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STUDY OBJECTIVE: Airway management is a crucial part of out-of-hospital care. It is not known if the rate of overall agency intubation attempts is associated with intubation success. We sought to evaluate the association between agency intubation attempt rate and intubation success using a national out-of-hospital database. METHODS: We conducted a retrospective secondary analysis of the ESO Data Collaborative from 2018 to 2019, and included all adult cases with an endotracheal intubation attempt. We calculated the number of intubations attempted per 100 responses, advanced life support responses, and transports for each agency. We excluded cases originating at health care facilities and outliers. We used multivariable logistic regression to evaluate the association between agency intubation attempt rate and 1) intubation success and 2) first-pass success. We adjusted for confounders. RESULTS: We included 1,005 agencies attempting 58,509 intubations. Overall, the intubation success rate was 78.8%, and the first-pass success rate was 68.5%. Per agency, the median rate of intubation attempts per 100 emergency medical service responses was 0.8 (interquartile range 0.6 to 1.1). Rates of intubation attempts per 100 responses (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.6 to 1.8), advanced life support responses (aOR 1.18; 95% CI 1.16 to 1.20), and transports (aOR 1.21; 95% CI 1.18 to 1.22) were all associated with intubation success. These relationships were similar for first-pass success but with smaller effect sizes. CONCLUSION: Higher agency rates of intubation attempts were associated with increased rates of intubation success and first-pass success.
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Servicios Médicos de Urgencia , Intubación Intratraqueal , Humanos , Intubación Intratraqueal/estadística & datos numéricos , Intubación Intratraqueal/métodos , Estudios Retrospectivos , Femenino , Masculino , Servicios Médicos de Urgencia/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Anciano , Manejo de la Vía Aérea/métodos , Manejo de la Vía Aérea/estadística & datos numéricos , Estados Unidos , Modelos LogísticosRESUMEN
Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) syndemic interactions are a major global health concern. Despite the clinical significance of coinfection, our understanding of the cellular pathophysiology and the therapeutic pharmacodynamic impact of coinfection is limited. Here, we use single-round infectious HIV-1 pseudotyped viral particles expressing green fluorescent protein alongside M. tuberculosis expressing mCherry to study pathogenesis and treatment. We report that HIV-1 infection inhibited intracellular replication of M. tuberculosis and demonstrate the therapeutic activity of antiviral treatment (efavirenz) and antimicrobial treatment (rifampicin). The described method could be applied for detailed mechanistic studies to inform the development of novel treatment strategies.
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Coinfección , Infecciones por VIH , VIH-1 , Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis/microbiología , Coinfección/tratamiento farmacológico , Rifampin/uso terapéutico , Infecciones por VIH/tratamiento farmacológicoRESUMEN
The scalability of quantum networking will benefit from quantum and classical communications coexisting in shared fibers, the main challenge being spontaneous Raman scattering noise. We investigate the coexistence of multi-channel O-band quantum and C-band classical communications. We characterize multiple narrowband entangled photon pair channels across 1282 nm-1318 nm co-propagating over 48 km of installed standard fiber with record C-band power (>18 dBm) and demonstrate that some quantum-classical wavelength combinations significantly outperform others. We analyze the Raman noise spectrum, optimal wavelength engineering, multi-photon pair emission in entangled photon-classical coexistence, and evaluate the implications for future quantum applications.
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Parasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effects that soluble egg antigen (SEA) from Schistosoma mansoni had on modulating HIV-1 infection and cytokine/chemokine production in vitro. We determined that SEA, specifically through kappa-5, can potently bind to DC-SIGN and thereby blocks DC-SIGN mediated HIV-1 trans-infection (p<0.05) whilst not interfering with cis-infection. DCs exposed to SEA whilst maturing under Th2 promoting conditions, will upon co-culture with naïve T-cells induce a T-cell population that was less susceptible to HIV-1 R5 infection (p<0.05) compared to DCs unexposed to SEA, whereas HIV-1 X4 virus infection was unaffected. This was not observed for DCs exposed to SEA while maturing under Th1 or Th1/Th2 (Tmix) promoting conditions. All T-cell populations induced by SEA exposed DCs demonstrate a reduced capacity to produce IFN-γ and MIP-1ß. The infection profile of T-cells infected with HIV-1 R5 was not associated with down-modulation of CCR5 cell surface expression. We further show that DCs maturing under Tmix conditions exposed to plant recombinant omega-1 protein (rω-1), which demonstrates similar functions to natural ω-1, induced T-cell populations that were less sensitive for HIV-1 R5 infection (p<0.05), but not for X4 virus infection. This inhibition associated again with a reduction in IFN-γ and MIP-1ß expression, but additionally correlated with reduced CCR5 expression. We have shown that SEA parasite antigens and more specifically rω-1 can modulate HIV-1 infectivity with the potential to influence disease course in co-infected individuals.
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Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Proteínas del Huevo/inmunología , Infecciones por VIH/metabolismo , Animales , Anticuerpos Antihelmínticos/metabolismo , Antígenos Helmínticos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Proteínas del Huevo/metabolismo , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , VIH-1/inmunología , Humanos , Activación de Linfocitos , Receptores CCR5/metabolismo , Schistosoma mansoni/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Replicación Viral/inmunologíaRESUMEN
OBJECTIVES: Community health worker (CHW) programs are a promising strategy to improve maternal and child health outcomes, particularly among low-resource women. Yet, little is known about which aspects of CHW-client relationships are most salient for promoting positive change. This paper examines features of the CHW-client relationship that perinatal women with chronic conditions reported as being beneficial for their experience of prenatal care and pregnancy. METHODS: Focus groups and interviews were conducted with 18 CHWs and 39 clients from three Merck for Mothers-funded programs in the Eastern United States. Data were analyzed using a grounded theory-informed thematic approach. RESULTS: CHWs built trust-based relationships through emotional attendance, authenticity, and prioritization of clients' needs. They provided instrumental, informational, and emotional support that clients reported facilitated greater engagement with the healthcare system, improved health behaviors, and reduced stress. CHWs and clients alike viewed their relationships as having long-lasting impacts, made possible by the trust-based bond between them. DISCUSSION: Strong, trusting relationships with CHWs may be one avenue through which to improve maternal and infant health for vulnerable perinatal women. Community health care programs should promote trust-building as an explicit program goal. Trust-based CHW-client relationships may serve as an exemplar for transforming traditional care relationships between providers and clients, leading to greater client engagement in care and improved health.
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Agentes Comunitarios de Salud , Confianza , Niño , Servicios de Salud Comunitaria , Femenino , Grupos Focales , Humanos , Lactante , Motivación , EmbarazoRESUMEN
Tuberculosis (TB) is the leading cause of death among HIV-1-infected individuals and Mycobacterium tuberculosis (Mtb) co-infection is an early precipitate to AIDS. We aimed to determine whether Mtb strains differentially modulate cellular susceptibility to HIV-1 infection (cis- and trans-infection), via surface receptor interaction by their cell envelope lipids. Total lipids from pathogenic (lineage 4 Mtb H37Rv, CDC1551 and lineage 2 Mtb HN878, EU127) and non-pathogenic (Mycobacterium bovis BCG and Mycobacterium smegmatis) Mycobacterium strains were integrated into liposomes mimicking the lipid distribution and antigen accessibility of the mycobacterial cell wall. The resulting liposomes were tested for modulating in vitro HIV-1 cis- and trans-infection of TZM-bl cells using single-cycle infectious virus particles. Mtb glycolipids did not affect HIV-1 direct infection however, trans-infection of both R5 and X4 tropic HIV-1 strains were impaired in the presence of glycolipids from M. bovis, Mtb H37Rv and Mtb EU127 strains when using Raji-DC-SIGN cells or immature and mature dendritic cells (DCs) to capture virus. SL1, PDIM and TDM lipids were identified to be involved in DC-SIGN recognition and impairment of HIV-1 trans-infection. These findings indicate that variant strains of Mtb have differential effect on HIV-1 trans-infection with the potential to influence HIV-1 disease course in co-infected individuals.
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Infecciones Oportunistas Relacionadas con el SIDA/metabolismo , Coinfección/metabolismo , Glucolípidos/metabolismo , VIH-1/fisiología , Liposomas/metabolismo , Mycobacterium tuberculosis/metabolismo , Tuberculosis/metabolismo , Infecciones Oportunistas Relacionadas con el SIDA/virología , Moléculas de Adhesión Celular/metabolismo , Pared Celular/metabolismo , Células HEK293 , Humanos , Lectinas Tipo C/metabolismo , Infecciones por Mycobacterium no Tuberculosas/metabolismo , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium bovis/metabolismo , Mycobacterium smegmatis/metabolismo , Receptores de Superficie Celular/metabolismo , Tuberculosis/microbiología , Internalización del VirusRESUMEN
BACKGROUND: Intimate partner violence (IPV) during pregnancy is associated with adverse maternal and child health outcomes, including poor mental health. Previous IPV research has largely focused on women's victimization experiences; however, evidence suggests young women may be more likely to engage in bilateral violence (report both victimization and perpetration) or perpetrate IPV (unilateral perpetration) during pregnancy than to report being victimized (unilateral victimization). This study examined prevalence of unilateral victimization, unilateral perpetration, and bilateral violence, and the association between these IPV profiles and mental health outcomes during pregnancy among young, low-income adolescents. METHODS: Survey data were collected from 930 adolescents (14-21 years; 95.4% Black and Latina) from fourteen Community Health Centers and hospitals in New York City during second and third trimester of pregnancy. Multivariable regression models tested the association between IPV profiles and prenatal depression, anxiety, and distress, adjusting for known predictors of psychological morbidity. RESULTS: Thirty-eight percent of adolescents experienced IPV during their third trimester of pregnancy. Of these, 13% were solely victims, 35% were solely perpetrators, and 52% were engaged in bilateral violence. All women with violent IPV profiles had significantly higher odds of having depression and anxiety compared to individuals reporting no IPV. Adolescents experiencing bilateral violence had nearly 4-fold higher odds of depression (OR = 3.52, 95% CI: 2.43, 5.09) and a nearly 5-fold increased likelihood of anxiety (OR = 4.98, 95% CI: 3.29, 7.55). Unilateral victims and unilateral perpetrators were also at risk for adverse mental health outcomes, with risk of depression and anxiety two- to three-fold higher, compared to pregnant adolescents who report no IPV. Prenatal distress was higher among adolescents who experienced bilateral violence (OR = 2.84, 95% CI: 1.94, 4.16) and those who were unilateral victims (OR = 2.21, 95% CI: 1.19, 4.12). CONCLUSIONS: All violent IPV profiles were associated with adverse mental health outcomes among pregnant adolescents, with bilateral violence having the most detrimental associations. Comprehensive IPV screening for both victimization and perpetration experiences during pregnancy is warranted. Clinical and community prevention efforts should target pregnant adolescents and their partners to reduce their vulnerability to violence and its adverse consequences. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00628771 . Registered 29 February 2008.
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Violencia de Pareja , Salud Mental , Embarazo/psicología , Mujeres Embarazadas/psicología , Adolescente , Femenino , Infecciones por VIH/prevención & control , Humanos , Salud Mental/etnología , Ciudad de Nueva York/epidemiología , Mujeres Embarazadas/etnología , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Adulto JovenRESUMEN
We have described self-reported exposure to gun violence in an urban community of color to inform the movement toward a public health approach to gun violence prevention. The Community Alliance for Research and Engagement at Yale School of Public Health conducted community health needs assessments to document chronic disease prevalence and risk, including exposure to gun violence. We conducted surveys with residents in six low-income neighborhoods in New Haven, Connecticut, using a neighborhood-stratified, population-based sample (n = 1189; weighted sample to represent the neighborhoods, n = 29 675). Exposure to violence is pervasive in these neighborhoods: 73% heard gunshots; many had family members or close friends hurt (29%) or killed (18%) by violent acts. Although all respondents live in low-income neighborhoods, exposure to violence differs by race/ethnicity and social class. Residents of color experienced significantly more violence than did White residents, with a particularly disparate increase among young Black men aged 18 to 34 years. While not ignoring societal costs of horrific mass shootings, we must be clear that a public health approach to gun violence prevention means focusing on the dual epidemic of mass shootings and urban violence.
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Exposición a la Violencia/estadística & datos numéricos , Incidentes con Víctimas en Masa , Heridas por Arma de Fuego/epidemiología , Adolescente , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Connecticut/epidemiología , Exposición a la Violencia/etnología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Áreas de Pobreza , Prevalencia , Factores de Riesgo , Autoinforme , Encuestas y Cuestionarios , Población Urbana , Población Blanca/estadística & datos numéricos , Heridas por Arma de Fuego/etnologíaRESUMEN
BACKGROUND: Cycles of alcohol and stress are hypothesized to contribute to alcohol use disorders. How this occurs is poorly understood, although both alcohol and stress activate the neuroimmune system-the immune molecules and cells that interact with the nervous system. The effects of alcohol and stress on the neuroimmune system are mediated in part by peripheral signaling molecules. Alcohol and stress both enhance immunomodulatory molecules such as corticosterone and endotoxin to impact neuroimmune cells, such as microglia, and may subsequently impact neurons. In this study, we therefore examined the effects of acute and chronic ethanol (EtOH) on the corticosterone, endotoxin, and microglial and neuronal response to acute stress. METHODS: Male Wistar rats were treated intragastrically with acute EtOH and acutely stressed with restraint/water immersion. Another group of rats was treated intragastrically with chronic intermittent EtOH and acutely stressed following prolonged abstinence. Plasma corticosterone and endotoxin were measured, and immunohistochemical stains for the microglial marker CD11b and neuronal activation marker c-Fos were performed. RESULTS: Acute EtOH and acute stress interacted to increase plasma endotoxin and microglial CD11b, but not plasma corticosterone or neuronal c-Fos. Chronic EtOH caused a lasting sensitization of stress-induced plasma endotoxin, but not plasma corticosterone. Chronic EtOH also caused a lasting sensitization of stress-induced microglial CD11b, but not neuronal c-Fos. CONCLUSIONS: These results find acute EtOH combined with acute stress enhanced plasma endotoxin, as well as microglial CD11b in many brain regions. Chronic EtOH followed by acute stress also increased plasma endotoxin and microglial CD11b, suggesting a lasting sensitization to acute stress. Overall, these data suggest alcohol and stress interact to increase plasma endotoxin, resulting in enhanced microglial activation that could contribute to disease progression.
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Encéfalo/citología , Encéfalo/metabolismo , Etanol/farmacología , Microglía/metabolismo , Neuronas/metabolismo , Estrés Psicológico/metabolismo , Animales , Encéfalo/efectos de los fármacos , Antígeno CD11b/metabolismo , Sensibilización del Sistema Nervioso Central/efectos de los fármacos , Corticosterona/sangre , Endotoxinas/sangre , Masculino , Proteínas Proto-Oncogénicas c-fos/metabolismo , RatasRESUMEN
BACKGROUND: Despite biomedical advances and intervention efforts, rates of preterm birth and other adverse outcomes in the United States have remained relatively intransigent. Evidence suggests that group prenatal care can reduce these risks, with implications for maternal and child health as well as substantial cost savings. However, widespread dissemination presents challenges, in part because training and health systems have not been designed to deliver care in a group setting. This manuscript describes the design and evaluation of Expect With Me, an innovative model of group prenatal care with a strong integrated information technology (IT) platform designed to be scalable nationally. METHODS/DESIGN: Expect With Me follows clinical guidelines from the American Congress of Obstetricians and Gynecologists. Expect With Me incorporates the best evidence-based features of existing models of group care with a novel integrated IT platform designed to improve patient engagement and support, enhance health behaviors and decision making, connect providers and patients, and improve health service delivery. A multisite prospective longitudinal cohort study is being conducted to examine the impact of Expect With Me on perinatal and postpartum outcomes, and to identify and address barriers to national scalability. Process and outcome evaluation will include quantitative and qualitative data collection at patient, provider, and organizational levels. Mixed-method data collection includes patient surveys, medical record reviews, patient focus groups; provider surveys, session evaluations, provider focus groups and in-depth interviews; an online tracking system; and clinical site visits. A two-to-one matched cohort of women receiving individual care from each site will provide a comparison group (n = 1,000 Expect With Me patients; n = 2,000 individual care patients) for outcome and cost analyses. DISCUSSION: By bundling prevention and care services into a high-touch, high-tech group prenatal care model, Expect With Me has the potential to result in fundamental changes to the health care system to meet the "triple aim:" better healthcare quality, improved outcomes, and lower costs. Findings from this study will be used to optimize the dissemination and effectiveness of this model. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02169024 . Retrospectively registered on June 18, 2014.
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Procesos de Grupo , Atención Prenatal/métodos , Evaluación de Programas y Proyectos de Salud/métodos , Estudios de Casos y Controles , Femenino , Humanos , Tecnología de la Información , Estudios Longitudinales , Embarazo , Resultado del Embarazo , Atención Prenatal/normas , Estudios Prospectivos , Calidad de la Atención de SaludAsunto(s)
Doulas , Medicaid , Doulas/economía , Doulas/educación , Doulas/legislación & jurisprudencia , Doulas/normas , Femenino , Disparidades en Atención de Salud , Humanos , Reembolso de Seguro de Salud , Medicaid/economía , Medicaid/legislación & jurisprudencia , New York , Embarazo , Estados UnidosRESUMEN
BACKGROUND Nephro-colic fistulas are uncommon, generally caused by local inflammation, trauma, or neoplasia affecting the kidney or the colon. Their association with a coralliform stone is described in a few case reports, but their management is difficult and differs quite a lot, depending on the clinical situation. We report an atypical clinical case of a reno-colic fistula associated with a staghorn calculus. This case adds to the literature an iconography rarely found. CASE REPORT A 68-year-old woman presented to the Emergency Department with respiratory symptoms and chronic abdominal pain. The biological results showed a high inflammatory syndrome. The radiological assessment revealed a retroperitoneal and left retro-renal abscess, attributed to a left nephro-colic fistula associated with the partial passage of a lithiasis within the colonic lumen. Colonoscopy confirmed the diagnosis. Multiple recurrences of diverticulitis in this region could be the origin of the complication. First, the patient was treated with antibiotic therapy and radiological drainage. Second, she benefited from a left nephrectomy, left segmental colectomy, and splenectomy. The clinical and radiological evolution were favorable after surgery. The follow-up was disrupted by hospitalizations in the Cardiology Department for cardiac decompensation. CONCLUSIONS Kidney stones along with local inflammatory phenomena can be the cause of a nephro-colic fistula. Due to the lack of guidelines in such cases, their diagnosis and management are difficult to ascertain. Surgery is the right course of treatment.
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Absceso Abdominal , Cólico , Fístula Intestinal , Cálculos Renales , Cálculos Coraliformes , Femenino , Humanos , Anciano , Cálculos Coraliformes/complicaciones , Cólico/complicaciones , Absceso/complicaciones , Absceso Abdominal/diagnóstico por imagen , Absceso Abdominal/etiología , Fístula Intestinal/diagnóstico por imagen , Fístula Intestinal/etiología , Fístula Intestinal/cirugíaRESUMEN
OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked with menopause symptoms (eg, vasomotor, urinary) and their sequelae (eg, sexual difficulties). However, PTSD is a heterogeneous disorder, and less is known about which aspects may be most associated with menopause-related health. METHODS: Using confirmatory factor analyses, we evaluated five structural models of PTSD symptoms in 208 predominately postmenopausal women veterans (aged 45-64 years). We investigated associations between PTSD-operationalized as a probable diagnosis and symptom dimensions of the best-fitting model-and common menopause-related health concerns, including (1) vasomotor, urinary, and vaginal symptoms; (2) vasomotor symptom interference; and (3) sexual functioning. RESULTS: A six-factor anhedonia model-comprising re-experiencing, avoidance, negative affect, anhedonia, anxious arousal, and dysphoric arousal-provided optimal fit. Both probable PTSD and greater symptoms across all dimensions were linked with presence of urinary and vasomotor, but not vaginal, symptoms. Comparing dimensions revealed that negative affect and dysphoric arousal were particularly associated with urinary symptoms, whereas dysphoric arousal was the factor most strongly related to vasomotor symptom interference. Associations between PTSD and sexual dysfunction were mixed; whereas there was no relation with probable diagnosis, all dimensions were linked with adverse sexual sequelae. CONCLUSIONS: PTSD-considered categorically and dimensionally-was relevant to menopause-related health in midlife women veterans. Further, symptoms of negative affect and dysphoric arousal were particularly related to urinary and vasomotor symptoms. These specific symptoms may drive associations between PTSD and these aspects of menopause-related health. Clinical interventions targeting these symptoms may promote midlife women's health.
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Menopausia , Trastornos por Estrés Postraumático , Veteranos , Humanos , Femenino , Persona de Mediana Edad , Trastornos por Estrés Postraumático/fisiopatología , Veteranos/psicología , Menopausia/fisiología , Menopausia/psicología , Salud de la Mujer , Disfunciones Sexuales Fisiológicas/psicología , Disfunciones Sexuales Fisiológicas/fisiopatología , Análisis Factorial , Posmenopausia/psicología , Posmenopausia/fisiología , Sofocos/fisiopatología , Sofocos/psicologíaRESUMEN
BACKGROUND: Discrimination is an important social determinant of perinatal depression; however, evidence is limited regarding modifiable social and psychological factors that may moderate this association. We examined whether social support and resilience could protect against the adverse effects of discrimination on perinatal depressive symptoms. METHODS: Pregnant people (N = 589) receiving Expect With Me group prenatal care in Nashville, TN and Detroit, MI completed surveys during third trimester of pregnancy and six months postpartum. Linear regression models tested the association between discrimination and depressive symptoms, and the moderating effects of social support and resilience, during pregnancy and postpartum. RESULTS: The sample was predominantly Black (60.6 %), Hispanic (15.8 %) and publicly insured (71 %). In multivariable analyses, discrimination was positively associated with depressive symptoms during pregnancy (B = 4.44, SE = 0.37, p ≤0.001) and postpartum (B = 3.78, SE = 0.36, p < 0.001). Higher social support and resilience were associated with less depressive symptoms during pregnancy (B = -0.49, SE = 0.08, p < 0.001 and B = -0.67, SE = 0.10, p < 0.001, respectively) and postpartum (B = -0.32, SE = 0.07, p < 0.001 and B = -0.56, SE = 0.08, p < 0.001, respectively). Social support was protective against discrimination (pregnancy interaction B = -0.23, SE = 0.09, p = 0.011; postpartum interaction B = -0.35, SE = 0.07, p < 0.001). There was no interaction between discrimination and resilience at either time. LIMITATIONS: The study relied on self-reported measures and only included pregnant people who received group prenatal care in two urban regions, limiting generalizability. CONCLUSIONS: Social support and resilience may protect against perinatal depressive symptoms. Social support may also buffer the adverse effects of discrimination on perinatal depressive symptoms, particularly during the postpartum period.
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Depresión Posparto , Resiliencia Psicológica , Embarazo , Femenino , Humanos , Depresión/psicología , Periodo Posparto/psicología , Apoyo Social , Atención Prenatal , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Depresión Posparto/prevención & controlRESUMEN
The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has highlighted the threat that viral outbreaks pose to global health. A key tool in the arsenal to prevent and control viral disease outbreaks is disinfection of equipment and surfaces with formulations that contain virucidal agents (VA). However, assessment of the efficacy of virus inactivation often requires live virus assays or surrogate viruses such as Modified Vaccinia Virus Ankara (MVA), which can be expensive, time consuming and technically challenging. Therefore, we have developed a pseudo-typed virus (PV) based approach to assess the inactivation of enveloped viruses with a fast and quantitative output that can be adapted to emerging viruses. Additionally, we have developed a method to completely remove the cytotoxicity of virucidal agents while retaining the required sensitivity to measure PV infectivity. Our results indicated that the removal of cytotoxicity was an essential step to accurately measure virus inactivation. Further, we demonstrated that there was no difference in susceptibility to virus inactivation between PVs that express the envelopes of HIV-1, SARS-CoV-2, and Influenza A/Indonesia. Therefore, we have developed an effective and safe alternative to live virus assays that enables the rapid assessment of virucidal activity for the development and optimization of virucidal reagents.
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Gripe Humana , Virosis , Virus , Humanos , Desinfección/métodos , ViriónRESUMEN
Limited spatial separation within small islands suggests that observed population divergence may occur due to habitat differences without interruption to gene flow but strong evidence of this is scarce. The wall lizard Teira dugesii lives in starkly contrasting shingle beach and inland habitats on the island of Madeira. We used a matched pairs sampling design to examine morphological and genomic divergence between four beach and adjacent (<1 km) inland areas. Beach populations are significantly darker than corresponding inland populations. Geometric morphometric analyses reveal divergence in head morphology: beach lizards have generally wider snouts. Genotyping-by-sequencing allows the rejection of the hypothesis that beach populations form a distinct lineage. Bayesian analyses provide strong support for models that incorporate gene flow, relative to those that do not, replicated at all pairs of matched sites. Madeiran lizards show morphological divergence between habitats in the face of gene flow, revealing how divergence may originate within small islands.
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Variación Genética , Lagartos , Animales , Flujo Génico , Lagartos/genética , Lagartos/anatomía & histología , Teorema de Bayes , EcosistemaRESUMEN
Inducible laryngeal obstruction (ILO)/vocal cord dysfunction is frequently encountered in the specialist asthma clinic, where it is often misdiagnosed as asthma or is coexistent with asthma. It causes recurrent distressing episodes of acute dyspnea that can lead to hospital admissions, endotracheal intubation, and fruitless asthma treatment escalation, often including oral glucocorticoids.1-4 Early diagnosis and treatment of ILO offers the prospect of connecting patients with an effective speech- and language-based intervention earlier and avoiding these unnecessary and potentially harmful interventions.
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Obstrucción de las Vías Aéreas , Asma , Enfermedades de la Laringe , Humanos , Pliegues Vocales , Laringoscopía/efectos adversos , Obstrucción de las Vías Aéreas/diagnóstico , Enfermedades de la Laringe/complicaciones , Asma/complicacionesRESUMEN
PURPOSE: Early life adversity (ELA) is associated with sexual risk, but ELA dimensions-and potential mechanisms-have been less examined. We evaluated associations between threat and deprivation-two key ELA dimensions-and sexual behaviors in adolescents. Secondary analyses investigated age at menarche as a mechanism linking ELA with sexual outcomes in girls. We predicted associations between threat and sexual behaviors, with younger age at menarche as a pathway. METHODS: Data were from the National Comorbidity Survey, Adolescent Supplement. Adolescents and caregivers reported on youths' ELA experiences, which were categorized as threat- or deprivation-related. Adolescents reported if they engaged in sex (N = 9,937) and on specific sexual risk indicators, including age at first sex, number of past-year sexual partners, and condom use consistency ("always" vs. "not always" used). Girls reported age at menarche. RESULTS: Threat (odds ratio [OR] = 1.76 [95% confidence interval [CI], 1.62-1.92]) and deprivation (OR = 1.51 [95% CI, 1.24-1.83]) were each linked with engagement in sex, ps<.05. Threat-related experiences were associated with multiple sexual risk markers, even when accounting for deprivation: earlier age at first sex (b = -0.20 [95% CI, -0.27 to 0.13]), greater number of partners (b = 0.17 [95% CI, 0.10-0.25]), and inconsistent condom use (OR = 0.72 [95% CI, 0.64-0.80]), ps <.001. Deprivation was not associated with sexual risk when adjusting for threat. We observed no significant indirect effects through age at menarche. DISCUSSION: Although threat and deprivation were related to engagement in sexual activity, threat-related experiences were uniquely associated with sexual risk. Screening for threat-related ELA may identify adolescents at-risk for poor sexual health.
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Conducta del Adolescente , Conducta Sexual , Femenino , Adolescente , Humanos , Parejas Sexuales , Factores de Riesgo , ComorbilidadRESUMEN
Human immunodeficiency virus type 1 (HIV-1) is able to infect a variety of cell types with differences in entry efficiency and replication kinetics determined by the host cell type or the viral phenotype. The phenotype of the virus produced from these various cell types, including infectivity, co-receptor usage and neutralisation sensitivity, may also be affected by the characteristics of the producing cell. This can be due to incorporation of variant cell-specific molecules or differences in post-translational modifications of the gp41/120 envelope. In this study we produced genetically identical virus strains from macrophages, CD4-enriched lymphocytes as well as Th1 and Th2 CD4+ cell lines and compared each different virus stock for their infectivity in various cell types and sensitivity to neutralisation. In order to study the effect of the producer host cell on the virus phenotype, virus stocks were normalised on infectivity and were sequenced to confirm env gene homogeneity. Virus production by Th1 or Th2 cells did not compromise infectivity of the variant cell types tested. We observed no difference in sensitivity to co-receptor blocking agents upon viral passage through Th1 and Th2 CD4+ cell lineages nor did this affect DC-SIGN-mediated viral capture as measured in a transfer assay to CD4+ lymphocytes. Virus produced by macrophages was comparably sensitive to CC-chemokine inhibition as was virus generated from the array of CD4+ lymphocytes. We identified that virus produced from macrophages was fourteen times more resistant to 2G12 neutralisation than virus produced from CD4+ lymphocytes. Macrophage-produced dual-tropic (R5/X4) virus was six times more efficiently transmitted to CD4+ cells than lymphocyte-derived HIV-1 (p<0.0001) after DCSIGN capture. These results provide further insights to what extent the host cell influences viral phenotype and thereby various aspects of HIV-1 pathogenesis but suggest that viruses generated from Th1 versus Th2 cells are consistent in phenotype.
Asunto(s)
VIH-1 , Humanos , VIH-1/fisiología , Linfocitos T CD4-Positivos/metabolismo , Células Th2/metabolismo , Fenotipo , Macrófagos , Polisacáridos/metabolismoRESUMEN
Fixed-timed artificial insemination (FTAI) protocols for beef cattle in South America are primarily based on estradiol esters and intravaginal progesterone-releasing devices (IVPD). The objective of this study was to determine the optimal gonadotropin-releasing hormone (GnRH)-based protocol as an alternative to the use of estrogen-based protocols in grazing Bos taurus suckling beef cows. All cows received an IVPD on the day of protocol initiation and prostaglandin F2α (PG) plus equine chorionic gonadotropin (eCG) treatments at the time of IVPD removal. In Experiment 1, cows (n = 235) were randomly assigned to one of four treatments: (i) 7-day estradiol = 2 mg of estradiol benzoate (EB) at IVPD insertion on Day 9 and 1 mg of estradiol cypionate (ECP) at IVPD removal on Day 2; (ii) 7-day GnRH = 10 µg of GnRH at IVPD insertion on Day 10, IVPD removal on Day 3 and GnRH at FTAI; (iii) 7 & 7 estradiol = PG at IVPD insertion on Day 16, EB on Day 9 and ECP at IVPD removal on Day 2; (iv) 7 & 7 GnRH = PG at IVPD insertion on Day 17, GnRH on Day 10, IVPD removal on Day 3 and GnRH at FTAI. In Experiment 2, cows (n = 462) were randomly assigned to one of four treatments: (i) 6-day estradiol = EB at IVPD insertion on Day 9, IVPD removal on Day 3 and GnRH at FTAI; (ii) 7-day estradiol; (iii) 7-day GnRH; (iv) 7 & 7 GnRH. In Experiment 1, plasma progesterone concentrations and percentage of cows with a corpus luteum (CL) at IVPD removal, and pregnancy per AI (P/AI) were greater for cows subjected to GnRH-based protocols compared with cows subjected to estrogen-based protocols (p < 0.01). In Experiment 2, cows subjected to the 7 & 7 GnRH protocol had the greatest P/AI (p < 0.01). In summary, GnRH-based FTAI protocols resulted in similar or greater P/AI compared to estrogen-based FTAI protocols in grazing postpartum Bos taurus suckled beef cows. The greatest P/AI was attained with the 7 & 7 GnRH protocol.