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Conventional dendritic cells (cDC) are central to maintaining the balance between protective immune responses and tolerance to harmless antigens, especially in the intestine. Short chain fatty acids (SCFAs) such as butyrate play critical roles in regulating intestinal immunity, but the underlying mechanisms remain unclear. Here we demonstrate that microbiota-derived butyrate alters intestinal cDC populations in vivo resulting in decreased numbers of the cDC2 lineage. By establishing a novel in vitro culture model, we show that butyrate has a direct and selective ability to repress the development of cDC2 from cDC precursors, an effect that is independent of G-protein coupled receptors (GPCRs) and is due to inhibition of histone deacetylase 3. Finally, cDC derived from pre-cDC in the presence of butyrate in vitro express lower levels of costimulatory molecules and have a decreased ability to prime naïve T cells. Together, our data show that butyrate affects the developmental trajectory of cDC, selectively repressing the cDC2 lineage and reducing their ability to stimulate T cells. These properties may help explain the ability of butyrate to maintain homeostasis in the intestine.
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Advocacy should be thought of as a permanent part of recognition efforts during Neurodiagnostic Week (April 16-22, 2023) for Neurodiagnostic professionals. It is the perfect opportunity to engage in advocacy and educate others on the importance of using well qualified Neurodiagnostic Technologists to perform neurodiagnostic procedures. Why is advocacy important? Because there is strength in numbers and constituent voices matter. If Neurodiagnostic Technologists do not advocate for the profession and educate decision makers, legislators, and the public about the importance of professional competency in Neurodiagnostics, no one else will. Advocacy works and is a critical part of moving the profession forward to ensure that lawmakers and policy understand that those performing the procedures should be the best qualified professionals to do so.
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Fibrosing mediastinitis (FM) is a rare disorder of inflammation and fibrosis involving the mediastinum. The formation of fibroinflammatory mass in the mediastinum can lead to obstruction of mediastinal structures and cause severe debilitating and life-threatening symptoms. Superior vena cava syndrome (SVCS) is a dreaded complication of FM with no medical therapy proven to be efficacious. Spiral vein grafting has long been utilized as first-line therapy for SVC syndrome due to FM. Endovascular repair with stents and angioplasty for malignant causes of SVC syndrome is well established. However, there are limited data on their utility in SVC syndrome due to FM. We present two cases of SVC syndrome due to FM treated with endovascular stenting and a detailed review of current literature on its utility in SVCS due to benign causes.
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Angioplastia de Balón/instrumentación , Mediastinitis/complicaciones , Esclerosis/complicaciones , Stents , Síndrome de la Vena Cava Superior/terapia , Vena Cava Superior/fisiopatología , Adulto , Angioplastia de Balón/efectos adversos , Femenino , Hemodinámica , Humanos , Masculino , Mediastinitis/diagnóstico , Persona de Mediana Edad , Esclerosis/diagnóstico , Síndrome de la Vena Cava Superior/diagnóstico por imagen , Síndrome de la Vena Cava Superior/etiología , Síndrome de la Vena Cava Superior/fisiopatología , Resultado del Tratamiento , Vena Cava Superior/diagnóstico por imagenRESUMEN
The recognition of inferior vena cava filter related complications has motivated increased attentiveness in clinical follow-up of patients with inferior vena cava filters and has led to development of multiple approaches for retrieving filters that are challenging or impossible to remove using conventional techniques. Endobronchial forceps and excimer lasers are tools for designed to aid in complex inferior vena cava filter removals. This article discusses endobronchial forceps-assisted and excimer laser-assisted inferior vena cava filter retrievals.
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Remoción de Dispositivos/instrumentación , Láseres de Excímeros/uso terapéutico , Implantación de Prótesis/instrumentación , Instrumentos Quirúrgicos , Filtros de Vena Cava , Vena Cava Inferior , Angiografía por Tomografía Computarizada , Remoción de Dispositivos/métodos , Diseño de Equipo , Humanos , Flebografía/métodos , Radiografía Intervencional , Resultado del Tratamiento , Vena Cava Inferior/diagnóstico por imagenRESUMEN
Inferior vena cava filters have been placed in patients for decades for protection against pulmonary embolism. The widespread use of filters has dramatically increased owing at least in part to the approval of retrievable vena cava filters. Retrievable filters have the potential to protect against pulmonary embolism and then be retrieved once no longer needed to avoid potential long-term complications. There are several retrievable vena cava filters available for use. This article discusses the different filter designs as well as the published data on these available filters. When selecting a filter for use, it is important to consider the potential short-term complications and the filters' window for retrieval. Understanding potential long-term complications is also critical, as these devices are approved for permanent placement and many filters are not retrieved. Finally, this article will address research into new designs that may be the future of vena cava filtration.
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Ruptured aortic aneurysms uniformly require emergent attention. Historically, urgent surgical repair or medical management was the only treatment options. The development of covered stent grafts has introduced a third approach in the care of these critical patients. The clinical status of the patient and local physician expertise drive the treatment modalities in the majority of cases. The goal of therapy in these patients is to stabilize the patient as quickly as possible, establish maximum survival with minimum morbidity, and provide a long lasting result. The endovascular approach has become an acceptable treatment option in an increasing number of patients presenting with ruptured aneurysmal disease of both the descending thoracic and abdominal aorta. Major factors influencing treatment include patient clinical status, characteristics of the aorta, physician preference, institutional experience, and availability of appropriate equipment. Planning, experience, and the ability to improvise effective solutions are keys to the success of the procedure when endovascular techniques are utilized. Three separate cases, requiring intraprocedural improvisation, are presented followed by a review of the literature.
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OPINION STATEMENT: Filter technology seems relatively stable, although absorbable devices are an area of investigational interest. The indications for filter placement remain controversial, with wide variations in adherence to guidelines, and relatively poor quality of data about the specific prophylactic indications of trauma or bariatric surgery. The outcomes of filters are not well-defined despite widespread clinical use, and good data remains difficult to obtain. Several larger database and institutional retrospective studies support the notions that while filters prevent pulmonary embolism, they may be associated with venous thrombotic complications. Some subsets of cancer patients may be at increased risk of these complications, but whether the filter or the underlying hypercoagulable state is the cause is not clear. Lastly, although the benefits of filter retrieval are widely assumed (but not proven), filter retrieval rates remain lower than expected. The single most influential factor in improving filter retrieval rates is dedicated follow-up with intent to retrieve the filter.
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BACKGROUND: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro-ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury. OBJECTIVES: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents. METHODS: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis. RESULTS: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation. CONCLUSIONS: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting.
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Reestenosis Coronaria/metabolismo , Stents Liberadores de Fármacos , MicroARNs/metabolismo , Remodelación Vascular , Lesiones del Sistema Vascular/metabolismo , Animales , Reestenosis Coronaria/prevención & control , Inflamación/metabolismo , Masculino , Ratones Noqueados , PorcinosRESUMEN
Speech patterns are modulated by the emotional and neurophysiological state of the speaker. There exists a growing body of work that computationally examines this modulation in patients suffering from depression, autism, and post-traumatic stress disorder. However, the majority of the work in this area focuses on the analysis of structured speech collected in controlled environments. Here we expand on the existing literature by examining bipolar disorder (BP). BP is characterized by mood transitions, varying from a healthy euthymic state to states characterized by mania or depression. The speech patterns associated with these mood states provide a unique opportunity to study the modulations characteristic of mood variation. We describe methodology to collect unstructured speech continuously and unobtrusively via the recording of day-to-day cellular phone conversations. Our pilot investigation suggests that manic and depressive mood states can be recognized from this speech data, providing new insight into the feasibility of unobtrusive, unstructured, and continuous speech-based wellness monitoring for individuals with BP.
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A 20-year-old woman presented to the emergency department for evaluation of a wound to left hand (Fig. 1). She admitted having a history of chronic severe headaches requiring daily use of analgesics. She first noted the ulcer approximately 10 months prior to presentation. Her examination was remarkable for a 10-cm by 8-cm ulceration to the dorsum of her left hand with exposed and necrotic metacarpals. Fibrous exudate was present in the wound-bed, and the ulcer was associated with a foul odor. She was afebrile on presentation with a peripheral white blood cell count of 6.4 x109/L, CRP 1.9 mg/dL, and ESR 15 mm/h.
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Analgésicos Opioides/envenenamiento , Pentazocina/envenenamiento , Úlcera Cutánea/inducido químicamente , Trastornos Relacionados con Sustancias , Amputación Quirúrgica , Analgésicos Opioides/administración & dosificación , Enfermedad Crónica , Sobredosis de Droga , Femenino , Mano/patología , Mano/cirugía , Humanos , Inyecciones Intravenosas , Necrosis/inducido químicamente , Necrosis/patología , Osteomielitis/inducido químicamente , Osteomielitis/patología , Osteomielitis/terapia , Pentazocina/administración & dosificación , Úlcera Cutánea/patología , Úlcera Cutánea/terapia , Adulto JovenRESUMEN
OBJECTIVE: Cells of the monocytic lineage play fundamental roles in the regulation of health, ranging from the initiation and resolution of inflammation to bone homeostasis. In rheumatoid arthritis (RA), the inflamed synovium exhibits characteristic infiltration of macrophages along with local osteoclast maturation, which, together, drive chronic inflammation and downstream articular destruction. The aim of this study was to explore an entirely novel route of immunoglobulin-mediated regulation, involving simultaneous suppression of the inflammatory and erosive processes in the synovium. METHODS: Using in vivo and in vitro studies of human cells and a murine model of RA, the ability of staphylococcal protein A (SPA) to interact with and modulate cells of the monocytic lineage was tested. In addition, the efficacy of SPA as a therapeutic agent was evaluated in murine collagen-induced arthritis (CIA). RESULTS: SPA showed a capacity to appropriate circulating IgG, by generating small immunoglobulin complexes that interacted with monocytes, macrophages, and preosteoclasts. Formation of these complexes resulted in Fcγ receptor type I-dependent polarization of macrophages to a regulatory phenotype, rendering them unresponsive to activators such as interferon-γ. The antiinflammatory complexes also had the capacity to directly inhibit differentiation of preosteoclasts into osteoclasts in humans. Moreover, administration of SPA in the early stages of disease substantially alleviated the clinical and histologic erosive features of CIA in mice. CONCLUSION: These findings demonstrate the overarching utility of immunoglobulin complexes for the prevention and treatment of inflammatory diseases. The results shed light on the interface between immunoglobulin complex-mediated pathways, osteoclastogenesis, and associated pathologic processes. Thus, therapeutic agents designed to harness all of these properties may be an effective treatment for arthritis, by targeting both the innate inflammatory response and prodestructive pathways.
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Complejo Antígeno-Anticuerpo/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Diferenciación Celular/fisiología , Inmunoglobulinas/uso terapéutico , Inflamación/tratamiento farmacológico , Osteoclastos/fisiología , Proteína Estafilocócica A/uso terapéutico , Células Madre/fisiología , Animales , Complejo Antígeno-Anticuerpo/farmacología , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Artritis Experimental/inmunología , Artritis Experimental/fisiopatología , Proliferación Celular , Células Cultivadas , Citocinas/fisiología , Modelos Animales de Enfermedad , Humanos , Inmunoglobulinas/fisiología , Inflamación/fisiopatología , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/fisiología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Noqueados , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Receptores de IgG/genética , Receptores de IgG/fisiología , Proteína Estafilocócica A/farmacología , Células Madre/citología , Células Madre/efectos de los fármacosRESUMEN
Minimal hepatic encephalopathy (MHE) is a neurocognitive disorder that affects up to 80% of cirrhotic patients. Similar to overt hepatic encephalopathy, ammonia and oxidative stress play key roles in the pathogenesis of MHE. However, MHE is characterized by subtle deficits and psychomotor abnormalities that can only be elicited by specialized psychometric tests. Although no gold standard exists for the diagnosis, MHE remains an important entity for clinicians to recognize because of its negative impact on a patient's health-related quality of life and association with driving impairment and vehicle accidents. MHE has also been associated with an increased rate in the development of overt hepatic encephalopathy and increased mortality; therefore, identification and treatment should not be delayed. Treatment to date has been focused on reducing serum ammonia levels with agents such as lactulose, probiotics, and synbiotics. MHE is a real and growing problem that is epidemic in cirrhosis, and increasing awareness of this condition is necessary for adequate management of these patients.
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Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/epidemiología , Encefalopatía Hepática/etiología , Humanos , Cirrosis Hepática/fisiopatología , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Pruebas Neuropsicológicas , Calidad de VidaRESUMEN
Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence® herbal tonic is a complex mixture of eight herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. In this study four experimental groups of female MMTV-Neu mice were left untreated or treated with 3% Flor-Essence® in utero, from birth until 5 weeks of age, or throughout their lifetime. Palpable mammary tumor incidence and body weight was determined weekly for each group. The mice were sacrificed at 28 weeks of age and mammary tumors were enumerated to determine average tumor incidence and multiplicity for each group. Female mice exposed to Flor-Essence® herbal tonic in utero weighed significantly more than the control group (p < 0.001). The average tumor incidence and tumor multiplicity in the experimental mice treated with Flor-Essence® herbal tonic did not differ from the control animals. Flor-Essence® does not inhibit mammary tumor incidence or mammary tumor multiplicity in MMTV-Neu transgenic mice. Flor-Essence® exposure in utero causes increased body weight in experimental animals. This conclusion challenges widely available anecdotal information as well as the hopes of the consumer that this product will inhibit or suppress tumor development.
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Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias Mamarias Experimentales/prevención & control , Extractos Vegetales/uso terapéutico , Receptores de Estrógenos/metabolismo , Animales , Antineoplásicos Fitogénicos/farmacología , Peso Corporal/efectos de los fármacos , Femenino , Incidencia , Estimación de Kaplan-Meier , Masculino , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Transgénicos , Extractos Vegetales/farmacología , Receptor ErbB-2/metabolismoRESUMEN
OBJECTIVES: Anemia is a well-recognized factor for local recurrence and decreased survival in cancer patients undergoing radiotherapy. Additionally, lower hemoglobin (Hb) levels have a negative impact on radiotherapy efficacy and response rates. The objective of this audit was to investigate how frequently Hb levels were observed in head and neck cancer patients receiving radiotherapy within a multidisciplinary team setting. METHODS: We performed a retrospective first-cycle audit in a university hospital in Glasgow that is a tertiary referral center for head and neck cancer. Included were 78 patients with head and neck cancer who were undergoing radiotherapy. Online laboratory services and clinical case sheets were checked for each patient to monitor the frequency of observation of Hb levels before, during, and after radiotherapy. RESULTS: Of these 78 patients, only 49 had their Hb level checked before radiotherapy treatment, only 9 during radiotherapy, and only 27 after completion of radiotherapy treatment (p < 0.0001). Of the 49 patients with preradiotherapy Hb levels available, 24% were found to be anemic; none of these patients had their Hb monitored during radiotherapy, and only 4 had Hb levels recorded after completion of treatment. CONCLUSIONS: This audit has highlighted that despite evidence emphasizing that anemia in cancer is an independent prognostic factor for recurrence, there is no formal protocol for Hb monitoring in head and neck cancer patients undergoing radiotherapy. The audit has also demonstrated that Hb monitoring is infrequently performed and that subsequent observation of the Hb level is suboptimal.
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Neoplasias de Cabeza y Cuello/sangre , Hemoglobinas/análisis , Anciano , Anemia/etiología , Anemia/fisiopatología , Femenino , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/fisiopatología , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Monitoreo FisiológicoRESUMEN
BACKGROUND: To establish whether a treatment regimen of silver nitrate cautery and 4 weeks of antiseptic nasal cream is superior to antiseptic cream treatment alone in the management of pediatric epistaxis. STUDY DESIGN: Double-blind randomized controlled trial. SUBJECTS AND METHODS: Children with epistaxis and visible anterior septal vessels were invited to participate. Patients were randomized to receive treatment or control. Treatment patients received silver nitrate cautery, followed by antiseptic cream for 4 weeks. Control patients received sham cautery followed by antiseptic cream for 4 weeks. RESULTS: A total of 109 patients were randomized and results were available for 93 (85%). Of those receiving cautery, 21 (45.7%) of 46 had no bleeding in the 4 weeks before follow-up. Of those receiving only antiseptic cream 14 (29.8%) of 47 had no bleeding. (chi(2) = 2.49; P = 0.114). More children in the active treatment group had an improvement in their symptoms compared with controls (42 of 46; 91.3%) in the treatment group vs 33 of 47 (70.2%) controls (chi(2) = 6.626; P = 0.01; relative risk reduction = 71 percent, number needed to treat = 4.7). CONCLUSION: When using subjective improvement in symptoms as the outcome measure, silver nitrate cautery with antiseptic cream twice daily for 4 weeks appears to give a small but statistically significant benefit when compared to antiseptic cream alone.
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Cauterización/métodos , Clorhexidina/uso terapéutico , Epistaxis/terapia , Neomicina/uso terapéutico , Nitrato de Plata/uso terapéutico , Administración Intranasal , Administración Tópica , Adolescente , Distribución de Chi-Cuadrado , Niño , Preescolar , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Lactante , Masculino , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited. METHODS: We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB)-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA). RESULTS: We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA)-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition. CONCLUSION: While ETRB antagonists reduce the viability of glioma cells in vitro, it appears unlikely that this effect is mediated by ETRB inhibition or cross-reaction with ETRA. Instead, we present evidence that A-192621 affects glioma and melanoma viability by activating stress/DNA damage response pathways, which leads to cell cycle arrest and apoptosis. This is the first evidence linking ETRB antagonist treatment to enhanced expression of DNA damage-inducible genes.