. These mutations arise as a result of both endogenous and exogenous factors. Genes that are commonly mutated in cancer cells are involved in cell cycle regulation, growth and proliferation. It is known that both nature and nurture play important roles in cancer development through complex gene-environment interactions; however, the exact mechanism of these interactions in carcinogenesis is presently unclear. Key environmental factors that play a role in carcinogenesis include smoking, UV light and oncoviruses. Angiogenesis, inflammation and altered cell metabolism are important factors in carcinogenesis and are influenced by both genetic and environmental factors. Although the exact mechanism of nature-nurture interactions in solid tumour formation are not yet fully understood, it is evident that neither nature nor nurture can be considered in isolation. By understanding more about gene-environment interactions, it is possible that cancer mortality could be reduced.