INTRODUCTION: Maternal deaths increased in the United States during 2018-2021, with documented racial disparities. Respectful maternity care is a component of quality care that includes preventing harm and mistreatment, engaging in effective communication, and providing care equitably. Improving respectful maternity care can be part of multilevel strategies to reduce pregnancy-related deaths. METHODS: CDC analyzed data from the PN View Moms survey administered during April 24-30, 2023, to examine the following components of respectful care: 1) experiences of mistreatment (e.g., violations of physical privacy, ignoring requests for help, or verbal abuse), 2) discrimination (e.g., because of race, ethnicity or skin color; age; or weight), and 3) reasons for holding back from communicating questions or concerns during maternity (pregnancy or delivery) care. RESULTS: Among U.S. mothers with children aged <18 years, 20% reported mistreatment while receiving maternity care for their youngest child. Approximately 30% of Black, Hispanic, and multiracial respondents and approximately 30% of respondents with public insurance or no insurance reported mistreatment. Discrimination during the delivery of maternity care was reported by 29% of respondents. Approximately 40% of Black, Hispanic, and multiracial respondents reported discrimination, and approximately 45% percent of all respondents reported holding back from asking questions or discussing concerns with their provider. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Approximately one in five women reported mistreatment during maternity care. Implementing quality improvement initiatives and provider training to encourage a culture of respectful maternity care, encouraging patients to ask questions and share concerns, and working with communities are strategies to improve respectful maternity care.

INTRODUCTION: Definitive vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been rarely reported. We present a case of a third trimester pregnancy with fetal distress necessitating cesarean section that demonstrated maternal, placental, and infant infection with the SARS-CoV-2 Alpha variant/B.1.1.7. METHODS: CDC's Influenza SARS-CoV-2 Multiplex RT-PCR Assay was used to test for SARS-CoV-2 in a maternal NP swab, maternal plasma, infant NP swab, and formalin-fixed paraffin-embedded (FFPE) placental tissue specimens. Whole genome sequencing (WGS) was performed on maternal plasma, infant, and placental specimens to determine the SARS-CoV-2 genotype. Histopathological evaluation, SARS-CoV-2 immunohistochemistry testing (IHC), and electron microscopy (EM) analysis were performed on placenta, umbilical cord, and membrane FFPE blocks. RESULTS: All specimens tested positive for SARS-CoV-2 by RT-PCR. WGS further revealed identical SARS-CoV-2 sequences from clade 20I/501Y.V1 (lineage Alpha/B.1.1.7) in maternal plasma, infant, and placental specimens. Histopathologic evaluation of the placenta showed histiocytic and neutrophilic intervillositis with fibrin deposition and trophoblast necrosis with positive SARS-CoV-2 immunostaining in the syncytiotrophoblast and electron microscopy evidence of coronavirus. DISCUSSION: These findings suggest vertical transmission of SARS-CoV-2, supported by clinical course timing, identical SARS-CoV-2 genotypes from maternal, placental, and infant samples, and IHC and EM evidence of placental infection. However, determination of the timing or distinction between prepartum and peripartum SARS-CoV-2 transmission remains unclear.

Objectives. To describe prevalence of breast milk feeding among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and examine associations between breast milk feeding, timing of maternal infection before delivery, and rooming-in status during delivery hospitalization. Methods. We performed a retrospective cohort study using data from Massachusetts, Minnesota, Nebraska, Pennsylvania, and Tennessee of whether people with confirmed SARS-CoV-2 infection during pregnancy in 2020 initiated breast milk feeding at birth. Results. Among 11114 (weighted number) people with SARS-CoV-2 infection in pregnancy, 86.5% (95% confidence interval [CI]=82.4%, 87.6%) initiated breast milk feeding during birth hospitalization. People with infection within 14 days before delivery had significantly lower prevalence of breast milk feeding (adjusted prevalence ratio [APR]=0.88; 95% CI=0.83, 0.94) than did those with infection at least 14 days before delivery. When stratified by rooming-in status, the association between timing of infection and breast milk feeding remained only among infants who did not room in with their mother (APR=0.77; 95% CI=0.68, 0.88). Conclusions. Pregnant and postpartum people with SARS-CoV-2 infection should have access to lactation support and be advised about the importance of breast milk feeding and how to safely feed their infants in the same room. (Am J Public Health. 2022;112(S8):S787-S796. https://doi.org/10.2105/AJPH.2022.307023).

BACKGROUND: Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of two methods for monitoring of terminal cleaning effectiveness. METHODS: Six intensive care units (ICUs) at three medical centers received both interventions sequentially, in randomized order. Ten surfaces were surveyed each in five rooms weekly, after terminal cleaning, with ATP monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services staff in real-time with failing surfaces recleaned. We measured monthly rates of MDRO infection or colonization, including methicillin-resistant Staphylococcus aureus, Clostridioides difficile, vancomycin-resistant Enterococcus, and MDR gram-negative bacilli (MDR-GNB) during a 12-month baseline period and sequential 6-month intervention periods, separated by a 2-month washout. Primary analysis compared only the randomized intervention periods, while secondary analysis included the baseline. RESULTS: The ATP method was associated with a reduction in incidence rate of MDRO infection or colonization compared to the UV/F period (incidence rate ratio (IRR) 0.876, 95% confidence-interval (CI) 0.807 - 0.951, P=0.002). Including the baseline period, the ATP method was associated with reduced infection with MDROs (IRR 0.924, 95% CI 0.855 - 0.998, P=0.04), and MDR-GNB infection or colonization (IRR 0.856, 95% CI 0.825 - 0.887, P<0.001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turn-around time increased by a median of one minute with the ATP intervention and 4.5 minutes with UV/F compared to baseline. CONCLUSIONS: Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a reduction of MDRO infection and colonization.

Sex-ratio distorters based on X-chromosome shredding are more efficient than sterile male releases for population suppression. X-shredding is a form of sex distortion that skews spermatogenesis of XY males towards the preferential transmission of Y-bearing gametes, resulting in a higher fraction of sons than daughters. Strains harboring X-shredders on autosomes were first developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion. Since autosomal X-shredders are transmitted in a Mendelian fashion and can be selected against, their frequency in the population declines once releases are halted. However, unintended transfer of X-shredders to the Y-chromosome could produce an invasive meiotic drive element, that benefits from its biased transmission to the predominant male-biased offspring and its effective shielding from female negative selection. Indeed, linkage to the Y-chromosome of an active X-shredder instigated the development of the nuclease-based X-shredding system. Here, we analyze mechanisms whereby an autosomal X-shredder could become unintentionally Y-linked after release by evaluating the stability of an established X-shredder strain that is being considered for release, exploring its potential for remobilization in laboratory and wild-type genomes of An. gambiae and provide data regarding expression on the mosquito Y-chromosome. Our data suggest that an invasive X-shredder resulting from a post-release movement of such autosomal transgenes onto the Y-chromosome is unlikely.

BACKGROUND: Antimicrobial resistance in Mycoplasma genitalium (MG), a cause of urethritis, is a growing concern. Yet little is known about the geographic distribution of MG resistance in the U.S. or associated clinical outcomes. We evaluated the frequency of MG among men with urethritis, resistance mutations, and post-treatment symptom persistence. METHODS: We enrolled men presenting with urethritis symptoms to 6 U.S. sexually transmitted disease (STD) clinics during June 2017-July 2018; men with urethritis were eligible for follow-up contact and (if persistent symptoms or MG) chart review. Urethral specimens were tested for MG and other bacterial STDs. Mutations in 23S rRNA loci (macrolide-associated mutations [MRMs]) and parC and gyrA (quinolone-associated mutations [QRMs]) were detected by targeted amplification/Sanger sequencing. RESULTS: Among 914 evaluable participants, 28.7% (95% CI 23.8-33.6) had MG. Men with MG were more often black (79.8% vs 66%), <30 years (72.9% vs 56.1%), and reported only female partners (83.7% vs 74.2%) than men without MG. Among MG-positive participants, 64.4% (95% CI 58.2%-70.3%) had MRM, 11.5% (95% CI 7.9-16.0%) had parC mutations, and 0% had gyrA mutations. Among participants treated with azithromycin-based therapy at enrollment and who completed the follow-up survey, persistent symptoms were reported by 25.8% of MG-positive/MRM-positive men, 13% of MG-positive/MRM-negative men, and 17.2% of MG-negative men. CONCLUSIONS: MG infection was common among men with urethritis; MRM prevalence was high among men with MG. Persistent symptoms following treatment were frequent among men with and without MG.

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

BACKGROUND: Many cases of Fuchs' uveitis have been associated with persistent rubella virus infection. A 73-year-old male patient with typical Fuchs' Uveitis Syndrome (FUS) first experienced heterochromia of the left eye at the age fourteen, when rubella was endemic in the US. OBJECTIVES: The purposes of this report are to describe the patient's FUS clinical presentations and to characterize the virus detected in the vitreous fluid. STUDY DESIGN: The patient underwent a therapeutic pars plana vitrectomy in May 2013. A real-time RT-PCR assay for rubella virus was performed on the vitreous fluid by Focus Diagnostics. Additional real-time RT-PCR assays for rubella virus detection and RT-PCR assays for generation of templates for sequencing were performed at the Centers for Disease Control and Prevention (CDC). RESULTS: The results from Focus Diagnostics were positive for rubella virus RNA. Real-time RT-PCR assays at CDC were also positive for rubella virus. A rubella virus sequence of 739 nucleotides was determined and phylogenetic analysis showed that the virus was the sole member of a new phylogenetic group when compared to reference virus sequences. CONCLUSIONS: While FUS remains a clinical diagnosis, findings in this case support the association between rubella virus and the disease. Phylogenetic analysis provided evidence that this rubella virus was likely a previously undetected genotype which is no longer circulating. Since the patient had rubella prior to 1955, this sequence is from the earliest rubella virus yet characterized.

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Silent cerebral infarct (SCI) is the most commonly recognized cause of neurological injury in sickle cell anaemia (SCA). We tested the hypothesis that magnetic resonance angiography (MRA)-defined vasculopathy is associated with SCI. Furthermore, we examined genetic variations in glucose-6-phosphate dehydrogenase (G6PD) and HBA (alpha-globin) genes to determine their association with intracranial vasculopathy in children with SCA. Magnetic resonance imaging (MRI) of the brain and MRA of the cerebral vasculature were available in 516 paediatric patients with SCA, enrolled in the Silent Infarct Transfusion (SIT) Trial. All patients were screened for G6PD mutations and HBA deletions. SCI were present in 41.5% (214 of 516) of SIT Trial children. The frequency of intracranial vasculopathy with and without SCI was 15.9% and 6.3%, respectively (P < 0.001). Using a multivariable logistic regression model, only the presence of a SCI was associated with increased odds of vasculopathy (P = 0.0007, odds ratio (OR) 2.84; 95% Confidence Interval (CI) = 1.55-5.21). Among male children with SCA, G6PD status was associated with vasculopathy (P = 0.04, OR 2.78; 95% CI = 1.04-7.42), while no significant association was noted for HBA deletions. Intracranial vasculopathy was observed in a minority of children with SCA, and when present, was associated with G6PD status in males and SCI.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

Rifapentine (RPT) is an antituberculosis drug that may shorten treatment duration when substituted for rifampin (RIF). The maximal tolerated daily dose of RPT and its potential for cytochrome 3A4 induction and autoinduction at clinically relevant doses are unknown. In this phase I, dose-escalation study among healthy volunteers, daily doses as high as a prespecified maximum of 20 mg/kg/day were well tolerated. Steady-state RPT concentrations increased with dose from 5 to 15 mg/kg, but area under the plasma concentration-time curve (AUC(0-24)) and maximum concentration (C(max)) were similar in the 15- and 20-mg/kg cohorts. Although RPT pharmacokinetics (PK) appeared to be time-dependent, accumulation occurred with daily dosing. The mean AUC(0-12) of oral midazolam (MDZ), a cytochrome 3A (CYP3A) probe drug, was reduced by 93% with the coadministration of RPT and by 74% with the coadministration of RIF (P < 0.01). Changes in the oral clearance of MDZ did not vary by RPT dose. In conclusion, RPT was tolerated at doses as high as 20 mg/kg/day, its PK were less than dose-proportional, and its CYP3A induction was robust.

AIMS: We sought to quantitatively describe the distribution of rectally administered gels and seminal fluid surrogates using novel concentration-distance parameters that could be repeated over time. These methods are needed to rationally develop rectal microbicides to target and prevent HIV infection. METHODS: Eight subjects were dosed rectally with radiolabeled and gadolinium-labeled gels to simulate microbicide gel and seminal fluid. Rectal doses were given with and without simulated receptive anal intercourse. Twenty-four hour distribution was assessed with indirect single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance (MR) imaging, and direct assessment via sigmoidoscopic brushes. Concentration-distance curves were generated using an algorithm for fitting SPECT data in 3-dimensions. Three novel concentration-distance parameters were defined to quantitatively describe the distribution of radiolabels: maximal distance (D(max) ), distance at maximal concentration (D(Cmax) ), mean residence distance (D(ave) ). RESULTS: The SPECT/CT distribution of microbicide and semen surrogates was similar. Between 1 hour and 24 hours post-dose, the surrogates migrated retrograde in all three parameters (relative to coccygeal level; geometric mean [95% confidence interval]): maximal distance (D(max) ), 10 cm (8.6-12) to 18 cm (13-26); distance at maximal concentration (D(Cmax) ), 3.8 cm (2.7-5.3) to 4.2 cm (2.8-6.3); mean residence distance (D(ave) ), 4.3 cm (3.5-5.1) to7.6 cm (5.3-11). Sigmoidoscopy and MRI correlated only roughly with SPECT/CT. CONCLUSIONS: Rectal microbicide surrogates migrated retrograde during the 24 hours following dosing. Spatial kinetic parameters estimated using three dimensional curve fitting of distribution data should prove useful for evaluating rectal formulations of drugs for HIV prevention and other indications. (2012 (c) The Authors. British Journal of Clinical Pharmacology (c) 2012 The British Pharmacological Society.)