In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimA(Bm) allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer.

OBJECTIVE: To provide comprehensive epidemiological information about the distribution and occurrence of rabies during 2022 in the US, Canada, and Mexico. METHODS: The US National Rabies Surveillance System collected 2022 animal rabies data from US state and territorial public health departments and USDA Wildlife Services. Temporal and geographic analyses were conducted to evaluate trends in animal rabies cases. RESULTS: During 2022, 54 US jurisdictions reported 3,579 animal rabies cases, reflecting a 2.3% decline from 3,663 cases reported in 2021. Six states collectively reported > 50% of animal rabies cases: Texas (395 [11.0%]), Virginia (337 [9.4%]), Pennsylvania (329 [9.2%]), New York (267 [7.5%]), North Carolina (264 [7.4%]), and California (241 [6.7%]). Out of the total reported rabies animal cases, 3,234 (90.4%) were attributed to wildlife, with bats (1,218 [34.0%]), raccoons (1,014 [28.3%]), skunks (660 [18.4%]), and foxes (269 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (222 [6.2%]), cattle (42 [1.2%]), and dogs (50 [1.4%]) constituted > 90% of reported domestic animal rabies cases. CONCLUSIONS: In 2022, there was an increase in the number of animal samples submitted for rabies testing in the US and Canada. A notable geographic expansion of gray fox rabies virus variant was detected in the US. Three human rabies deaths due to vampire bat rabies infection occurred in Mexico; none were reported from the US and Canada. CLINICAL RELEVANCE: Laboratory diagnosis of rabies in animals is critical to ensure judicious use of human rabies postexposure prophylaxis.

BACKGROUND: Unintentional injuries disproportionately impact American Indian and Alaska Native (AI/AN) populations. Developing effective and culturally tailored data collection and intervention programs requires an understanding of past prevention efforts in AI/AN communities, but limited peer-reviewed literature on the topic is available. This scoping review aims to summarize efforts that have been published in the Primary Care Provider newsletter, a source of gray literature available through the Indian Health Service. METHODS: The research team obtained all injury related articles in the Provider newsletter and excluded those that did not describe an unintentional injury prevention effort. Included articles were organized chronologically and by topic, and outcomes were described in a data abstraction form. RESULTS: A total of 247 articles from the Provider newsletter were screened, and 68 were included in this review. The most number of articles were published in 2007 (n = 15). Many focused not specifically on one tribal community but on the AI/AN community as a whole (n = 27), while others reported that certain tribes were the focus of study but did not identify tribes by name (n = 24). The following is a list of 14 tribal communities explicitly mentioned: Omaha, Cherokee, Ute, Yakama, Chippewa, Apache, Ho-Chunk, The Crow Tribe, Tohono O'odham Nation, Fort Mojave Tribe, Chemehuevi Tribe, The Rosebud Tribe, Navajo, and The Pueblo of Jemez. Published unintentional injury prevention efforts have covered the following 7 topics in AI/AN communities: falls, motor vehicle crashes, poisonings, improving data, burns, children, and other. CONCLUSION: This scoping review makes available and searchable information on injury prevention work conducted in and for AI/AN communities that is not currently found in the peer-reviewed literature.

BACKGROUND: Violence is a serious public health concern disproportionately experienced by American Indian and Alaska Native (AIAN) people. While the burden and impact of violence may be explained by the presence of risk factors among this group, AIAN communities benefit from unique protective factors and universal strategies which may be tailored with tribal adaptations. We sought to identify and explore violence prevention strategies specific to AIAN populations. METHODS: A review was conducted to systematically identify violence prevention programs, policies, and practices implemented in AIAN communities. We searched nine electronic databases and relevant gray literature released between January 1980 and June 2018. We included intervention-focused records targeting at least one violence topic area (child abuse/neglect, elder abuse, intimate partner violence, sexual violence, youth violence, and suicide) in a majority (> 50%) AIAN population. RESULTS: A total of 5220 non-duplicate records were screened, yielding 318 full-text records. After applying exclusion criteria, 57 records describing 60 program, policy, or practice implementations of 43 unique interventions were identified. All six violence types were represented, although more than half (58%; n = 25/43) focused on suicide prevention. Among suicide prevention programs, the most common strategies were identifying and supporting people at risk (80%; n = 20), teaching coping and problem-solving skills (56%; n = 14), and promoting connectedness (48%; n = 12). Two-thirds of the implementations (67%; n = 40/60) were in fully (100%) AIAN communities. Programs were implemented across many settings, though schools were the most common (35%, n = 21/60) setting. Of the 60 total implementations, a majority (80%; n = 48) were new approaches developed by and for AIAN communities, while the remainder were AIAN adaptations of programs previously created for non-AIAN populations. Most implementations (60%; n = 36/60) provided some evaluation data although less than half (45%; n = 27/60) reported evaluation results. CONCLUSIONS: This review identified many violence prevention strategies specific to AIAN populations. While programs developed in one tribe may not be completely generalizable to others, shared tribal risk and protective factors suggest programs could be successful across diverse communities. Findings indicate there is a need to develop and evaluate violence prevention programs, policies and practices for AIAN populations.

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23-0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18-0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming.

The designs and liquid formulations of Electronic Nicotine Delivery System (ENDS) devices continue to rapidly evolve. Thus, it is important to monitor and characterize ENDS aerosols for changes in toxic constituents. Many ENDS liquid formulations now include the addition of organic acids in a 1 to 1 molar ratio with nicotine. Metal concentrations in aerosols produced by ENDS devices with different nicotine salt formulations were analyzed. Aerosols from devices containing lactic acid had higher nickel, zinc, copper, and chromium concentrations than aerosols produced by devices containing benzoic acid or levulinic acid. Our scanning electron microscope with energy dispersive X-ray analytical findings showed that the metals determined in the inductively coupled plasma-mass spectrometry analytical results were consistent with the metal compositions of the ENDS device components that were exposed to the liquids and that nickel is a major constituent in many ENDS internal components. As a result of the exposure of the nickel-containing components to the ENDS liquids, resulting aerosol nickel concentrations per puff were higher from devices that contained lactic acid in comparison to devices with benzoic or levulinic acid. The aerosol nickel concentrations in 10 puffs from ENDS-containing lactic acid were, in some cases, hundreds of times higher than cigarette mainstream smoke nickel deliveries. Thus, the design of an ENDS device in terms of both physical construction components and the liquid chemical formulations could directly impact potential exposures to toxic constituents such as metals.

BACKGROUND: Multimorbidity is increasing among adults in the United States. Yet limited research has examined multimorbidity clusters in persons aged 50 years and older with and without a history of cancer. An increased understanding of multimorbidity clusters may improve the cancer survivorship experience for survivors with multimorbidity. METHODS: We identified 7580 adults aged 50 years and older with 2 or more diseases-including 811 adults with a history of primary breast, colorectal, cervical, prostate, or lung cancer-from the 2018 National Health Interview Survey. Exploratory factor analysis identified clusters of multimorbidity among cancer survivors and individuals without a history of cancer (controls). Frequency tables and chi-square tests were performed to determine overall differences in sociodemographic characteristics, health-related characteristics, and multimorbidity between groups. RESULTS: Cancer survivors reported a higher prevalence of having 4 or more diseases compared to controls (57% and 38%, respectively). Our analysis identified 6 clusters for cancer survivors and 4 clusters for controls. Three clusters (pulmonary, cardiac, and liver) included the same diseases for cancer survivors and controls. CONCLUSIONS: Diseases clustered differently across adults ≥ 50 years of age with and without a history of cancer. Findings from this study may be used to inform clinical care, increase the development and dissemination of multilevel public health interventions, escalate system improvements, and initiate innovative policy reform.

Table 2 of the Recommended Adult Immunization Schedule, United States, 2019 (1), contains an error. The gray blocks indicating “no recommendation” for zoster vaccination (recombinant zoster vaccine [RZV] or zoster vaccine live [ZVL]) in adults with asplenia or complement deficiencies should have been displayed as yellow blocks, indicating “recommended vaccination for adults who meet age requirement, lack documentation of vaccination, or lack evidence of past infection.”

The authors regret the oversight of table labeling and placement in the manuscript. Particularly, the misrepresentation of Box 1 as Table 6; this is incorrectly labeled, and we sincerely apologize for this oversight. The Table 6 icon at the bottom of page 55 should be placed at the bottom of page 52 as Box 1, and the Table 6 at the top of page 57 should be moved up as Box 1 to page 52, before the results section. | | The authors would like to apologize for any inconvenience caused.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.

Birth is an inflammatory event for the newborn, characterized by elevations in interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α peripherally and/or centrally, as well as changes in brain microglia. However, the mechanism(s) underlying these responses is unknown. Toll-like receptors (TLRs) play crucial roles in innate immunity and initiate inflammatory cascades upon recognition of endogenous or exogenous antigens. Most TLR signaling depends on the adaptor molecule myeloid differentiation primary response 88 (MyD88). We independently varied MyD88 gene status in mouse dams and their offspring to determine whether the inflammatory response to birth depends on MyD88 signaling and, if so, whether that signaling occurs in the offspring, the mother, or both. We find that the perinatal surges in plasma IL-6 and brain expression of TNF-α depend solely on MyD88 gene status of the offspring, whereas postnatal increases in plasma IL-10 and TNF-α depend on MyD88 in both the pup and dam. Interestingly, MyD88 genotype of the dam primarily drives differences in offspring brain microglial density and has robust effects on developmental neuronal cell death. Milk cytokines were evaluated as a possible source of postnatal maternal influence; although we found high levels of CXCL1/GROα and several other cytokines in ingested post-partum milk, their presence did not require MyD88. Thus, the inflammatory response previously described in the late-term fetus and newborn depends on MyD88 (and, by extension, TLRs), with signaling in both the dam and offspring contributing. Unexpectedly, naturally-occuring neuronal cell death in the newborn is modulated primarily by maternal MyD88 gene status.

BACKGROUND: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. METHODS: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). RESULTS: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. CONCLUSIONS: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis.

OBJECTIVE: To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer. DESIGN: Multinational cohort study. SETTING: Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). PARTICIPANTS: 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. MAIN OUTCOME MEASURES: Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer. RESULTS: The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos. CONCLUSIONS: This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings.

Part 1 of this tutorial addressed how environmental contamination may be minimized by using proper personal analytical practices, sample preparation environmental suggestions, avoidance of glass and low purity quartz contact with samples and standards during sample collection and preparation, and appropriate choices of high purity solvents during sample collection and preparation. Part 2 continues the discussion in terms of minimizing sample contamination issues by using high purity polymer materials for sample collection and preparation, as well as discuss the differences between instrument and method limits of detection (LODs). Accepted and appropriate procedures for calculating method LODs are related to variability in instrument response and unavoidable environmental contamination during even the cleanest sample preparation. Adherence to such practices will help analysts avoid false positives and report results with a high level of confidence. © 2023 Advanstar Communications Inc.. All rights reserved.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years, but as new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and the population groups driving transmission have evolved over a 15 year period from 2003 to 2018 in Uganda. HIV viral suppression increased more rapidly in women than men, resulting in 1.5-2 fold higher suppression rates in women with HIV by 2018 across age groups. Incidence declined more slowly in women than men, increasing pre-existing gender imbalance in HIV burden. Age-specific transmission flows shifted; the share of transmission to girls and women aged 15-24 years from older men declined by approximately one third, whereas the contribution of transmission to women aged 25-34 years from men aged 0-6 years older doubled from 2003 to 2018. We estimated closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018 and ended gender disparities in incidence. This study suggests that male-targeted HIV programs to increase HIV suppression are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Introduction: Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including bar work and transportation. However, data on changes in prevalence of untreated HIV infection and HIV incidence within occupations following rollout of antiretroviral therapy and voluntary medical male circumcision programs in 2004 are limited. Method(s): We evaluated 12 rounds of survey data collected between 1999-2016, from the Rakai Community Cohort Study, a population-based study of adolescents and adults 15-49 years in Uganda, to assess changes in the prevalence of untreated HIV infection and incidence by self-reported primary occupation. Adjusted prevalence risk ratios (adjPRR) for untreated HIV and incidence rate ratios for HIV incidence with 95% confidence intervals (CIs) were estimated using Poisson regression. Primary outcomes were stratified by gender and HIV incidence compared over three time periods (1999-2004; 2005-2011; 2011-2016) representing, respectively, the period prior to scale up of combined HIV prevention and treatment, the scale up period, and full implementation. Result(s): 33,866 individuals, including 19,113 (56%) women participated. Of these participants, 17,840 women and 14,244 men who were HIV-negative at their first study visit contributed 57,912 and 49,403 person-years of follow-up, respectively. Agriculture was the most common occupation at all study visits, though its prevalence declined from 39 to 29% among men and from 61 to 40% among women between 1999 and 2016. Untreated HIV infection substantially declined between 1999 and 2016 across most occupational subgroups, including by 70% among men (12 to 4.2%; adjPRR=0.30; 95%CI:0.23-0.41) and by 78% among women working in agriculture (14.7 to 4.0%; adjPRR=0.22; 95%CI:0.18-0.27), along with increasing antiretroviral therapy coverage. Exceptions included men working in transportation and women working in tailoring/laundry services. HIV incidence declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers or men working in transportation. Conclusion(s): Untreated HIV infection and HIV incidence have declined in most occupational sub-groups in Rakai, Uganda. However, women working in bars and restaurants and men working in transportation continue to have relatively high burden of untreated HIV and HIV incidence, and as such should be considered key priority populations for targeted HIV programming. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Lagomorphs-principally rabbits and hares-have been implicated as hosts for vectors and reservoirs for pathogens associated with multiple rickettsial diseases. Western North America is home to diverse rickettsial pathogens which circulate among multiple wild and domestic hosts and tick and flea vectors. The purpose of this study was to assess lagomorphs and their ectoparasites in 2 locations in northern Baja California, Mexico, for exposure to and infection with rickettsial organisms. In total, 55 desert cottontail rabbits (Sylvilagus audubonii) (Baird) and 2 black-tailed jackrabbits (Lepus californicus) (Gray) were captured. In Mexicali, ticks were collected from 44% (14/32) of individuals, and were exclusively Haemaphysalis leporispalustris Neumann (Acari: Ixodidae); in Ensenada, ticks were collected from 70% (16/23) individuals, and 95% were Dermacentor parumapertus. Euhoplopsyllus glacialis affinis Baker (Siphonaptera: Pulicidae) fleas were collected from 72% of rabbits and 1 jackrabbit from Mexicali, while the few fleas found on hosts in Ensenada were Echidnophaga gallinacea Westwood (Siphonaptera: Pulicidae) and Cediopsylla inaequalis (Siphonaptera: Pulicidae). Rickettsia bellii was the only rickettsial organism detected and was identified in 88% of D. parumapertus and 67% of H. leporispalustris ticks from Ensenada. A single tissue sample from a jackrabbit was positive for R. belli (Rickettsiales: Rickettsiaceae). Hosts in Ensenada had a significantly higher prevalence of rickettsial antibodies than hosts in Mexicali (52.3% vs. 21.4%). Although R. bellii is not regarded as pathogenic in humans or other mammals, it may contribute to immunity to other rickettsiae. The marked difference in distribution of ticks, fleas, and rickettsial exposure between the 2 locations suggests that disease transmission risk may vary markedly between communities within the same region.

The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt-Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrP(D) type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrP(D) T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (p(GM)) or the white matter (p(WM)) of sCJD cases with the PrP 129MM genotype (sCJDMM). Prevalence of p(GM)- and p(WM)-CJD proved comparable and was estimated to be ~ 0.6% among sporadic prion diseases and ~ 1.1% among the sCJDMM group. Mean age at onset (61 and 68 years) and disease duration (~ 7 months) of p(WM)- and p(GM)-CJD did not differ significantly. PrP plaques were mostly confined to the cerebellar cortex in p(GM)-CJD, but were ubiquitous in p(WM)-CJD. Typing of resPrP(D) T1 showed an unglycosylated fragment of ~ 20 kDa (T1(20)) in p(GM)-CJD and sCJDMM1 patients, while a doublet of ~ 21-20 kDa (T1(21-20)) was a molecular signature of p(WM)-CJD in subcortical regions. In addition, conformational characteristics of p(WM)-CJD resPrP(D) T1 differed from those of p(GM)-CJD and sCJDMM1. Inoculation of p(WM)-CJD and sCJDMM1 brain extracts to transgenic mice expressing human PrP reproduced the histotype with PrP plaques only in mice challenged with p(WM)-CJD. Furthermore, T1(20) of p(WM)-CJD, but not T1(21), was propagated in mice. These data suggest that T1(21) and T1(20) of p(WM)-CJD, and T1(20) of sCJDMM1 are distinct prion strains. Further studies are required to shed light on the etiology of p-CJD cases, particularly those of T1(20) of the novel p(GM)-CJD subtype.

BACKGROUND: South Africa is disproportionately impacted by non-communicable diseases (NCDs) and HIV/AIDS. We investigated the prevalence of known/unknown NCD risk factors, HIV, and NCD risk factor-HIV comorbidity; and treatment status on known diseases to determine the prevalence of controlled/uncontrolled disease. METHODS: This cross-sectional study (June 2018-March 2019) within an integrated testing centre in Soweto, South Africa, screened adults (aged ≥18 years) for body mass index (BMI), hypertension (HT), rapid glucose and cholesterol, and HIV. Results were stratified by age group, sex, HIV-status, and self-reported ART use. Analysis included Fisher's exact, chi-squared, Kruskal Wallis, and Student's T-tests. FINDINGS: Of 780 enrolled participants, 19.2% were HIV-positive, 37.5% were overweight/obese, 18.0% hypertensive, 10.8% hyperglycaemic, and 8.1% had hypercholesterolaemia. Significantly more women had overweight/obese BMI than men (46.8% vs 19.7%; p<0.0001), and women aged 25-34 years had significantly more hypercholesterolaemia than same-aged men (18.2% vs 5.6%; p = 0.02). HIV-positive participants had significantly more hyperglycaemia than HIV-negative participants (16.1% vs 9.6%; p = 0.02), and those on ART (63.9%) had significantly more hypercholesterolaemia than those not on ART (21.7% vs. 4.9%; p = 0.002). Of participants with HT, hyperglycaemia, and hypercholesterolaemia; 72.4%, 96.1%, and 93.3% were newly diagnosed. All participants with previously diagnosed NCDs remained with uncontrolled disease. INTERPRETATION: There is a high burden of HIV, NCD risk factors, and comorbidity in Soweto, and amongst young adults (18-34 years), especially women. Lowering age requirements for glucose/cholesterol screening to 18+ years, regardless of BMI, HIV-status, or ART use, may yield timely NCD diagnosis/management.

Research gaps exist in toxic metals characterization in e-cigarette, or vaping, products (EVPs) as these analytes typically have low concentrations and most standard aerosol trapping techniques have high metals background. An additional complication arises from differences in the EVP liquid formulations with nicotine products having polar properties and non-nicotine products often being non-polar. Differences in polar and non-polar matrices and the subsequent aerosol chemistries from various EVPs required modifications of our previously reported nicotine-based EVP aerosol method. Validation and application of the expanded method, suitable for both hydrophobic and hydrophilic aerosols, are reported here. The metals analyzed for this study were Al, Cr, Fe, Co, Ni, Cu, Cd, Sn, Ba, and Pb. The method limits of detection for the modified method ranged from 0.120 ng/10 puffs for Cd to 29.3 ng/10 puffs for Al and were higher than reported for the previous method. Results of the analyses for metals in aerosols obtained from 50 EVP products are reported. Cannabinoid based EVP aerosols were below reportable levels, except for one sample with 16.08 ng/10 puffs for Cu. Nicotine-based EVP results ranged from 6.72 ng/10 puffs for Pb to 203 ng/10 puffs for Sn. Results of the analyses for these metals showed that aerosols from only 5 of the 50 devices tested had detectable metal concentrations. Concentrations of toxic elements in the aerosols for nicotine-based EVP aerosol metal concentration ranges were consistent with previously published results of aerosol analyses from this class of devices.

BACKGROUND: The COVID-19 pandemic disrupted healthcare in the United States and raised concerns about certain antihypertensives, and may have impacted both prescribing practices and access to blood pressure (BP) medications. METHODS: We assessed trends in BP prescription fills before and during the first year of the COVID-19 pandemic, using cross-sectional data for BP fills and tablets in the IQVIA (IMS Health) National Prescription Audit® database. Drugs filled via retail (92% coverage), mail-order (78% coverage), and long-term care (72% coverage) channels from January 2018 through December 2020 were included. Data were projected nationally and by state. RESULTS: Between 2.9 to 3.4 billion BP tablets were dispensed monthly until February 2020, increasing sharply to 3.8 billion in March 2020 and declining to 3.4 billion in April, then increasing at three-month intervals until December 2020. The number of tablets per fill increased slightly over time, with the largest increase (from 66.7 to 68.6) during February-March, 2020. Tablets were dispensed through retail channels (99.7 billion), mail-order (14.7 billion), and long-term care (5.3 billion). Rates of patients initiating new medications decreased during 2020 compared to prior years. Fills did not vary significantly by drug class. CONCLUSIONS: A sharp increase in BP fills occurred with COVID-19 emergence, suggesting patients may have secured medications in preparation for potential access limitations. A decrease in new fills, indicating decreased initiation and/or modification of treatment regimens, suggests need for efforts to re-engage patients in the healthcare system and provide alternative ways to obtain medication refills and adjustments.

To help explain the diversity of COVID-19 outcomes by country, research teams worldwide are studying national government response efforts. However, these attempts have not focused on a critical national authority that exists in half of the countries in the world: national public health institutes (NPHIs). NPHIs serve as an institutional home for public health systems and expertise and play a leading role in epidemic responses. To characterize the role of NPHIs in the COVID-19 response, we conducted a descriptive literature review that explored the research documented during March 2020-May 2021. We conducted a name-based search of 61 NPHIs in the literature, representing over half of the world's NPHIs. We identified 33 peer-reviewed and 300 gray articles for inclusion. We describe the most common NPHI-led COVID-19 activities that are documented and identify gaps in the literature. Our findings underscore the value of NPHIs for epidemic control and establish a foundation for primary research.

In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent persons age ≥ 50 years, with the 2nd dose recommended 2-6 months after the 1st dose. We estimated second-dose RZV series completion in the U.S. among 50-64-year-olds using two administrative databases. Second-dose RZV series completion was ∼70% within 6-months and 80% within 12-months of first dose. Among those who received only 1 RZV dose with at least 12 months of follow-up time, 96% had a missed opportunity for a second-dose vaccination, defined as a provider or pharmacy visit, among whom 36% had a visit for influenza or pneumococcal vaccination within 2-12 months of their first-dose of RZV. We found that RZV series completion rates in 50-64-year-olds was high. Availability of RZV at pharmacies has potentially helped increase series completion, but missed opportunities remain.

INTRODUCTION: A strategic framework for 2021-2030 developed by the World Health Organization (WHO) Regional Office for the Western Pacific emphasizes the need for high-quality and integrated vaccine-preventable disease (VPD) surveillance. We conducted a literature review to document the barriers, enabling factors, and innovations for integrating surveillance functions for VPDs and other communicable diseases in Western Pacific Region (WPR) countries. METHODS: We searched published and gray literature on integrated VPD surveillance from 2000 to 2021. Articles in English, Spanish, or French were screened to identify those relating to VPD surveillance in a WPR country and not meeting defined exclusion criteria. We categorized articles using the 8 WHO surveillance support functions and abstracted data on the country; type of surveillance; and reported barriers, enabling factors, and best practices for integration. RESULTS: Of the 3,137 references screened, 87 met the eligibility criteria. Of the 8 surveillance support functions, the proportion of references that reported integration related to the laboratory was 56%, followed by workforce capacity (54%), governance (51%), data management and use (47%), field logistics and communication (47%), coordination (15%), program management (13%), and supervision (9%). Several references noted fragmented systems and a lack of coordination between units as barriers to integration, highlighting the importance of engagement across public health units and between the public and private sectors. The literature also indicated a need for interoperable information systems and revealed the use of promising new technologies for data reporting and laboratory testing. In some WPR countries, workforce capacity was strengthened at all administrative levels by the implementation of integrated trainings on data monitoring and use and on laboratory techniques applicable to multiple VPDs. CONCLUSION: This literature review supports integrating VPDs into broader communicable disease surveillance systems in WPR countries while ensuring that the minimal WHO-recommended standards for VPD surveillance are met.

Standing supports have been used in coal mines for decades to enhance roof support capability. Sometimes standing supports are used as a tool to resist the lateral movement of spalled ribs. Researchers from the National Institute for Occupational Safety and Health (NIOSH) are conducting a testing program for different types of standing supports (steel and timber) to investigate the effect of lateral loading on their vertical loading capacities and the factors affecting their lateral loading capacities. In this paper, the mine roof simulator (MRS), at the NIOSH Pittsburgh research facility, was used to determine the response of steel props to vertical and horizontal loadings. Finite element models (FEMs) were developed and verified using the tested steel props. To justify the testing program for testing standing supports with end-conditions of rock-like materials, the verified prop models were used to study the effect of a wide range of roof and floor materials (gray shale, shale, and claystone) on the critical buckling loads of the steel props. Also, several lateral loading scenarios were evaluated in which the steel props were laterally loaded at different heights. The critical buckling load for steel props setting up against a claystone roof and floor was found to be one-half of that shown by the MRS test where roof and floor platens are made of steel. Minimum prop performance was observed when the lateral load was applied at the mid-height of the steel prop, especially at small lateral displacement (less than 2 in). 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

BACKGROUND: Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies. METHODS AND FINDINGS: Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify virological failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended virological failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes. CONCLUSIONS: This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml virological failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens.

Synthetic cathinones (known as psychoactive bath salts) are a class of potent central nervous stimulants that mimic the effects produced by cocaine, methamphetamine, and methylenedioxymethamphetamine (MDMA; known as ecstasy). Synthetic cathinones have been sold as MDMA (1), distributed as nondrug products (e.g., bath salts) to conceal their sale as an illicit drug and also sold as illicit drug products.* From 2017 to 2021, the supply of eutylone† (a synthetic cathinone) rapidly increased in the United States. During January–June 2017, eutylone was detected in fewer than 10 drug items such as powders, capsules, or tablets obtained through law enforcement activities such as drug seizures, arrests, or undercover buys and tested; during January–June 2021, eutylone was detected in 8,379 drug items, making it the seventh most identified drug during this period (2). Public alerts have been issued and include concern about elevated overdose risk associated with eutylone being sold as MDMA§ (1). Little is known about the relative potencies and pharmacological profile of synthetic cathinones compared with MDMA, and using counterfeit tablets potentially increases the risk for overdose; however, additional investigation is needed.

OBJECTIVE: World Health Organization recommends promoting breastfeeding without restricting its duration among HIV-positive women on lifelong antiretroviral treatment (ART). There is little data on breastfeeding duration and mother to child transmission (MTCT) beyond 24 months. We compared the duration of breastfeeding in HIV-exposed and HIV-unexposed children and we identified factors associated with postpartum-MTCT in a semi-rural population of Mozambique. METHODS: This cross-sectional assessment was conducted from October-2017 to April-2018. Mothers who had given birth within the previous 48-months in the Manhiça district were randomly selected to be surveyed and to receive an HIV-test along with their children. Postpartum MTCT was defined as children with an initial HIV positive result beyond 6 weeks of life who initiated breastfeeding if they had a first negative PCR result during the first 6 weeks of life or whose mother had an estimated date of infection after the child's birth. Cumulative incidence accounting for right-censoring was used to compare breastfeeding duration in HIV-exposed and unexposed children. Fine-Gray regression was used to assess factors associated with postpartum-MTCT. RESULTS: Among the 5000 mother-child pairs selected, 69.7% (3486/5000) were located and enrolled. Among those, 27.7% (967/3486) children were HIV-exposed, 62.2% (2169/3486) were HIV-unexposed and for 10.0% (350/3486) HIV-exposure was unknown. Median duration of breastfeeding was 13.0 (95%CI:12.0-14.0) and 20.0 (95%CI:19.0-20.0) months among HIV-exposed and HIV-unexposed children, respectively (p<0.001). Of the 967 HIV-exposed children, 5.3% (51/967) were HIV-positive at the time of the survey. We estimated that 27.5% (14/51) of the MTCT occurred during pregnancy and delivery, 49.0% (2551) postpartum-MTCT and the period of MTCT remained unknown for 23.5% (12/51) of children. In multivariable analysis, mothers' ART initiation after the date of childbirth was associated (aSHR:9.39 [95%CI:1.75-50.31], p = 0.001), however breastfeeding duration was not associated with postpartum-MTCT (aSHR:0.99 [95%CI:0.96-1.03], p = 0.707). CONCLUSION: The risk for postpartum MTCT was nearly tenfold higher in women newly diagnosed and/or initiating ART postpartum. This highlights the importance of sustained HIV screening and prompt ART initiation in postpartum women in Sub-Saharan African countries. Under conditions where HIV-exposed infants born to mothers on ART receive adequate PMTCT, extending breastfeeding duration may be recommended.

OBJECTIVE: This study investigated whether young women's participation in a combination HIV-prevention intervention was associated with accessing and using condoms and other contraceptives. STUDY DESIGN: A cross-sectional household survey was conducted from 2017 - 2018 among a representative sample of young women aged 15 - 24 years old living in six South African districts in which the intervention was implemented. Cross-tabulations and multivariate regression analyses of weighted data were performed to examine access to and use of condoms and other contraceptives. RESULTS: In total 4399 young women participated, representing a 60.6% response rate. Of participants, 61.0% (n=2685) reported accessing condoms and other contraceptives in the past year. Among those who ever had sex (n=3009), 51.0% used condoms and 37.4% other contraceptives at last sex. Among 15-19 year old, participation in the combination intervention was positively associated with reporting contraceptive use other than condoms at last sex (Prevalence Ratio (PR): 1.36; 95% CI: 1.21 - 1.53) and reporting use of both condoms and other contraceptives at last sex (PR: 1.45; 95% CI: 1.26 - 1.68). No associations were observed in the age group 20-24. CONCLUSION: Our findings suggest that combination HIV prevention interventions may lead to increased access and use of condoms and other methods of contraception among adolescent women, but this needs to be confirmed in experimental studies. We need to test different or more intensive interventions to increase contraceptive use in young women aged 20-24.