Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 691
Filtrar
1.
Front Hum Neurosci ; 18: 1394948, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841124

RESUMEN

Communication is often impaired in individuals with Parkinson's disease (PD), typically secondary to sensorimotor deficits impacting voice and speech. Language may also be diminished in PD, particularly for production and comprehension of verbs. Evidence exists that verb processing is influenced by motor system modulation suggesting that verb deficits in PD are underpinned by similarities in the neural representations of actions that span motor and semantic systems. Conversely, subtle differences in cognition in PD may explain difficulty in processing of complex syntactic forms, which increases cognitive demand and is linked to verb use. Here we investigated whether optimizing motor system support for vocal function (improving loudness) affects change in lexical semantic, syntactic, or informativeness aspects of spoken discourse. Picture description narratives were compared for 20 Control participants and 39 with PD, 19 of whom underwent Lee Silverman Voice Treatment (LSVT LOUD®). Treated PD narratives were also contrasted with those of untreated PD and Control participants at Baseline and after treatment. Controls differed significantly from the 39 PD participants for verbs per utterance, but this difference was largely driven by untreated PD participants who produced few utterances but with verbs, inflating their verbs per utterance. Given intervention, there was a significant increase in vocal loudness but no significant changes in language performance. These data do not support the hypothesis that targeting this speech motor system results in improved language production. Instead, the data provide evidence of considerable variability in measures of language production across groups, particularly in verbs per utterance.

2.
Nature ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862027

RESUMEN

The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions entering space and preparations for exploration-class (>1 year) missions. Such rapid advancement into space from many new companies, countries, and space-related entities has enabled a"Second Space Age." This new era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, encompassing multi-omic, single-cell, and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring, and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics (PGx), as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this review, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration (NASA), Japan Aerospace Exploration Agency (JAXA), European Space Agency (ESA), and other space agencies, and also detail the commercial spaceflight sector's (e.g. SpaceX, Blue Origin, Axiom, Sierra Space) entrance into aerospace medicine and space biology, the first aerospace medicine biobank, and the myriad upcoming missions that will utilize these tools to ensure a permanent human presence beyond LEO, venturing out to other planets and moons.

3.
Mitochondrion ; 78: 101905, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38797357

RESUMEN

Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy. Treatment with high dose bezafibrate and nicotinamide riboside resulted in marked clinical improvement including reduced lactate and NT-pro-brain type natriuretic peptide levels, with stabilized echocardiographic measures. After a long stable period, the child succumbed from cardiac failure with infection at 10.5 months. Therapy was well tolerated. Peak bezafibrate levels exceeded its EC50. The clinical improvement with this treatment illustrates its potential, but weak PPAR agonist activity of bezafibrate limited its efficacy.

4.
Horm Behav ; 163: 105563, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38772158

RESUMEN

Vasopressin (AVP) regulates various social behaviors, often in sex-specific ways, including social play behavior, a rewarding behavior displayed primarily by juveniles. Here, we examined whether and how AVP acting in the brain's reward system regulates social play behavior in juvenile rats. Specifically, we focused on AVP signaling in the ventral pallidum (VP), a brain region that is a part of the reward system. First, we examined the organization of the VP-AVP system in juvenile rats and found sex differences, with higher density of both AVP-immunoreactive fibers and AVP V1a receptor (V1aR) binding in males compared to females while females show a greater number of V1aR-expressing cells compared to males. We further found that, in both sexes, V1aR-expressing cells co-express a GABA marker to a much greater extent (approx. 10 times) than a marker for glutamate. Next, we examined the functional involvement of V1aR-expressing VP cells in social play behavior. We found that exposure to social play enhanced the proportion of activated V1aR-expressing VP cells in males only. Finally, we showed that infusion of a specific V1aR antagonist into the VP increased social play behaviors in juvenile male rats while decreasing these behaviors in juvenile female rats. Overall, these findings reveal structural and functional sex differences in the AVP-V1aR system in the VP that are associated with the sex-specific regulation of social play behavior.


Asunto(s)
Prosencéfalo Basal , Receptores de Vasopresinas , Caracteres Sexuales , Conducta Social , Vasopresinas , Animales , Masculino , Femenino , Ratas , Receptores de Vasopresinas/metabolismo , Prosencéfalo Basal/metabolismo , Prosencéfalo Basal/fisiología , Vasopresinas/metabolismo , Juego e Implementos de Juego , Arginina Vasopresina/metabolismo , Conducta Animal/fisiología , Ratas Long-Evans , Antagonistas de los Receptores de Hormonas Antidiuréticas/farmacología
5.
Epilepsy Behav ; 156: 109830, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759426

RESUMEN

Epilepsy affects millions of people and when medications are insufficient to maintain seizure control, individuals are diagnosed with refractory epilepsy (RE). Medical ketogenic diet therapy (KDT), a diet high in fat and low in carbohydrates and sufficient in protein, is a well-established treatment for RE. However, compliance is one of the main reasons for discontinuation of KDT and, with pediatric RE patients, the ability of informal caregivers, typically family members, to maintain diet adherence is vital for successful KDT treatment. The central role that informal caregivers play for effective KDT implementation is recognized, however, there is a need to elucidate the rationale and theoretical underpinnings of effective KDT caregiver support programs to inform best practices. Therefore, this systematic literature review aims to identify the existing fundamental understandings of KDT caregiver support to help build a foundation of theory-based knowledge to promote evidenced practice. After screening 137 publications, three studies that discussed potential underlying components of effective caregiver support were included in this review. These articles followed a similar approach as they 1) employed qualitative methods delving into caregiver needs, 2) findings highlighted the importance of support from family, friends, fellow caregivers and their child's medical team, and 3) the inclusion of caregiver support findings were a supplement to the main purpose of the manuscript. Research focused on KDT caregivers is in its infancy. There is a clear need for the systematic examination of support for KDT caregivers to build a foundation for effective support programs and to increase the access to quality support programming to foster KDT implementation, desirable patient outcomes, and caregiver well being. In this article we discuss opportunities to apply self-determination theory to the KDT caregiver support research and practice.


Asunto(s)
Cuidadores , Dieta Cetogénica , Epilepsia , Humanos , Dieta Cetogénica/métodos , Cuidadores/psicología , Epilepsia/dietoterapia , Niño , Enfermedades del Sistema Nervioso/dietoterapia
6.
Arthroscopy ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38697329

RESUMEN

PURPOSE: To investigate a radiographic sign believed to be indicative of hip instability and acetabular suction seal disruption in the native hip, coined the "windshield wiper" (WSW) sign. METHODS: A retrospective review was performed for patients who underwent periacetabular osteotomy (PAO) with the senior author between March 2021 and September 2023. A WSW sign was identified on plain films as a concave or flat osteochondral defect on the anterolateral femoral head extending medial to the head-neck junction with resultant loss of femoral head sphericity in the native hip. Every patient underwent a standardized series of radiographs, as well as computed tomography and magnetic resonance imaging. All patients underwent arthroscopy before PAO to address intra-articular pathology and other indicated procedures. The osteochondral defect and resultant suction seal disruption were verified during arthroscopy. These patients were then compared with a control group of arthroscopically treated hips without hip instability. RESULTS: Of 250 patients reviewed, a total of 19 hips in 17 patients (prevalence of 7.6%) demonstrated radiographic evidence of the WSW sign. All patients with a WSW sign presented with symptomatic clinical hip instability requiring a PAO. The mean patient age was 31.2 years, with a mean lateral center-edge angle (LCEA) of 14.3°. There were 13 hips (68.4%) with dysplasia, 4 (21.1%) with borderline dysplasia, and 2 (10.5%) with a normal LCEA. All patients with a WSW sign and LCEA ≥ 20° displayed significant femoral antetorsion abnormalities. All arthroscopic videos and images demonstrated a compromised suction seal. Of the 50 control group hips reviewed, the WSW sign was not identified. CONCLUSIONS: The WSW sign is an uncommon radiographic finding in patients with hip instability. When identified, it can be predictive of substantial instability, especially in cases which are otherwise considered borderline dysplasia or normal based on LCEA. LEVEL OF EVIDENCE: Level III, retrospective comparative case control study.

7.
J Craniofac Surg ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771209

RESUMEN

Submucous cleft palate (SMCP) is a common congenital anomaly characterized by a diastasis of the levator veli palitini muscle. The subtlety of SMCP on physical examination can contribute to diagnostic delays. This study aims to analyze the factors contributing to delays in care and subsequent postoperative outcomes in patients with SMCP. All patients with surgical indications for SMCP who underwent palatoplasty at an urban academic children's hospital were included. Patient socioeconomic characteristics, medical history, and postoperative outcomes were collected. Patients were compared based on insurance type and government assistance utilization. Statistical analyses including independent t-test, Wilcoxon ranked sum test, χ2 analyses, Fisher's exact test, and stepwise logistic regression were performed. Among the 105 patients with SMCP, 69.5% (n=73) had public insurance and 30.5% (n=32) private. Patients with public insurance were diagnosed later (5.5±4.6 versus 2.6±2.4 years old; p<0.001) and underwent palatoplasty later (7.3±4.1 versus 4.4±3.4 years old; p<0.001) than those with private insurance. Patients receiving government assistance experienced higher rates of post-surgical persistent velopharyngeal insufficiency (74.5% versus 44.8%; p=0.006). The authors' results suggest a disparity in the recognition and treatment of surgical SMCP. Hence, financially vulnerable populations may experience an increased risk of inferior speech outcomes and subsequent therapies and procedures.

8.
Contraception ; : 110493, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38762198

RESUMEN

OBJECTIVES: We examined differences between hospital-affiliated clinics and non-hospital-affiliated clinics (independent or Planned Parenthood clinics) regarding abortion service innovation and cash-pay availability in response to COVID-19. STUDY DESIGN: We analyzed data from all three phases of a longitudinal nationwide survey of abortion providers conducted by the Society of Family Planning. RESULTS: This study utilizes a convenience sample of 74 voluntarily participating clinics, representing 5% of clinics nationwide. Compared to non-hospital-affiliated clinics, hospital-affiliated clinics were more likely to initiate care innovations but were less likely to offer cash-pay during the pandemic. CONCLUSIONS: Both hospital-affiliated and non-hospital-affiliated clinics enacted patient-centered care innovations during the pandemic. Hospital-affiliated clinics were more likely to initiate innovative services, particularly surrounding telemedicine. Hospital-affiliated clinics can improve cash-pay availability to expand access to abortion care in times of national emergencies.

9.
JAMA Netw Open ; 7(5): e249531, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38696165

RESUMEN

Importance: Pregnancy represents a window of opportunity for vaccination due to established maternal and fetal benefits of vaccination. Little is known about receipt of routinely recommended vaccines in pregnancy, specifically tetanus, diphtheria, plus acellular pertussis (Tdap) and influenza, among pregnant people living with HIV (PLHIV). Objective: To estimate prevalence of vaccination receipt among pregnant people with HIV (PLHIV) and identify demographic and clinical characteristics associated with vaccination. Design, Setting, and Participants: This multicenter cohort study included women participating in Women's Health Study (WHS) of the Surveillance Monitoring for ART Toxicities (SMARTT) Study of the Pediatric HIV/AIDS Cohort Study. The network has been enrolling pregnant PLHIV at 22 US sites since 2007. Participants for this study enrolled between December 2017 and July 2019. Data analysis was conducted from October 2021 to March 2022. Exposure: Data on vaccination in pregnancy were collected through medical record abstraction. Main Outcomes and Measures: Vaccination receipt was defined as Tdap vaccination received at less than 36 weeks' gestation and influenza vaccination at any gestational age, based on current guidelines. Log-binomial and modified Poisson regression models with generalized estimating equations were fit to identify factors associated with successful receipt of (1) Tdap, (2) influenza, and (3) both vaccinations. Results: A total of 310 pregnancies among 278 people participating in the WHS were included (mean [SD] age, 29.5 [6.1] years; 220 [71%] Black, 77 [25%] Hispanic, and 77 [25%] race and ethnicity other than Black; 64 [21%] with perinatally acquired HIV). Less than one-third of pregnancies were vaccinated as recommended (Tdap, 32.6% [95% CI, 27.4%-38.1%]; influenza, 31.6% [95% CI, 26.5%-37.1%]; both, 22.6% [95% CI, 18.0%-27.6%]). People living with perinatally acquired HIV, those who did not identify as Black, or those who were multiparous had adjusted risk ratios (aRRs) less than 1, while older PLHIV had aRRs greater than 1, but these differences did not reach statistical significance (perinatally acquired HIV: adjusted risk ratio [aRR], 0.46; 95% CI, 0.21-1.02; race other than Black: aRR, 0.53; 95% CI, 0.26-1.08; multiparous: aRR, 0.59; 95% CI, 0.35-1.00; age 24-29 years: aRR, 2.03; 95% CI, 0.92-4.48). Conclusions and Relevance: In this diverse, multicenter cohort of pregnant PLHIV, receipt of recommended vaccinations was low. Identifying and addressing barriers to vaccination receipt is urgently needed for pregnant people with HIV.


Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Infecciones por VIH , Vacunas contra la Influenza , Complicaciones Infecciosas del Embarazo , Vacunación , Humanos , Femenino , Embarazo , Adulto , Infecciones por VIH/epidemiología , Estados Unidos/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Vacunación/estadística & datos numéricos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra la Influenza/administración & dosificación , Estudios de Cohortes , Gripe Humana/prevención & control , Adulto Joven
10.
J Trauma Nurs ; 31(3): 158-163, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742724

RESUMEN

BACKGROUND: Early administration of antibiotics in the presence of open fractures is critical in reducing infections and later complications. Current guidelines recommend administering antibiotics within 60 min of patient arrival to the emergency department, yet trauma centers often struggle to meet this metric. OBJECTIVES: This study aims to evaluate the impact of a nurse-initiated evidence-based treatment protocol on the timeliness of antibiotic administration in pediatric patients with open fractures. METHODS: A retrospective pre-post study of patients who met the National Trauma Data Standard registry inclusion criteria for open fractures of long bones, amputations, or lawn mower injuries was performed at a Midwestern United States Level II pediatric trauma center. The time of patient arrival and time of antibiotic administration from preimplementation (2015-2020) to postimplementation (2021-2022) of the protocol were compared. Patients transferred in who received antibiotics at an outside facility were excluded. RESULTS: A total of N = 73 participants met the study inclusion criteria, of which n = 41 were in the preimplementation group and n = 32 were in the postimplementation group. Patients receiving antibiotics within 60 min of arrival increased from n = 24/41 (58.5%) preimplementation to n = 26/32 (84.4%) postimplementation (p< .05). CONCLUSIONS: Our study demonstrates that initiating evidence-based treatment orders from triage helped decrease the time from arrival to time of antibiotic administration in patients with open fractures. We sustained improvement for 24 months after the implementation of our intervention.


Asunto(s)
Antibacterianos , Fracturas Abiertas , Centros Traumatológicos , Humanos , Fracturas Abiertas/enfermería , Fracturas Abiertas/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/administración & dosificación , Masculino , Niño , Femenino , Preescolar , Protocolos Clínicos , Adolescente , Tiempo de Tratamiento/normas , Factores de Tiempo , Medio Oeste de Estados Unidos
11.
Int J Radiat Oncol Biol Phys ; 119(2): 669-680, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38760116

RESUMEN

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, screening, and comprehending radiation therapy-related late effects in children, drawing insights from individual organ-specific PENTEC reports. We further explore how the development of imaging biomarkers for key organ systems, alongside technical advancements and translational imaging approaches, may enhance the systematic application of imaging evaluations in childhood cancer survivors. Moreover, the review critically examines knowledge gaps and identifies technical and practical limitations of existing imaging modalities in the pediatric population. Addressing these challenges may expand access to, minimize the risk of, and optimize the real-world application of, new imaging techniques. The PENTEC team envisions this document as a roadmap for the future development of imaging strategies in childhood cancer survivors, with the overarching goal of improving long-term health outcomes and quality of life for this vulnerable population.


Asunto(s)
Traumatismos por Radiación , Humanos , Niño , Traumatismos por Radiación/diagnóstico por imagen , Supervivientes de Cáncer , Órganos en Riesgo/diagnóstico por imagen , Órganos en Riesgo/efectos de la radiación , Neoplasias/radioterapia , Neoplasias/diagnóstico por imagen , Radioterapia/efectos adversos , Diagnóstico por Imagen/métodos
12.
Cancer Discov ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38564707

RESUMEN

Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas (PRCC). Here, using comprehensive genomic profiling among >600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ~0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential, and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors.

13.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38635784

RESUMEN

CASE: We describe the unique case of a 20-year-old man with a history of Legg-Calve-Perthes disease, hip dysplasia, and osteochondral fragmentation of the medial femoral head. We performed arthroscopic femoroplasty and femoral head allografting, followed by a valgus-producing derotational femoral osteotomy (DFO) and periacetabular osteotomy (PAO). At 1-year follow-up, the patient achieved osseous union and complete femoral head healing with return to his active hobbies. CONCLUSION: We describe the successful utilization of arthroscopic allografting for medial femoral head osteochondral fragmentation. To our knowledge, this is the first report on femoral head arthroscopic allografting before DFO and PAO.


Asunto(s)
Cabeza Femoral , Enfermedad de Legg-Calve-Perthes , Masculino , Humanos , Adulto Joven , Adulto , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Enfermedad de Legg-Calve-Perthes/diagnóstico por imagen , Enfermedad de Legg-Calve-Perthes/cirugía , Enfermedad de Legg-Calve-Perthes/complicaciones , Osteotomía , Fémur/cirugía , Progresión de la Enfermedad , Aloinjertos
14.
J Exp Psychol Anim Learn Cogn ; 50(2): 77-98, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38587939

RESUMEN

Rescorla (2000, 2001) interpreted his compound test results to show that both common and individual error terms regulate associative change such that the element of a conditioned compound with the greater prediction error undergoes greater associative change than the one with the smaller prediction error. However, it has recently been suggested that uncertainty, not prediction error, is the primary determinant of associative change in people (Spicer et al., 2020, 2022). The current experiments use the compound test in a continuous outcome allergist task to assess the role of uncertainty in associative change, using two different manipulations of uncertainty: outcome uncertainty (where participants are uncertain of the level of the outcome on a particular trial) and causal uncertainty (where participants are uncertain of the contribution of the cue to the level of the outcome). We replicate Rescorla's compound test results in the case of both associative gains (Experiment 1) and associative losses (Experiment 3) and then provide evidence for greater change to more uncertain cues in the case of associative gains (Experiments 2 and 4), but not associative losses (Experiments 3 and 5). We discuss the findings in terms of the notion of theory protection advanced by Spicer et al., and other ways of thinking about the compound test procedure, such as that proposed by Holmes et al. (2019). (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Aprendizaje por Asociación , Señales (Psicología) , Humanos , Incertidumbre , Aprendizaje por Asociación/fisiología
15.
J Natl Compr Canc Netw ; : 1-7, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38670152

RESUMEN

BACKGROUND: Recent modifications to low-dose CT (LDCT)-based lung cancer screening guidelines increase the number of eligible individuals, particularly among racial and ethnic minorities. Because these populations disproportionately live in metropolitan areas, we analyzed the association between travel time and initial LDCT completion within an integrated, urban safety-net health care system. METHODS: Using Esri's StreetMap Premium, OpenStreetMap, and the r5r package in R, we determined projected private vehicle and public transportation travel times between patient residence and the screening facility for LDCT ordered in March 2017 through December 2022 at Parkland Memorial Hospital in Dallas, Texas. We characterized associations between travel time and LDCT completion in univariable and multivariable analyses. We tested these associations in a simulation of 10,000 permutations of private vehicle and public transportation distribution. RESULTS: A total of 2,287 patients were included in the analysis, of whom 1,553 (68%) completed the initial ordered LDCT. Mean age was 63 years, and 73% were underrepresented minorities. Median travel time from patient residence to the LDCT screening facility was 17 minutes by private vehicle and 67 minutes by public transportation. There was a small difference in travel time to the LDCT screening facility by public transportation for patients who completed LDCT versus those who did not (67 vs 66 min, respectively; P=.04) but no difference in travel time by private vehicle for these patients (17 min for both; P=.67). In multivariable analysis, LDCT completion was not associated with projected travel time to the LDCT facility by private vehicle (odds ratio, 1.01; 95% CI, 0.82-1.25) or public transportation (odds ratio, 1.14; 95% CI, 0.89-1.44). Similar results were noted across travel-type permutations. Black individuals were 29% less likely to complete LDCT screening compared with White individuals. CONCLUSIONS: In an urban population comprising predominantly underrepresented minorities, projected travel time is not associated with initial LDCT completion in an integrated health care system. Other reasons for differences in LDCT completion warrant investigation.

16.
Elife ; 132024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656290

RESUMEN

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines. Methods: The immune response to the COVID-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and 7 d after the second dose (V2D7) using anti-spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified 6 mo after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response. Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development. Conclusions: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance HD subjects comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of ESRD. Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628. This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003.


Asunto(s)
Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Fallo Renal Crónico , Diálisis Renal , SARS-CoV-2 , Humanos , Masculino , Femenino , Persona de Mediana Edad , COVID-19/inmunología , COVID-19/prevención & control , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anciano , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Antivirales/sangre , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Fallo Renal Crónico/inmunología , Transcriptoma , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunoglobulina G/sangre , Vacunas de ARNm/inmunología , Vacunación
17.
Biotechnol Bioeng ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38686918

RESUMEN

Microbial-derived natural products remain a major source of structurally diverse bioactive compounds and chemical scaffolds that have the potential as new therapeutics to target drug-resistant pathogens and cancers. In particular, genome mining has revealed the vast number of cryptic or low-yield biosynthetic gene clusters in the genus Streptomyces. However, low natural product yields-improvements to which have been hindered by the lack of high throughput methods-have slowed the discovery and development of many potential therapeutics. Here, we describe our efforts to improve yields of landomycins-angucycline family polyketides under investigation as cancer therapeutics-by a genetically modified Streptomyces cyanogenus 136. After simplifying the extraction process from S. cyanogenus cultures, we identified a wavelength at which the major landomycin products are absorbed in culture extracts, which we used to systematically explore culture medium compositions to improve total landomycin titers. Through correlational analysis, we simplified the culture optimization process by identifying an alternative wavelength at which culture supernatants absorb yet is representative of total landomycin titers. Using the subsequently improved sample throughput, we explored landomycin production during the culturing process to further increase landomycin yield and reduce culture time. Testing the antimicrobial activity of the isolated landomycins, we report broad inhibition of Gram-positive bacteria, inhibition of fungi by landomycinone, and broad landomycin resistance by Gram-negative bacteria that is likely mediated by the exclusion of landomycins by the bacterial membrane. Finally, the anticancer activity of the isolated landomycins against A549 lung carcinoma cells agrees with previous reports on other cell lines that glycan chain length correlates with activity. Given the prevalence of natural products produced by Streptomyces, as well as the light-absorbing moieties common to bioactive natural products and their metabolic precursors, our method is relevant to improving the yields of other natural products of interest.

18.
Am J Ophthalmol ; 264: 216-223, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38490339

RESUMEN

PURPOSE: To evaluate trends associated with email communication from potentially predatory publishers to faculty in ophthalmology. DESIGN: Cross-sectional study METHODS: Ophthalmologists (n = 14) from various subspecialties and institutions were recruited to participate. Participants identified unsolicited emails that they had received originating from publishers in May 2021. Information collected included details on email contents and publisher organizations. Trends in communications from predatory publishers were evaluated. RESULTS: Over a 30-day study period, a total of 1813 emails were received from 383 unique publishers and 696 unique journals, with a mean (SD) of 4.73 (2.46) emails received per day per participant. Of the 1813 emails identified, 242 (13%) emails were invitations to conferences, whereas 1440 (80%) were solicitations for article submissions to open-access, pay-to-publish journals. A total of 522 (29.0%) emails were related to ophthalmology, and reference to a prior publication of the participant occurred in 262 emails (14%). Of the 696 unique journals identified, 174 (25%) journals were indexed on PubMed and 426 (61%) were listed on Beall's list. When comparing journals that were listed on PubMed vs those that were not, PubMed indexed journals had a higher impact factor (2.1 vs 1.5, P = .002), were less likely to use "greetings" (76% vs 91%, P < .001), had fewer spelling/grammar errors (40% vs 51%, P = .01), and were less likely to offer rapid publication (16% vs 25%, P = .02). CONCLUSIONS: Unsolicited requests to publish occur frequently and may diminish the quality of the scientific literature. We encourage individuals in ophthalmology to be aware of these trends in predatory publishing.

19.
J Am Dent Assoc ; 155(6): 475-483, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38530692

RESUMEN

BACKGROUND: Tooth autotransplantation (AT) involves the surgical relocation of a tooth from 1 site in the mouth to another site within the same patient. This approach is a good option in a growing patient when dental implant placements or fixed bridges are not suitable and when preserving natural teeth is a priority. Tooth AT is a complex procedure that requires specialized skills from a multidisciplinary team with careful patient and tooth selection and treatment planning. TYPES OF STUDIES REVIEWED: The authors provided a review of the state of knowledge and research on tooth AT and presented a case scenario and barriers to adoption, with a focus on the United States. RESULTS: Success rates for tooth AT can vary depending on several factors, including the patient's overall health, specific tooth involved, skill of the dental surgeon, and postoperative care provided. Long-term outcomes of autotransplanted teeth have been cited in the literature with impressive longitudinal follow-up spanning up to 26 years. Results of several systematic reviews showed survival rates from 75% through 98%. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Adoption of tooth AT has grown over the years, owing to advancements in dental techniques, improved patient outcomes, and increased awareness among both dentists and patients. Increasing awareness and availability of tooth AT to replace missing teeth can provide a natural and functional alternative to traditional prosthetic options. Tooth AT helps preserve the alveolar bone in growing patients and can offer excellent esthetic and functional outcomes.


Asunto(s)
Diente , Trasplante Autólogo , Humanos , Diente/trasplante , Femenino
20.
Am J Sports Med ; 52(6): 1563-1571, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38544383

RESUMEN

BACKGROUND: An everted acetabular labrum (EL) is a pathologic variant in which the labrum is flipped to the capsular side of the acetabular rim. An iatrogenic EL is a known complication of a poorly executed labral repair, and a recent study described the native acetabular EL. PURPOSE: To analyze surgical outcomes after advancement or reconstruction of an EL in a native hip. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This was a multicenter retrospective review of prospectively collected data on primary hip arthroscopic surgeries performed between 2013 and 2023. An EL was identified arthroscopically as a labrum-femoral head gap while off traction in the native hip. All patients with EL who were analyzed in this study underwent arthroscopic labral repair and advancement or labral augmentation or reconstruction. Patients with hip dysplasia also underwent periacetabular osteotomy with or without a derotational femoral osteotomy. Patient-reported outcomes (PROs) were assessed using the 12-item International Hip Outcome Tool (iHOT-12) and the Nonarthritic Hip Score. PROs were obtained preoperatively and up to 24 months after surgery. PROs were compared with those of a case-matched control cohort in a 1:2 ratio. Only patients with PROs available at ≥1 year postoperatively were included in the outcome analysis. RESULTS: A total of 111 patients (129 hips) with EL during the study period were identified, with PROs available in 96 hips. The mean age of patients with EL was 30.5 years, and women made up 87% of the cohort. Of the 129 hips with an EL, an isolated diagnosis of an EL was present in 11.6% of hips. Deficient acetabular coverage (lateral center-edge angle <25°) was seen in 40.6% of EL hips. No difference was seen in iHOT-12 scores between EL and control groups at 12- or 24-month follow-up (P = .18 and .94, respectively). Patients with EL reported a significant improvement of PROs at latest follow-up (P < .001 for iHOT-12 and Nonarthritic Hip Score). CONCLUSION: Surgical management of a native EL with restoration of the labral seal on the femoral head and correction of concomitant pathologies resulted in significant clinical improvement, with postoperative outcome scores comparable to those of patients without an EL. These findings provide evidence supporting surgical intervention for a native EL.


Asunto(s)
Acetábulo , Artroscopía , Medición de Resultados Informados por el Paciente , Humanos , Acetábulo/cirugía , Femenino , Estudios Retrospectivos , Masculino , Adulto , Adulto Joven , Adolescente , Osteotomía/métodos , Persona de Mediana Edad , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA