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Background An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an attack rate of 55% (22/40 workers) occurred at a public-facing office in England from August to September 2021. Published evidence regarding outbreaks in office workplaces remains limited. Aims To describe an investigation of workplace- and worker-related risk factors following an outbreak of SARS-CoV-2 in a public-facing office. Methods The COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook an investigation of the outbreak. This included surface sampling, occupational environmental assessment, molecular and serological testing of workers, and detailed questionnaires. Results Despite existing COVID-19 control measures, surface sampling conducted during a self-imposed 2-week temporary office closure identified viral contamination (10/60 samples, 17% positive), particularly in a small, shared security office (6/9, 67% positive) and on a window handle in one open-plan office. Targeted enhanced cleaning was, therefore, undertaken before the office reopened. Repeat surface sampling after this identified only one positive (2%) sample. Ventilation was deemed adequate using carbon dioxide monitoring (typically ≤1000 ppm). Twelve workers (30%) responded to the COVID-OUT questionnaire, and all had been vaccinated with two doses. One-third of respondents (4/12) reported direct physical or close contact with members of the public; of these, 75% (3/4) reported a divider/screen between themselves and members of the public. Conclusions The results highlight the potential utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies. [ABSTRACT FROM AUTHOR]

Canine parvovirus (CPV) is a common cause of enteritis, immune suppression and systemic inflammation in young dogs. Endothelial markers, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and molecules that upregulate their expression, such as high mobility group box 1 protein (HMGB-1), provide insight into the state of the endothelium during inflammation. This study aimed to determine if circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 were altered in CPV enteritis compared to healthy controls, and whether a correlation existed between these molecules and the degree of inflammation. Thirty dogs with naturally occurring CPV enteritis and ten control dogs were included. Physical examinations, complete blood count and C-reactive protein (CRP) measurements were performed on all dogs at presentation. The concentrations of ICAM-1, VCAM-1 and HMGB-1 were measured using commercially available canine-specific enzyme-linked immunosorbent assay (ELISA) kits. In dogs with CPV enteritis, ICAM-1 concentrations were significantly lower (median: 5.9 [IQR: 4.3–8.3]) and CRP higher (134 [IQR: 85–195]) compared to controls (8.0 [IQR: 6.9–10.3], p = 0.008; 1 [IQR: 0–7], p < 0.001). No significant difference was found for VCAM-1 and HMGB-1. A strong correlation was identified between VCAM-1 and segmented neutrophil count (r = 0.612, p < 0.001). Despite the presence of systemic inflammation in CPV enteritis, evidenced by high CRP concentrations, our results suggest circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 failed to show an increase. Endothelial activation with subsequent leukocyte adhesion and transmigration through the endothelium may be affected in CPV enteritis and these findings require further investigation. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis virus (TBEV) is the most prevalent tick-borne viral disease in Europe and Asia. There are three main subtypes of the virus: European, Siberian, and Far Eastern, each of which having distinctive ecology, clinical presentation, and geographic distribution. In recent years, other TBEV subtypes have been described, namely the Himalayan and Baikalian subtypes. Differences in virulence between TBEV subtypes have been described, with the Far Eastern subtype causing the most severe disease in humans. Considering the emergence of new TBEV foci, the genetic characterisation of the virus in endemic regions is crucial to not only better understand its epidemiology, but also to identify possible genetic determinants of virulence, as well as develop accurate diagnostics and therapeutics. In our previous study, we identified TBEV in six localities of the Kyrgyz Republic (Kyrgyzstan), and Ala-Archa National Nature Park as a focus of TBEV transmission. Whilst we were able to retrieve the first partial TBEV sequence from Kyrgyzstan from Ixodes persulcatus ticks, we were unable to retrieve a complete genome sequence at that time. In this study, we have utilised a sequence-independent single-primer amplification (SISPA) protocol and retrieved the complete genome sequence of our previous 2009 TBEV tick sample (strain KY09) producing the third complete TBEV genome from Kyrgyzstan, and the first genome from the region clustering within the Vasilchenko lineage, suggesting a wider distribution for the lineage than was previously thought. We have also developed a tiling amplicon scheme for Siberian TBEV (TBEV-Sib) which produced > 90 % reference coverage at 100x sequencing depths for samples with as little as 1.13×10 4 RNA copies/ml. Since high viral loads are rare in TBEV clinical samples, the developed protocol adds value to TBEV-Sib endemic regions by offering a novel set of primers to further amplify the viral genome prior to sequencing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Chicken ceca are a rich source of bacteria, including zoonotic pathogens such as Salmonella enterica. The microbiota includes strains/species carrying antimicrobial resistance genes and horizontal transfer of resistance determinants between species may increase the risk to public health and farming systems. Possible sources of these antimicrobial resistance donors - the eggshell carrying bacteria from the hen vertically transmitted to the offspring, or the barn environment where chicks are hatched and raised - has been little explored. In this study, we used Salmonella enterica serovar Heidelberg to evaluate if layer chicks raised in different environments (using combinations of sterilized or non-sterile eggs placed in sterilized isolation chambers or non-sterile rooms) acquired transferable tetracycline resistance genes from surrounding bacteria, especially Escherichia coli. Two-day old chicks were challenged with an antibiotic-susceptible S. Heidelberg strain SH2813 nal R and Salmonella recovered from the cecum of birds at different timepoints to test the in vivo acquisition of tetracycline resistance. Tetracycline-resistant E. coli isolates recovered from birds from the in vivo experiment were used to test the in vitro transfer of tetracycline resistance genes from E. coli to Salmonella. Even though Salmonella SH2813 nal R colonized the 2-day old chicks after oral challenge, tetracycline-resistant Salmonella transconjugants were not recovered, as previously observed. In vitro experiments provided similar results. We discuss several hypotheses that might explain the absence of transconjugants in vitro and in vivo, despite the presence of diverse plasmids in the recovered E. coli. The factors that can inhibit/promote antimicrobial resistance transfers to Salmonella for different plasmid types need further exploration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Clinical trials of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics often include virological secondary endpoints to compare viral clearance and viral load reduction between treatment and placebo arms. This is typically achieved using quantitative reverse-transcriptase PCR (RT-qPCR), which cannot differentiate replicant competent virus from non-viable virus or free RNA, limiting its utility as an endpoint. Culture-based methods for SARS-CoV-2 exist; however, these are often insensitive and poorly standardized for use as clinical trial endpoints. We report optimization of a culture-based approach evaluating three cell lines, three detection methods, and key culture parameters. We show that Vero-angiotensin-converting enzyme 2-transmembrane serine protease 2 cells in combination with RT-qPCR of culture supernatants from the first passage provides the greatest overall detection of Delta viral replication (22 of 32, 68.8%), being able to identify viable virus in 83.3% (20 of 24) of clinical samples with initial Ct values of <30. Likewise, we demonstrate that RT-qPCR using culture supernatants from the first passage of Vero human signaling lymphocytic activation molecule cells provides the highest overall detection of Omicron viral replication (9 of 31, 29%), detecting live virus in 39.1% (9 of 23) of clinical samples with initial Ct values of <25. This assessment demonstrates that combining RT-qPCR with virological endpoint analysis has utility in clinical trials of therapeutics for SARS-CoV-2; however, techniques may require optimization based on dominant circulating strain., Importance: RT-qPCR is commonly used for virological endpoints during clinical trials for antiviral therapy to determine the quantity and presence of virus in a sample. However, RT-qPCR identifies viral RNA and cannot determine if viable virus is present. Existing culture-based techniques for SARS-CoV-2 are insensitive and not sufficiently standardized to be employed as clinical study endpoints. The use of a culture system to monitor replicating viruses could mitigate the possibility of molecular techniques identifying viral RNA from inactive or lysed viral particles. The methodology optimized in this study for detecting infectious viruses may have application as a secondary virological endpoint in clinical trials of therapeutics for SARS-CoV-2 in addition to numerous research processes., Competing Interests: The authors declare no conflict of interest.

Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing cGMP manufacturing capability. Here we report the engineering of an anti-CD4 binding-site (CD4bs) bnAb, N49P9.3, purified from the plasma of an HIV elite-neutralizer. Through a series of rational modifications we produced a variant that demonstrates: enhanced potency; superior antiviral activity in combination with other bnAbs; low polyreactivity; and longer circulating half-life. Additional engineering for manufacturing produced a final variant, eN49P9, with properties conducive to cGMP production. Overall, these efforts demonstrate the feasibility of developing enhanced anti-CD4bs bnAbs with greatly improved antiviral properties as well as potential translational value.

Background: The public order and safety (POS) sector remains susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, as workplace attendance is typically compulsory and close physical contact is often needed. Here, we report on a SARS-CoV-2 outbreak with an attack rate of 39% (9/23), which occurred between 19 and 29 June 2021 among a cohort of new POS recruits participating in a mandatory 18-week training programme in England., Methods: The COVID-OUT (COVID-19 Outbreak investigation to Understand Transmission) study team undertook a multidisciplinary outbreak investigation, including viral surface sampling, workplace environmental assessment, participant viral and antibody testing, and questionnaires, at the two associated training facilities between 5 July and 24 August 2021., Results: Environmental factors, such as ventilation, were deemed inadequate in some areas of the workplace, with carbon dioxide (CO2) levels exceeding 1,500 ppm on multiple occasions within naturally ventilated classrooms. Activities during safety training required close contact, with some necessitating physical contact, physical exertion, and shouting. Furthermore, most participants reported having physical contact with colleagues (67%) and more than one close work contact daily (97%)., Conclusions: Our investigation suggests that site- and activity-specific factors likely contributed to the transmission risks within the POS trainee cohort. Potential interventions for mitigating SARS-CoV-2 transmission in this POS training context could include implementing regular rapid lateral flow testing, optimizing natural ventilation, using portable air cleaning devices in classrooms, and expanding use of well-fitted FFP2/FFP3 respirators during activities where prolonged close physical contact is required., (© Crown copyright 2024.)

Ossa cordis, bones located within the heart trigones, are often classified as heterotopic or ectopic bones. Despite their high prevalence in cattle and some other bovids, little is known about their structure or development. Scanning electron microscopy, X-ray microtomography, gross dissections, and measurements showed the anatomical locations, prevalence, shapes, and measurements of the cardiac bones in both Egyptian Baladi cattle and Holstein-Friesians. All cattle (n = 12) had an Ossa cordis dextrum (average = 50.70 × 20.91 × 5.40 mm). Additionally, 80% Egyptian Baladi and 57% Holstein-Friesian had a smaller Ossa cordis sinistrum (average = 24.94 × 12.75 × 4.12 mm). Egyptian Baladi Ossa cordis were smaller than observed in Holstein-Friesians. Energy-dispersive X-ray analysis showed the elemental constitution (carbon, oxygen, calcium, nitrogen, phosphorus, sodium, and magnesium) of Ossa cordis and Cartilago cordis. These imaging techniques, plus four histological stains (hematoxylin and eosin, Crossman's trichrome, Alcian blue with Van Gieson, and Sirius Red) and microscopy, demonstrated osteoblasts, osteocytes, osteoclasts, astrocytes, blood vessels, bone marrow, lamellar and woven bone, cortical bone, trabeculations with pores and canaliculi, and fibrous components including collagen in the Ossa cordis dextrum and sinistrum. Hyaline cartilage and fibrocartilage (chondrocytes and cartilage matrix) were found within and surrounding the Ossa cordis. These findings were additionally compared against other cattle breeds and species., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Microscopy Society of America.)

An outbreak of SARS-CoV-2 (1 March to 10 May 2021) with an attack rate of 26.5% among approximately 1150 workers at a storage and distribution centre in England prompted a multidisciplinary outbreak investigation (5 May to 6 August 2021), with the aim of better understanding worker- and workplace-related risk factors for viral transmission in the warehousing sector. Overall, environmental factors (e.g., ventilation, humidity and temperature) were assessed to be appropriate at the facility. Nevertheless, 39 (51.3%) surface samples from across the site tested positive for low/ very low levels of SARS-CoV-2 RNA (Ct value ≥ 32.0 for all). Among the study participants, of whom 35.6% were confirmed or suspected cases, 95.5% reported having received COVID-19 prevention training, 100.0% reported handwashing, and 80.0% reported use of face coverings at work. Notably, 43.9% and 19.0% reported working with a symptomatic and a positive contact respectively. Furthermore, 80.5% and 46.3% had concerns regarding reduction in their income and future unemployment, respectively, due to self-isolation. The findings of this study suggest that, in addition to targeted workplace infection control measures and tailored work area specific risk assessments, an enhanced and equitable sick leave policy may help limit presenteeism and viral transmission in large workplaces., (© 2024. Crown.)

Aims: To utilize environmental surface sampling to evaluate areas of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contamination within workplaces to identify trends and improve local coronavirus disease 2019 (COVID-19) control measures., Methods and Results: Surface sampling was undertaken at 12 workplaces that experienced a cluster of COVID-19 cases in the workforce between March 2021 and March 2022. A total of 7.4% (61/829) samples collected were positive for SARS-CoV-2 RNA by the quantitative PCR (qPCR) with only 1.8% (15/829) of samples identified with crossing threshold (Ct) values <35.0. No sample returned whole-genome sequence inferring RNA detected was degraded., Conclusions: Few workplace surface samples were positive for SARS-CoV-2 RNA and positive samples typically contained low levels of nucleic acid. Although these data may infer a low probability of fomite transmission within the workplace, Ct values may have been lower at the time of contamination. Workplace environmental sampling identified lapses in COVID-19 control measures within individual sites and showed trends throughout the pandemic., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1-nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.

Non-small cell lung cancer (NSCLC) is the most fatal non-AIDS defining cancer in people living with HIV (PWH) on antiretroviral therapy (ART). Treatment of malignancies in PWH requires concomitant cancer therapy and ART, which can lead to potential drug-drug interactions (DDIs) and overlapping toxicities. In this study, we hypothesize that replacement of ART with HIV broadly neutralizing antibodies (bNAbs) during cancer chemotherapy (chemo) may maintain HIV suppression and tumor inhibition while minimizing DDIs and overlapping toxicities. We compared HIV suppression, tumor inhibition, and toxicity between conventional treatment (ART plus chemo) and a new modality (bNAbs plus chemo) in humanized mice. Humanized mice infected with HIV YU2 and xenografted with human NSCLC A549 cells were treated with NSCLC chemo (cisplatin and gemcitabine) and first-line ART (dolutegravir, tenofovir disoproxil difumarate, and emtricitabine) or bNAbs (N49P9.6-FR and PGT 121) at human equivalent drug doses. We monitored plasma HIV RNA, tumor volume, and toxicities over five cycles of chemo. We found that chemo plus ART or bNAbs were equally effective at maintaining suppression of HIV viremia and tumor growth. Comparative analysis showed that mice on ART and chemo had significant reductions in body weight and significant increases in plasma creatinine concentrations compared with mice on bNAbs and chemo, which suggests that a combination of bNAbs and chemo produces less renal toxicity than an ART and chemo combination. These data suggest that bNAb therapy during concomitant chemo may be an improved treatment option over ART for PWH and NSCLC, and possibly other cancers, because bNAbs maintain HIV suppression while minimizing DDIs and toxicities.

The elevated use of salt as a de-icing agent on roads in Canada is causing an increase in the chloride concentration of freshwater ecosystems. Freshwater Unionid mussels are a group of organisms that are sensitive to increases in chloride levels. Unionids have greater diversity in North America than anywhere else on Earth, but they are also one of the most imperiled groups of organisms. This underscores the importance of understanding the effect that increasing salt exposure has on these threatened species. There are more data on the acute toxicity of chloride to Unionids than on chronic toxicity. This study investigated the effect of chronic sodium chloride exposure on the survival and filtering activity of two Unionid species (Eurynia dilatata, and Lasmigona costata) and assessed the effect on the metabolome in L. costata hemolymph. The concentration causing mortality after 28 days of exposure was similar for E. dilatata (1893 mg Cl - /L) and L. costata (1903 mg Cl - /L). Significant changes in the metabolome of the L. costata hemolymph were observed for mussels exposed to non-lethal concentrations. For example, several phosphatidylethanolamines, several hydroxyeicosatetraenoic acids, pyropheophorbide-a, and alpha-linolenic acid were significantly upregulated in the hemolymph of mussels exposed to 1000 mg Cl - /L for 28 days. While no mortality occurred in the treatment, elevated metabolites in the hemolymph are an indicator of stress., (© 2023. Crown.)

Background: A SARS-CoV-2 outbreak with an attack rate of 14.3% was reported at a plastics manufacturing plant in England., Methods: Between 23 rd March and 13 th May 2021, the COVID-OUT team undertook a comprehensive outbreak investigation, including environmental assessment, surface sampling, molecular and serological testing, and detailed questionnaires, to identify potential SARS-CoV-2 transmission routes, and workplace- and worker-related risk factors., Results: While ventilation, indicated using real-time CO 2 proxy measures, was generally adequate on-site, the technical office with the highest localized attack rate (21.4%) frequently reached peaks in CO 2 of 2100ppm. SARS-CoV-2 RNA was found in low levels (Ct ≥35) in surface samples collected across the site. High noise levels (79dB) were recorded in the main production area, and study participants reported having close work contacts (73.1%) and sharing tools (75.5%). Only 20.0% of participants reported using a surgical mask and/or FFP2/FFP3 respirator at least half the time and 71.0% expressed concerns regarding potential pay decreases and/or unemployment due to self-isolation or workplace closure., Conclusions: The findings reinforce the importance of enhanced infection control measures in manufacturing sectors, including improved ventilation with possible consideration of CO 2 monitoring, utilising air cleaning interventions in enclosed environments, and provision of good-quality face masks (i.e., surgical masks or FFP2/FFP3 respirators) especially when social distancing cannot be maintained. Further research on the impacts of job security-related concerns is warranted., (© 2023. Crown.)

Surfaces contaminated with infectious SARS-CoV-2 particles have the potential to cause human infection and any increase in surface survivability of a SARS-CoV-2 variant may increase its prevalence over other variants. This study investigated whether there were differences in surface persistence between Delta and Omicron variants leading to Omicron's dominance globally. Stainless steel coupons were inoculated with suspensions of either Delta or Omicron variant and exposed to typical environmental conditions within a containment level 3 laboratory. Coupons were recovered at different timepoints and enumerated using plaque assay. Both variants were recoverable for >48 h on the coupons. Omicron showed a greater reduction of viability after 48 h compared to Delta with a 20-fold decrease versus 15-fold respectively, but this difference was not statistically significant (p = 0.424). These results indicate that Omicron's surface persistence is unlikely to contribute to it becoming the dominant variant over Delta., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

An experimental infection using Babesia (B.) rossi was performed in healthy male Beagle dogs to assess the changes in endocrine variables during disease. Two dogs were infected with a low dose (LD) of parasite inoculum (10 4 parasites) and three dogs were infected with a high dose (HD) (10 8 parasites). Basal serum cortisol, thyroxine (T4), and thyrotropin (TSH) concentrations were measured every second day. Samples were analyzed using a solid- phase, competitive chemiluminescent enzyme immunoassay (Immulyte® 2000, Siemens). Variables were compared between groups and timepoints using linear mixed models. In both groups, the median cortisol concentration increased, whilst the median T4 concentration decreased after infection, with a return towards baseline concentration post treatment. The highest cortisol and the lowest T4 concentrations were reached at 96 h and 108 h post infection, respectively, in the HD group and slightly later at 108 and 144 h post-infection, respectively, in the LD group. A higher cortisol concentration with a more rapid increase, and a lower T4 concentration with a more rapid decline, were associated with disease severity and a higher dose of parasite inoculum. The TSH concentration remained within the reference interval throughout the study period. This study illustrated the temporal changes in endocrine parameters during experimental B. rossi infection and demonstrated that cortisol and T4 tracked the severity of disease, albeit in opposite directions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier GmbH.)

Background: An outbreak of monkeypox virus infections in non-endemic countries was recognised on May 12, 2022. As of September 29, more than 67 000 infections have been reported globally, with more than 3400 confirmed cases in the UK by September 26. Monkeypox virus is believed to be predominantly transmitted through direct contact with lesions or infected body fluids, with possible involvement of fomites and large respiratory droplets. A case of monkeypox in a health-care worker in the UK in 2018 was suspected to be due to virus exposure while changing bedding. We aimed to measure the extent of environmental contamination in the isolation rooms of patients with symptomatic monkeypox., Methods: We investigated environmental contamination with monkeypox virus from infected patients admitted to isolation rooms at the Royal Free Hospital (London, UK) between May 24 and June 17, 2022. Surface swabs of high-touch areas in five isolation rooms, of the personal protective equipment (PPE) of health-care workers in doffing areas in three rooms, and from air samples collected before and during bedding changes in five rooms were analysed using quantitative PCR to assess monkeypox virus contamination levels. Virus isolation was performed to confirm presence of infectious virus in selected positive samples., Findings: We identified widespread surface contamination (56 [93%] of 60 samples were positive) in occupied patient rooms (monkeypox DNA cycle threshold [Ct] values 24·7-37·4), on health-care worker PPE after use (Ct 26·1-35·6), and in PPE doffing areas (Ct 26·3-36·8). Of 20 air samples taken, five (25%) were positive. Three (75%) of four air samples collected before and during a bedding change in one patient's room were positive (Ct 32·7-36·2). Replication-competent virus was identified in two (50%) of four samples selected for viral isolation, including from air samples collected during bedding change., Interpretation: These data show contamination in isolation facilities and potential for suspension of monkeypox virus into the air during specific activities. PPE contamination was observed after clinical contact and changing of bedding. Contamination of hard surfaces in doffing areas supports the importance of cleaning protocols, PPE use, and doffing procedures., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Although the world is currently focused on the COVID-19 pandemic, HIV/AIDS remains a significant threat to public health. To date, the HIV/AIDS pandemic has claimed the lives of over 36 million people, while nearly 38 million people are currently living with the virus. Despite the undeniable success of antiretroviral therapy (ART) in controlling HIV, the medications are not curative. Soon after initial infection, HIV integrates into the genome of infected cells as a provirus, primarily, within CD4+ T lymphocytes and tissue macrophages. When not actively transcribed, the provirus is referred to as a latent reservoir because it is hidden to the immune system and ART. Following ART discontinuation, HIV may emerge from the replication-competent proviruses and resumes the infection of healthy cells. Thus, these latent reservoirs are a major obstacle to an HIV cure, and their removal remains a priority. A vital aspect in the development of curative therapies is the demonstration of efficacy in an animal model, such as the humanized mouse model. Therefore, optimization, standardization, and validation of the humanized mouse model are a priority. The purpose of this review article is to provide an update on existing humanized mouse models, highlighting the advantages and disadvantages of each as they pertain to HIV cure studies and to review the approaches to curative therapies that are under investigation.

An imported case of monkeypox was diagnosed in December 2019 in a traveller returning from Nigeria to the UK. Subsequently, environmental sampling was performed at two adjoining single-room residences occupied by the patient and their sibling. Monkeypox virus DNA was identified in multiple locations throughout both properties, and monkeypox virus was isolated from several samples 3 days after the patient was last in these locations. Positive samples were identified following the use of both vacuum and surface sampling techniques; these methodologies allowed for environmental analysis of potentially contaminated porous and non-porous surfaces via real-time quantitative reverse transcriptase PCR analysis in addition to viral isolation to confirm the presence of infection-competent virus. This report confirms the potential for infection-competent monkeypox virus to be recovered in environmental settings associated with known positive cases and the necessity for rapid environmental assessment to reduce potential exposure to close contacts and the general public. The methods adopted in this investigation may be used for future confirmed cases of monkeypox in order to establish levels of contamination, confirm the presence of infection-competent material and to identify locations requiring additional cleaning., (© 2022 Crown copyright. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Oral HIV pre-exposure prophylaxis (PrEP) is effective at preventing HIV. However, low adherence is common and undermines these protective effects. This is particularly relevant for groups with disproportionately higher rates of HIV, including Black men who have sex with men (MSM). The current study tested the feasibility, acceptability, and preliminary efficacy of a gamified mobile health contingency management intervention for PrEP adherence-called mSMART (Mobile App-Based Personalized Solutions for Medication Adherence of Rx Pill Tool). Fifteen Black MSM already prescribed PrEP in the community completed baseline and follow-up assessments separated by 8 weeks of using mSMART. Regarding feasibility, there was no study attrition, no mSMART functional difficulties that significantly interfered with use, and a mean rate of 82% daily mSMART use. Acceptability ratings were in the moderately to extremely satisfied range for factors such as willingness to recommend mSMART to others and user-friendliness, and in the low range for ratings on difficulty learning how to use mSMART. Scores on a system usability measure were in the acceptable range for 73% of the sample. Qualitative analysis of follow-up interviews identified individual components of mSMART that could be modified in future iterations to make it more engaging. PrEP composite adherence scores from biomarkers indicated an improvement from baseline to follow-up with a medium effect size, as well as a decrease in the number of perceived barriers to medication adherence. Findings indicate a future efficacy trial is needed to examine the effects of this gamified mobile health contingency management intervention on PrEP adherence., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It is estimated that 16 to 25% of patients in hospital have diabetes and 1 in 25 inpatients with Type 1 Diabetes develop diabetic ketoacidosis (DKA). It is vital that non-specialist doctors recognize and appropriately manage diabetes emergencies. Simulation training is increasingly being used in healthcare and virtual reality (VR) based educational resources is transforming medical education. This study aimed to evaluate the use of virtual reality to help non-specialist clinicians manage clinical scenarios related to diabetes., Methods: This pilot project, titled 'DEVICE' (Diabetes Emergencies: Virtual Interactive Clinical Education) was developed in collaboration with Oxford Medical Simulation. Fully interactive immersive VR scenarios were created to stimulate real life diabetes emergencies. Users then received personalized feedback and performance metrics. Feedback surveys were provided before and after the participation in the VR scenario. Kirkpatrick's training evaluation model was used., Results: Thirty-nine participants from 2 hospitals in UK provided feedback up to 3 months after attending the VR education sessions. Overall feedback was extremely positive, and participants found this immersive teaching experience very helpful. After use of virtual reality scenarios, the mean trainee confidence in managing DKA (on an 8-point Likert scale) increased from 3.92 (3.38-4.47) 95% CI to 5.41 (4.79-6.03) 95% CI (statistically significant). The VR study demonstrates Kirkpatrick level 3 in the follow up survey., Conclusion: VR based training scenarios in this pilot project increased confidence in managing diabetes emergencies and demonstrated positive changes in their behavior. VR education is a safe, useful and a well-liked training tool for diabetes emergencies.

Babesia rossi causes severe morbidity and mortality in dogs in sub-Saharan Africa, and the complications associated with this disease are likely caused by an unfocused, excessive inflammatory response. During this experimental B. rossi study we investigated inflammatory marker and cytokine kinetics during infection and after treatment. We aimed to determine whether infectious dose and treatment would influence the progression of the inflammatory response and clinical disease. Six healthy male beagle dogs formed the study population, one was used to raise the infectious inoculum, three were administered a high B. rossi infectious dose (HD group) and two a low infectious dose (LD group). Clinical examination, complete blood count (CBC) and C-reactive protein (CRP) were determined daily. Cytokines were quantified on stored plasma collected during the study, using a canine specific cytokine magnetic bead panel (Milliplex©). The experiment was terminated and treatment administered when predetermined experimental or humane endpoints were reached. Parasitemia occurred on day 1 and 3 in the HD and LD groups respectively. The rate of increase in parasitemia in the HD group was significantly faster than that seen in the LD group. Significant differences were found in heart rate, blood pressure, interferon gamma (INFγ), keratinocyte chemoattractant (KC), INFγ-induced protein 10 (IP10), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP1), tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), IL-6, IL-7, IL-8, IL-10 IL-15, IL-18, CRP, neutrophils and monocytes between groups at multiple time points during the course of the infection. Our findings suggest that the initiation of inflammation occurs before the onset of clinical disease in B. rossi infection and infectious dose influences the onset of the inflammatory response. Treatment enhances the inflammatory response in the immediate post-treatment period which may contribute to disease associated complications. Finally, we found that there is an imbalance in pro/anti-inflammatory cytokine concentrations during infection which may promote parasite replication., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Workplace-related outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to occur globally. The manufacturing sector presents a particular concern for outbreaks, and a better understanding of transmission risks are needed. Between 9 March and 24 April 2021, the COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook a comprehensive investigation of a SARS-CoV-2 outbreak at an automotive manufacturing site in England. The site had a total of 266 workers, and 51 SARS-CoV-2 infections. Overall, ventilation, humidity, and temperature at the site were assessed to be appropriate for the number of workers and the work being conducted. The company had implemented a number of infection control procedures, including provision of face coverings, spacing in the work, and welfare areas to allow for social distancing. However, observations of worker practices identified lapses in social distancing, although all were wearing face coverings. A total of 38 workers, including four confirmed cases, participated in the COVID-OUT study. The majority of participants received COVID-19 prevention training, though 42.9% also reported that their work required close physical contact with co-workers. Additionally, 73.7% and 34.2% had concerns regarding reductions in future income and future unemployment, respectively, due to self-isolation. This investigation adds to the growing body of evidence of SARS-CoV-2 outbreaks from the manufacturing sector. Despite a layered COVID-19 control strategy at this site, cases clustered in areas of high occupancy and close worker proximity.

Public health interventions require evidence-based decision-making to maximize impact. Spatial decision support systems (SDSS) are designed to collect, store, process and analyze data to generate knowledge and inform decisions. This paper discusses how the use of a SDSS, the Campaign Information Management System (CIMS), to support malaria control operations on Bioko Island has impacted key process indicators of indoor residual spraying (IRS): coverage, operational efficiency and productivity. We used data from the last five annual IRS rounds (2017 to 2021) to estimate these indicators. IRS coverage was calculated as the percentage of houses sprayed per unit area, represented by 100x100 m map-sectors. Optimal coverage was defined as between 80% and 85%, and under and overspraying as coverage below 80% and above 85%, respectively. Operational efficiency was defined as the fraction of map-sectors that achieved optimal coverage. Daily productivity was expressed as the number of houses sprayed per sprayer per day (h/s/d). These indicators were compared across the five rounds. Overall IRS coverage (i.e. percent of total houses sprayed against the overall denominator by round) was highest in 2017 (80.2%), yet this round showed the largest proportion of oversprayed map-sectors (36.0%). Conversely, despite producing a lower overall coverage (77.5%), the 2021 round showed the highest operational efficiency (37.7%) and the lowest proportion of oversprayed map-sectors (18.7%). In 2021, higher operational efficiency was also accompanied by marginally higher productivity. Productivity ranged from 3.3 h/s/d in 2020 to 3.9 h/s/d in 2021 (median 3.6 h/s/d). Our findings showed that the novel approach to data collection and processing proposed by the CIMS has significantly improved the operational efficiency of IRS on Bioko. High spatial granularity during planning and deployment together with closer follow-up of field teams using real-time data supported more homogeneous delivery of optimal coverage while sustaining high productivity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 García et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)