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This commentary highlights a need for comprehensive measures of structural racism tailored to cancer health disparities, in particular Black-White disparities in multiple myeloma (MM). Recent political and social calls and advances in the ability to quantitate structural racism have led to rapidly growing research on the health consequences of structural racism. However, to date, most studies have used unidimensional measures of structural racism that do not capture cumulative influences or enable the identification of factors most responsible for driving disparities. Furthermore, measures may not reflect aspects of structural racism most relevant to underlying disease processes and risks. This study proposes a multifaceted approach to measuring structural racism relevant to MM that includes comprehensive, disease- and at-risk population-tailored social and environmental data and biomarkers of susceptibility and progression related to underlying biological changes associated with structural racism. Such novel measures of structural racism may improve the ability to assess the influence of structural racism on cancer health disparities, which may advance understanding of disease etiology and differences observed by racialized groups.
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BACKGROUND: The introduction of vaccines during the COVID-19 pandemic provided an opportunity to slow transmission of SARS-CoV-2, but initial uptake of COVID-19 vaccination was slow. We analyzed data from a randomized clinical trial of the mRNA-1273 vaccine (NCT04811664) to describe the patterns of uptake of COVID-19 vaccines among young adults. METHODS: The CoVPN 3006 trial randomized adults ages 18-29 from 44 sites in the United States to receive 1) immediate mRNA-1273 vaccination from the study site, or 2) standard of care, including the option to seek vaccination at any time in the future. Randomization occurred between March and November 2021, and an observational arm of adults who declined vaccination was enrolled beginning June 2021. Among participants in the standard of care (SoC) or Vaccine Declined arms, we estimated demographic, behavioral, and health history correlates of vaccination, and the four-month cumulative incidence of COVID-19 vaccination using inverse probability weighted Kaplan-Meier estimators. RESULTS: Among 728 SoC and 470 Vaccine Declined participants, 79% and 16% received COVID-19 vaccination, respectively. SoC and Vaccine Declined participants were more likely to seek and receive vaccination if they reported COVID-19 preventive behaviors, including wearing masks, physically distancing, and avoiding large gatherings. We identified strong predictors of vaccination in the Vaccine Declined arm, including attending class in person (adjusted risk ratio [aRR]: 0.47, 95% confidence interval [CI] 0.21, 1.03), having a COVID-19 relevant medical condition (aRR: 1.95, 95% CI: 0.89, 4.26), and avoiding large gatherings (aRR: 2.24, 95% CI: 1.18, 4.25), though low vaccination rates in this arm led to imprecise estimates. CONCLUSIONS: Individuals who initially decline vaccination can be convinced to vaccinate, particularly if they are already practicing other forms of COVID-19 prevention. Continued outreach and education from the scientific community can combat low vaccine confidence.
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BACKGROUND: Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. METHODS: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. RESULTS: We observed an 18% increase in MM risk for every 5 kg/m2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m2) had the highest risk compared to those with a normal usual adult BMI (18.5-24.9 kg/m2; OR = 1.87, 95% CI 1.25-2.80), particularly among Black men (OR = 3.94, 95% CI 0.90-17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m2) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09-2.40), deletion 13q (OR = 1.73, 95% CI 1.08-2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82-7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31-0.81). CONCLUSIONS: Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.
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Índice de Masa Corporal , Mieloma Múltiple , Obesidad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antropometría , Negro o Afroamericano/estadística & datos numéricos , Mieloma Múltiple/epidemiología , Mieloma Múltiple/genética , Obesidad/complicaciones , Obesidad/epidemiología , Factores de Riesgo , Factores Sexuales , BlancoRESUMEN
Introduction: The use of tattoos for radiation therapy (RT) treatment is common practice. The Comfort Marker 2.0 (CQ Medical, Iowa, USA) has been designed to apply tattoos with a controlled depth injection, potentially resulting in tattoos that fade over time. The aim of this study was to investigate the clinical implementation of the Comfort Marker 2.0 tattoo device including the patient experience and clinical workflow. Methods: Patients undergoing RT treatment for breast cancer were invited to participate in this prospective pilot study. Patients completed a questionnaire after the planning session rating the level of pain experienced during tattoo application. Staff rated ease of use after each patient recording any feedback regarding the device. To evaluate tattoo fading, patients were followed up at 6 and 12 months after treatment to assess if tattoos could be visualised. Results: Between August and December 2021, 50 breast cancer patients were recruited to the study. All patients received at least 3 tattoos. The majority of patients (80%) rated their pain between not hurting or hurting a little. More than 85% of staff indicated the device was easy or very easy to use. The three most common areas staff identified for improvement were: cordless device (39.1%), pen size (20.3%) and consumable rubbish (13.0%). All tattoos remained visible at the final follow up appointment. Conclusion: Clinical implementation of the Comfort Marker tattoo device has been successful. Overall, patients found the process reasonably painless and staff found the device easy to use, providing a consistent result.
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[This corrects the article DOI: 10.1021/acs.estlett.2c00902.].
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The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.
RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.
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Administración Rectal , Infecciones por VIH , Homosexualidad Masculina , Minorías Sexuales y de Género , Humanos , Masculino , Tailandia , Infecciones por VIH/prevención & control , Malaui , Minorías Sexuales y de Género/psicología , Estados Unidos , Adulto , Femenino , Adulto Joven , Sudáfrica , Homosexualidad Masculina/psicología , Supositorios , Adolescente , Perú , Prioridad del Paciente , Conducta Sexual , Personas Transgénero/psicología , Antiinfecciosos/administración & dosificación , Placebos/administración & dosificación , Formas de DosificaciónRESUMEN
Introduction: Telehealth utilization surged during the COVID-19 pandemic, offering expanded health care access. Audio-only visits emerged as a crucial tool for patients facing technology or connectivity barriers to still use telehealth. This qualitative study aims to better understand patient perceptions of audio-only versus video telehealth visits during the COVID-19 pandemic, and how patients perceive the role of each in their overall health care. Methods: Semi-structured interviews were conducted with 14 adult patients seeking care at an academic medical center located in the Southeast region of the United States. Patients had experienced both an audio-only and video telehealth visit within the past 6 months. Topics covered in the interview included comfort, preference, quality, and communication during each type of visit. Interviews were transcribed verbatim, coded, and analyzed using a general inductive approach. Results: Participants valued having both modalities available largely due to convenience and saw these visits as supplemental or supporting their in-person care. Preferences for visit types were varied among participants and were context-specific, influenced by visit purpose and provider rapport. Patients viewed audio-only visits favorably for informational follow-ups and highlighted their convenience, particularly for multitasking and caregiving duties. In contrast, video visits were seen as more effective for communication due to visual cues and better suited for demonstrating health conditions. Audio-only visits were also seen as less technology-dependent and served as a vital back-up to failed video encounters. Discussion: Despite varied preferences, patients perceived both modalities as complementary to in-person care. Concerns around the quality of care were mitigated by patients' and providers' judicious use of visit types based on clinical appropriateness and existing rapport. The results emphasize the necessity and flexibility of audio-only visits in ensuring equitable access to telehealth, especially for those with technology limitations or demanding responsibilities. To maintain the access and convenience afforded by telehealth and ensure these benefits are offered equitably, policy makers and health care organizations must continue to provide flexible telehealth options, including audio-only visits.
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Although genome-wide association studies (GWAS) have identified loci for sleep-related traits, they do not directly uncover the underlying causal variants and corresponding effector genes. The majority of such variants reside in non-coding regions and are therefore presumed to impact cis-regulatory elements. Our previously reported 'variant-to-gene mapping' effort in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs), combined with validation in both Drosophila and zebrafish, implicated phosphatidyl inositol glycan (PIG)-Q as a functionally relevant gene at the insomnia "WDR90" GWAS locus. However, importantly that effort did not characterize the corresponding underlying causal variant. Specifically, our previous 3D genomic datasets nominated a shortlist of three neighboring single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium within an intronic enhancer region of WDR90 that contacted the open PIG-Q promoter. We sought to investigate the influence of these SNPs collectively and then individually on PIG-Q modulation to pinpoint the causal "regulatory" variant. Starting with gross level perturbation, deletion of the entire region in NPCs via CRISPR-Cas9 editing and subsequent RNA sequencing revealed expression changes in specific PIG-Q transcripts. Results from individual luciferase reporter assays for each SNP in iPSCs revealed that the region with the rs3752495 risk allele (RA) induced a ~2.5-fold increase in luciferase expression. Importantly, rs3752495 also exhibited an allele-specific effect, with the RA increasing the luciferase expression by ~2-fold versus the non-RA. In conclusion, our variant-to-function approach and in vitro validation implicate rs3752495 as a causal insomnia variant embedded within WDR90 while modulating the expression of the distally located PIG-Q.
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Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Trastornos del Inicio y del Mantenimiento del Sueño , Polimorfismo de Nucleótido Simple/genética , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Células Madre Pluripotentes Inducidas , Animales , Células-Madre Neurales , Desequilibrio de Ligamiento/genéticaRESUMEN
BACKGROUND: Following the outbreak of the COVID-19 pandemic, several clinical trials have evaluated postexposure prophylaxis (PEP) among close contacts of an index individual with a confirmed SARS-CoV-2 infection. Because index individuals do not directly inform the efficacy of prevention interventions, they are seldom enrolled in COVID-19 PEP studies. However, adjusting for prognostic covariates such as an index individual's COVID-19 illness and risk behaviors can increase precision in PEP efficacy estimates, so approaches to accurately collecting this information about the index individual are needed. This analysis aimed to assess whether surveying household contacts captures the same information as surveying the index individual directly. METHODS: REGN 2069/CoVPN 3502, a randomized controlled trial of COVID-19 PEP, enrolled household contacts of SARS-CoV-2 index individuals. CoVPN 3502-01 retrospectively enrolled and surveyed the index individuals. We compared responses to seven similar questions about the index individuals' transmission cofactors that were asked in both studies. We estimated the percent concordance between index individuals and their household contacts on each question, with 50% concordance considered equivalent to random chance. RESULTS: Concordance between index individuals and contacts was high on the most objective questions, approximately 97% (95% CI: 90-99%) for index individual age group and 96% (88-98%) for hospitalization. Concordance was moderate for symptoms, approximately 85% (75-91%). Concordance on questions related to the index individual's behavior was only slightly better or no better than random: approximately 62% (51-72%) for whether they received COVID-19 treatment, 68% (57-77%) for sharing a bedroom, 70% (59-79%) for sharing a common room, and 49% (39-60%) for mask wearing at home. However, while contacts were surveyed within 96 h of the index individual testing positive for SARS-CoV-2, the median time to enrollment in CoVPN 3502-01 was 240 days, which may have caused recall bias in our results. CONCLUSIONS: Our results suggest a need to survey index individuals directly in order to accurately capture their transmission cofactors, rather than relying on their household contacts to report on their behavior. The lag in enrolling participants into CoVPN 3502-01 also highlights the importance of timely enrollment to minimize recall bias.
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COVID-19 , Humanos , COVID-19/epidemiología , Tratamiento Farmacológico de COVID-19 , Pandemias/prevención & control , Estudios Retrospectivos , SARS-CoV-2 , AutoinformeRESUMEN
The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.
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Colitis , Microbioma Gastrointestinal , Ratones , Animales , Ácido Hialurónico/metabolismo , Mucosa Intestinal/metabolismo , Trasplante de Microbiota Fecal , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Colon/metabolismoRESUMEN
BACKGROUND: There is a motivation for organizations to understand race and racism from the perspective of minoritized individuals. Academic health centers (AHC) are ideal organizations to have these conversations as they educate healthcare providers, support research in health disparities, and care for diverse patients. METHODS: We piloted and evaluated a virtual Modified Privilege Walk (MPW) with faculty, staff, and students at an AHC in July 2020 to promote difficult conversations about race/racism, social class, and privilege. Each MPW session was voluntary, held virtually over Zoom, and lasted one hour and thirty minutes. Before attending, participants answered questions based on their race/ethnicity and social class to calculate a "privilege score." After each session, attendees were asked to complete an evaluation survey. RESULTS: There were five virtual MPWs with 132 attendees, and 74 participants completed an evaluation survey (56% response rate). Many respondents were students (n = 29, 39.2%). Most respondents either agreed (n = 36, 48.6%) or strongly agreed (n = 32, 43.2%) that the virtual MPW positively impacted how they will interact with those of a different race/ethnicity. Attendees requested having more virtual MPWs with leadership, incorporating virtual MPWs in various program curricula, and requiring new employees to participate. CONCLUSIONS: American organizations, particularly AHCs, should provide safe spaces and support these discussions surrounding race and racism as many were founded, built, or operated during a time of free labor and segregation that exerted power and control over minoritized individuals. Authors provide recommendations to dismantle organizational racism and support minoritized employees, patients, and students.
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Racismo , Racismo Sistemático , Humanos , Estados Unidos , Curriculum , Etnicidad , Clase SocialRESUMEN
INTRODUCTION: End-user perspectives are vital to the design of new biomedical HIV prevention products. Conjoint analysis can support the integration of end-user perspectives by examining their preferences of potential pre-exposure prophylaxis (PrEP) products. The Microbicides Trial Network (MTN) 035 protocol examined three placebo rectal dosage forms (insert, enema and suppository) that could deliver PrEP prior to receptive anal sex (RAS). METHODS: Between April 2019 and July 2020, we enrolled 217 HIV-negative, cisgender men who have sex with men (MSM; n = 172; 79.3%) and transgender people (n = 47; 20.7%) ages 18-35 into a randomized cross-over trial across Malawi, Peru, South Africa, Thailand and the United States. Participants used each product prior to RAS over 4-week periods. Participants completed a conjoint experiment where they selected between random profiles using seven features (dosage form, timing of use before sex, side effects, duration of protection, effectiveness, frequency of use and need for a prescription). RESULTS: Effectiveness was the strongest determinant of choice (30.4%), followed by modality (18.0%), potential side effects (17.2%), frequency of use (10.8%), duration of protection (10.4%), timing of use before sex (7.4%) and need for a prescription (5.9%). Relative utility scores indicated that the most desirable combination of attributes was a product with 95% efficacy, used 30 minutes before sex, offering a 3- to 5-day protection window, used weekly, having no side effects, in the form of an enema and available over-the-counter. CONCLUSIONS: Choice in next-generation PrEP products is highly desired by MSM and transgender people, as no one-size-fits-all approach satisfies all the preferences. MTN-035 participants weighed product features differently, recognizing the need for diverse, behaviourally congruent biomedical options that fit the needs of intended end-users.
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Antiinfecciosos , Infecciones por VIH , Minorías Sexuales y de Género , Humanos , Masculino , Antiinfecciosos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Conducta Sexual , Estados Unidos , Femenino , Adolescente , Adulto Joven , AdultoRESUMEN
OBJECTIVE: To determine if a discrepancy exists in the number and type of cases logged between female and male urology residents. MATERIALS AND METHODS: ACGME case log data from 13 urology residency programs was collected from 2007 to 2020. The number and type of cases for each resident were recorded and correlated with resident gender and year of graduation. The median, 25th and 75th percentiles number of cases were calculated by gender, and then compared between female and male residents using Wilcoxon rank sum test. RESULTS: A total of 473 residents were included in the study, 100 (21%) were female. Female residents completed significantly fewer cases, 2174, compared to male residents, 2273 (P = .038). Analysis by case type revealed male residents completed significantly more general urology (526 vs 571, P = .011) and oncology cases (261 vs 280, P = .026). Additionally, female residents had a 1.3-fold increased odds of logging a case in the assistant role than male residents (95% confidence interval: 1.27-1.34, P < .001). CONCLUSION: Gender-based disparity exists within the urology training of female and male residents. Male residents logged nearly 100 more cases than female residents over 4years, with significant differences in certain case subtypes and resident roles. The ACGME works to provide an equal training environment for all residents. Addressing this finding within individual training programs is critical.
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Internado y Residencia , Urología , Humanos , Masculino , Femenino , Educación de Postgrado en Medicina , Urología/educación , Competencia ClínicaRESUMEN
P4 ATPases (i.e., lipid flippases) are eukaryotic enzymes that transport lipids across membrane bilayers. In plants, P4 ATPases are named Aminophospholipid ATPases (ALAs) and are organized into five phylogenetic clusters. Here we generated an Arabidopsis mutant lacking all five cluster-2 ALAs (ala8/9/10/11/12), which is the most highly expressed ALA subgroup in vegetative tissues. Plants harboring the quintuple knockout (KO) show rosettes that are 2.2-fold smaller and display chlorotic lesions. A similar but less severe phenotype was observed in an ala10/11 double KO. The growth and lesion phenotypes of ala8/9/10/11/12 mutants were reversed by expressing a NahG transgene, which encodes an enzyme that degrades salicylic acid (SA). A role for SA in promoting the lesion phenotype was further supported by quantitative PCR assays showing increased mRNA abundance for an SA-biosynthesis gene ISOCHORISMATE SYNTHASE 1 (ICS1) and two SA-responsive genes PATHOGENESIS-RELATED GENE 1 (PR1) and PR2. Lesion phenotypes were also reversed by growing plants in liquid media containing either low calcium (~0.1 mM) or high nitrogen concentrations (~24 mM), which are conditions known to suppress SA-dependent autoimmunity. Yeast-based fluorescent lipid uptake assays revealed that ALA10 and ALA11 display overlapping substrate specificities, including the transport of LysoPC signaling lipids. Together, these results establish that the biochemical functions of ALA8-12 are at least partially overlapping, and that deficiencies in cluster-2 ALAs result in an SA-dependent autoimmunity phenotype that has not been observed for flippase mutants with deficiencies in other ALA clusters.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Salicílico/metabolismo , Filogenia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Adenosina Trifosfatasas/genética , LípidosRESUMEN
BACKGROUND AND OBJECTIVES: Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS: Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS: Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS: Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.
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COVID-19 , Lactante , Femenino , Embarazo , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , SARS-CoV-2 , Estudios Prospectivos , Vacunación , Inmunoglobulina G , Anticuerpos Neutralizantes , MadresRESUMEN
Deficits in chemosensory processing are associated with healthy aging, as well as numerous neurodegenerative disorders, including Alzheimer's Disease (AD). In many cases, chemosensory deficits are harbingers of neurodegenerative disease, and understanding the mechanistic basis for these changes may provide insight into the fundamental dysfunction associated with aging and neurodegeneration. The fruit fly, Drosophila melanogaster , is a powerful model for studying chemosensation, aging, and aging-related pathologies, yet the effects of aging and neurodegeneration on chemosensation remain largely unexplored in this model, particularly with respect to taste. To determine whether the effects of aging on taste are conserved in flies, we compared the response of flies to different appetitive tastants. Aging impaired response to sugars, but not medium-chain fatty acids that are sensed by a shared population of neurons, revealing modality-specific deficits in taste. Selective expression of the human amyloid beta (Aß) 1-42 peptide bearing the Arctic mutation (E693E) associated with early onset AD in the neurons that sense sugars and fatty acids phenocopies the effects of aging, suggesting that the age-related decline in response is localized to gustatory neurons. Functional imaging of gustatory axon terminals revealed reduced response to sugar, but not fatty acids. Axonal innervation of the fly taste center was largely intact in aged flies, suggesting that reduced sucrose response does not derive from neurodegeneration. Conversely, expression of the amyloid peptide in sweet-sensing taste neurons resulted in reduced innervation of the primary fly taste center. A comparison of transcript expression within the sugar-sensing taste neurons revealed age-related changes in 66 genes, including a reduction in odorant-binding protein class genes that are also expressed in taste sensilla. Together, these findings suggest that deficits in taste detection may result from signaling pathway-specific changes, while different mechanisms underly taste deficits in aged and AD model flies. Overall, this work provides a model to examine cellular deficits in neural function associated with aging and AD.