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2.
JAMA Intern Med ; 184(8): 973-974, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38829668

RESUMEN

This clinical insights article examines reasons behind the increase in tick-borne diseases and what clinicians should know about diagnosis and mitigation.


Asunto(s)
Enfermedades por Picaduras de Garrapatas , Humanos , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/prevención & control , Animales , Garrapatas , Factores de Riesgo
3.
Int J Pediatr Otorhinolaryngol ; 179: 111922, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38574651

RESUMEN

BACKGROUND: Neonatal unilateral vocal fold paralysis may arise iatrogenically, idiopathically, or in the context of an underlying neurologic disorder. Management is often supportive, focusing on diet modification to allow for safe oral feeding. We describe the clinical course of six infants with unilateral vocal fold paralysis who developed predominantly unilateral laryngomalacia ipsilateral to the affected vocal fold with associated severe respiratory symptoms and feeding difficulty. METHODS: Retrospective review of six infants with unilateral vocal fold paralysis and predominantly unilateral laryngomalacia. Charts were reviewed for etiology of vocal fold paralysis, presenting symptoms, operative details, postoperative course, and outcomes for breathing and swallowing. RESULTS: Etiology of vocal fold paralysis included cardiac surgery in four patients, intubation-related in one, and idiopathic in one. Presenting symptoms included increased work of breathing, stridor, feeding difficulty, respiratory failure requiring noninvasive respiratory support, and weak cry. All infants were on nasogastric tube feedings. Direct microlaryngoscopy with unilateral or predominantly unilateral (conservative contralateral aryepiglottic fold division) supraglottoplasty was performed. Stridor and work of breathing improved in all six patients within 1 week postoperatively. Oral feeding improved in three patients within 2 weeks. Three patients had persistent feeding impairment with improvement within one year. CONCLUSIONS: Predominantly unilateral laryngomalacia may arise in the context of unilateral vocal fold paralysis. Addressing the ipsilateral cuneiform collapse can improve breathing and feeding. This may be an under-described phenomenon and represents an additional reason to include the otolaryngologist early in the care of infants with suspected possible new unilateral vocal fold paralysis. Breathing and swallow can improve post-operatively, but feeding may remain limited by the vocal fold paralysis and any medical comorbidities. Ongoing follow-up and collaboration with speech-language pathology to optimize feeding are important.


Asunto(s)
Laringomalacia , Parálisis de los Pliegues Vocales , Lactante , Recién Nacido , Humanos , Pliegues Vocales , Laringomalacia/complicaciones , Laringomalacia/diagnóstico , Laringomalacia/cirugía , Ruidos Respiratorios/etiología , Parálisis de los Pliegues Vocales/complicaciones , Parálisis de los Pliegues Vocales/diagnóstico , Deglución , Estudios Retrospectivos
4.
J Voice ; 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38538409

RESUMEN

Vocal tics can occur in neuropsychiatric disorders and result in familial distress. Management is challenging, particularly in children with developmental delay. A 5-year-old with cerebral dysgenesis presented with a high amplitude, high-frequency vocal tic. Type II thyroplasty with bilateral cricothyroid muscle myectomy was performed after initial botulinum toxin trial. Amount, volume, and pitch of tics significantly decreased, without change in swallow. Benefits persisted at 1-year follow-up. This is the first description of combined type II thyroplasty with cricothyroid myectomy for high-frequency vocal tic. This can be done safely and provide sustained benefit for a rare, impactful voice disorder.

5.
Plast Reconstr Surg ; 154(3): 473-483, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38412359

RESUMEN

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL. METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants were included for analysis. Meta-analyses were performed and reviewed by experts selected by the American Association of Plastic Surgeons using a Delphi consensus method. RESULTS: A total of 840 articles published between January of 2011 and January of 2023 were initially identified and screened. The full text of 188 articles was assessed. An additional 43 articles were excluded for focus, and 145 articles were included in the synthesis of results, with 105 of them being case reports or case series. The analysis encompassed a comprehensive examination of the selected articles to determine the incidence, risk factors, clinical presentation, diagnostic approaches, and treatment modalities related to BIA-ALCL. CONCLUSIONS: Plastic surgeons should be aware of the elevated risks by implant surface type, implement appropriate patient surveillance, and follow the recommendations outlined in this statement to ensure patient safety and optimize outcomes. Ongoing research on the pathogenesis, genetic drivers, and preventative and prophylactic measures for BIA-ALCL is crucial for improving patient care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Linfoma Anaplásico de Células Grandes , Humanos , Linfoma Anaplásico de Células Grandes/etiología , Linfoma Anaplásico de Células Grandes/epidemiología , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/prevención & control , Linfoma Anaplásico de Células Grandes/terapia , Implantes de Mama/efectos adversos , Femenino , Neoplasias de la Mama/etiología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/diagnóstico , Implantación de Mama/efectos adversos , Consenso , Estados Unidos/epidemiología , Sociedades Médicas/normas , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control
6.
Laryngoscope ; 134(7): 3187-3192, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38279973

RESUMEN

OBJECTIVES: Nonselective laryngeal reinnervation is an effective procedure to improve voice quality after unilateral vocal fold paralysis. Few studies have captured long-term outcome data, and the revision rate for this operation is currently unknown. The objective of this study is to describe the long-term outcomes and revision rates of unilateral, nonselective reinnervation in pediatric and adult patients. METHODS: Patients who underwent laryngeal reinnervation from 2000 to 2022 with a single surgeon were identified for inclusion. Patients who underwent bilateral, super selective, deinnervation and reinnervation, and/or concurrent arytenoid adduction procedures were excluded. Outcome measures included maximum phonation time [MPT], voice handicap index score [VHI], patient-reported percent normal voice, revision procedures, and complications. Data were compiled and analyzed using paired t-tests, repeated measures analysis of covariance, and binary logistic regression analysis. RESULTS: One hundred thirty-two patients underwent unilateral, nonselective ansa-recurrent laryngeal nerve [RLN] laryngeal reinnervation. Reinnervation significantly improved MPT and patient-reported percentage of normal voice and significantly decreased VHI. Eleven patients underwent revision procedures, corresponding to a revision rate of 8.3%. Additional procedures included medialization laryngoplasty [n = 3], medialization laryngoplasty with arytenoid adduction [n = 3] and injection augmentation greater than 1 year after reinnervation [n = 5]. The only factor associated with the need for additional surgery was time lapse from nerve injury to reinnervation. The overall complication rate was 6.8%; no patient required reintubation or tracheostomy. CONCLUSION: Unilateral, nonselective laryngeal reinnervation can provide reliable improvement in vocal symptoms after recurrent laryngeal nerve injury. The revision rate after laryngeal reinnervation is favorable and comparable to framework surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3187-3192, 2024.


Asunto(s)
Nervio Laríngeo Recurrente , Reoperación , Parálisis de los Pliegues Vocales , Calidad de la Voz , Humanos , Parálisis de los Pliegues Vocales/cirugía , Parálisis de los Pliegues Vocales/etiología , Masculino , Femenino , Adulto , Reoperación/estadística & datos numéricos , Persona de Mediana Edad , Resultado del Tratamiento , Nervio Laríngeo Recurrente/cirugía , Niño , Adolescente , Adulto Joven , Estudios Retrospectivos , Anciano , Traumatismos del Nervio Laríngeo Recurrente/cirugía , Laringoplastia/métodos , Fonación/fisiología , Preescolar
8.
Ticks Tick Borne Dis ; 15(2): 102301, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38134511

RESUMEN

A bite from an infected tick is the primary means of transmission for tick-borne flaviviruses (TBFV). Ticks ingest the virus while feeding on infected blood. The traditional view is that the virus first replicates in and transits the tick midgut prior to dissemination to other organs, including salivary glands. Thus, understanding TBFV infection in the tick midgut is a key first step in identifying potential countermeasures against infection. Ex vivo midgut cultures prepared from unfed adult female Ixodes scapularis ticks were viable and remained morphologically intact for more than 8 days. The midgut consisted of two clearly defined cell layers separated by a basement membrane: an exterior network of smooth muscle cells and an internal epithelium composed of digestive generative cells. The smooth muscle cells were arranged in a stellate circumferential pattern spaced at regular intervals along the long axis of midgut diverticula. When the cultures were infected with the TBFV Langat virus (LGTV), virus production increased by two logs with a peak at 96 hours post-infection. Infected cells were readily identified by immunofluorescence staining for the viral envelope protein, nonstructural protein 3 (NS3) and dsRNA. Microscopy of the stained cultures suggested that generative cells were the primary target for virus infection in the midgut. Infected cells exhibited an expansion of membranes derived from the endoplasmic reticulum; a finding consistent with TBFV infected cell cultures. Electron microscopy of infected cultures revealed virus particles in the basolateral region between epithelial cells. These results demonstrated LGTV replication in midgut generative cells of artificially infected, ex vivo cultures of unfed adult female I. scapularis ticks.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas , Flavivirus , Ixodes , Femenino , Animales , Flavivirus/genética , Virus de la Encefalitis Transmitidos por Garrapatas/genética , Glándulas Salivales , Microscopía Electrónica , ARN Bicatenario
9.
Support Care Cancer ; 32(1): 6, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38051438

RESUMEN

PURPOSE: In response to a demonstrable need for 24/7, specialist oncology advice for patients undergoing systemic anti-cancer therapy, many healthcare institutions have adopted a telephone triage (TT) service. This is true of the Clatterbridge Cancer Centre which uses the UKONS framework to guide its decisions. This study aims to investigate the utilisation and outcomes of this TT service, with a focus on the most unwell call outcomes and factors leading to referrals to accident and emergency departments that could be mitigated with service development and modifications. METHODS: A retrospective evaluation study was conducted of calls occurring between 1st September 2021 and 31st August 2022. A descriptive analysis of call UKONS grading, triage outcome and primary complaint was performed. RESULTS: The TT hotline received 23,766 calls of which only 9066 were for clinical advice. Of the clinical calls, 45.2% were UKONS red. The majority of red calls 53.3% were directed to AED. The proportion of red calls going to AED changed drastically depending on the timing of call and the corresponding services available at those times, with 38.3% of reds being sent to AED in hours but 72.3% out of hours. The profile of complaints also showed significant differences in hours versus out of hours. CONCLUSION: Significant use of the hotline supports a genuine demand for oncology TT services. In order to reduce referrals to AED, this study supports the creation of alternative destinations of emergency care, especially out of hours.


Asunto(s)
Servicios Médicos de Urgencia , Triaje , Humanos , Líneas Directas , Estudios Retrospectivos , Servicio de Urgencia en Hospital , Teléfono
10.
Cancers (Basel) ; 15(21)2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37958303

RESUMEN

INTRODUCTION: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists' interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. METHODS: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. RESULTS: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250-500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels > 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. CONCLUSIONS: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (<20 min) and can be performed without special equipment by non-specialized personnel, suggesting future point-of-care testing for BIA-ALCL may be feasible.

11.
J Clin Invest ; 134(3)2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38032740

RESUMEN

This study investigates a mechanistic link of bacterial biofilm-mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.


Asunto(s)
Implantes de Mama , Humanos , Femenino , Ratones , Animales , Implantes de Mama/efectos adversos , Implantes de Mama/microbiología , Oxilipinas , Biopelículas , Inmunidad
12.
Am J Hematol ; 98(11): E312-E314, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37646570

RESUMEN

More than 1300 women with breast implants have developed an anaplastic large cell lymphoma (ALCL) in fluid (seroma) around their implant. More often, seromas are due to benign causes, for example, capsule contracture, leakage, or trauma. Our report in American Journal of Hematology identified several cytokines (IL-9, IL-10, IL-13) as significantly elevated only in seromas due to ALCL. We further showed that the most robust biomarker, IL-10, could be detected by a lateral flow assay (similar to COVID detection) within minutes allowing physicians to quickly plan management, eliminate or reduce costly testing and patient time away from family. Early detection of ALCL in seromas before infiltration may avoid need for cytotoxic or immunotherapy and is possibly life-saving.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , COVID-19 , Linfoma Anaplásico de Células Grandes , Femenino , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/etiología , Linfoma Anaplásico de Células Grandes/patología , Implantes de Mama/efectos adversos , Interleucina-10 , Seroma/diagnóstico , Seroma/etiología , Seroma/patología , Citocinas , COVID-19/complicaciones , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/complicaciones , Prueba de COVID-19
13.
BMC Health Serv Res ; 23(1): 867, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37582788

RESUMEN

BACKGROUND: Language discordance occurs in healthcare when staff and service users do not share proficiency in the same language. It is a global phenomenon impacting on the quality of health services, as person-centred practice requires communication to establish partnerships and rapport. In a country as linguistically diverse as South Africa, effective ways to navigate language discordance in health care are urgently required, yet there is limited research. This study aimed to describe how occupational therapists navigated language discordance when working in the public health sector in KwaZulu-Natal. METHODS: A qualitative descriptive design involved using purposive sampling to recruit occupational therapists as participants (n = 8) for 15 semi-structured interviews. Thematic analysis was used to analyse the data, which included reflective journal entries from all participants. RESULTS: The four emergent themes were: (1) concurrent use of strategies, (2) I'm doing as much I can, what more can I do? (3) Language definitely impacts that therapy process and lastly, (4) systemic oppression perpetuating language discordance. CONCLUSION: Language discordance is a complex context-specific phenomenon, therefore insight into concurrent use of strategies is important to practitioners to enable them to navigate language discordance and ensure provision of quality services. These insights are significant for healthcare professionals and resource allocators as they shed light on the shortcomings of advocating for a single strategy such as providing trained interpreters. Successful navigation is characterised by determination, being kind to oneself, willingness to learn and use of pragmatic and flexible approaches. To prepare to navigate language discordance in a low-resource context, education should extend in time and scope, to include multiple strategies, culture and relevant languages.


Asunto(s)
Terapeutas Ocupacionales , Salud Pública , Humanos , Sudáfrica , Lenguaje , Comunicación , Investigación Cualitativa
14.
J Hosp Infect ; 139: 1-5, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37343770

RESUMEN

BACKGROUND: Having a false penicillin-allergy label is linked to longer hospital stays and to an increased risk of Clostridioides difficile and meticillin-resistant Staphylococcus aureus infection. AIM: To assess a penicillin-allergy de-labelling tool designed for use by the non-allergist. METHODS: Patients attending the surgical preoperative assessment clinic (POAC) at a large UK teaching hospital, who reported a penicillin allergy, were directly de-labelled by nursing or pharmacy staff, where appropriate. A penicillin-allergy de-labelling tool designed for use by the non-allergist was adapted and applied; nursing staff were provided with supporting information and education to enable removal of spurious labels. Antimicrobial pharmacists (AMPs) provided follow-up, cross-checked prophylactic antibiotics administered, interrogated clinical notes, and telephoned patients following their surgery, for details of any adverse reactions suffered. FINDINGS: A total of 163 patients reporting a penicillin allergy were identified for intervention. Twenty-nine (17.8%) patients reported a penicillin-allergy history appropriate for direct de-labelling, of whom eight (27.6%) declined to consent. The remaining 21 patients (12.8%) were directly de-labelled, with 12 (7.4%) patients consenting during their POAC appointment; the remaining nine (5.5%) patients were consented and de-labelled after their surgery by an AMP. CONCLUSION: The POAC was identified as an appropriate location and time-point in the patient pathway to enable the direct removal of spurious penicillin-allergy labels prior to surgery. Results suggest that this could be undertaken by nursing staff, although support from AMPs enabled a greater number of patients to be de-labelled.


Asunto(s)
Hipersensibilidad a las Drogas , Hipersensibilidad , Staphylococcus aureus Resistente a Meticilina , Humanos , Antibacterianos/efectos adversos , Farmacéuticos , Penicilinas/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/prevención & control , Hospitales de Enseñanza
15.
Blood ; 142(15): 1297-1311, 2023 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-37339580

RESUMEN

Anaplastic large cell lymphoma (ALCL), a subgroup of mature T-cell neoplasms with an aggressive clinical course, is characterized by elevated expression of CD30 and anaplastic cytology. To achieve a comprehensive understanding of the molecular characteristics of ALCL pathology and to identify therapeutic vulnerabilities, we applied genome-wide CRISPR library screenings to both anaplastic lymphoma kinase positive (ALK+) and primary cutaneous (pC) ALK- ALCLs and identified an unexpected role of the interleukin-1R (IL-1R) inflammatory pathway in supporting the viability of pC ALK- ALCL. Importantly, this pathway is activated by IL-1α in an autocrine manner, which is essential for the induction and maintenance of protumorigenic inflammatory responses in pC-ALCL cell lines and primary cases. Hyperactivation of the IL-1R pathway is promoted by the A20 loss-of-function mutation in the pC-ALCL lines we analyze and is regulated by the nonproteolytic protein ubiquitination network. Furthermore, the IL-1R pathway promotes JAK-STAT3 signaling activation in ALCLs lacking STAT3 gain-of-function mutation or ALK translocation and enhances the sensitivity of JAK inhibitors in these tumors in vitro and in vivo. Finally, the JAK2/IRAK1 dual inhibitor, pacritinib, exhibited strong activities against pC ALK- ALCL, where the IL-1R pathway is hyperactivated in the cell line and xenograft mouse model. Thus, our studies revealed critical insights into the essential roles of the IL-1R pathway in pC-ALCL and provided opportunities for developing novel therapeutic strategies.


Asunto(s)
Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutáneo Primario de Células Grandes , Neoplasias Cutáneas , Humanos , Animales , Ratones , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patología , Proteínas Tirosina Quinasas Receptoras/genética , Quinasa de Linfoma Anaplásico/genética , Interleucinas/metabolismo
16.
Sci Rep ; 13(1): 4687, 2023 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-36949107

RESUMEN

Rocky Mountain spotted fever (RMSF) is a rapidly progressive and often fatal tick-borne disease caused by Rickettsia rickettsii. Its discovery and characterization by Howard Ricketts has been hailed as a remarkable historical example of detection and control of an emerging infectious disease, and subsequently led to the establishment of the Rocky Mountain Laboratories (RML). Here, we examined an unopened bottle of a vaccine, labeled as containing RMSF inactivated by phenol-formalin of infected ticks, developed prior to 1944 at RML by DNA analysis using Illumina high throughput sequencing technology. We found that it contains DNA from the Rocky Mountain wood tick (Dermacentor andersoni), the vector of RMSF, the complete genome of Rickettsia rickettsii, the pathogen of RMSF, as well as the complete genome of Coxiella burnetii, the pathogen of Q-fever. In addition to genomic reads of Rickettsia rickettsii and Coxiella burnetii, smaller percentages of the reads are from Rickettsia rhipicephali and Arsenophonus nasoniae, suggesting that the infected ticks used to prepare the vaccine carried more than one pathogen. Together, these findings suggest that this early vaccine was likely a bivalent vaccine for RMSF and Q-fever. This study is the among the first molecular level examinations of an historically important vaccine.


Asunto(s)
Coxiella burnetii , Fiebre Maculosa de las Montañas Rocosas , Garrapatas , Vacunas , Animales , Fiebre Maculosa de las Montañas Rocosas/prevención & control , Fiebre Maculosa de las Montañas Rocosas/microbiología , Rickettsia rickettsii/genética , Garrapatas/microbiología
17.
mBio ; 14(2): e0360622, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-36809119

RESUMEN

Powassan infection is caused by two closely related, tick-transmitted viruses of the genus Flavivirus (family Flaviviridae): Powassan virus lineage I (POWV) and lineage II (known as deer tick virus [DTV]). Infection is typically asymptomatic or mild but can progress to neuroinvasive disease. Approximately 10% of neuroinvasive cases are fatal, and half of the survivors experience long-term neurological sequelae. Understanding how these viruses cause long-term symptoms as well as the possible role of viral persistence is important for developing therapies. We intraperitoneally inoculated 6-week-old C57BL/6 mice (50% female) with 103 focus-forming units (FFU) DTV and assayed for infectious virus, viral RNA, and inflammation during acute infection and 21, 56, and 84 days postinfection (dpi). Although most mice (86%) were viremic 3 dpi, only 21% of the mice were symptomatic and 83% recovered. Infectious virus was detected only in the brains of mice sampled during the acute infection. Viral RNA was detected in the brain until 84 dpi, but the magnitude decreased over time. Meningitis and encephalitis were visible in acute mice and from mice sampled at 21 dpi. Inflammation was observed until 56 dpi in the brain and 84 dpi in the spinal cord, albeit at low levels. These results suggest that the long-term neurological symptoms associated with Powassan disease are likely caused by lingering viral RNA and chronic inflammation in the central nervous system rather than by a persistent, active viral infection. The C57BL/6 model of persistent Powassan mimics illness in humans and can be used to study the mechanisms of chronic disease. IMPORTANCE Half of Powassan infection survivors experience long-term, mild to severe neurological symptoms. The progression from acute to chronic Powassan disease is not well understood, severely limiting treatment and prevention options. Infection of C57BL/6 mice with DTV mimics clinical disease in humans, and the mice exhibit CNS inflammation and viral RNA persistence until at least 86 dpi, while infectious virus is undetectable after 12 dpi. These findings suggest that the long-term neurological symptoms of chronic Powassan disease are in part due the persistence of viral RNA and the corresponding long-term inflammation of the brain and spinal cord. Our work demonstrates that C57BL/6 mice can be used to study the pathogenesis of chronic Powassan disease.


Asunto(s)
Encefalitis Transmitida por Garrapatas , Humanos , Femenino , Animales , Ratones , Masculino , Ratones Endogámicos C57BL , Encéfalo/patología , Inflamación , ARN Viral
18.
Leukemia ; 37(2): 396-407, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36456744

RESUMEN

Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (HL) share a similar cytological and high surface expression of CD30, and novel therapeutic strategies are needed. The EP300 and CREBBP acetyltransferases play essential roles in the pathogenesis of non-Hodgkin B cell lymphoma, but their functions in ALCL and HL are unknown. In the current study, we investigated the physiological roles of EP300 and CREBBP in both ALCL and HL, and exploited the therapeutic potential of EP300/CREBBP small molecule inhibitors that target either the HAT or bromodomain activities. Our studies demonstrated distinct roles for EP300 and CREBBP in supporting the viability of ALCL and HL, which was bolstered by the transcriptome analyses. Specifically, EP300 but not CREBBP directly modulated the expression of oncogenic MYC/IRF4 network, surface receptor CD30, immunoregulatory cytokines IL10 and LTA, and immune checkpoint protein PD-L1. Importantly, EP300/CREBBP HAT inhibitor A-485 and bromodomain inhibitor CPI-637 exhibited strong activities against ALCL and HL in vitro and in xenograft mouse models, and inhibited PD-L1 mediated tumor immune escape. Thus, our studies revealed critical insights into the physiological roles of EP300/CREBBP in these lymphomas, and provided opportunities for developing novel strategies for both targeted and immune therapies.


Asunto(s)
Enfermedad de Hodgkin , Linfoma Anaplásico de Células Grandes , Linfoma , Humanos , Animales , Ratones , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/metabolismo , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/metabolismo , Antígeno B7-H1 , Acetiltransferasas , Proteína p300 Asociada a E1A/genética , Proteína de Unión a CREB/genética
19.
Psychol Health ; 38(12): 1623-1634, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35137665

RESUMEN

OBJECTIVES: The study aimed to determine whether perceived goal sharing (i.e., perceiving a partner as having the same health-related goal) and/or perceived goal congruence (i.e., being able to spend time together in health-related goal activities) with a romantic partner are associated with health-related goal commitment and importance. DESIGN AND MAIN OUTCOME MEASURES: 80 participants with a health-related goal in a larger study on newly dating relationships completed two self-report questionnaires 3 months apart using validated assessments of goal commitment and importance. RESULTS: Perceived goal congruence was associated with concurrent goal commitment and importance and higher goal commitment over time. However, perceived goal sharing was not associated with the health-related goal dimensions (even when interacting with goal congruence) with the exception of increased goal importance over time for those scoring lower than the average on relationship satisfaction. CONCLUSION: One way to enhance health-related goal importance and commitment is to ensure goal congruence exists within romantic relationships, and partners can spend time together engaging in goal-related activities with their partner. Moreover, the results suggest that romantic partners exert an influence even among the newly dating, who are often presumed to be less impactful on health outcomes and processes.

20.
Int J Pediatr Otorhinolaryngol ; 164: 111382, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36413933

RESUMEN

OBJECTIVE: To compare outcomes using an open surgical incision and drainage (S-ID) versus an aspiration under interventional radiology drainage (A-ID) of pediatric neck abscesses. The primary outcome measure was successful drainage requiring one intervention, and the secondary outcome measures were readmission rates and overall cost to the healthcare system. METHODS: Retrospective data collection of all pediatric patients treated at the Primary Children's Hospital for neck abscess from 2008 to 2020. Patients who did not require drainage were not included. Comparison between S-ID and A-ID was performed according to the primary and secondary outcomes. RESULTS: Two hundred fifty nine patients were included in the study. Twenty-six patients had A-IR and 234 patients had S-ID. Patient demographics were not significantly different between both groups. Overall length of stay was greater in the A-ID group (5 vs 3.3 days) (p < 0.05). A second procedure was more frequent in the A-ID group with 11/26 (42%) versus 12/234(5%) in the S-ID group (P = 0.001) even after controlling for multiple possible confounding factors. The rate of readmission was also higher in the A-ID group with 3/26 (11%) versus 7/234 (3%) in the S-ID group (P = 0.006). Both groups showed similar overall cost (P = 0.621). CONCLUSIONS: A-ID and S-ID are both methods to treat head and neck abscess requiring drainage. However, overall results indicate a higher rate of failure requiring a second intervention and a higher rate of readmission in the A-ID group. In our study cost was noted to be similar between both methods.


Asunto(s)
Absceso , Radiología Intervencionista , Humanos , Niño , Absceso/cirugía , Estudios Retrospectivos , Drenaje/métodos , Cuello
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