Identification of bacteria-derived HLA-bound peptides in melanoma.

A variety of species of bacteria are known to colonize human tumours1-11, proliferate within them and modulate immune function, which ultimately affects the survival of patients with cancer and their responses to treatment12-14. However, it is not known whether antigens derived from intracellular bacteria are presented by the human leukocyte antigen class I and II (HLA-I and HLA-II, respectively) molecules of tumour cells, or whether such antigens elicit a tumour-infiltrating T cell immune response. Here we used 16S rRNA gene sequencing and HLA peptidomics to identify a peptide repertoire derived from intracellular bacteria that was presented on HLA-I and HLA-II molecules in melanoma tumours. Our analysis of 17 melanoma metastases (derived from 9 patients) revealed 248 and 35 unique HLA-I and HLA-II peptides, respectively, that were derived from 41 species of bacteria. We identified recurrent bacterial peptides in tumours from different patients, as well as in different tumours from the same patient. Our study reveals that peptides derived from intracellular bacteria can be presented by tumour cells and elicit immune reactivity, and thus provides insight into a mechanism by which bacteria influence activation of the immune system and responses to therapy.

TLR signaling is required for Salmonella typhimurium virulence.

Toll-like receptors (TLRs) contribute to host resistance to microbial pathogens and can drive the evolution of virulence mechanisms. We have examined the relationship between host resistance and pathogen virulence using mice with a functional allele of the nramp-1 gene and lacking combinations of TLRs. Mice deficient in both TLR2 and TLR4 were highly susceptible to the intracellular bacterial pathogen Salmonella typhimurium, consistent with reduced innate immune function. However, mice lacking additional TLRs involved in S. typhimurium recognition were less susceptible to infection. In these TLR-deficient cells, bacteria failed to upregulate Salmonella pathogenicity island 2 (SPI-2) genes and did not form a replicative compartment. We demonstrate that TLR signaling enhances the rate of acidification of the Salmonella-containing phagosome, and inhibition of this acidification prevents SPI-2 induction. Our results indicate that S. typhimurium requires cues from the innate immune system to regulate virulence genes necessary for intracellular survival, growth, and systemic infection.

State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI.

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

Micrometeorite collections: a review and their current status.

Micrometeorites are estimated to represent the main part of the present flux of extraterrestrial matter found on the Earth's surface and provide valuable samples to probe the interplanetary medium. Here, we describe large and representative collections of micrometeorites currently available to the scientific community. These include Antarctic collections from surface ice and snow, as well as glacial sediments from the eroded top of nunataks-summits outcropping from the icesheet-and moraines. Collections extracted from deep-sea sediments (DSS) produced a large number of micrometeorites, in particular, iron-rich cosmic spherules that are rarer in other collections. Collections from the old and stable surface of the Atacama Desert show that finding large numbers of micrometeorites is not restricted to polar regions or DSS. The advent of rooftop collections marks an important step into involving citizen science in the study of micrometeorites, as well as providing potential sampling locations over all latitudes to explore the modern flux. We explore their strengths of the collections to address specific scientific questions and their potential weaknesses. The future of micrometeorite research will involve the finding of large fossil micrometeorite collections and benefit from recent advances in sampling cosmic dust directly from the air. This article is part of the theme issue 'Dust in the Solar System and beyond'.

Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study.

BACKGROUND: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. OBJECTIVE: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. DESIGN: Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment. SETTING: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). PATIENTS: 44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. MEASUREMENTS: The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis. RESULTS: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). LIMITATION: Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment. CONCLUSION: The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19, but nirmatrelvir plus ritonavir reduced this risk further. PRIMARY FUNDING SOURCE: National Institutes of Health.

Oral Antiviral Therapy Utilization Among Adults with Recent COVID-19 in the United States.

BACKGROUND: This is the first study, to our knowledge, to assess uptake of oral antiviral treatment (OAV) for COVID-19 in the US and assess whether it is reaching recommended groups. OBJECTIVE: The study evaluated uptake among persons of all ages, with emphasis on utilization among individuals ages 65 + who comprise 75% of all COVID-19 deaths. To maximize public health outreach and benefit, we sought to understand reasons for use and non-use of OAV among individuals 65 + with at least mild COVID-19 symptoms. DESIGN: Data were collected from phase 3.5 of the US Census Household Pulse Survey, during three 2022 time periods: June 1-13, June 29-July 11, and July 27-August 8. PARTICIPANTS: Respondents (n = 12,299) were ages 18 + with active or resolved COVID-19 within the last 4 weeks of their survey participation. MAIN MEASURE(S): Comparisons of demographic variables were made for OAV uptake using the chi-square test of independence. A logistic regression was conducted to identify characteristics of participants independently associated with receipt of an OAV. Comparisons were made with chi-square testing, between those ages 65 + with at least mild symptoms who endorsed one of a number of specific reasons for not using OAV. KEY RESULTS: Utilization was low-17.9% of all respondents, 20.5% of respondents ages 50-64, and 33.9% of respondents 65 years and older received guideline-concordant treatment for their infection. Receipt did not differ by income or sex. The average response across the three phases was 5.4%. Most common reasons for not receiving treatment included having minimal symptoms, not thinking that they needed treatment, and not receiving a recommendation from their healthcare provider. CONCLUSIONS: A minority of increased-risk US residents have accessed early therapy for COVID-19 despite being made available without cost. Responses suggest that efforts to improve patient and provider knowledge could improve utilization to mitigate future COVID-19 hospitalizations.

The impact of break duration, time of break onset, and prior shift duration on the amount of sleep between shifts in heavy vehicle drivers.

This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.

Improving identification of symptomatic cancer at primary care clinics: A predictive modeling analysis in Botswana.

In resource-limited settings, augmenting primary care provider (PCP)-based referrals with data-derived algorithms could direct scarce resources towards those patients most likely to have a cancer diagnosis and benefit from early treatment. Using data from Botswana, we compared accuracy of predictions of probable cancer using different approaches for identifying symptomatic cancer at primary clinics. We followed cancer suspects until they entered specialized care for cancer treatment (following pathologically confirmed diagnosis), exited from the study following noncancer diagnosis, or died. Routine symptom and demographic data included baseline cancer probability assessed by the primary care provider (low, intermediate, high), age, sex, performance status, baseline cancer probability by study physician, predominant symptom (lump, bleeding, pain or other) and HIV status. Logistic regression with 10-fold cross-validation was used to evaluate classification by different sets of predictors: (1) PCPs, (2) Algorithm-only, (3) External specialist physician review and (4) Primary clinician augmented by algorithm. Classification accuracy was assessed using c-statistics, sensitivity and specificity. Six hundred and twenty-three adult cancer suspects with complete data were retained, of whom 166 (27%) were diagnosed with cancer. Models using PCP augmented by algorithm (c-statistic: 77.2%, 95% CI: 73.4%, 81.0%) and external study physician assessment (77.6%, 95% CI: 73.6%, 81.7%) performed better than algorithm-only (74.9%, 95% CI: 71.0%, 78.9%) and PCP initial assessment (62.8%, 95% CI: 57.9%, 67.7%) in correctly classifying suspected cancer patients. Sensitivity and specificity statistics from models combining PCP classifications and routine data were comparable to physicians, suggesting that incorporating data-driven algorithms into referral systems could improve efficiency.

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa.

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional and global level in 2020. Proportions of cervical cancer (a) diagnosed in women living with HIV (WLHIV), and (b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted toward younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention.

Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana.

BACKGROUND: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown. METHODS: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals. RESULTS: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35). CONCLUSIONS: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.).

Short-Chain Fatty Acids Modulate Healthy Gut Microbiota Composition and Functional Potential.

Many studies have focused on the metabolic capacity of human gut microbiota to produce short-chain fatty acids and subsequent effects on host physiology. Given scarce data on how SCFAs produced by gut bacteria participate in cross-feeding to influence community structure and function, we evaluated the potential of SCFAs to modulate human gut microbiota in vitro. We employed anaerobic fecal cultivation in chemically defined medium supplemented with one of nine SCFAs to determine effects on both gut microbial community structure via 16S rRNA sequencing and function via genome reconstruction analysis. Each SCFA displayed significant and unique modulatory potential with respect to the relative abundance of bacterial taxa. Analysis of SCFA-supplemented communities revealed that alterations of individual closely related phylotypes displayed coherent changes, although exceptions were also observed which suggest strain-dependent differences in SCFA-induced changes. We used genome reconstruction to evaluate the functional implications of SCFA-mediated restructuring of fecal communities. We note that some SCFA-supplemented cultures displayed a reduction in the predicted abundance of SCFA producers, which suggests a possible undefined negative feedback mechanism. We conclude that SCFAs are not simply end-products of metabolism but also serve to modulate the gut microbiota through cross-feeding that alters the fitness of specified taxa. These results are important in the identification of prebiotics that elevate specific SCFAs for therapeutic benefit and highlight SCFA consumers as a salient part of the overall metabolic flux pertaining to bacterial fermentative processes.

Concreteness and levels of processing: a test of the dual-coding hypothesis using dynamic visual noise.

Concreteness and levels of processing (LOP) effects have been attributed to the differential availability of visual images for concrete words, and at deeper levels of processing, respectively. Interestingly, the concreteness effect has been shown to disappear under conditions involving dynamic visual noise (DVN), which is thought to suppress the generation of visual images from long-term memory. The present study further investigated the role of visual imagery in concreteness and LOP effects. Across four experiments, DVN was manipulated during study, and participants' memory for concrete and abstract words was measured using recall and recognition tests. Although some support for dual-coding was found, concreteness and LOP effects were not fully explained by visual imagery because they were present under DVN conditions. We conclude that concreteness and LOP effects may be better explained by an "extended dual-coding theory" that incorporates the role of context availability in accounting for this pattern of results.

Service learning and self-efficacy in exercise science: outcomes of a community fitness training program involving undergraduate Exercise Science students.

There is increasing awareness of the importance of civic engagement in higher education. Service-learning activities in undergraduate programs, in particular, have been linked to positive academic outcomes and gains in various forms of self-efficacy. Exercise Science students at our university complete two service-learning courses as part of the curriculum, each of which involves implementing a structured 12-week individualized fitness training program with a community member client. The aim of this study was to investigate the effect of these service-learning experiences on Exercise Science students' self-efficacy for fitness assessment and exercise prescription. Students completed a seven-item self-efficacy questionnaire administered at both the beginning and end of each service-learning course and reflected on their experience using an end-of-course survey. Our results showed significant improvements in self-efficacy from pretest to posttest for each of the two service-learning experiences, with the second experience producing additional gains in self-efficacy over and above the first. Students also reported improved confidence in their fitness assessment and exercise prescription skills in the end-of-course survey. Community members involved in the fitness training program reported a positive experience with students' knowledge of fitness assessment and exercise prescription as well as their own progression to independence in a home exercise program. Our findings highlight the benefits of including a structured service-learning experience in the Exercise Science curriculum.NEW & NOTEWORTHY This study was done to investigate the effect of a structured fitness training experience on Exercise Science students' self-efficacy for fitness assessment and exercise prescription. Our results indicate a significant improvement in self-efficacy from pretest to posttest. Students also reported improved confidence in their fitness assessment and exercise prescription skills. Community members reported a positive experience with students' knowledge of fitness assessment and exercise prescription and their progression to independence in a home exercise program.

Beneficial Effects of Cannabis on Blood-Brain Barrier Function in Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity. METHODS: We studied persons with HIV (PWH) and HIV-negative (HIV-) individuals who had used cannabis recently. We assessed 2 biomarkers of BBB permeability: the cerebrospinal fluid (CSF) to serum albumin ratio (CSAR) and CSF levels of soluble urokinase plasminogen activator receptor (suPAR), a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay. RESULTS: Participants were 45 PWH and 30 HIV- individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r = 0.47, P < .001). PWH had higher (more abnormal) BBB index values than HIV- individuals (mean ± SD, 0.361 ± 1.20 vs -0.501 ± 1.11; P = .0214). HIV serostatus interacted with cannabis use frequency, such that more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV- individuals. Worse BBB index values were associated with higher NFL in CSF (r = 0.380, P = .0169). CONCLUSIONS: Cannabis may have a beneficial impact on HIV-associated BBB injury. Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity.

Gut microbiota dysbiosis is associated with worse emotional states in HIV infection.

The biological mechanisms underlying emotional distress in HIV infection are likely to be complex but remain understudied. We investigated whether dysbiotic signatures in the gut microbiome of persons living with HIV (PLWH) are associated with their emotional status. We retrospectively examined the gut microbiome and clinical evaluation of 129 adults (94 PLWH and 35 HIV-) enrolled at UC San Diego's HIV Neurobehavioral Research Program. A subset of participants (32 PLWH vs. 13 HIV-) underwent an emotional assessment using the NIH Toolbox Emotion Battery summarized by three composite scores (negative affect, social satisfaction, and psychological well-being). We then sequenced the 16S rDNA V3-V4 regions from stool and performed taxonomic assignment using CLC Microbial Genomics Module. The gut microbiota profiles were evaluated in relation to participants' emotional assessment. All analyses were done in R statistical software. We found that the relative abundance of aerotolerant bacteria was significantly higher in PLWH (p < 0.01) and was associated with a lifetime major depression diagnosis independently of HIV status (p = 0.05). Moreover, PLWH experienced significantly worse psychological well-being (p = 0.02), less social satisfaction (p = 0.03), and more negative affect (p = 0.02). Higher levels of aerotolerant bacteria were associated with worse psychological well-being (rho = -0.35, p = 0.02), less social satisfaction (r = - 0.42, p < 0.01), and more negative affect (rho = 0.46, p < 0.01). The association of aerotolerant bacteria with social satisfaction and negative affect was independent of HIV status (p < 0.05, for both). The over-representation of aerotolerant bacteria in the gut may reflect worse oxidative stress and barrier defects and may contribute to emotional distress during HIV infection.

Modest reduction in adverse birth outcomes following the COVID-19 lockdown.

BACKGROUND: Widespread lockdowns imposed during the coronavirus disease 2019 crisis may impact birth outcomes. OBJECTIVE: This study aimed to evaluate the association between the COVID-19 lockdown and the risk of adverse birth outcomes in Botswana. STUDY DESIGN: In response to the coronavirus disease 2019 crisis, Botswana enforced a lockdown that restricted movement within the country. We used data from an ongoing nationwide birth outcomes surveillance study to evaluate adverse outcomes (stillbirth, preterm birth, small-for-gestational-age fetuses, and neonatal death) and severe adverse outcomes (stillbirth, very preterm birth, very-small-for-gestational-age fetuses, and neonatal death) recorded prelockdown (January 1, 2020-April 2, 2020), during lockdown (April 3, 2020-May 7, 2020), and postlockdown (May 8, 2020-July 20, 2020). Using difference-in-differences analyses, we compared the net change in each outcome from the prelockdown to lockdown periods in 2020 relative to the same 2 periods in 2017-2019 with the net change in each outcome from the prelockdown to postlockdown periods in 2020 relative to the same 2 periods in 2017-2019. RESULTS: In this study, 68,448 women delivered a singleton infant in 2017-2020 between January 1 and July 20 and were included in our analysis (mean [interquartile range] age of mothers, 26 [22-32] years). Across the included calendar years and periods, the risk of any adverse outcome ranged from 27.92% to 31.70%, and the risk of any severe adverse outcome ranged from 8.40% to 11.38%. The lockdown period was associated with a 0.81 percentage point reduction (95% confidence interval, -2.95% to 1.30%) in the risk of any adverse outcome (3% relative reduction) and a 0.02 percentage point reduction (95% confidence interval, -0.79% to 0.75%) in the risk of any severe adverse outcome (0% relative reduction). The postlockdown period was associated with a 1.72 percentage point reduction (95% confidence, -3.42% to 0.02%) in the risk of any adverse outcome (5% relative reduction) and a 1.62 percentage point reduction (95% confidence interval, -2.69% to -0.55%) in the risk of any severe adverse outcome (14% relative reduction). Reductions in adverse outcomes were largest among women with human immunodeficiency virus and among women delivering at urban delivery sites, driven primarily by reductions in preterm birth and small-for-gestational-age fetuses. CONCLUSION: Adverse birth outcomes decreased from the prelockdown to postlockdown periods in 2020, relative to the change during the same periods in 2017-2019. Our findings may provide insights into associations between mobility and birth outcomes in Botswana and other low- and middle-income countries.

Novel Vitamin C and E and Green Tea Polyphenols Combination Serum Improves Photoaged Facial Skin.

BACKGROUND: Skin aging is a multifactorial process induced by intrinsic factors such as metabolic processes and senescence as well as environmental factors, including smoking, air pollution, and solar radiation. UV-induced production of reactive oxygen species induces skin photoaging. Antioxidants, including vitamin C and E and green tea polyphenols represent a promising strategy for the aesthetic improvement of clinical features associated with aging. OBJECTIVE: To assess the safety, tolerability, and efficacy of a novel vitamin C and E and green tea polyphenols (CE-GTP) combination serum on photoaged facial skin. METHODS: 31 healthy females aged 43 to 65 years (mean age, 57.9) participated in this single-center, 12-week clinical trial. Subjects applied CE-GTP serum twice daily for the duration of the study. Clinical grading of efficacy parameters, safety and tolerability evaluations, ultrasound measurements, and self-assessment questionnaires were conducted at several study milestones. RESULTS: Statistically significant improvements were observed in all clinically graded efficacy parameters. Highlights include reduction in fine lines around the eye area and facial wrinkles and enhanced skin smoothness and radiance. Ultrasound measurements showed a statistically significant increase in skin density at week 12 compared with baseline, indicating thickening of the epidermal and dermal tissue, associated with youthful, healthier skin. Subjects self-reported numerous improvements, including reduction of fine lines and wrinkles, improved skin tone and texture, diminished look of dark spots, and improved skin elasticity. CONCLUSION: Novel CE-GTP serum is safe and effective, as shown by statistically significant improvements in multiple aesthetically important objective, subjective, and patient reported outcomes. J Drugs Dermatol. 2021;20(9):996-1003. doi:10.36849/JDD.5818.

Lifetime Prevalence of Cervical Cancer Screening in 55 Low- and Middle-Income Countries.

Importance: The World Health Organization is developing a global strategy to eliminate cervical cancer, with goals for screening prevalence among women aged 30 through 49 years. However, evidence on prevalence levels of cervical cancer screening in low- and middle-income countries (LMICs) is sparse. Objective: To determine lifetime cervical cancer screening prevalence in LMICs and its variation across and within world regions and countries. Design, Setting, and Participants: Analysis of cross-sectional nationally representative household surveys carried out in 55 LMICs from 2005 through 2018. The median response rate across surveys was 93.8% (range, 64.0%-99.3%). The population-based sample consisted of 1 136 289 women aged 15 years or older, of whom 6885 (0.6%) had missing information for the survey question on cervical cancer screening. Exposures: World region, country; countries' economic, social, and health system characteristics; and individuals' sociodemographic characteristics. Main Outcomes and Measures: Self-report of having ever had a screening test for cervical cancer. Results: Of the 1 129 404 women included in the analysis, 542 475 were aged 30 through 49 years. A country-level median of 43.6% (interquartile range [IQR], 13.9%-77.3%; range, 0.3%-97.4%) of women aged 30 through 49 years self-reported to have ever been screened, with countries in Latin America and the Caribbean having the highest prevalence (country-level median, 84.6%; IQR, 65.7%-91.1%; range, 11.7%-97.4%) and those in sub-Saharan Africa the lowest prevalence (country-level median, 16.9%; IQR, 3.7%-31.0%; range, 0.9%-50.8%). There was large variation in the self-reported lifetime prevalence of cervical cancer screening among countries within regions and among countries with similar levels of per capita gross domestic product and total health expenditure. Within countries, women who lived in rural areas, had low educational attainment, or had low household wealth were generally least likely to self-report ever having been screened. Conclusions and Relevance: In this cross-sectional study of data collected in 55 low- and middle-income countries from 2005 through 2018, there was wide variation between countries in the self-reported lifetime prevalence of cervical cancer screening. However, the median prevalence was only 44%, supporting the need to increase the rate of screening.

Methodological Challenges When Studying Distance to Care as an Exposure in Health Research.

Distance to care is a common exposure and proposed instrumental variable in health research, but it is vulnerable to violations of fundamental identifiability conditions for causal inference. We used data collected from the Botswana Birth Outcomes Surveillance study between 2014 and 2016 to outline 4 challenges and potential biases when using distance to care as an exposure and as a proposed instrument: selection bias, unmeasured confounding, lack of sufficiently well-defined interventions, and measurement error. We describe how these issues can arise, and we propose sensitivity analyses for estimating the degree of bias.

HIV infection is not associated with the initiation of curative treatment in women with cervical cancer in Botswana.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Sub-Saharan Africa. The risk of developing cancer is increased for women living with human immunodeficiency virus (HIV) infection. It is unknown which factors predict the initiation of curative chemoradiotherapy (CRT) in resource-limited settings and whether HIV is associated with initiating curative CRT in settings with a high HIV burden. METHODS: All women living with and without HIV infection who were initiating curative and noncurative CRT for locally advanced cervical cancer in Botswana were prospectively enrolled in an observational study. The factors associated with receiving CRT were evaluated in all patients and the subgroup of women living with HIV. RESULTS: Of 519 enrolled women, 284 (55%) initiated CRT with curative intent. The curative cohort included 200 women (70.4%) who were living with HIV and had a median CD4 count of 484.0 cells/µL (interquartile range, 342.0-611.0 cells/µL). In the noncurative cohort, 157 of 235 women (66.8%) were living with HIV and had a median CD4 count of 476.5 cells/µL (interquartile range, 308.0-649.5 cells/µL). HIV status was not associated with initiating curative CRT (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.58-1.56). The factors associated with receiving curative CRT treatment on multivariable analysis in all patients included baseline hemoglobin levels ≥10 g/dL (OR, 1.80; 95% CI, 1.18-2.74) and stage I or II versus stage III or IV disease (OR, 3.16; 95% CI, 2.10-4.75). Women aged >61 years were less likely to receive curative treatment (OR, 0.43; 95% CI, 0.24-0.75). Among women who were living with HIV, higher CD4 cell counts were associated with higher rates of CRT initiation. CONCLUSIONS: The initiation of CRT with curative intent does not depend on HIV status. Significant predictors of CRT initiation include baseline hemoglobin level, disease stage, and age.