Disturbances in the IgG Antibody Profile in HIV-Exposed Uninfected Infants Associated with Maternal Factors.

Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%-42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.

Patient perspectives on emergency department initiation of medication for alcohol use disorder.

OBJECTIVE: Alcohol use disorder (AUD) is a leading cause of preventable death and is a frequent diagnosis in the emergency department (ED). Treatment in the ED, however, typically focuses on managing the sequelae of AUD, such as acute withdrawal, rather than addressing the underlying addiction. For many patients, these ED encounters are a missed opportunity to connect with medication for AUD. In 2020, our ED created a pathway to offer patients with AUD treatment with naltrexone (NTX) during their ED visit. The aim of this study was to identify what barriers and facilitators patients perceive to NTX initiation in the ED. METHODS: Adopting the theoretical framework of the behavior change wheel (BCW), we conducted qualitative interviews with patients to elicit their perspectives on ED initiation of NTX. Interviews were coded and analyzed using both inductive and deductive approaches. Themes were categorized according to patients' capabilities, opportunities, and motivations. Barriers were then mapped through the BCW to design interventions that will improve our treatment pathway. RESULTS: Twenty-eight patients with AUD were interviewed. Facilitators of accepting NTX included having recently experienced sequelae of AUD, rapid management of withdrawal symptoms by the ED provider, having a choice between intramuscular and oral formulations of the medication, and experiencing positive interactions in the ED that destigmatized the patient's AUD. Barriers to accepting treatment included lack of provider knowledge about NTX, dependence on alcohol as self-treatment for psychiatric trauma and physical pain, perceived discriminatory treatment and stigma about AUD, aversion to potential side effects, and lack of access to continued treatment. CONCLUSIONS: Initiation of treatment of AUD with NTX in the ED is acceptable to patients and can be facilitated by knowledgeable ED providers who create a destigmatizing environment, effectively manage withdrawal symptoms, and connect patients to providers who will continue treatment.

The hormonal physiology of immune components in breast milk and their impact on the infant immune response.

During pregnancy, the maternal body undergoes a considerable transformation regarding the anatomy, metabolism, and immune profile that, after delivery, allows for protection and nourishment of the offspring via lactation. Pregnancy hormones are responsible for the development and functionality of the mammary gland for breast milk production, but little is known about how hormones control its immune properties. Breast milk composition is highly dynamic, adapting to the nutritional and immunological needs that the infant requires in the first months of life and is responsible for the main immune modeling of breastfed newborns. Therefore, alterations in the mechanisms that control the endocrinology of mammary gland adaptation for lactation could disturb the properties of breast milk that prepare the neonatal immune system to respond to the first immunologic challenges. In modern life, humans are chronically exposed to endocrine disruptors (EDs), which alter the endocrine physiology of mammals, affecting the composition of breast milk and hence the neonatal immune response. In this review, we provide a landscape of the possible role of hormones in the control of passive immunity transferred by breast milk and the possible effect of maternal exposure to EDs on lactation, as well as their impacts on the development of neonatal immunity.

Impaired T helper cell responses in human immunodeficiency virus-exposed uninfected newborns.

INTRODUCTION: HIV-exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV-unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T-cell receptor diversity, and activation markers have been found in HEU newborns, suggesting alterations in T cell ontogeny and differentiation. However, little is known about the ability of these cells to produce specialized Th responses from CD4+ T cells. METHOD: To characterize the Th cell profile, we evaluated the frequency of Th1 (CD183+ CD194- CD196- /CXCR3+ CCR4- CCR6- ), Th2 (CD183- CD194+ CD196- /CXCR3- CCR4+ CCR6- ), Th17 (CD183- CD194+ CD196+ /CXCR3- CCR4+ CCR6+ ), and CD4+ CD25++ blood T-cell phenotypes in 50 HEU and 25 HUU newborns. Early activation markers on CD4+ T cells and the Th cytokine profile produced from mononuclear cells under polyclonal T cell stimulation were also studied. Additionally, we probed the ability of CD4+ T cells to differentiate into interferon (IFN)-γ-producing Th1 CD4+ T cells in vitro. RESULTS: Lower percentages of differentiated Th1 , Th2 , Th17, and CD4+ CD25++ T cells were found in blood from HEU newborns than in blood from HUU newborns. However, polyclonally stimulated Th cells showed a similar ability to express CD69 and CD279 but produced less secreted interleukin (IL)-2 and IL-4. Interestingly, under Th1 differentiation conditions, the percentages of CD4+ IFN-γ+ T cells and soluble IFN-γ were higher in HEU newborns than in HUU newborns. CONCLUSION: HEU neonates are born with reduced proportions of differentiated Th1 /Th2 /Th17 and CD4+ CD25++ T cells, but the intrinsic abilities of CD4+ T cells to acquire a Th1 profile are not affected by the adverse maternal milieu during development.

Composición química y toxicidad aguda oral del aceite esencial de Lippia alba en ratones / Chemical composition and oral acute toxicity of Lippia alba essential oil in mice

La Lippia alba (L. alba), de la familia Verbenaceae, conocida popularmente como “Cidrón” o “poleo”; dependiendo de su ubicación geográfica, el suelo donde se desarrolla y tejido o órgano, presenta aceites esenciales en su composición, que son empleados en medicina natural y tradicional para el tratamiento de trastornos digestivos, respiratorios, enfermedades de la piel y sedante, a través de infusión o decocción de hojas, partes aéreas o flores. Por lo que posee un elevado potencial terapéutico, siendo importante detectar posibles efectos tóxicos post administración. Por lo cual, el objetivo del estudio fue evaluar la composición química y la toxicidad aguda oral del aceite esencial de L. alba a dosis única y dosis repetida. Se extrajo el aceite esencial de las hojas y partes aéreas, por destilación con arrastre de vapor utilizando una Trampa de Clevenger y se analizó por cromatografía de gases acoplada a detector de masas. Se evaluó la toxicidad, utilizando ratones NRMI de ambos sexos y las Guías OECD 423 y 407. Se obtuvieron 34 constituyentes del aceite esencial, los mayoritarios fueron: geranial (45,30%), neral (30,23%), beta-farnesol (7,78%), cariofileno (2,85%), azuleno (2,52%) y beta- irceno (2,38%). Se evidenciaron (Guía OECD 423) signos y síntomas de daño neurológico y motor moderado (900 mg/Kg del aceite esencial) con 100% de supervivencia y severo (1500 mg/ Kg) letales para los machos y, con 2000 mg/Kg todos los animales fallecieron. Se concluye que en el aceite esencial predominaron los constituyentes geranial y neral; clasificados como quimiotipo “citral” y que de acuerdo a la Clasificación de Toxicidad del Sistema Globalmente Armonizado de Clasificación y Etiquetado de Productos Químicos (ONU-SGA, 2011), corresponde a la categoría 4 (DL50 se ubica entre 300-2000 mg/Kg).

The Lippia alba (alba L.) of the Verbenaceae family, popularly known as “Cidrón” or “pennyroyal”; depending on your geographic location, soil which develops and tissue or organ, presents essential oils in its composition, which are used in natural and traditional medicine for the treatment of digestive, respiratory, skin diseases and sedative disorders through infusion or decoction of leaves, aerial parts or flowers. So it has a high therapeutic potential, being important to detect possible toxic effects post administration. Therefore, the aim of the study was to evaluate the chemical composition and oral acute toxicity of essential oil of L. alba single dose and repeat dose. the essential oil of the leaves and aerial parts extracted by steam stripping using a Clevenger trap and analyzed by gas chromatography coupled to mass detector. Toxicity was evaluated using NRMI mice of both sexes and OECD Guidelines 423 and 407. 34 constituents of the essential oil, the majority were were obtained: geranialdehyde (45.30%), neral (30.23%), beta-farnesol (7.78%), caryophyllene (2.85%), azulene (2.52%) and myrcene beta (2.38%). (OECD Guidelines 423) were evident signs and symptoms of neurological damage and moderate engine (900 mg / kg of essential oil) with 100% survival and severe (1500 mg / kg) lethal for males and with 2000 mg / kg all the animals died. It is concluded that in the essential oil predominated geranialdehyde and neral constituents; classified as “citral” chemotypes and according to the Classification of toxicity Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS, 2011), corresponds to category 4 (LD50 is between 300-2000 mg / kg).