Development of atmospheric characteristics of chlorine-free alternative fluorocarbons. Report on R-134a and E-143a

Rate constants have been measured for the gas phase reaction of OH radicals with 1,1,1,2-tetrafluoroethane R-134a (CH{sub 2}F-CF{sub 3}) and methyl trifluoromethyl ether E-143a (CH{sub 3}-O-CF{sub 3}) over the temperature range 298--460 K. Arrhenius expressions were derived for atmospheric modeling. The infrared absorption cross-sections for R-134a and E-143a have been measured in the region from 400 to 1600 cm{sup {minus}1} and the integrated band strengths have been calculated. The atmospheric lifetimes R-134a and E-143a have been estimated to be 11.6 years and 4.1 years respectively. Global warming potentials have been estimated over time horizons of 20, 50, 100, 200, and 500 years

Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580

Cross-sectional survey of sexual health professionals’ experiences and perceptions of the 2022 mpox outbreak in the UK

Objective: To understand the experiences and perceptions of sexual health professionals responding to the May 2022 mpox outbreak in the UK. Design: Cross-sectional, anonymous, online survey collecting quantitative and qualitative data. Convenience sample recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media. Survey domains included: clinical workload; preparedness, support, and training; safety at work; vaccination; and well-being. Qualitative descriptive analysis of open-text responses was conducted to support interpretation of the quantitative data. Participants: Participants who were employed as sexual health professionals in the UK and had direct clinical experience of mpox were included in the analysis. The survey was completed between 11 August and 31 October 2022 by 139 respondents, the majority of whom were doctors (72.7%), cis-female (70.5%) and White (78.4%). Results: 70.3% reported that they were required to respond to mpox in addition to their existing clinical responsibilities, with 46.8% working longer hours as a result. In the open-text data, respondents highlighted that workload pressures were exacerbated by a lack of additional funding for mpox, pre-existing pressures on sexual health services, and unrealistic expectations around capacity. 67.6% of respondents reported experiencing negative emotional impact due to their mpox work, with stress (59.0%), fatigue (43.2%) and anxiety (36.0%) being the most common symptoms. 35.8% stated that they were less likely to remain in their profession because of their experiences during the mpox outbreak. In the open-text data, these feelings were ascribed to post-COVID exhaustion, understaffing and frustration among some participants at the handling of the mpox response. Conclusions: These findings indicate that sexual health services require increased funding and resources, along with evidence-based well-being interventions, to support sexual health professionals’ outbreak preparedness and recovery

Chemical Kinetics and Photochemical Data for Use in Atmospheric Studies Evaluation Number 15

This is the fifteenth in a series of evaluated sets of rate constants and photochemical cross sections compiled by the NASA Panel for Data Evaluation. The data are used primarily to model stratospheric and upper tropospheric processes, with particular emphasis on the ozone layer and its possible perturbation by anthropogenic and natural phenomena. Copies of this evaluation are available in electronic form and may be printed from the following Internet URL: http://jpldataeval.jpl.nasa.gov/

Can mental health treatments help prevent or reduce intimate partner violence in low- and middle-income countries? A systematic review

Background Epidemiological research suggests an interrelationship between mental health problems and the (re)occurrence of intimate partner violence (IPV). However, little is known about the impact of mental health treatments on IPV victimization or perpetration, especially in low- and middle-income countries (LMIC). Methods We conducted a systematic review to identify prospective, controlled studies of mental health treatments in LMIC. We defined ‘mental health treatment’ as an intervention for individuals experiencing mental ill health (including substance misuse) including a substantial psychosocial or pharmacological component. Studies had to measure a mental health and IPV outcome. We searched across multi-disciplinary databases using a structured search strategy. Screening of title/abstracts and full-text eligibility assessments were conducted by two researchers independently, data were extracted using a piloted spreadsheet, and a narrative synthesis was generated. Results We identified seven studies reported in 11 papers conducted in five middle-income countries. With the exception of blinding, studies overall showed acceptable levels of risk of bias. Four of the seven studies focused on dedicated mental health treatments in various populations, including: common mental disorders in earthquake survivors; depression in primary care; alcohol misuse in men; and alcohol misuse in female adult sex workers. The dedicated mental health treatments targeting depression or alcohol misuse consistently reduced levels of these outcomes. The two studies targeting depression also reduced short-term IPV, but no IPV benefits were identified in the two alcohol-focused studies. The other three studies evaluated integrated interventions, in which a focus on substance misuse was part of efforts to reduce HIV/AIDS and violence against particularly vulnerable women. In contrast to the dedicated mental health interventions, the integrated interventions did not consistently reduce mental ill health or alcohol misuse compared to control conditions. Conclusions Too few studies have been conducted to judge whether mental health treatments may provide a beneficial strategy to prevent or reduce IPV in LMIC. Key future research questions include: whether promising initial evidence on the effects of depression interventions on reducing IPV hold more broadly, the required intensity of mental health components in integrated interventions, and the identification of mechanisms of IPV that are amenable to mental health intervention

Mpox in people with past infection or a complete vaccination course : a global case series

We thank the individuals with mpox who agreed to allow their medical team to share their data; the medical staff who looked after the participants; and all the listed contributors for their efforts in collecting the data.Background: Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity. Methods: In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive. Findings: We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30-45; range 21-58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion. Interpretation: The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak-predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced

Improving education in primary care: development of an online curriculum using the blended learning model

<p>Abstract</p> <p>Background</p> <p>Standardizing the experiences of medical students in a community preceptorship where clinical sites vary by geography and discipline can be challenging. Computer-assisted learning is prevalent in medical education and can help standardize experiences, but often is not used to its fullest advantage. A blended learning curriculum combining web-based modules with face-to-face learning can ensure students obtain core curricular principles.</p> <p>Methods</p> <p>This course was developed and used at The Case Western Reserve University School of Medicine and its associated preceptorship sites in the greater Cleveland area. Leaders of a two-year elective continuity experience at the Case Western Reserve School of Medicine used adult learning principles to develop four interactive online modules presenting basics of office practice, difficult patient interviews, common primary care diagnoses, and disease prevention. They can be viewed at <url>http://casemed.case.edu/cpcp/curriculum</url>. Students completed surveys rating the content and technical performance of each module and completed a Generalist OSCE exam at the end of the course.</p> <p>Results</p> <p>Participating students rated all aspects of the course highly; particularly those related to charting and direct patient care. Additionally, they scored very well on the Generalist OSCE exam.</p> <p>Conclusion</p> <p>Students found the web-based modules to be valuable and to enhance their clinical learning. The blended learning model is a useful tool in designing web-based curriculum for enhancing the clinical curriculum of medical students.</p

Postnatal Development of Hepatic Innate Immune Response

The liver is an immunocompetent organ that plays a key role in the immune response to infections, and the development of hepatic immune function during early postnatal stages has not been thoroughly characterized. This study analyzed the constitutive expression of complement factors, namely C3 and C9, and pattern recognition receptors, namely CD14, toll-like receptor (TLR)-4, and lipopolysaccharide binding protein (LBP), in the liver of postnatal day (P)1, P21, and P70 rats, and compared the kinetics of induction of cytokines and chemokines in the liver of P 1 and P 21 animals. Our studies found that while the mRNA expression of C3, C9, CD14, and TLR-4 was lower in P1 animals, the mRNA level of LBP was higher in P1 animals as compared to older animals, and that the kinetics of induction of cytokines and chemokines was significantly delayed in P1 as compared to P21 liver following LPS stimulation. Our data suggest that hepatic innate immunity is deficient in the neonates and undergo significant development during early postnatal life

Human monkeypox virus infection in women and non-binary individuals during the 2022 outbreaks: a global case series.

BACKGROUND: Between May and November, 2022, global outbreaks of human monkeypox virus infection have been reported in more than 78 000 people worldwide, predominantly in men who have sex with men. We describe the epidemiological and clinical characteristics of monkeypox virus infection in cisgender (cis) and transgender (trans) women and non-binary individuals assigned female sex at birth to improve identification and understanding of risk factors. METHODS: International collaborators in geographical locations with high numbers of diagnoses of monkeypox virus infection were approached and invited to contribute data on women and non-binary individuals with confirmed monkeypox virus infection. Contributing centres completed deidentified structured case-report spreadsheets, adapted and developed by participating clinicians, to include variables of interest relevant to women and non-binary individuals assigned female at birth. We describe the epidemiology and clinical course observed in the reported infections. FINDINGS: Collaborators reported data for a total of 136 individuals with monkeypox virus infection who presented between May 11 and Oct 4, 2022, across 15 countries. Overall median age was 34 years (IQR 28-40; range 19-84). The cohort comprised 62 trans women, 69 cis women, and five non-binary individuals (who were, because of small numbers, grouped with cis women to form a category of people assigned female at birth for the purpose of comparison). 121 (89%) of 136 individuals reported sex with men. 37 (27%) of all individuals were living with HIV, with a higher proportion among trans women (31 [50%] of 62) than among cis women and non-binary individuals (six [8%] of 74). Sexual transmission was suspected in 55 (89%) trans women (with the remainder having an unknown route of transmission) and 45 (61%) cis women and non-binary individuals; non-sexual routes of transmission (including household and occupational exposures) were reported only in cis women and non-binary individuals. 25 (34%) of 74 cis women and non-binary individuals submitted to the case series were initially misdiagnosed. Overall, among individuals with available data, rash was described in 124 (93%) of 134 individuals and described as anogenital in 95 (74%) of 129 and as vesiculopustular in 105 (87%) of 121. Median number of lesions was ten (IQR 5-24; range 1-200). Mucosal lesions involving the vagina, anus, or oropharynx or eye occurred in 65 (55%) of 119 individuals with available data. Vaginal and anal sex were associated with lesions at those sites. Monkeypox virus DNA was detected by PCR from vaginal swab samples in all 14 samples tested. 17 (13%) individuals were hospitalised, predominantly for bacterial superinfection of lesions and pain management. 33 (24%) individuals were treated with tecovirimat and six (4%) received post-exposure vaccinations. No deaths were reported. INTERPRETATION: The clinical features of monkeypox in women and non-binary individuals were similar to those described in men, including the presence of anal and genital lesions with prominent mucosal involvement. Anatomically, anogenital lesions were reflective of sexual practices: vulvovaginal lesions predominated in cis women and non-binary individuals and anorectal features predominated in trans women. The prevalence of HIV co-infection in the cohort was high. FUNDING: None

Read-through Activation of Transcription in a Cellular Genomic Context

Read-through transcription from the adjacent E1a gene region is required for wild-type (wt) activity of the downstream adenovirus E1b promoter early after infection (read-through activation). However, whether a cellular chromosomal template can support read-through activation is not known. To address this issue, read-through activation was evaluated in the context of stably expressed templates in transfected cells. Inhibition of read-through transcription by insertion of a transcription termination sequence between the E1a and E1b promoters reduced downstream gene expression from stably integrated templates. The results indicate that the mechanism of read-through activation does not depend on the structure of early adenovirus nucleoprotein complexes, a structure that is likely to be different from that of cellular chromatin. Accordingly, this regulatory interaction could participate in the coordinated control of the expression of closely linked cellular genes