Prevalence and severity of abscesses and cellulitis, and their associations with other health outcomes, in a community-based study of people who inject drugs in London, UK.

BACKGROUND: Skin and soft tissue infections (SSTI) are a common but preventable cause of morbidity and mortality among people who inject drugs (PWID). They can be severe, and hospitalisations of PWID with SSTI are rising. The most common SSTI presentations are abscesses and cellulitis. METHODS: We used data from Care & Prevent, a cross-sectional community survey of PWID in London. We reported the lifetime prevalence of SSTI, severity of infections, key risk factors, and associated sequelae. Pictorial questions were used to assess SSTI severity. RESULTS: We recruited 455 PWID. SSTI lifetime prevalence was high: 64% reported an abscess and/or cellulitis. Over one-third (37%) reported a severe infection, 137 (47%) reported hospitalisation. SSTIrisk factors were: aged 35+ years, injecting once or more times a day, subcutaneous or intra-muscular injections, and making four or more attempts to achieve an injection. Those who reported having other health conditions were at higher odds of having an abscess or cellulitis, with risk tending to increase with number of reported conditions. Half (46%) employed self-care for their worst SSTI, and 43% waited for ten or more days before seeking medical care or not seeking medical care at all. CONCLUSIONS: Abscess and cellulitis are very common among PWID in London. We corroborate findings indicating SSTIs are associated with risks, e.g. venous access problems, as well as other co-morbid conditions: septicaemia, endocarditis, DVT, and kidney disease. These co-morbidities may impact SSTIs severity and outcomes. Delayed healthcare seeking potentially exacerbates infection severity, which in turn increases poorer health outcomes and complications

Navigating environmental constraints to injection preparation: the use of saliva and other alternatives to sterile water among unstably housed PWID in London.

BACKGROUND: The United Kingdom is experiencing an increase in drug-related deaths and serious bacterial infections among its most vulnerable citizens. Cuts to essential services, coupled with a growing homeless population, create a challenging environment to tackle this public health crisis. In this paper, we highlight an underexplored environmental constraint faced by people living and injecting drugs on the streets. Access to water for injection is restricted in the UK, due to legislative and financial barriers. Austerity measures, such as public toilet closures, further restrict the ability of people made homeless to access clean water and protect themselves from health harms. METHODS: We generated questionnaire (n = 455) and in-depth qualitative interview (n = 32) data with people who inject drugs in London for the Care and Prevent study. Participants provided detail on their life history; drug use, injecting and living environments; health conditions and care seeking practices. FINDINGS: A high proportion of the survey sample reported lifetime history of street homelessness (78%), bacterial infections (65%) and related hospitalisation (30%). Qualitative accounts highlight unsafe, potentially dangerous, injection practices in semi-public spaces. Multiple constraints to sourcing sterile water for injection preparation were reported. Alternatives to sterile water included puddle water, toilet cistern water, whisky, cola soda and saliva. Participants who injected heroin and crack cocaine together unanimously reported adding water at two stages during injection preparation: first, adding water as a vehicle for heroin (which was then heated); second, adding cold water to the heroin mixture prior to adding the crack cocaine. This new finding of a stage addition of solvent may represent an additional risk of infection. CONCLUSION: Currently, harm reduction equipment and resources for safe injecting are not meeting the needs of people who inject drugs who are street homeless or unstably housed. Preparation of injections with non-sterile water sources could precipitate bacterial and fungal infections, particularly when used without the application of heat. It is crucial that water for injection, also skin cleaning, is made available for the unstably housed and that harm reduction messaging is tailored to speak to the everyday realities of people who prepare and inject drugs in public spaces

Differentiation-Induced Remodelling of Store-Operated Calcium Entry Is Independent of Neuronal or Glial Phenotype but Modulated by Cellular Context

Neurogenesis is a complex process leading to the generation of neuronal networks and glial cell types from stem cells or intermediate progenitors. Mapping subcellular and molecular changes accompanying the switch from proliferation to differentiation is vital for developing therapeutic targets for neurological diseases. Neuronal (N-type) and glial (S-type) phenotypes within the SH-SY5Y neuroblastoma cell line have distinct differentiation responses to 9-cis-retinoic acid (9cRA). In both cell phenotypes, these were accompanied at the single cell level by an uncoupling of Ca2+ store release from store-operated Ca2+ entry (SOCE), mediated by changes in the expression of calcium release-activated calcium pore proteins. This remodelling of calcium signalling was moderated by the predominant cell phenotype within the population. N- and S-type cells differed markedly in their phenotypic stability after withdrawal of the differentiation inducer, with the phenotypic stability of S-type cells, both morphologically and with respect to SOCE properties, in marked contrast to the lability of the N-type phenotype. Furthermore, the SOCE response of I-type cells, a presumed precursor to both N- and S-type cells, varied markedly in different cell environments. These results demonstrate the unique biology of neuronal and glial derivatives of common precursors and suggest that direct or indirect interactions between cell types are vital components of neurogenesis that need to be considered in experimental models.</p

Injecting-related health harms and overuse of acidifiers among people who inject heroin and crack cocaine in London: a mixed-methods study.

BACKGROUND: Venous access is a priority for people who inject drugs (PWID). Damage and scarring of peripheral veins can exacerbate health harms, such as skin and soft tissue infections (SSTI), and promote transitions to femoral and subcutaneous injecting. Brown heroin available in Europe requires acidification for injection preparation. In this paper, we present mixed-methods data to explore our hypothesis of a link between overly acidic injection solutions, venous damage and SSTI risk. METHODS: We present a structured survey (n = 455) and in-depth qualitative interview (n = 31) data generated with PWID in London for the Care & Prevent study. Participants provided life history data and detail on injecting environments and drug preparation practices, including the use of acidifiers. Bivariate and multivariate analyses were conducted using a logistic regression for binary outcomes to explore associations between outcomes and excessive acidifier use. Grounded theory principles informed inductive qualitative analysis. Mixed-methods triangulation was iterative with results comparison informing the direction and questions asked of further analyses. RESULTS: Of the 455 participants, most (92%) injected heroin and/or crack cocaine, with 84% using citric as their primary acid for drug preparation. Overuse of acidifier was common: of the 418 who provided an estimate, 36% (n = 150) used more than ½ a sachet, with 30% (n = 127) using a whole sachet or more. We found associations between acidifier overuse, femoral injecting and DVT, but not SSTI. Qualitative accounts highlight the role of poor heroin quality, crack cocaine use, information and manufacturing constraints in acidifier overuse. Painful injections and damage to peripheral veins were common and often attributed to the use of citric acid. CONCLUSIONS: To reduce injecting-related injury and associated consequences, it is crucial to understand the interplay of environmental and practice-based risks underpinning venous damage among PWID. Overuse of acidifier is a modifiable risk factor. In the absence of structural supports such as safe injecting facilities or the prescribing of pharmaceutical diamorphine, there is an urgent need to revisit injecting paraphernalia design and distribution in order to alleviate health harms and distress among the most marginalised

High prevalence of albuminuria amongst people who inject drugs: A cross-sectional study.

Albuminuria is a key biomarker for cardiovascular disease and chronic kidney disease. Our study aimed to describe the prevalence of albuminuria amongst people who inject drugs in London and to test any potential associations with demographic characteristics, past diagnoses, and drug preparation and administration practices. We carried out a cross-sectional survey amongst people who use drugs in London. The main outcome measure was any albuminuria including both microalbuminuria and macroalbuminuria. Three-hundred and sixteen samples were tested by local laboratory services. Our study initially employed point-of-care testing methods but this resulted in a high number of false positives. Our findings suggest the prevalence of albuminuria amongst PWID is twice that of the general population at 19% (95%CI 15.3-24.0%). Risk factors associated with albuminuria were HIV (aOR 4.11 [95% CI 1.37-12.38]); followed by overuse of acidifier for dissolving brown heroin prior to injection (aOR 2.10 [95% CI 1.04-4.22]). Albuminuria is high amongst people who inject drugs compared to the general population suggesting the presence of increased cardiovascular and renal pathologies. This is the first study to demonstrate an association with acidifier overuse. Dehydration may be common amongst this population and may affect the diagnostic accuracy of point-of-care testing for albuminuria

Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic

A multicenter cross-sectional survey study involving four Italian University Hospitals was performed to test the hypothesis that negative affect and positive affect (affective dimensions) mediate the association between risk perception (perceived risk of infection and death; cognitive dimensions) and the feeling of work exhaustion (WE) among obstetrics healthcare providers (HCPs) during the Coronavirus Disease 2019 (COVID-19) pandemic. Totally, 570 obstetrics HCPs were invited to complete the 104-item IPSICO survey in May 2020. A theoretical model built on the tested hypothesis was investigated by structural equation modelling. The model explained 32.2% of the WE variance. Only negative affect mediated the association between cognitive dimensions and WE and also the association between WE and psychological well-being before the pandemic, experiences of stressful events, female gender, and dysfunctional coping. Non-mediated associations with WE were observed for work perceived as a duty, experience of stressful events, support received by colleagues, and the shift strategy. Only previous psychological well-being, support by colleagues, and shift strategies were inversely associated with WE. Based on study results, monitoring negative than positive affect appears superior in predicting WE, with practical implications for planning psychological interventions in HCPs at the individual, interpersonal, and organizational levels

Non Destructive Evaluation of Containment Walls in Nuclear Power Plants

Two functions are regularly tested on the containment walls in order to anticipate a possible accident. The first is mechanical to resist at a possible internal over-pressure and the second is to prevent leakage. The reference accident LLOCA (Large Loss of Coolant Accident) is the rupture of a pipe in the primary circuit of a nuclear plant. In this case, the pressure and temperature can reach 5 bar and 180°C in 20 seconds. The national project ‘Non-destructive testing of the containment structures of nuclear plants’ aims at studying the non-destructive techniques capable to evaluate the concrete properties and its damaging or progression of cracks. This 4-year-project is segmented into two parts. The first consists in developing and selecting the most relevant NDEs (Non Destructive Evaluations) in the laboratory to reach these goals. These evaluations are developed in conditions representing the real conditions of the stresses generated during ten-yearly visits of the plants or those related to an accident. The second part consists in applying the selected techniques to two containment structures under pressure. The first (technique) is proposed by the ONERA (National Office for Aerospace Studies and Research of France) and the second is a mock-up of a containment wall on a 1/3 scale made by EDF (Electricity of France) within the VeRCoRs program. Communication bears on the part of the project that concerns the damaging and cracking follow-up. The tests are done in bending on 3 or 4 points in order to study the cracks’ generation, their propagation, as well as their opening and closing. The mostly ultrasonic techniques developed concern linear or non-linear acoustic: acoustic emission [1], LOCADIFF (Locating with diffuse ultrasound) [2], energy diffusion, surface waves velocity and attenuation, DAET (Dynamic Acousto-Elasticity Testing) [3]. The data contribute to providing the mapping of the parameters searched for, either in volume, in surface or globally. Image correlation is an important additional asset to validate the coherence of the data. The spatial normalization of the data allows proposing algorithms on the combination of the experimental data. The tests results are presented and they show the capacity and the limits of the evaluation of the volume, surface or global data. A data fusion procedure is associated with these results

Schedule-dependent response of neuroblastoma cell lines to combinations of etoposide and cisplatin

The growth inhibitory effects of cisplatin and etoposide on neuroblastoma cell lines were investigated in several scheduled combinations. Results were analyzed using median effect and combination index analyses. In all schedules in which cisplatin was administered prior to etoposide a synergistic effect was observed. Conversely, an antagonistic effect was seen in all schedules where etoposide was administered before cisplatin

Nutritional Factors Modulating Alu Methylation inan Italian Sample from The Mark-Age StudyIncluding Offspring of Healthy Nonagenarians

Alu hypomethylation promotes genomic instability and is associated with aging and age-related diseases. Dietary factors affect global DNA methylation, leading to changes in genomic stability and gene expression with an impact on longevity and the risk of disease. This preliminary study aims to investigate the relationship between nutritional factors, such as circulating trace elements, lipids and antioxidants, and Alu methylation in elderly subjects and offspring of healthy nonagenarians. Alu DNA methylation was analyzed in sixty RASIG (randomly recruited age-stratified individuals from the general population) and thirty-two GO (GeHA offspring) enrolled in Italy in the framework of the MARK-AGE project. Factor analysis revealed a different clustering between Alu CpG1 and the other CpG sites. RASIG over 65 years showed lower Alu CpG1 methylation than those of GO subjects in the same age class. Moreover, Alu CpG1 methylation was associated with fruit and whole-grain bread consumption, LDL2-Cholesterol and plasma copper. The preserved Alu methylation status in GO, suggests Alu epigenetic changes as a potential marker of aging. Our preliminary investigation shows that Alu methylation may be affected by food rich in fibers and antioxidants, or circulating LDL subfractions and plasma copper