RESUMEN

OBJECTIVE: Research is needed to examine discrimination-related stressors and their social and psychological shaping of mental health and sleep outcomes of Latinx youth. The background, design, and methodology of a longitudinal study of Mexican families in Indiana and the initial findings of associations between discrimination-related stressors and youth mental health and sleep outcomes are presented. METHOD: Initiating wave 1 of a 3-wave (yearly) longitudinal study, investigators surveyed an ethnically homogeneous sample of 344 Mexican-origin adolescents (ages 12-15) and their primary caregivers, assessing risks and protective factors for mental health and sleep outcomes. Youth also completed a one-time 21-day daily diary after wave 1. Self-reported measures of youth mental health, sleep, and discrimination across wave 1 and the daily diary were evaluated to compare the cross-sectional (wave 1) and daily associations between discrimination and youth mental health and sleep outcomes. RESULTS: Of youth, 88.1% reported at least one incident of lifetime discrimination. Almost one-third had elevated depressive symptoms, 44.5% had probable generalized anxiety disorder, and 50.9% had poor sleep quality. Between-youth correlations at wave 1 and in the daily diary were consistent in that perceived racial discrimination was positively correlated with worse mental health and poorer sleep quality. Smaller within-youth correlations were observed in the daily diary, but there was striking variability in the effect of discrimination across youth. CONCLUSION: The present results illustrate the powerful methods of combining yearly and daily time data to investigate how and for whom discrimination-related stressors lead to adverse outcomes. PLAIN LANGUAGE SUMMARY: Latinx youth are the largest and fastest growing minoritized youth group in the United States. This study surveyed 344 Mexican-origin adolescents and their primary caregivers to assess risk and protective factors for mental health and sleep outcomes. The authors found that 88.1% of youth reported at least one incident of lifetime discrimination, 29.7% reported elevated depressive symptoms, 44.5% reported elevated anxiety symptoms, and 50.9% reported poor sleep quality. Youth who experienced racial discrimination were more likely to have worse mental health and lower sleep quality than those who did not experience racial discrimination. DIVERSITY & INCLUSION STATEMENT: We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. CLINICAL TRIAL REGISTRATION INFORMATION: Seguimos Avanzando - Latino Youth Coping With Discrimination; https://clinicaltrials.gov/; NCT04875208.

Asunto(s)

Salud Mental , Americanos Mexicanos , Estrés Psicológico , Humanos , Adolescente , Masculino , Femenino , Estudios Longitudinales , Estrés Psicológico/etnología , Niño , Americanos Mexicanos/estadística & datos numéricos , Salud Mental/etnología , Indiana , Estudios Transversales , Sueño , Depresión/etnología , Racismo/etnología

RESUMEN

Systemic lupus erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect any organ in the body, including the neurological system. Multiple factors, such as environmental (infections), genetic (many HLA alleles including DR2 and DR3, and genes including C4), and immunological influences on self-antigens, such as nuclear antigens, lead to the formation of multiple autoantibodies that cause deleterious damage to bodily tissues and organs. The production of autoantibodies, such as anti-dsDNA, anti-SS(A), anti-SS(B), anti-Smith, and anti-neuronal DNA are characteristic features of this disease. This autoimmune disease results from a failure of the mechanisms responsible for maintaining self-tolerance in T cells, B cells, or both. Immune complexes, circulating antibodies, cytokines, and autoreactive T lymphocytes are responsible for tissue injury in this autoimmune disease. The diagnosis of SLE is a rheumatological challenge despite the availability of clinical criteria. NPSLE was previously referred to as lupus cerebritis or lupus sclerosis. However, these terms are no longer recommended because there is no definitive pathological cause for the neuropsychiatric manifestations of SLE. Currently, the treatment options are primarily based on symptomatic presentations. These include the use of antipsychotics, antidepressants, and anxiolytic medications for the treatment of psychiatric and mood disorders. Antiepileptic drugs to treat seizures, and immunosuppressants (e.g., corticosteroids, azathioprine, and mycophenolate mofetil), are directed against inflammatory responses along with non-pharmacological interventions.

Asunto(s)

Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Humanos , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/tratamiento farmacológico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/genética , Autoanticuerpos , Inmunosupresores/uso terapéutico , Convulsiones/tratamiento farmacológico

RESUMEN

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

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RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

RESUMEN

Plasmodium vivax is a major challenge for malaria control due to its wide geographic distribution, high frequency of submicroscopic infections, and ability to induce relapses due to the latent forms present in the liver (hypnozoites). Deepening our knowledge of parasite biology and its molecular components is key to develop new tools for malaria control and elimination. This study aims to investigate and characterize a P. vivax protein (PvVir14) for its role in parasite biology and its interactions with the immune system. We collected sera or plasma from P.vivax-infected subjects in Brazil (n = 121) and Cambodia (n = 55), and from P. falciparum-infected subjects in Mali (n = 28), to assess antibody recognition of PvVir14. Circulating antibodies against PvVir14 appeared in 61% and 34.5% of subjects from Brazil and Cambodia, respectively, versus none (0%) of the P. falciparum-infected subjects from Mali who have no exposure to P. vivax. IgG1 and IgG3 most frequently contributed to anti-PvVir14 responses. PvVir14 antibody levels correlated with those against other well-characterized sporozoite/liver (PvCSP) and blood stage (PvDBP-RII) antigens, which were recognized by 7.6% and 42% of Brazilians, respectively. Concerning the cellular immune profiling of Brazilian subjects, PvVir14 seroreactive individuals displayed significantly higher levels of circulating atypical (CD21- CD27-) B cells, raising the possibility that atypical B cells may be contribute to the PvVir14 antibody response. When analyzed at a single-cell level, the B cell receptor gene hIGHV3-23 was only seen in subjects with active P.vivax infection where it comprised 20% of V gene usage. Among T cells, CD4+ and CD8+ levels differed (lower and higher, respectively) between subjects with versus without antibodies to PvVir14, while NKT cell levels were higher in those without antibodies. Specific B cell subsets, anti-PvVir14 circulating antibodies, and NKT cell levels declined after treatment of P. vivax. This study provides the immunological characterization of PvVir14, a unique P. vivax protein, and possible association with acute host's immune responses, providing new information of specific host-parasite interaction. Trial registration: TrialClinicalTrials.gov Identifier: NCT00663546 & ClinicalTrials.gov NCT02334462.

Asunto(s)

Malaria Falciparum , Malaria Vivax , Humanos , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Antígenos de Protozoos , Plasmodium falciparum , Anticuerpos Antiprotozoarios , Malaria Vivax/parasitología , Malaria Falciparum/epidemiología , Brasil/epidemiología , Familia , Inmunoglobulina G , Malí/epidemiología

RESUMEN

PURPOSE: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. METHODS: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. RESULTS: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. CONCLUSIONS: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

Asunto(s)

Neoplasias del Ojo , Melanoma , Neoplasias Cutáneas , Agudeza Visual , Vitrectomía , Cuerpo Vítreo , Humanos , Melanoma/secundario , Melanoma/terapia , Melanoma/patología , Estudios Retrospectivos , Anciano , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/secundario , Masculino , Adulto , Anciano de 80 o más Años , Persona de Mediana Edad , Femenino , Cuerpo Vítreo/patología , Neoplasias del Ojo/terapia , Neoplasias del Ojo/secundario , Neoplasias del Ojo/patología , Resultado del Tratamiento , Melanoma Cutáneo Maligno

RESUMEN

BACKGROUND: Preoperative opioid use strongly correlates with greater postoperative opioid use and complications following total joint arthroplasty (TJA). However, there is a lack of information regarding the effect of opioid consumption during the hospital stay and within the operating room on postoperative opioid use. METHODS: We retrospectively reviewed 369 consecutive patients undergoing primary TJA at an academic center over a 9-month period. Ninety-day preoperative and postoperative opioid prescriptions were obtained from the state's drug monitoring database. In-hospital opioid consumption data was obtained from the preoperative unit, operating room, postanesthesia care unit (PACU), and hospital floor. Multivariate analysis was utilized to compare patients' total in-hospital opioid consumption with their preoperative and postoperative use, along with opioid use throughout the hospitalization. RESULTS: Total in-hospital opioid consumption was independently associated with postoperative opioid use (rs = 0.17, P = .0010). Opioids consumed on the hospital floor correlated with opioid use in the preoperative unit (rs = 0.11, P = .0338) and PACU (rs = 0.15, P = .0032). Increased preoperative opioid consumption was the greatest risk factor for excessive postoperative use (rs = 0.44, P < .0001). A greater proportion of patients <65 years of age were high posthospital opioid consumers (P = .0146) and significantly more TKA patients were in the higher use groups (P = .0006). CONCLUSION: In-hospital opioid use is independently associated with preoperative and postoperative consumption. Preoperative opioid use remains the greatest risk factor for increased opioid consumption after TJA. Multimodal approaches to decrease reliance on opioids for pain control during hospitalization may offer hope to further decrease postoperative usage. LEVEL OF EVIDENCE: III.

Asunto(s)

Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Hospitales , Humanos , Trastornos Relacionados con Opioides/etiología , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Retrospectivos

RESUMEN

Policy Points In low-income communities in the South Bronx and Puerto Rico, Puerto Rican youth are exposed to many of the same risk and protective factors for developing depression, anxiety, or psychological distress; yet it is unclear how the ethnic minority context of the South Bronx and ethnic majority context of Puerto Rico influence risk. Results from our quasi-experimental, longitudinal study demonstrate the importance of addressing social factors (parent-child relationships, youth peer relationships) for youth living in the majority context, and neighborhood and cultural factors (residential mobility, perceived discrimination, perceived social position in the neighborhood) for youth living in the minority context. Our findings support the need for tailoring programs specific to the needs of youth who reside in an ethnic majority or a minority context, since some of the risk factors might operate differently depending on context. Housing and neighborhood environment policies that address discrimination and eliminate structural inequities for ethnic minority groups may protect against the harm of minoritization on young people's mental health. CONTEXT: Puerto Rican youth growing up in low-income communities in the South Bronx and Puerto Rico are exposed to many of the same risk factors for major depressive disorder, generalized anxiety disorder, and psychological distress. One potentially powerful factor differs: Puerto Ricans have been socially marginalized as an ethnic minority group in the South Bronx, but are the ethnic majority of the population in Puerto Rico. A growing body of literature demonstrates the influence of neighborhood, cultural, and social factors and parental psychopathology in the development of mental health problems. An important unanswered question is whether these risk and protective factors have the same impact for youth raised as members of an ethnic majority versus minority group. METHODS: Using a population-based cohort study, with four waves of assessment from early childhood into young adulthood, we investigated whether ethnic minority context alters risk and protective factors for depression, anxiety, and psychological distress. Our longitudinal data set includes 2,491 young children at baseline (82.8% retained at wave 4). Using a quasi-experimental design, we examine how ethnic minority context can alter the development of mental health disorders as Latinx children transition to late adolescence and young adulthood. FINDINGS: Some risk and protective factors operated differently across minority and majority contexts. Higher discrimination and social position were more powerful risk and protective factors, respectively, in the minority context, whereas positive peer relationships mattered more in the majority context. Children of mothers with depression were significantly more likely to develop anxiety in late adolescence and young adulthood in the majority context (60.0%) compared to the minority context (4.5%). CONCLUSIONS: Preventing depression and anxiety disorders in Latinx young adults may require targeting different childhood factors depending on whether they reside within the ethnic majority or minority context. People in the ethnic minority context may benefit more from policies aimed at reducing discrimination and improving economic opportunity, while people in the majority context may benefit more from opportunities for strengthening family and peer relationships.

Asunto(s)

Trastorno Depresivo Mayor , Trastornos Mentales , Distrés Psicológico , Adolescente , Adulto , Preescolar , Estudios de Cohortes , Minorías Étnicas y Raciales , Etnicidad , Hispánicos o Latinos , Humanos , Estudios Longitudinales , Trastornos Mentales/epidemiología , Salud Mental , Grupos Minoritarios/psicología , Puerto Rico/epidemiología , Adulto Joven

RESUMEN

PURPOSE: The patterns or trajectories of serious antisocial behavior (ASB) in children are examined to determine the extent to which context, gender, and the severity and persistence of ASB from childhood/early adolescence to later adolescence/early adulthood is associated with negative outcomes. METHODS: A four wave longitudinal study obtained data on two multi-stage probability household samples of Puerto Rican background children (5-13 years at baseline) living in the San Juan Metropolitan Area of Puerto Rico (PR) and the South Bronx (SBx) of New York. The outcomes studied were any psychiatric disorder including substance use disorders and teenage pregnancy. RESULTS: Both males and females raised in the SBx had much higher risk of serious ASB (42.3%) as compared to those in PR (17.8%). Concurrent ASB4 + in the fourth wave was strongly related to SUD and MDD for both males and females at Wave 4. CONCLUSIONS: Serious ASB is likely to persist at least to the next developmental period of a child and is likely to be associated with substance use disorders and major depression later in life.

Asunto(s)

Trastorno de Personalidad Antisocial , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Trastorno de Personalidad Antisocial/diagnóstico , Trastorno de Personalidad Antisocial/epidemiología , Niño , Femenino , Hispánicos o Latinos , Humanos , Estudios Longitudinales , Masculino , Embarazo , Puerto Rico/epidemiología

RESUMEN

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).

Asunto(s)

Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Interferón beta-1a/uso terapéutico , Adenosina Monofosfato/uso terapéutico , Adulto , Anciano , Alanina/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Japón , Masculino , México , Persona de Mediana Edad , Oxígeno , Saturación de Oxígeno , República de Corea , SARS-CoV-2 , Singapur , Resultado del Tratamiento , Estados Unidos

RESUMEN

Neutrophil extracellular traps (NETs) evolved as a unique effector mechanism contributing to resistance against infection that can also promote tissue damage in inflammatory conditions. Malaria infection can trigger NET release, but the mechanisms and consequences of NET formation in this context remain poorly characterized. Here we show that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma. We used cultured erythrocytes and isolated human neutrophils to show that Plasmodium-infected red blood cells release macrophage migration inhibitory factor (MIF), which in turn caused NET formation by neutrophils in a mechanism dependent on the C-X-C chemokine receptor type 4 (CXCR4). NET production was dependent on histone citrullination by peptidyl arginine deiminase-4 (PAD4) and independent of reactive oxygen species (ROS), myeloperoxidase (MPO) or NE. In vitro, NETs functioned to restrain parasite dissemination in a mechanism dependent on MPO and NE activities. Finally, C57/B6 mice infected with P. berghei ANKA, a well-established model of cerebral malaria, presented high amounts of circulating DNA, while treatment with DNAse increased parasitemia and accelerated mortality, indicating a role for NETs in resistance against Plasmodium infection.

Asunto(s)

Eritrocitos/inmunología , Trampas Extracelulares/inmunología , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Malaria/inmunología , Neutrófilos/inmunología , Plasmodium/inmunología , Receptores CXCR4/metabolismo , Animales , Eritrocitos/metabolismo , Eritrocitos/parasitología , Trampas Extracelulares/metabolismo , Trampas Extracelulares/parasitología , Humanos , Malaria/metabolismo , Malaria/parasitología , Malaria/patología , Ratones , Ratones Endogámicos C57BL , Neutrófilos/metabolismo , Neutrófilos/parasitología , Parasitemia/inmunología , Parasitemia/metabolismo , Parasitemia/parasitología , Parasitemia/patología

RESUMEN

OBJECTIVE: Neuroimmune cells, particularly microglia and astrocytes, play a critical role in neurodevelopment. Neurocognitive delays are common in children with congenital heart disease, but their etiology is poorly understood. Our objective was to determine whether prenatal hypoxemia, at levels common in congenital heart disease, induced neuroimmune activation to better understand the origins of neurobehavioral disorders in congenital heart disease. METHODS: Eight fetal sheep at gestational age 109 ± 3 days (term ∼145 days) were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid environment for 22 ± 2 days under normoxic (n = 4) or hypoxic (n = 4) conditions. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were stained with ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein antibodies to quantify microglia and astrocytes, respectively, in gray and white matter in frontotemporal and cerebellar sections. Microglia were classified into 4 morphologic types based on cell shape. Data were analyzed with 1-way analysis of variance or Fisher exact test, as appropriate. RESULTS: Oxygen delivery was significantly reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min; P < .01). Rates of apoptosis were similar in hypoxic, normoxic, and intrauterine control animals in all examined areas. There were also no differences between groups in area occupied by glial fibrillary acidic protein-labeled astrocytes or ionized calcium-binding adaptor molecule 1-labeled microglia in all examined areas. However, round microglia were significantly increased in hypoxic animals compared with normoxic animals (33% vs 6%; P < .01) and control animals (33% vs 11%; P < .01). CONCLUSIONS: Prenatal hypoxemia altered microglial morphology without significant gliosis. Additional studies characterizing these mechanisms may provide insight into the origins of neurobehavioral disabilities in children with congenital heart disease.

RESUMEN

OBJECTIVE: We tested the hypothesis that chronic fetal hypoxia, at a severity present in many types of congenital heart disease, would lead to abnormal neurodevelopment. METHODS: Eight mid-gestation fetal sheep were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid-filled environment for 22 ± 2 days under normoxic or hypoxic conditions. Total parenteral nutrition was provided. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were fixed for histopathology. Neurons were quantified in white matter tracts, and the thickness of the external granular layer of the cerebellum was measured to assess neuronal migration. Capillary density and myelination were quantified in white matter. Data were analyzed with unpaired Student t tests or 1-way analysis of variance, as appropriate. RESULTS: Oxygen delivery was reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min, P < .01), but umbilical blood flow and caloric delivery were not different between the 2 groups. Compared with normoxic and control animals, hypoxic fetuses had reduced neuronal density and increased external granular layer thickness. Compared with normoxic and control animals, hypoxic fetuses had increased capillary density in white matter. Cortical myelin integrity score was lower in the hypoxic group compared with normoxic and control animals. There was a significant negative correlation between myelin integrity and capillary density. CONCLUSIONS: Chronic fetal hypoxia leads to white matter hyper-vascularity, decreased neuronal density, and impaired myelination, similar to the neuropathologic findings observed in children with congenital heart disease. These findings support the hypothesis that fetal hypoxia, even in the setting of normal caloric delivery, impairs neurodevelopment.

Asunto(s)

Encefalopatías/fisiopatología , Encéfalo/crecimiento & desarrollo , Capilares/fisiopatología , Hipoxia Fetal/fisiopatología , Neovascularización Fisiológica , Neurogénesis , Neuronas , Animales , Apoptosis , Encéfalo/metabolismo , Encéfalo/patología , Encefalopatías/sangre , Encefalopatías/patología , Capilares/patología , Enfermedad Crónica , Modelos Animales de Enfermedad , Femenino , Sangre Fetal/metabolismo , Desarrollo Fetal , Hipoxia Fetal/sangre , Hipoxia Fetal/patología , Edad Gestacional , Vaina de Mielina/metabolismo , Neuronas/metabolismo , Neuronas/patología , Oxígeno/sangre , Embarazo , Oveja Doméstica

RESUMEN

PURPOSE: The manuscript compares the rates of psychiatric disorder among island Puerto Ricans, the US population and US Puerto Ricans in order to examine whether social support explains differences in psychiatric disorder among these three groups. METHODS: Unadjusted and adjusted rates for sociodemographic factors and social support of main psychiatric disorders are compared among three population-based psychiatric epidemiology studies carried in Puerto Rico (PR) and the United States (US) as part of the NCS-R and NLAAS studies. RESULTS: Comparison of adjusted rates showed island Puerto Ricans had similar overall rates of psychiatric disorder as those of the US, lower rates of anxiety disorders, but higher rates of substance use disorders. US Puerto Ricans had higher rates of adjusted anxiety and depression but not of overall psychiatric disorder, as compared to the island. When the rates of disorder were adjusted also for social support, the differences between these two groups disappeared. CONCLUSIONS: The findings suggest that social support is a variable worthy of further exploration for explaining differences in disorder prevalence particularly among Puerto Ricans depending on where they live.

Asunto(s)

Ansiedad/epidemiología , Depresión/epidemiología , Trastornos Mentales/epidemiología , Apoyo Social , Adolescente , Adulto , Ansiedad/etnología , Depresión/etnología , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Trastornos Mentales/etnología , Persona de Mediana Edad , Prevalencia , Puerto Rico/epidemiología , Puerto Rico/etnología , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

Plants allocate nutrients to specific leaf cell types; eudicots are thought to predominantly allocate phosphorus (P) to epidermal/bundle sheath cells. However, three Proteaceae species have been shown to preferentially allocate P to mesophyll cells instead. These Proteaceae species are highly adapted to P-impoverished habitats, with exceptionally high photosynthetic P-use efficiencies (PPUE). We hypothesized that preferential allocation of P to photosynthetic mesophyll cells is an important trait in species adapted to extremely P-impoverished habitats, contributing to their high PPUE. We used elemental X-ray mapping to determine leaf cell-specific nutrient concentrations for 12 Proteaceae species, from habitats of strongly contrasting soil P concentrations, in Australia, Brazil, and Chile. We found that only species from extremely P-impoverished habitats preferentially allocated P to photosynthetic mesophyll cells, suggesting it has evolved as an adaptation to their extremely P-impoverished habitat and that it is not a family-wide trait. Our results highlight the possible role of soil P in driving the evolution of ecologically relevant nutrient allocation patterns and that these patterns cannot be generalized across families. Furthermore, preferential allocation of P to photosynthetic cells may provide new and exciting strategies to improve PPUE in crop species.

Asunto(s)

Adaptación Fisiológica , Calcio/metabolismo , Fósforo/metabolismo , Proteaceae/fisiología , Australia , Brasil , Chile , Ecosistema , Células del Mesófilo/metabolismo , Fósforo/análisis , Fósforo/farmacocinética , Fotosíntesis , Hojas de la Planta/anatomía & histología , Hojas de la Planta/metabolismo , Transpiración de Plantas , Proteaceae/citología , Suelo/química

RESUMEN

OBJECTIVES: In Latin America and the Caribbean, pneumococcal infections are estimated to account for 12000-18000 deaths, 327000 pneumonia cases, 4000 meningitis cases and 1229 sepsis cases each year in children under five years old. Pneumococcal antimicrobial resistance has evolved into a worldwide health problem in the last few decades. This study aimed to determine the antimicrobial susceptibility profiles of pneumococcal isolates collected in Trinidad and Tobago and their associated genetic determinants. METHODS: Whole-genome sequences were obtained from 98 pneumococcal isolates recovered at several regional hospitals, including 83 invasive and 15 non-invasive strains, recovered before (n=25) and after (n=73) introduction of pneumococcal conjugate vaccines (PCVs). A bioinformatics pipeline was used to identify core genomic and accessory elements conferring antimicrobial resistance phenotypes, including ß-lactam non-susceptibility. RESULTS AND DISCUSSION: Forty-one isolates (41.8%) were predicted as resistant to at least one antimicrobial class, including 13 (13.3%) resistant to at least three classes. The most common serotypes associated with antimicrobial resistance were 23F (n=10), 19F (n=8), 6B (n=6) and 14 (n=5). The most common serotypes associated with penicillin non-susceptibility were 19F (n=7) and 14 (n=5). Thirty-nine isolates (39.8%) were positive for PI-1 or PI-2 type pili: 30 (76.9%) were PI-1+, 4 (10.3%) were PI-2+ and 5 (12.8%) were positive for both PI-1 and PI-2. Of the 13 multidrug-resistant isolates, 10 belonged to globally distributed clones PMEN3 and PMEN14 and were isolated in the post-PCV period, suggesting clonal expansion.

Asunto(s)

Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Infecciones Estreptocócicas/microbiología , Streptococcus/aislamiento & purificación , Secuenciación Completa del Genoma/métodos , Preescolar , Femenino , Genoma Bacteriano , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Streptococcus/efectos de los fármacos , Streptococcus/genética , Trinidad y Tobago

RESUMEN

Context: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis. Few genetic causes of CPP have been identified, with the most common being mutations in the paternally expressed imprinted gene MKRN3. Objective: To identify the genetic etiology of CPP in a large multigenerational family. Design: Linkage analysis followed by whole-genome sequencing was performed in a family with five female members with nonsyndromic CPP. Detailed phenotyping was performed at the time of initial diagnosis and long-term follow-up, and circulating levels of Delta-like 1 homolog (DLK1) were measured in affected individuals. Expression of DLK1 was measured in mouse hypothalamus and in kisspeptin-secreting neuronal cell lines in vitro. Setting: Endocrine clinic of an academic medical center. Patients: Patients with familial CPP were studied. Results: A complex defect of DLK1 (∼14-kb deletion and 269-bp duplication) was identified in this family. This deletion included the 5' untranslated region and the first exon of DLK1, including the translational start site. Only family members who inherited the defect from their father have precocious puberty, consistent with the known imprinting of DLK1. The patients did not demonstrate additional features of the imprinted disorder Temple syndrome except for increased fat mass. Serum DLK1 levels were undetectable in all affected individuals. Dlk1 was expressed in mouse hypothalamus and in kisspeptin neuron-derived cell lines. Conclusion: We identified a genomic defect in DLK1 associated with isolated familial CPP. MKRN3 and DLK1 are both paternally expressed imprinted genes. These findings suggest a role of genomic imprinting in regulating the timing of human puberty.

Asunto(s)

Hormona Liberadora de Gonadotropina/agonistas , Péptidos y Proteínas de Señalización Intercelular/genética , Proteínas de la Membrana/genética , Herencia Paterna/genética , Pubertad Precoz/genética , Población Negra , Brasil , Proteínas de Unión al Calcio , Niño , Femenino , Eliminación de Gen , Humanos , Péptidos y Proteínas de Señalización Intercelular/sangre , Proteínas de la Membrana/sangre , Linaje , Reacción en Cadena de la Polimerasa , Pubertad Precoz/tratamiento farmacológico , Análisis de Secuencia de ADN

RESUMEN

This study examined factors that predicted children's gender intergroup attitudes at age 5 and the implications of these attitudes for intergroup behavior. Ethnically diverse children from low-income backgrounds (N = 246; Mexican-, Chinese-, Dominican-, and African American) were assessed at ages 4 and 5. On average, children reported positive same-gender and negative other-gender attitudes. Positive same-gender attitudes were associated with knowledge of gender stereotypes. In contrast, positive other-gender attitudes were associated with flexibility in gender cognitions (stereotype flexibility, gender consistency). Other-gender attitudes predicted gender-biased behavior. These patterns were observed in all ethnic groups. These findings suggest that early learning about gender categories shape young children's gender attitudes and that these gender attitudes already have consequences for children's intergroup behavior at age 5.

Asunto(s)

Asiático , Actitud/etnología , Negro o Afroamericano/etnología , Hispánicos o Latinos , Pobreza/etnología , Sexismo/etnología , Identificación Social , Estereotipo , Preescolar , República Dominicana/etnología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Americanos Mexicanos

RESUMEN

Staphylococcus aureus continues to pose major public health challenges in many areas because of antibiotic resistance problems. In the Caribbean, especially Trinidad and Tobago, the challenge is not different. This study was performed to evaluate the antimicrobial resistance gene prevalence among S. aureus isolates in Trinidad and Tobago. Standard and molecular microbiological methods, including the Microscan automated system, DNA microarray and multi locus sequence typing (MLST) analysis, were performed on 309 clinical S. aureus isolates recovered from patients who were treated at three of the country's main health institutions. S. aureus exhibited susceptibilities ≥80% to eleven of the 19 antimicrobials tested against it, and these belong to the most commonly used and available antibiotics in the country. While the antibiotic to which it was most susceptible of the commonly used antibiotics was trimethoprim/sulfamethoxazole, the antibiotics to which it was least susceptible or most resistant to were ampicillin and penicillin. S. aureus isolates from the pediatric ward produced the greatest rate of susceptibility among the isolates recovered from patients admitted into hospitals, while isolates from Accident and Emergency rooms displayed the greatest susceptibilities among patients from the community. S. aureus isolates from the country did not harbor acquired resistant genes targeting clindamycin/macrolides (ermB), linezolid (cfr) or vancomycin (vanA). The blaZ gene, which is the most common beta lactam (Penicillinase) resistance mechanism for S. aureus, was observed in 88.7% of the methicillin susceptible S. aureus, while methicillin resistance mediated by the mec gene was present in 13.6%. Most of the resistance markers found in MRSA isolates were significantly associated with the ST239-MRSA-III strain in this study, and all isolates that belonged to the USA300 strain, which additionally encoded both the PVL gene and ACME cluster, belonged to CC8. Several resistant genes, such as vanA, cfr and ermB, mediating resistance in S. aureus, are currently non-existent in Trinidad and Tobago. However, the majority of SCCmec genes were observed, suggesting that there is ongoing nosocomial transmission with minimal community transmission. This calls for stringent antibiotic stewardship and policies in the country.

Asunto(s)

Farmacorresistencia Bacteriana/genética , Regulación Bacteriana de la Expresión Génica/fisiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Antibacterianos/farmacología , Humanos , Trinidad y Tobago/epidemiología

RESUMEN

Geographic spread of vancomycin-resistant enterococci (VRE) clones in cities, countries, or even continents has been identified by molecular techniques. This study aimed at characterizing virulent genes and determining genetic relatedness of 45 VRE isolates from Trinidad and Tobago using molecular tools, including polymerase chain reaction, pulsed-field gel electrophoresis (PFGE), and Random Amplification Polymorphic DNA (RAPD). The majority (84%) of the isolates were Enterococcus faecium possessing vanA gene while the rest (16%) were Enterococcus faecalis possessing vanB. The esp gene was found in all 45 VRE isolates while hyl genes were found only in E. faecium species. The E. faecium species expressed five distinct PFGE patterns. The predominant clones with similar or common patterns belonged to clones one and three, and each had 11 (29%) of the VRE isolates. Plasmid content was identified in representative isolates from each clonal group. By contrast, the E. faecalis species had one PFGE pattern suggesting the presence of an occult and limited clonal spread. The emergence of VRE in the country seems to be related to intra/interhospital dissemination of an epidemic clone carrying the vanA element. Therefore, infection control measures will be warranted to prevent any potential outbreak and spread of VRE in the country.