RESUMEN

Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease.

Asunto(s)

Infecciones por Bunyaviridae , Humanos , Estados Unidos/epidemiología , Femenino , Adulto , Masculino , Infecciones por Bunyaviridae/epidemiología , Persona de Mediana Edad , Anciano , Orthobunyavirus/aislamiento & purificación , Viaje , Adulto Joven , Enfermedad Relacionada con los Viajes , Brotes de Enfermedades , Cuba/epidemiología

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AIM: To test the effect of the glucagon-like peptide-1 receptor agonist, liraglutide, on residual beta-cell function in adults with newly diagnosed type 1 diabetes. MATERIALS AND METHODS: In a multicentre, double-blind, parallel-group trial, adults with newly diagnosed type 1 diabetes and stimulated C-peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8-mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow-up with only insulin treatment. The primary endpoint was the between-group difference in C-peptide area under the curve (AUC) following a liquid mixed-meal test after 52 weeks of treatment. RESULTS: Sixty-eight individuals were randomized. After 52 weeks, the 4-hour AUC C-peptide response was maintained with liraglutide, but decreased with placebo (P = .002). Six weeks after end-of-treatment, C-peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 (P < .001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo-treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient. CONCLUSIONS: Treatment with liraglutide improves residual beta-cell function and reduces the dose of insulin during the first year after diagnosis. Beta-cell function was similar at 6 weeks postliraglutide treatment.

RESUMEN

Background: Collagen hydrolysates (CH) in functional foods and supplements are dietary sources of amino acids (AAs) and di-and tripeptides linked to various health benefits. This study aimed to investigate the single-dose bioavailability of skin- and hide-derived CH from fish, porcine and bovine origin with different molecular weights (bovine 2,000 and 5,000 Da). Methods: A randomized, double-blind crossover clinical study was performed with healthy volunteers assessing the plasma concentration of free and peptide-bound hydroxyproline (Hyp) as well as selected peptides reported to be abundantly present in collagen. Results: The pharmacokinetic endpoints demonstrated comparable uptake of free Hyp from all CH. A higher amount of total compared to free Hyp indicated the uptake of substantial amounts of Hyp-containing di- or tripeptides. Conclusion: Independently of source and molecular weight, all CH yielded relevant plasma concentrations of the investigated metabolites. Larger studies are needed to estimate an ideal level of selected circulating metabolites needed to trigger distinct physiological reactions in target tissues.

RESUMEN

Immunochemotherapy has been the mainstay of treatment for newly diagnosed diffuse large B-cell lymphoma (ndDLBCL) yet is inadequate for many patients. In this work, we perform unsupervised clustering on transcriptomic features from a large cohort of ndDLBCL patients and identify seven clusters, one called A7 with poor prognosis, and develop a classifier to identify these clusters in independent ndDLBCL cohorts. This high-risk cluster is enriched for activated B-cell cell-of-origin, low immune infiltration, high MYC expression, and copy number aberrations. We compare and contrast our methodology with recent DLBCL classifiers to contextualize our clusters and show improved prognostic utility. Finally, using pre-clinical models, we demonstrate a mechanistic rationale for IKZF1/3 degraders such as lenalidomide to overcome the low immune infiltration phenotype of A7 by inducing T-cell trafficking into tumors and upregulating MHC I and II on tumor cells, and demonstrate that TCF4 is an important regulator of MYC-related biology in A7.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Factor de Transcripción Ikaros , Lenalidomida , Linfoma de Células B Grandes Difuso , Proteínas Proto-Oncogénicas c-myc , Factor de Transcripción 4 , Transcriptoma , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Humanos , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Lenalidomida/uso terapéutico , Lenalidomida/farmacología , Factor de Transcripción Ikaros/genética , Factor de Transcripción Ikaros/metabolismo , Factor de Transcripción 4/genética , Factor de Transcripción 4/metabolismo , Linfocitos B/metabolismo , Linfocitos B/inmunología , Pronóstico , Animales , Línea Celular Tumoral , Perfilación de la Expresión Génica/métodos , Ratones , Linfocitos T/inmunología , Linfocitos T/metabolismo , Variaciones en el Número de Copia de ADN

RESUMEN

Spectinamides are a novel class of narrow-spectrum antitubercular agents with the potential to treat drug-resistant tuberculosis infections. Spectinamide 1810 has shown a good safety record following subcutaneous injection in mice or infusion in rats but exhibits transient acute toxicity following bolus administration in either species. To improve the therapeutic index of 1810, an injectable prodrug strategy was explored. The injectable phosphate prodrug 3408 has a superior maximum tolerated dose compared to 1810 or Gentamicin. Following intravenous administration in rodents, prodrug 3408 was quickly converted to 1810. The resulting 1810 exposure and pharmacokinetic profile after 3408 administration was identical to equivalent molar amounts of 1810 given directly by intravenous administration. 3408 and the parent 1810 exhibited similar overall efficacy in a BALB/c acute tuberculosis efficacy model. Delivery of 1810 in phosphate prodrug form, therefore, holds the potential to improve further the therapeutic index of an already promising tuberculosis antibiotic.

Asunto(s)

Antituberculosos , Ratones Endogámicos BALB C , Profármacos , Profármacos/síntesis química , Profármacos/farmacología , Profármacos/química , Animales , Antituberculosos/síntesis química , Antituberculosos/farmacología , Antituberculosos/química , Antituberculosos/farmacocinética , Ratones , Ratas , Pruebas de Sensibilidad Microbiana , Espectinomicina/farmacología , Espectinomicina/síntesis química , Espectinomicina/química , Fosfatos/química , Fosfatos/farmacología , Fosfatos/síntesis química , Mycobacterium tuberculosis/efectos de los fármacos , Estructura Molecular , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad

RESUMEN

During early and middle adolescence, individuals are at heightened risk of poor body image and subsequent negative mental health outcomes, and the highly visual nature of social media may play a role in this process. It remains unclear, however, if appearance preoccupation on social media-such as appearance-related social media consciousness (ASMC)-influences offline body image, or if preexisting body image concerns influence online appearance preoccupation. The present study investigated between-person differences and potential bidirectional within-person associations in these experiences among eighth grade adolescents in the United States (n = 1,582; ages 11-15 years old; Mage = 13; 47.5% girls, 45.9% boys, 6.5% another gender identity; 37% Latine, 32% White, 18% Black, 7% Asian, 6% another racial/ethnic identity). Participants completed a longitudinal study over three waves within one academic year. Results indicated that within-person increases in ASMC preceded within-person increases in appearance-contingent self-worth and were bidirectionally associated with worse appearance esteem, with no differences in these associations by gender. Among girls only, self-objectification was associated with subsequent within-person increases in ASMC, but not vice versa. Findings indicate that online appearance preoccupation may influence and be reinforced by general body image concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

RESUMEN

BACKGROUND: A corrective radius osteotomy is often performed in patients with a symptomatic distal radius malunion. In 3D-planned osteotomies, the unaffected radius is mirrored over the malunited radius after adjusting for left-right length differences using both ulnae. This approach assumes that ulnar length differences in a malunion population are similar to those in a healthy population. This study was conducted to analyze the difference in ulnar length in a distal radius malunion population and to assess the potential influence of age, sex, or malunion side on this difference. METHODS: We evaluated 65 adult patients with distal radius malunion using bilateral forearm CT scans. 3D models of both ulnae were constructed, and length differences were determined along a standardized length axis. The results were compared to two populations without a radius malunion. RESULTS: The average absolute ulnar length difference was 2.57 mm (SD 1.81), which was comparable to the two healthy populations. This difference was not significantly affected by age, sex, or malunion side. CONCLUSION: This study demonstrated that using the ulnar length difference to correct for radial length difference in the current 3D planning process, before using the contralateral radius as a template for a corrective osteotomy in patients with radius malunion, is safe.

Asunto(s)

Fracturas Mal Unidas , Imagenología Tridimensional , Osteotomía , Fracturas del Radio , Radio (Anatomía) , Cúbito , Humanos , Osteotomía/métodos , Masculino , Femenino , Fracturas Mal Unidas/cirugía , Fracturas Mal Unidas/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Cúbito/cirugía , Cúbito/diagnóstico por imagen , Cúbito/anatomía & histología , Fracturas del Radio/cirugía , Fracturas del Radio/diagnóstico por imagen , Imagenología Tridimensional/métodos , Radio (Anatomía)/cirugía , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/anatomía & histología , Anciano , Adulto Joven , Tomografía Computarizada por Rayos X

RESUMEN

Background: Antibiotic use is a major risk factor for recurrent Clostridioides difficile infection (CDI) due to the associated disruption in gut microbiota. Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660), is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent CDI in adults following standard-of-care antibiotic treatment. To investigate the impact of non-CDI antibiotics on the durability of RBL, a subgroup analysis was conducted on PUNCH™ Open-Label study participants who received non-CDI antibiotics during the period between RBL administration and up to 2 years after. Methods: Participants in PUNCH™ Open-Label who received non-CDI antibiotics after RBL administration were included in this subgroup analysis. Treatment response was defined as the absence of CDI diarrhea needing retreatment at the last evaluable time point (8 weeks, 6 months, 1 year, or 2 years) after RBL administration. Results: Among participants from PUNCH™ Open-Label, 43 received non-CDI antibiotics after RBL administration but before CDI recurrence as evaluated over a 2-year period. Across all evaluable time points, 86% (37/43) of participants had a treatment response regardless of when non-CDI antibiotic exposure occurred. Treatment response was sustained for a median 470 days (IQR, 212-648) from the first day of non-CDI antibiotic use. Most participants (5/6) with CDI recurrences received a high-risk antibiotic. Conclusions: RBL remained efficacious in participants with a history of recurrent CDI after subsequent non-CDI antibiotic exposure. Clinical Trials Registration: NCT02589847 (https://clinicaltrials.gov/study/NCT02589847).

RESUMEN

BACKGROUND AND OBJECTIVES: Viral bronchiolitis is a common pediatric illness. Treatment is supportive; however, some children have concurrent serious bacterial infections (cSBIs) requiring antibiotics. Identifying children with cSBI is challenging and may lead to unnecessary treatment. Improved understanding of the prevalence of and risk factors for cSBI are needed to guide treatment. We sought to determine the prevalence of cSBI and identify factors associated with cSBI in children hospitalized with bronchiolitis. METHODS: We performed a retrospective cohort study of children <2 years old hospitalized with bronchiolitis at a free-standing children's hospital from 2012 to 2019 identified by International Classification of Diseases codes. cSBI was defined as bacteremia, urinary tract infection, meningitis, or pneumonia. Risk factors for cSBI were identified using logistic regression. RESULTS: We identified 7871 admissions for bronchiolitis. At least 1 cSBI occurred in 4.2% of these admissions; with 3.5% meeting our bacterial pneumonia definition, 0.4% bacteremia, 0.3% urinary tract infection, and 0.02% meningitis. cSBI were more likely to occur in children with invasive mechanical ventilation (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.63), a C-reactive protein ≥4 mg/dL (OR 2.20, 95% CI 1.47-3.32), a concurrent complex chronic condition (OR 1.67, 95% CI 1.22-2.25) or admission to the PICU (OR 1.46, 95% CI 1.02-2.07). CONCLUSIONS: cSBI is uncommon among children hospitalized with bronchiolitis, with pneumonia being the most common cSBI. Invasive mechanical ventilation, elevated C-reactive protein, presence of complex chronic conditions, and PICU admission were associated with an increased risk of cSBI.

Asunto(s)

Bronquiolitis , Humanos , Lactante , Femenino , Masculino , Estudios Retrospectivos , Bronquiolitis/epidemiología , Bronquiolitis/complicaciones , Factores de Riesgo , Prevalencia , Infecciones Bacterianas/epidemiología , Hospitalización/estadística & datos numéricos , Niño Hospitalizado/estadística & datos numéricos , Infecciones Urinarias/epidemiología , Hospitales Pediátricos

RESUMEN

BACKGROUND: Postpartum depression (PPD) affects 30-50% of women with a history of previous depression or bipolar disorder and 8% of women with no history of depression. Negative cognitive biases in the perception of infant cues and difficulties with emotion regulation are replicated risk factors. Current interventions focus on detecting and treating rather than preventing PPD. The aim of this randomized controlled intervention trial is therefore to investigate the potential prophylactic effects of prenatal affective cognitive training for pregnant women at heightened risk of PPD. METHODS: The study will enrol a total of 292 pregnant women: 146 at high risk and 146 at low risk of PPD. Participants undergo comprehensive assessments of affective cognitive processing, clinical depressive symptoms, and complete questionnaires at baseline. Based on the responses, pregnant women will be categorized as either at high or low risk of PPD. High-risk participants will be randomized to either prenatal affective cognitive training (PACT) or care as usual (CAU) immediately after the baseline testing. The PACT intervention is based on emerging evidence for efficacy of affective cognitive training approaches in depression, including cognitive bias modification, attention bias modification, mindfulness-inspired emotion regulation exercises, and working memory training. Participants randomised to PACT will complete five individual computerised and virtual reality-based training sessions over 5 weeks. The primary outcome is the difference between intervention arms in the incidence of PPD, assessed with an interview 6 months after birth. We will also assess the severity of depressive symptoms, rated weekly online during the first 6 weeks postpartum. DISCUSSION: The results will have implications for future early prophylactic interventions for pregnant women at heightened risk of PPD. If the PACT intervention reduces the incidence of PPD, it can become a feasible, non-invasive prophylactic strategy during pregnancy, with positive mental health implications for these women and their children. TRIAL REGISTRATION: ClinicalTrials.gov NCT06046456 registered 21-09-2023, updated 08-07-2024.

Asunto(s)

Depresión Posparto , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Femenino , Depresión Posparto/prevención & control , Depresión Posparto/psicología , Depresión Posparto/diagnóstico , Embarazo , Afecto , Adulto , Factores de Riesgo , Terapia Cognitivo-Conductual/métodos , Atención Prenatal/métodos , Cognición , Resultado del Tratamiento , Entrenamiento Cognitivo

RESUMEN

ABSTRACT: Using the Australiasian electronic Persistent Pain Outcomes Collaboration, a binational pain registry collecting standardized clinical data from paediatric ePPOC (PaedsePPOC) and adult pain services (AdultePPOC), we explored and characterized nationally representative chronic pain phenotypes and associations with clinical and sociodemographic factors, health care utilization, and medicine use of young people. Young people ≥15.0 and <25.0 years captured in PaedePPOC and AdultePPOC Australian data registry were included. Data from 68 adult and 12 paediatric pain services for a 5-year period January 2018 to December 2022 (first episode, including treatment information) were analysed. Unsupervised latent class analysis was applied to explore the existence of distinct pain phenotypes, with separate models for both services. A 3-phenotype model was selected from both paediatric and adult ePPOC data, with 693 and 3518 young people included, respectively (at least one valid indicator variable). Indicator variables for paediatric models were as follows: pain severity, functional disability (quasisurrogate "pain interference"), pain count, pain duration, pain-related worry (quasisurrogate "catastrophizing"), and emotional functioning; and, for adult models: pain severity, pain interference, pain catastrophizing, emotional functioning, and pain self-efficacy. From both services, 3 similar phenotypes emerged ("low," "moderate," "high"), characterized by an increasing symptom-severity gradient in multidimensional pain-related variables, showing meaningful differences across clinical and sociodemographic factors, health service utilization, and medicines use. Derived phenotypes point to the need for novel care models that differentially respond to the needs of distinct groups of young people, providing timely, targeted, age-appropriate care. To effectively scale such care, digital technologies can be leveraged to augment phenotype-informed clinical care.

RESUMEN

Currently, the role of DNA methylation in the IgM-monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multi-omics prospective analysis was conducted integrating DNA methylation, RNA-seq and WES data in 34 subjects [23 WM, 6 IgM-MGUS, 5 normal controls]. Analysis was focused on defining differences between IgM-gammopathies (WM/IgM-MGUS) compared to controls, and specifically between WM and IgM-MGUS. Between groups, genome-wide DNA methylation analysis demonstrated a significant number of differentially methylated regions which were annotated according to genomic region. Next, integration of RNA-seq data was performed to identify potentially epigenetically deregulated pathways. We found that pathways involved in cell cycle, metabolism, cytokine/immune signaling, cytoskeleton, tumor microenvironment, and intracellular signaling were differentially activated and potentially epigenetically regulated. Importantly, there was a positive enrichment of CXCR4 signaling pathway along with several interleukin (IL-6, IL-8, IL15) signaling pathways in WM compared to IgM-MGUS. Further assessment of known tumor suppressor genes and oncogenes uncovered differential promoter methylation of several targets with concordant change in gene expression, including CCND1 and CD79B. Overall, this report defines how aberrant DNA methylation in IgM-gammopathies may play a critical role in the epigenetic control of oncogenesis and key cellular functions.

RESUMEN

A comprehensive understanding of the spatial distribution and correlates of infection are key for the planning of disease control programs and assessing the feasibility of elimination and/or eradication. In this work, we used species distribution modeling to predict the environmental suitability of the Guinea worm (Dracunculus medinensis) and identify important climatic and sociodemographic risk factors. Using Guinea worm surveillance data collected by the Chad Guinea Worm Eradication Program (CGWEP) from 2010 to 2022 in combination with remotely sensed climate and sociodemographic correlates of infection within an ensemble machine learning framework, we mapped the environmental suitability of Guinea worm infection in Chad. The same analytical framework was also used to ascertain the contribution and influence of the identified climatic risk factors. Spatial distribution maps showed predominant clustering around the southern regions and along the Chari River. We also identified areas predicted to be environmentally suitable for infection. Of note are districts near the western border with Cameroon and southeastern border with Central African Republic. Key environmental correlates of infection as identified by the model were proximity to permanent rivers and inland lakes, farmlands, land surface temperature, and precipitation. This work provides a comprehensive model of the spatial distribution of Guinea worm infections in Chad 2010-2022 and sheds light on potential environmental correlates of infection. As the CGWEP moves toward elimination, the methods and results in this study will inform surveillance activities and help optimize the allocation of intervention resources.

Asunto(s)

Clima , Dracunculiasis , Dracunculus , Chad/epidemiología , Animales , Dracunculiasis/epidemiología , Dracunculus/aislamiento & purificación , Humanos , Factores Sociodemográficos , Factores de Riesgo , Aprendizaje Automático , Factores Socioeconómicos

RESUMEN

BackgroundNon-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination.AimTo describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.MethodsParticipants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021-November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination.ResultsWe received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23-1.54).ConclusionsOur study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.

Asunto(s)

Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunación , Humanos , Estudios Prospectivos , Femenino , Masculino , COVID-19/prevención & control , COVID-19/epidemiología , SARS-CoV-2/inmunología , Persona de Mediana Edad , Países Bajos/epidemiología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Adulto , Anticuerpos Antivirales/sangre , Vacunación/efectos adversos , Vacunación/estadística & datos numéricos , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven , Encuestas y Cuestionarios

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Eficacia de las Vacunas , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Países Bajos/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Estudios Prospectivos , Adulto , Masculino , Persona de Mediana Edad , Femenino , Vacunación , Anciano

RESUMEN

Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure. Tumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis was used to identify a signature associated with high risk of early clinical failure independent of IPI and COO. Further analysis revealed the signature was associated with metabolic reprogramming and identified cases with a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion of ARID1A mutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts. This novel and integrative approach is the first to identify a signature at diagnosis, in a real-world cohort of DLBCL, that identifies patients at high risk for early clinical failure and may have significant implications for design of therapeutic options.

Asunto(s)

Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Femenino , Perfilación de la Expresión Génica , Persona de Mediana Edad , Transcriptoma , Mutación , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción/genética , Biomarcadores de Tumor/genética , Anciano , Pronóstico , Microambiente Tumoral , Secuenciación del Exoma , Adulto , Proteínas de Unión al ADN/genética , Insuficiencia del Tratamiento

RESUMEN

Two doses of JYNNEOS vaccine are effective in preventing many mpox cases and can reduce the severity of symptoms in infected persons. However, infections among fully vaccinated persons can occur. During May 2022-May 2024, a total of 271 mpox cases among fully vaccinated persons were reported to CDC from 27 U.S. jurisdictions. These reported infections are estimated to have occurred in <1% of fully vaccinated persons. Compared with cases among unvaccinated persons, infections among fully vaccinated persons were more likely to occur among non-Hispanic White men aged 30-39 years, were associated with increased numbers of sexual partners, and resulted in less severe disease (p<0.001). Among infections in fully vaccinated persons with complete data, infections after vaccination were reported more commonly after receipt of heterologous (subcutaneous and intradermal) (46%) or homologous subcutaneous (32%) JYNNEOS vaccination than after homologous intradermal (22%) vaccination. Disparate time intervals from vaccination to infection among fully vaccinated persons suggest that immunity is not waning. The median interval between the second vaccine dose and illness onset was longer for cases among persons who had received 2 intradermal doses (median = 363 days; IQR = 221-444 days) compared with cases in persons who had received 2 subcutaneous doses (median = 263 days; IQR = 47-334 days) (p<0.001). The implications of this finding are not known; however, these data should increase confidence in the effectiveness of vaccine doses that were administered intradermally, the preferred method of administration during the peak of the outbreak when vaccine supply was limited. Persons recommended to receive the JYNNEOS vaccine should receive 2 doses, irrespective of the route of administration, and at this time, additional doses are not recommended for the affected population.

Asunto(s)

Mpox , Humanos , Masculino , Estados Unidos/epidemiología , Adulto , Adulto Joven , Femenino , Persona de Mediana Edad , Mpox/epidemiología , Mpox/prevención & control , Adolescente , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Inmunización Secundaria

RESUMEN

BACKGROUND: Dogs are exposed to increasing environmental risk for developing heat-related illness (HRI), with 2022 recorded as the hottest year to date in the UK and most of Europe. METHODS: This study used VetCompass data to report the incidence risk, event fatality rate and canine risk factors for HRI in dogs presenting to Vets Now emergency care practices in the UK during 2022. RESULTS: From the clinical records of 167,751 dogs under care at Vets Now emergency clinics in 2022, 384 HRI events were identified. The 2022 incidence risk of HRI within the Vets Now caseload was 0.23% (95% confidence interval [CI]: 0.21%‒0.25%), with an event fatality rate of 26.56% (95% CI: 21.66%-32.25%). Multivariable analysis identified breed, age and sex/neuter status as risk factors for HRI. Brachycephalic dogs had 4.21 times the odds of HRI compared to mesocephalic dogs (95% CI: 3.22‒5.49, p < 0.001). LIMITATIONS: The clinical data used in this study were not primarily recorded for research and had some substantial levels of missing data (especially patient bodyweight). CONCLUSION: In order to protect canine welfare, improved long-term mitigation strategies are urgently needed to minimise HRI risk and associated fatality in UK dogs.

Asunto(s)

Enfermedades de los Perros , Trastornos de Estrés por Calor , Animales , Perros , Enfermedades de los Perros/epidemiología , Reino Unido/epidemiología , Masculino , Femenino , Factores de Riesgo , Trastornos de Estrés por Calor/veterinaria , Trastornos de Estrés por Calor/epidemiología , Incidencia , Servicios Médicos de Urgencia/estadística & datos numéricos

RESUMEN

The spectinamides are novel, narrow-spectrum semisynthetic analogs of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead MBX-4888A (Lee-1810), exhibit promising therapeutic profiles in mice, as single drugs and as partner agents with other anti-tuberculosis antibiotics including rifampin and/or pyrazinamide. To demonstrate that this translates to more effective cure, we first confirmed the role of rifampin, with or without pyrazinamide, as essential to achieve effective bactericidal responses and sterilizing cure in the current standard of care regimen in chronically infected C3HeB/FeJ mice compared to BALB/c mice. Thus, demonstrating added value in testing clinically relevant regimens in murine models of increasing pathologic complexity. Next we show that MBX-4888A, given by injection with the front-line standard of care regimen, is treatment shortening in multiple murine tuberculosis infection models. The positive treatment responses to MBX-4888A combination therapy in multiple mouse models including mice exhibiting advanced pulmonary disease can be attributed to favorable distribution in tissues and lesions, retention in caseum, along with favorable effects with rifampin and pyrazinamide under conditions achieved in necrotic lesions. This study also provides an additional data point regarding the safety and tolerability of spectinamide MBX-4888A in long-term murine efficacy studies.

RESUMEN

Online appearance preoccupation may put adolescents at risk of developing mental health challenges, perhaps especially during early-to-middle adolescence. A random intercept cross-lagged panel model assessed within-person associations between appearance-related social media consciousness and depressive symptoms over three time-points with three months between waves. The sample (n = 1594) included U.S. adolescents aged 11-15 (Mage = 13; 47% girls, 46% boys, 7% another gender; 37% Latine, 33% White, 18% Black, 7% Asian). Within-person increases in appearance-related social media consciousness were associated with subsequent increases in depressive symptoms, but not vice versa. There was no evidence of gender differences and results were robust to controlling for both time on social media and offline self-objectification. Thus, online appearance concerns precede mental health challenges during early and middle adolescence.