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1.
BMC Neurol ; 24(1): 102, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519935

RESUMO

BACKGROUND: Facial paralysis due to parotid sialolithiasis-induced parotitis is a unusual clinical phenomenon that has not been reported in prior literature. This scenario can present a diagnostic challenge due to its rarity and complex symptomatology, particularly if a patient has other potential contributing factors such as facial trauma or bilateral forehead botox injections as in this patient. This case report elucidates such a complex presentation, aiming to increase awareness and promote timely recognition among clinicians. CASE PRESENTATION: A 56-year-old male, with a medical history significant for hyperlipidemia, recurrent parotitis secondary to parotid sialolithiasis, and recent bilateral forehead cosmetic Botox injections presented to the emergency department with right lower facial drooping. This onset was about an hour after waking up and was of 4 h duration. The patient also had a history of a recent ground level fall four days prior that resulted in facial trauma to his right eyebrow without any evident neurological deficits in the region of the injury. A thorough neurological exam revealed sensory and motor deficits across the entirety of the right face, indicating a potential lesion affecting the buccal and marginal mandibular branches of the facial nerve (CN VII). Several differential diagnoses were considered for the lower motor neuron lesion, including soft tissue trauma or swelling from the recent fall, compression due to the known parotid stone, stroke, and complex migraines. An MRI of the brain was conducted to rule out a stroke, with no significant findings. A subsequent CT scan of the neck revealed an obstructed and dilated right Stensen's duct with a noticeably larger and anteriorly displaced sialolith and evidence of parotid gland inflammation. A final diagnosis of facial palsy due to parotitis secondary to sialolithiasis was made. The patient was discharged and later scheduled for a procedure to remove the sialolith which resolved his facial paralysis. CONCLUSIONS: This case emphasizes the need for a comprehensive approach to the differential diagnosis in presentations of facial palsy. It underscores the potential involvement of parotid sialolithiasis, particularly in patients with a history of recurrent parotitis or facial trauma. Prompt recognition of such uncommon presentations can prevent undue interventions, aid in timely appropriate management, and significantly contribute to the patient's recovery and prevention of long-term complications.


Assuntos
Paralisia de Bell , Toxinas Botulínicas Tipo A , Paralisia Facial , Parotidite , Cálculos das Glândulas Salivares , Acidente Vascular Cerebral , Masculino , Humanos , Pessoa de Meia-Idade , Glândula Parótida/diagnóstico por imagem , Cálculos das Glândulas Salivares/complicações , Parotidite/complicações , Parotidite/diagnóstico , Paralisia Facial/etiologia , Paralisia de Bell/complicações , Acidente Vascular Cerebral/complicações
2.
Exp Dermatol ; 31(11): 1748-1760, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36320153

RESUMO

Inflammaging is a theory of ageing which purports that low-level chronic inflammation leads to cellular dysfunction and premature ageing of surrounding tissue. Skin is susceptible to inflammaging because it is the first line of defence from the environment, particularly solar radiation. To better understand the impact of ageing and photoexposure on epidermal biology, we performed a system biology-based analysis of photoexposed face and arm, and photoprotected buttock sites, from women between the ages of 20s to 70s. Biopsies were analysed by histology, transcriptomics, and proteomics and skin surface biomarkers collected from tape strips. We identified morphological changes with age of epidermal thinning, rete ridge pathlength loss and stratum corneum thickening. The SASP biomarkers IL-8 and IL-1RA/IL1-α were consistently elevated in face across age and cis/trans-urocanic acid were elevated in arms and face with age. In older arms, the DNA damage response biomarker 53BP1 showed higher puncti numbers in basal layers and epigenetic ageing were accelerated. Genes associated with differentiation and senescence showed increasing expression in the 30s whereas genes associated with hypoxia and glycolysis increased in the 50's. Proteomics comparing 60's vs 20's confirmed elevated levels of differentiation and glycolytic-related proteins. Representative immunostaining for proteins of differentiation, senescence and oxygen sensing/hypoxia showed similar relationships. This system biology-based analysis provides a body of evidence that young photoexposed skin is undergoing inflammaging. We propose the presence of chronic inflammation in young skin contributes to an imbalance of epidermal homeostasis that leads to a prematurely aged appearance during later life.


Assuntos
Epiderme , Pele , Humanos , Feminino , Idoso , Adulto Jovem , Adulto , Pele/metabolismo , Homeostase , Inflamação/metabolismo , Hipóxia/metabolismo , Senescência Celular
3.
Nanotechnology ; 33(13)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34929677

RESUMO

Block copolymer (BCP) self-assembly processes are often seen as reliable techniques for advanced nanopatterning to achieve functional surfaces and create templates for nanofabrication. By taking advantage of the tunability in pitch, diameter and feature-to-feature separation of the self-assembled BCP features, complex, laterally organized- and stacked- multicomponent nanoarrays comprising of gold and polymer have been fabricated. The approaches not only demonstrate nanopatterning of up to two levels of hierarchy but also investigate how a variation in the feature-to-feature gap at the first hierarchy affects the self-assembly of polymer features at the second. Such BCP self-assembly enabled multicomponent nanoarray configurations are rarely achieved by other nanofabrication approaches and are particularly promising for pushing the boundaries of block copolymer lithography and in creating unique surface architectures and complex morphologies at the nanoscale.

4.
Catheter Cardiovasc Interv ; 97(1): 2-7, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31985132

RESUMO

BACKGROUND: Debulking and ablative techniques are sometimes used for the treatment of in-stent restenosis (ISR) secondary to resistant stent under-expansion (SU). The safety and effectiveness of orbital atherectomy (OA) in this cohort of patients has not been reported. METHODS: We retrospectively evaluated consecutive patients treated with OA for ISR secondary to balloon undilatable SU at two academic tertiary care centers between October 2016 and June 2019. Angiographic or intravascular imaging identified SU. Technical success was defined as residual 0% stenosis with TIMI III flow. RESULTS: A total of 41 patients were included in the study. Patients had an average age of 65 ± 12 years; 73% male, 61% diabetic, 41% with prior coronary artery bypass grafting, 61% with a prior incident of ISR, 51% presented with stable angina, 17% unstable angina, and 32% non-ST elevation myocardial infarction (MI). Implantation of the under-expanded stents occurred between 2 months and 22 years prior to the index procedure. A total of 27% of patients had multiple layers of stents in the target lesion and 32% of patients had in-stent chronic total occlusion. Technical success was achieved in 40 (98%) patients. There were 2 (5%) major adverse cardiovascular events; both of them were periprocedural MI from the no-reflow phenomenon. There were 2 (5%) Ellis type II coronary perforations that required no intervention. CONCLUSIONS: OA can be effectively performed as an adjunctive tool in the treatment of ISR with balloon undilatable SU. The use of OA for SU is not approved by the U.S. Food and Drug Administration and is "off label" and caution must be used to limit any device/stent interaction.


Assuntos
Aterectomia Coronária , Reestenose Coronária , Idoso , Aterectomia , Aterectomia Coronária/efeitos adversos , Constrição Patológica , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/terapia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Estudos Retrospectivos , Stents , Resultado do Tratamento
5.
Catheter Cardiovasc Interv ; 97(4): E580-E587, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32894804

RESUMO

OBJECTIVES: We sought to document aortic cusps fluoroscopic projections and their distributions using leaflet alignment which is a novel concept to optimize visualization of leaflets and for guiding BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent coronary artery obstruction) and determine whether these projections were feasible in catheter laboratory. BACKGROUND: Optimal fluoroscopic projections of aortic valve cusps have not been well described. METHODS: A total of 128 pre-transcatheter aortic valve replacement (pre-TAVR) computed tomographies (CT) (72 native valves and 56 bioprosthetic surgical valves) were analyzed. Using CT software (3Mensio, Pie medical imaging, the Netherlands), leaflet alignment was performed and the feasibility of these angles, which were defined as rate of obtainable with efforts (within LAO/RAO of 85° and CRA/CAU of 50°) were evaluated. RESULTS: High feasibility was seen in right coronary cusp (RCC) front view (100%) and left coronary cusp (LCC) side view (99.2%), followed by noncoronary cusp side view (95.3%). In contrast, low feasibility of RCC side view (7.8%) and LCC front view (47.6%) was observed. No statistical differences were seen between the distribution of native valves and bioprosthetic surgical valves. With patient/table tilt of 20°LAO and 10°CRA, the feasibility of RCC side view and LCC front view increased to 43.7 and 85.2%, respectively. CONCLUSION: Distributions of each cusp's leaflet alignment follows "sigmoid curve" which can provide better understanding of aortic valve cusp orientation in TAVR and BASILICA. RCC side view used in right cusp BASILICA is commonly unachievable in catheter laboratory and may improve with patient/table tilt.


Assuntos
Estenose da Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Humanos , Desenho de Prótese , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
6.
Br J Clin Pharmacol ; 87(2): 352-374, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32478963

RESUMO

AIMS: To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin. METHODS: A systematic literature review was performed on 5 databases from inception up to 31 December 2019. These interactions were classified depending on the likelihood of interaction and supporting evidences. RESULTS: A total of 149 articles describing 78 herbs, food or dietary supplements were reported to interact with warfarin. These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics. Twenty unique herb and dietary supplements also reported to result in minor bleeding events, such as purpura and gum bleeding as well as major events such as intracranial bleeding that led to death. CONCLUSION: While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs. These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St. John's Wort, sushi and smoking tobacco. Patients should be counselled to continue to seek advice from their healthcare professionals when starting any new herbs, food or supplement.


Assuntos
Interações Ervas-Drogas , Varfarina , Suplementos Nutricionais/efeitos adversos , Ginkgo biloba , Humanos , Fitoterapia , Varfarina/efeitos adversos
7.
Sensors (Basel) ; 21(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073031

RESUMO

Fever is a common symptom of many infections, e.g., in the ongoing COVID-19 pandemic, keeping monitoring devices such as thermometers in constant demand. Recent technological advancements have made infrared (IR) thermometers the choice for contactless screening of multiple individuals. Yet, even so, the measurement accuracy of such thermometers is affected by many factors including the distance from the volunteers' forehead, impurities (such as sweat), and the location measured on the volunteers' forehead. To overcome these factors, we describe the assembly of an Arduino-based digital IR thermometer with distance correction using the MLX90614 IR thermometer and HC-SR04 ultrasonic sensors. Coupled with some analysis of these factors, we also found ways to programme compensation methods for the final assembled digital IR thermometer to provide more accurate readings and measurements.


Assuntos
COVID-19 , Termômetros , Temperatura Corporal , Humanos , Pandemias , SARS-CoV-2
8.
Int J Cosmet Sci ; 42(5): 501-511, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32657437

RESUMO

OBJECTIVE: To evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence-related biomarkers induced by environmental stressors. METHODS: Human epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3-D skin organotypic models were exposed to a combination of UVB and PM2.5 and treated with Nam or vehicle control. Quantitation of the SASP-related inflammatory mediators PGE2 , IL-6 and IL-8 was performed on cultured media. UVB-exposed keratinocytes treated with and without Nam were immunostained for the senescence biomarker Lamin B1 (LmnB1). Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed. A double-blind, placebo-controlled clinical was conducted on 40 female panellists that were pretreated on back sites for two weeks with 5% Nam or vehicle and then exposed to 1.5 minimal erythemal dose (MED) solar-simulated radiation (SSR). Treated sites were compared with non-treated exposed sites for erythema and the skin surface IL-1αRA/IL-1α inflammatory biomarkers. RESULTS: Ultraviolet B induced synthesis of PGE2 , IL-8 and IL-6 and reduced LmnB1 levels in keratinocytes. Urban dust and diesel exhaust only stimulated synthesis of IL-8 whereas cigarette smoke extract only stimulated levels of PGE2 . In all exposures, treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB-reduced LmnB1. In the 3D skin equivalent model, Nam reduced IL-8 levels stimulated by a combination of topical PM2.5 and UV exposure. In a UV challenge clinical, pretreatment with 5% Nam reduced erythema and skin surface IL-1αRA/IL-1α inflammatory biomarkers that were induced by SSR. CONCLUSION: Since it is known that Nam has anti-inflammatory properties, we tested whether Nam can inhibit environmental stress-induced inflammation and senescence-associated secretory phenotype (SASP) biomarkers. We show Nam can reduce PGE2 , IL-6 and IL-8 levels induced by environmental stressors. Additionally, in vivo pretreatment with Nam can reduce UV-induced erythema and skin surface inflammatory biomarkers. These findings add to the body of evidence that Nam can mitigate the skin's inflammatory response elicited by environmental stressors. This supports Nam can potentially inhibit senescence and premature ageing and thereby maintain skin's functionality and appearance.


OBJECTIF: Évaluer si le niacinamide (Nam) peut atténuer la production de biomarqueurs inflammatoireset liés à la sénescence induits par les facteurs de stress environnementaux. MÉTHODES: Leskératinocytes épidermiques H uman ont été exposés aux UVB, à la poussière urbaine, aux gaz d'échappement diesel et à l'extrait de fumée de cigarette et traités avec nam ou contrôle de véhicule. Les modèles organotypic de peau 3D de pleine épaisseur ont été exposés à une combinaison d'UVB et de PM2.5 et traités avec nam ou commande de véhicule. La quantitation des médiateurs inflammatoires liés à la SASP PGE2 ,IL-6 et IL-8 a été réalisée sur des médias cultivés. Les kératinocytes exposés aux UVB traités avec et sans Nam étaient immunotachés pour le biomarqueur de sénescence Lamin B1 (LmnB1). Le profilage de transcriptomique des effets d'extrait de fumée de cigarette sur les kératinocytes a été exécuté. Un placebo contrôlé clinique à double insu a été menée sur 40 panélistes féminins qui ont été prétraités sur les sites arrière pendant deux semaines avec 5% Nam ou véhicule, puis exposés à 1,5 dose erythémique minimale (MED) rayonnement solaire simulé (SSR). Les sites traités ont été comparés à des sites exposés non traités pour l'érythème et la surface de la peau IL-1▫RA/IL-1▫ biomarqueurs inflammatoiress. RÉSULTATS: Synthèse induite par UVB des niveaux de PGE2, IL-8 et IL-6 et réduit de LmnB1 dans les kératinocytes. La poussière urbaine et les gaz d'échappement diesel n'ont stimulé que la synthèse de l'IL-8 alors que l'extrait de fumée de cigarette ne stimulait que les niveaux de PGE2 . Dans toutes les expositions, le traitement avec Nam a significativement atténué la synthèse des médiateurs inflammatoires et les niveaux restaurés de LmnB1 UVB-réduit. Dans le modèle équivalent de la peau 3D, Nam a réduit les niveaux d'IL-8 stimulés par une combinaison de PM combination of topical PM 2.5 topique et d'exposition aux UV. Dans un uv-défi clinique, prétraitement avec 5% Nam réduit érythème et la surface de la peau IL-1▫RA/IL-1▫ biomarqueurs inflammatoires qui ont été induits par SSR. CONCLUSION: Puisqu'il est connu que Nam a des propriétés anti-inflammatoires, nous avons testé si Nam peut inhiber l'inflammation induite par le stressenvironnementaltion et les biomarqueurs sécrétoires sécrétoires sécrétoires (SASP) associés à la sénescence. We montrent Nam peut réduire PGE2 ,IL-6, et IL-8 niveaux induits par les facteurs de stress environnementaux. En outre, le prétraitement in vivo avec Nam peut réduire l'érythème induit par les UV et les biomarqueurs inflammatoires de surface de la peau. Ces résultats ajoutent à l'oody bde la preuve que Nam peut atténuer la réponse inflammatoire de la peau provoquée par lesfacteurs de stress environnementaux. Cela soutient Nam peut potentiellement inhiber la sénescence et le vieillissement prématuré et ainsi maintenir la fonctionnalité de la peau et l'apparence.


Assuntos
Epiderme/efeitos dos fármacos , Inflamação/prevenção & controle , Queratinócitos/efeitos dos fármacos , Niacinamida/farmacologia , Pele/efeitos dos fármacos , Biomarcadores/metabolismo , Senescência Celular/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Inflamação/induzido quimicamente
9.
Catheter Cardiovasc Interv ; 91(2): 343-344, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29405600

RESUMO

As indications for TAVR continue to grow, experienced centers strive to adopt further minimally invasive techniques and continue to improve outcomes. Meta-analysis of the available data demonstrate that conscious sedation is associated with decreased ICU and hospitalization time, and is not associated with decreased procedural efficacy or safety. Randomized Controlled clinical Trial data will be needed to confirm observational findings suggesting decreased mortality with conscious sedation versus general anesthesia.


Assuntos
Sedação Consciente , Substituição da Valva Aórtica Transcateter , Anestesia Geral , Valva Aórtica/cirurgia , Humanos , Resultado do Tratamento
10.
Am J Public Health ; 107(8): 1304-1307, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28640678

RESUMO

OBJECTIVES: To describe changes in mortality after Hurricane Sandy made landfall in New Jersey on October 29, 2012. METHODS: We used electronic death records to describe changes in all-cause and cause-specific mortality overall, in persons aged 76 years or older, and by 3 Sandy impact levels for the month and quarter following Hurricane Sandy compared with the same periods in earlier years adjusted for trends. RESULTS: All-cause mortality increased 6% (95% confidence interval [CI] = 2%, 11%) for the month, 5%, 8%, and 12% by increasing Sandy impact level; and 7% (95% CI = 5%, 10%) for the quarter, 5%, 8%, and 15% by increasing Sandy impact level. In elderly persons, all-cause mortality rates increased 10% (95% CI = 5%, 15%) and 13% (95% CI = 10%, 16%) in the month and quarter, respectively. Deaths that were cardiovascular disease-related increased by 6% in both periods, noninfectious respiratory disease-related by 24% in the quarter, infection-related by 20% in the quarter, and unintentional injury-related by 23% in the month. CONCLUSIONS: Mortality increased, heterogeneous by cause, for both periods after Hurricane Sandy, particularly in communities more severely affected and in the elderly, who may benefit from supportive services.


Assuntos
Causas de Morte/tendências , Tempestades Ciclônicas/mortalidade , Desastres , Idoso , Atestado de Óbito , Feminino , Humanos , Masculino , New Jersey/epidemiologia
11.
MMWR Morb Mortal Wkly Rep ; 66(29): 777-779, 2017 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-28749922

RESUMO

On March 6, 2017, the New Jersey Department of Health (NJDOH) was notified of three cases of septic arthritis in patients who had received intra-articular injections for osteoarthritic knee pain at a private outpatient practice. The practice voluntarily closed the next day. NJDOH, in conjunction with the local health department and the New Jersey Board of Medical Examiners, conducted an investigation and identified 41 cases of septic arthritis associated with intra-articular injections administered during 250 patient visits at the same practice, including 30 (73%) patients who required surgery. Bacterial cultures of synovial fluid or tissue from 15 (37%) patients were positive; all recovered organisms were oral flora. An infection prevention assessment of the practice identified multiple breaches of recommended infection prevention practices, including inadequate hand hygiene, inappropriate use of pharmacy bulk packaged (PBP) products as multiple-dose containers and handling PBP products outside of required pharmacy conditions, and preparation of syringes up to 4 days in advance of their intended use. No additional septic arthritis cases were identified after infection prevention recommendations were implemented within the practice.


Assuntos
Instituições de Assistência Ambulatorial , Artrite Infecciosa/epidemiologia , Surtos de Doenças , Injeções Intra-Articulares/efeitos adversos , Humanos , New Jersey/epidemiologia , Osteoartrite do Joelho/complicações , Dor/tratamento farmacológico , Dor/etiologia , Prática Privada
12.
Cardiovasc Ultrasound ; 15(1): 18, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28673293

RESUMO

BACKGROUND: Left ventricular outflow tract velocity time integral (LVOT VTI) is a measure of cardiac systolic function and cardiac output. Heart failure patients with low cardiac output are known to have poor cardiovascular outcomes. Thus, extremely low LVOT VTI may predict heart failure patients at highest risk for mortality. METHODS: Patients with heart failure and extremely low LVOT VTI were identified from a single-center database. Baseline characteristics and heart failure related clinical outcomes (death, LVAD) were obtained at 12 months. Correlation between clinical endpoints and the following variables were analyzed: ejection fraction (EF), pulmonary artery systolic pressure (PASP), NYHA class, renal function, Doppler cardiac output (CO), and LVOT VTI. RESULTS: Study cohort consisted of 100 patients. At the 12-month follow up period, 30 events (28 deaths, 2 LVADs) were identified. Occurrence of death and LVAD implantation was statistically associated with a lower LVOT VTI (p = 0.039) but not EF (p = 0.169) or CO (p = 0.217). In multivariate analysis, LVOT VTI (p = 0.003) remained statistically significant, other significant variables were age (p = 0.033) and PASP (p = 0.022). Survival analysis by LVOT VTI tertile demonstrated an unadjusted hazard ratio of 4.755 (CI 1.576-14.348, p = 0.006) for combined LVAD and mortality at one year. CONCLUSIONS: Extremely low LVOT VTI strongly predicts adverse outcomes and identifies patients who may benefit most from advanced heart failure therapies.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Ecocardiografia Doppler/métodos , Insuficiência Cardíaca/diagnóstico , Ventrículos do Coração/fisiopatologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , California/epidemiologia , Causas de Morte/tendências , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Prognóstico , Taxa de Sobrevida/tendências , Sístole
13.
J Biol Chem ; 290(30): 18662-70, 2015 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-26085085

RESUMO

The transcription factors glioma-associated oncogene homolog 1 (GLI1), a primary marker of Hedgehog pathway activation, and Forkhead box M1 (FOXM1) are aberrantly activated in a wide range of malignancies, including glioma. However, the mechanism of nuclear localization of GLI1 and whether FOXM1 regulates the Hedgehog signaling pathway are poorly understood. Here we found that FOXM1 promotes nuclear import of GLI1 in glioblastoma multiforme cells and thus increases the expression of its target genes. Conversely, knockdown of FOXM1 expression with FOXM1 siRNA abrogated its nuclear import and inhibited the expression of its target genes. Also, genetic deletion of FOXM1 in mouse embryonic fibroblasts abolished nuclear localization of GLI1. We observed that FOXM1 directly binds to the importin-7 (IPO7) promoter and increases its promoter activity. IPO7 interacted with GLI1, leading to enhanced nuclear import of GLI1. Depletion of IPO7 by IPO7 siRNA reduced nuclear accumulation of GLI1. In addition, FOXM1 induced nuclear import of GLI1 by promoting IPO7 expression. Moreover, the FOXM1/IPO7/GLI1 axis promoted cell proliferation, migration, and invasion in vitro. Finally, expression of FOXM1 was markedly correlated with that of GLI1 in human glioblastoma specimens. These data suggest that FOXM1 and GLI1 form a positive feedback loop that contributes to glioblastoma development. Furthermore, our study revealed a mechanism that controls nuclear import of GLI1 in glioblastoma multiforme cells.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Glioblastoma/genética , Carioferinas/biossíntese , Receptores Citoplasmáticos e Nucleares/biossíntese , Fatores de Transcrição/biossíntese , Movimento Celular/genética , Proliferação de Células/genética , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , Carioferinas/genética , Carioferinas/metabolismo , Invasividade Neoplásica/genética , Regiões Promotoras Genéticas , Ligação Proteica , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína GLI1 em Dedos de Zinco
14.
N Engl J Med ; 369(17): 1610-9, 2013 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-24152260

RESUMO

BACKGROUND: Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections. METHODS: We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification. RESULTS: Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis. CONCLUSIONS: The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).


Assuntos
Aracnoidite/epidemiologia , Surtos de Doenças , Contaminação de Medicamentos , Glucocorticoides , Meningite Fúngica/epidemiologia , Metilprednisolona , Acidente Vascular Cerebral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Aracnoidite/microbiologia , Aracnoidite/mortalidade , Ascomicetos/genética , Ascomicetos/isolamento & purificação , Aspergillus fumigatus/isolamento & purificação , Composição de Medicamentos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Injeções Epidurais , Injeções Espinhais , Masculino , Meningite Fúngica/microbiologia , Meningite Fúngica/mortalidade , Meningite Fúngica/patologia , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Acidente Vascular Cerebral/microbiologia , Acidente Vascular Cerebral/mortalidade , Estados Unidos/epidemiologia , Adulto Jovem
15.
J Pharmacol Exp Ther ; 357(1): 36-44, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26791603

RESUMO

Aberrant ligand-independent G protein-coupled receptor constitutive activity has been implicated in the pathophysiology of a number of cancers. The adenosine A2B receptor (A2BAR) is dynamically upregulated under pathologic conditions associated with a hypoxic microenvironment, including solid tumors. This, in turn, may amplify ligand-independent A2BAR signal transduction. The contribution of A2BAR constitutive activity to disease progression is currently unknown yet of fundamental importance, as the preferred therapeutic modality for drugs designed to reduce A2BAR constitutive activity would be inverse agonism as opposed to neutral antagonism. The current study investigated A2BAR constitutive activity in a heterologous expression system and a native 22Rv1 human prostate cancer cell line exposed to hypoxic conditions (2% O2). The A2BAR inverse agonists, ZM241385 [4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol] or PSB-603 (8-(4-(4-(4-chlorophenyl)piperazide-1-sulfonyl)phenyl)-1-propylxanthine), mediated a concentration-dependent decrease in baseline cAMP levels in both cellular systems. Proliferation of multiple prostate cancer cell lines was also attenuated in the presence of PSB-603. Importantly, both the decrease in baseline cAMP accumulation and the reduction of proliferation were not influenced by the addition of adenosine deaminase, demonstrating that these effects are not dependent on stimulation of A2BARs by the endogenous agonist adenosine. Our study is the first to reveal that wild-type human A2BARs have high constitutive activity in both model and native cells. Furthermore, our findings demonstrate that this ligand-independent A2BAR constitutive activity is sufficient to promote prostate cancer cell proliferation in vitro. More broadly, A2BAR constitutive activity may have wider, currently unappreciated implications in pathologic conditions associated with a hypoxic microenvironment.


Assuntos
Neoplasias da Próstata/patologia , Receptor A2B de Adenosina/efeitos dos fármacos , Agonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Adenosina Desaminase/metabolismo , Animais , Células CHO , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , Desenho de Fármacos , Humanos , Fosfatos de Inositol/metabolismo , Ligantes , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Triazinas/farmacologia , Triazóis/farmacologia , Xantinas/farmacologia
16.
J Gambl Stud ; 32(2): 643-59, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26499201

RESUMO

There has been emerging evidence regarding gambling experiences of young people in Asia recently, but to date, none in Malaysia. This study aimed to estimate the prevalence of gambling, and to identify individual, familial and high-risk behaviours factors among Malaysian adolescents. A cross-sectional study was conducted over 4 months at randomly selected secondary schools in Seremban in Negeri Sembilan state. A total of 2265 self-administered, anonymous questionnaires were distributed to the students. The students completed the questionnaire consisting of sociodemographic and family background, gambling behaviours, high risk behaviours and mental health questions. Approximately 29.6 % (95 % CI 27.7-31.5) of respondents reported participating in some forms of gambling activities in the previous 12 months. Among these, 3.6 % (95 % CI 2.8-4.3) of them were problem gamblers. Parental gambling was the strongest correlate with adolescent gambling behaviour. Signification association was found between gambling behaviour and gender (being males), but interestingly, not with ethnicity. Adolescents who reported engaging in high risk behaviours (such as smoking, alcohol consumption, involvement in physical fights, illegal vehicular racing) were also more likely to gamble. Gambling is not an uncommon phenomenon amongst Malaysian adolescents. Public awareness campaign, health education to targeted groups, revision of existing laws, and screening at primary care level should be implemented to address the issue of gambling among adolescents. This study also highlights the need to examine the national scope of the problem in Malaysia.


Assuntos
Comportamento do Adolescente/psicologia , Jogo de Azar/psicologia , Assunção de Riscos , Estudantes/psicologia , Adolescente , Consumo de Bebidas Alcoólicas/psicologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Malásia/epidemiologia , Masculino , Grupo Associado , Prevalência , Fatores de Risco , Fumar/epidemiologia , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/psicologia
17.
MMWR Morb Mortal Wkly Rep ; 64(49): 1363-4, 2015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26678414

RESUMO

On September 30, 2015, the New Jersey Department of Health (NJDOH) was notified by an out-of-state health services company that an experienced nurse had reused syringes for multiple persons earlier that day. This occurred at an employee influenza vaccination clinic on the premises of a New Jersey business that had contracted with the health services company to provide influenza vaccinations to its employees. The employees were to receive vaccine from manufacturer-prefilled, single-dose syringes. However, the nurse contracted by the health services company brought three multiple-dose vials of vaccine that were intended for another event. The nurse reported using two syringes she found among her supplies to administer vaccine to 67 employees of the New Jersey business. She reported wiping the syringes with alcohol and using a new needle for each of the 67 persons. One of the vaccine recipients witnessed and questioned the syringe reuse, and brought it to the attention of managers at the business who, in turn, reported the practice to the health services company contracted to provide the influenza vaccinations.


Assuntos
Vacinas contra Influenza/administração & dosagem , Injeções/efeitos adversos , Erros Médicos , Serviços de Saúde do Trabalhador , Serviços Contratados , Humanos , Licenciamento em Enfermagem , New Jersey , Padrões de Prática em Enfermagem/normas
18.
BMC Med Educ ; 15: 28, 2015 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-25879491

RESUMO

BACKGROUND: In 2008 the sub-Saharan FAIMER Regional Institute launched a faculty development programme aimed at enhancing the academic and research capacity of health professions educators working in sub-Saharan Africa. This two-year programme, a combination of residential and distance learning activities, focuses on developing the leadership, project management and programme evaluation skills of participants as well as teaching the key principles of health professions education-curriculum design, teaching and learning and assessment. Participants also gain first-hand research experience by designing and conducting an education innovation project in their home institutions. This study was conducted to determine the perceptions of participants regarding the personal and professional impact of the SAFRI programme. METHODS: A retrospective document review, which included data about fellows who completed the programme between 2008 and 2011, was performed. Data included fellows' descriptions of their expectations, reflections on achievements and information shared on an online discussion forum. Data were analysed using Kirkpatrick's evaluation framework. RESULTS: Participants (n=61) came from 10 African countries and included a wide range of health professions educators. Five key themes about the impact of the SAFRI programme were identified: (1) belonging to a community of practice, (2) personal development, (3) professional development, (4) capacity development, and (5) tools/strategies for project management and/or advancement. CONCLUSION: The SAFRI programme has a positive developmental impact on both participants and their respective institutions.


Assuntos
Pesquisa Biomédica/educação , Docentes/normas , Pessoal de Saúde/educação , Desenvolvimento de Pessoal/normas , Adulto , África Subsaariana , Pesquisa Biomédica/métodos , Pesquisa Biomédica/normas , Comportamento do Consumidor , Currículo/normas , Educação Continuada/métodos , Educação Continuada/organização & administração , Educação Continuada/normas , Educação a Distância/métodos , Educação a Distância/organização & administração , Educação a Distância/normas , Feminino , Pessoal de Saúde/normas , Humanos , Cooperação Internacional , Relações Interprofissionais , Liderança , Masculino , Pessoa de Meia-Idade , Satisfação Pessoal , Competência Profissional/normas , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde/métodos , Avaliação de Programas e Projetos de Saúde/normas , Desenvolvimento de Pessoal/métodos , Desenvolvimento de Pessoal/organização & administração , Ensino/métodos , Ensino/normas
19.
Nat Neurosci ; 27(5): 901-912, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514857

RESUMO

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination of the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) shows promising benefits for relapsing-remitting MS in open-label clinical studies, but the cellular mechanisms underlying its therapeutic effects remain unclear. Using single-nucleus RNA sequencing, we identify a reactive myeloid cell state in chronic experimental autoimmune encephalitis (EAE) associated with neuroprotection and immune suppression. HCT in EAE mice results in an increase of the neuroprotective myeloid state, improvement of neurological deficits, reduced number of demyelinated lesions, decreased number of effector T cells and amelioration of reactive astrogliosis. Enhancing myeloid cell incorporation after a modified HCT further improved these neuroprotective effects. These data suggest that myeloid cell manipulation or replacement may be an effective therapeutic strategy for chronic inflammatory conditions of the CNS.


Assuntos
Encefalomielite Autoimune Experimental , Camundongos Endogâmicos C57BL , Células Mieloides , Animais , Encefalomielite Autoimune Experimental/terapia , Encefalomielite Autoimune Experimental/patologia , Camundongos , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Neuroproteção/fisiologia
20.
Diabetes Metab Syndr ; 17(2): 102724, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36791634

RESUMO

BACKGROUND AND AIMS: Hypoglycaemia due to fasting during Ramadan may affect the ability to perform complex activities among people with type 2 diabetes mellitus (T2D), but it is unclear how this affects one's ability to drive. This study aims to explore driving experiences and coping strategies to ensure safe driving among people with T2D who fast during Ramadan. METHODS: We conducted an exploratory qualitative study and purposefully selected people with T2D who drove and fasted during the past Ramadan period in 2019. In-depth face-to-face interviews were conducted and transcribed verbatim. Data were analysed thematically using a constant comparative method until saturation was achieved (n = 16). RESULTS: Two major themes were identified, namely: (1) knowing oneself and (2) voluntary self-restriction. Participants described the importance of understanding how Ramadan fasting affected them and their level of alertness. As such, participants often adjusted their daily activities and tested their blood glucose levels to prevent experiencing hypoglycaemia. Other coping strategies reported include adjusting their medications and driving restrictions or driving in the mornings when they were more alert. Findings from this study shed light on participants' experiences and coping mechanisms while driving during Ramadan. CONCLUSION: Given the risks and effects of hypoglycaemia among those who fast, there is a need to provide appropriate and focused patient education during Ramadan to people with T2D to ensure they can perform complex activities such as driving safely, especially in Muslim majority countries.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Segurança do Paciente , Jejum/efeitos adversos , Islamismo , Hipoglicemia/prevenção & controle
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