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1.
Cell ; 154(4): 737-47, 2013 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-23953109

RESUMEN

Mitochondria have long been implicated in the pathogenesis of Parkinson's disease (PD). Mutations in the mitochondrial kinase PINK1 that reduce kinase activity are associated with mitochondrial defects and result in an autosomal-recessive form of early-onset PD. Therapeutic approaches for enhancing the activity of PINK1 have not been considered because no allosteric regulatory sites for PINK1 are known. Here, we show that an alternative strategy, a neo-substrate approach involving the ATP analog kinetin triphosphate (KTP), can be used to increase the activity of both PD-related mutant PINK1(G309D) and PINK1(WT). Moreover, we show that application of the KTP precursor kinetin to cells results in biologically significant increases in PINK1 activity, manifest as higher levels of Parkin recruitment to depolarized mitochondria, reduced mitochondrial motility in axons, and lower levels of apoptosis. Discovery of neo-substrates for kinases could provide a heretofore-unappreciated modality for regulating kinase activity.


Asunto(s)
Mitocondrias/metabolismo , Enfermedad de Parkinson/patología , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Adenosina Trifosfato/análogos & derivados , Secuencia de Aminoácidos , Animales , Apoptosis , Axones/metabolismo , Línea Celular , Células Cultivadas , Hipocampo/citología , Hipocampo/metabolismo , Humanos , Cinetina/metabolismo , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Neuronas/citología , Neuronas/metabolismo , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Fosforilación , Proteínas Quinasas/química , Ratas , Alineación de Secuencia , Ubiquitina-Proteína Ligasas/metabolismo , Proteína bcl-X/metabolismo
2.
Ann Surg Oncol ; 31(8): 5168-5179, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38717543

RESUMEN

BACKGROUND: Many women eligible for breast conservation therapy (BCT) elect unilateral mastectomy (UM) with or without contralateral prophylactic mastectomy (CPM) and cite a desire for "peace of mind." This study aimed to characterize how peace of mind is defined and measured and how it relates to surgical choice. METHODS: Nine databases were searched for relevant articles through 8 October 2023, and data were extracted from articles meeting the inclusion criteria. RESULTS: The inclusion criteria were met by 20 studies. Most were prospective cohort studies (65%, 13/20). In the majority of the studies (72%, 13/18), Non-Hispanic white/Caucasian women comprised 80 % or more of the study's sample. Almost half of the studies used the phrase "peace of mind" in their publication (45%, 9/20), and few directly defined the construct (15%, 3/20). Instead, words representing an absence of peace of mind were common, specifically, "anxiety" (85%, 17/20), "fear" (75%, 15/20), and "concern" (75%, 15/20). Most of the studies (90%, 18/20) measured peace of mind indirectly using questionnaires validated for anxiety, fear, worry, distress, or concern, which were administered at multiple postoperative time points (55%, 11/20). Most of the studies (95%, 18/19) reported at least one statistically significant result showing no difference in peace of mind between BCT, UM, and/or CPM at their latest time of assessment. CONCLUSION: Peace of mind is largely framed around concepts that suggest its absence, namely, anxiety, fear, and concern. Existing literature suggests that peace of mind does not differ among average-risk women undergoing BCT, UM, or CPM. Shared surgical decisions should emphasize at least comparable emotional and/or psychosocial well-being between CPM and breast conservation.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Humanos , Femenino , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/psicología , Mastectomía/psicología , Ansiedad/psicología , Ansiedad/prevención & control , Miedo/psicología , Mastectomía Profiláctica/psicología , Pronóstico
3.
J Cardiovasc Electrophysiol ; 35(5): 916-928, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38439119

RESUMEN

INTRODUCTION: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy. MATERIALS AND METHODS: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records. RESULTS: The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56). CONCLUSION: Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications.


Asunto(s)
Potenciales de Acción , Arritmias Cardíacas , Inteligencia Artificial , Ablación por Catéter , Valor Predictivo de las Pruebas , Tiempo de Tratamiento , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/cirugía , Ablación por Catéter/efectos adversos , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Fluoroscopía , Frecuencia Cardíaca , Tempo Operativo , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Estudios de Casos y Controles
4.
Br J Nutr ; 131(7): 1244-1258, 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37993119

RESUMEN

The Türkiye-Syria earthquake struck eleven provinces directly in Türkiye on 6 February 2023. Emergency nutrition care is indispensable for sustaining the lives of victims and rescue personnel. To optimally support their well-being, emergency food must be both healthy (i.e. aligned with dietary guidelines) and safe. However, globally, there is a dearth of research on the emergency nutrition conditions in shelters in the immediate aftermath of natural disasters. This lack of scientific evidence could limit the extent to which nutritional gaps can be identified and remedied for future relief efforts. Therefore, the aim of this research was to evaluate the nutrition environment and nutritional quality of emergency meals distributed to survivors in Malatya, a heavily affected province in Türkiye. The rapid assessment was conducted in thirteen locations by using an embedded case-study design to evaluate the nutrition environment both quantitatively and qualitatively. Meals served to earthquake victims and volunteers were found to be insufficient in protein, fat, fibre, vitamin C, Ca and Fe, but Na levels were higher than the maximum threshold in many of the centres. The qualitative analysis illustrated insufficiency in three domains of the emergency food and nutrition environment: foods and beverages offered, cooking/food preparation and food safety and dining areas and other facilities. Given the major nutritional gaps identified in this study, future disaster preparations should implement emergency nutrition plans that ensure healthy, nutritious and safe food for survivors. Better coordination and use of technology are necessary for interventions to prevent malnutrition.


Asunto(s)
Planificación en Desastres , Terremotos , Humanos , Siria , Turquía , Comidas
5.
Tech Coloproctol ; 28(1): 23, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38198036

RESUMEN

In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions. In addition to patients with a personal history of precancerous lesions and anal cancer, three groups are at very high risk of anal cancer: (i) men who have sex with men and are living with HIV, (ii) women with a history of high-grade squamous intraepithelial lesions (HSILs) or vulvar HPV cancer, and (iii) women who received a solid organ transplant more than 10 years ago. The purpose of screening is to detect HSILs so that they can be treated, thereby reducing the risk of progression to cancer. All patients with symptoms should undergo a proctological examination including standard anoscopy. For asymptomatic patients at risk, an initial HPV16 test makes it possible to target patients at risk of HSILs likely to progress to cancer. Anal cytology is a sensitive test for HSIL detection. Its sensitivity is greater than 80% and exceeds that of proctological examination with standard anoscopy. It is indicated in the event of a positive HPV16 test. In the presence of cytological abnormalities and/or lesions and a suspicion of dysplasia on clinical examination, high-resolution anoscopy is indicated. Performance is superior to that of proctological examination with standard anoscopy. However, this technique is not widely available, which limits its use. If high-resolution anoscopy is not possible, screening by a standard proctological examination is an alternative. There is a need to develop high-resolution anoscopy and triage tests and to evaluate screening strategies.


Asunto(s)
Neoplasias del Ano , Lesiones Precancerosas , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Virus del Papiloma Humano , Homosexualidad Masculina , Lesiones Precancerosas/diagnóstico , Neoplasias del Ano/diagnóstico
6.
Niger J Clin Pract ; 27(4): 489-495, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38679772

RESUMEN

BACKGROUND: The preoperative prediction of intraperitoneal adhesion (IPA) before repeated cesarean deliveries (CD), which are becoming more prevalent, is crucial for maternal health. AIM: The aim of the study was to preoperatively predict IPA in repeated CD with the stria gravidarum (SG) scoring system. METHODS: A total of 167 patients with at least one previous CD at or beyond 37 weeks of gestation were analyzed. Preoperative SG was calculated according to the Davey scoring system: 0-2 score were defined as mild SG (Group 1; n: 94, 56.2%), and 3-8 score were defined as severe SG (Group 2; n = 73, 43.8%). Preoperative previous cesarean incision features were evaluated according to the Vancouver scar scale. IPA was evaluated according to the Nair's and modified Nair's scoring systems. RESULTS: Parity, younger age at first pregnancy, higher body mass index, number of previous CDs, rate of scar symptoms, Nair's and the modified Nair's scores were statistically significant in Group 2 (P = 0.01; P = 0.04; P = 0.007; P = 0.004; P < 0.001; P = 0.007; P = 0.02, respectively). Davey score ≥3 and Vancouver score ≥4.5 were determined as the cut-off value to predict IPA (P = 0.1 and 0.07, respectively). According to multivariate analysis, both Davey and Vancouver scores are independent factors in predicting IPA (P = 0.02 and 0.04, respectively). CONCLUSION: Evaluating the SG score through the Davey score in women with a history of previous CD may assist in predicting IPA status before the planning of a subsequent surgery.


Asunto(s)
Cesárea Repetida , Humanos , Femenino , Embarazo , Adulto , Adherencias Tisulares , Estudios Transversales , Cesárea Repetida/estadística & datos numéricos , Factores de Riesgo , Enfermedades Peritoneales/diagnóstico , Índice de Severidad de la Enfermedad , Valor Predictivo de las Pruebas , Cesárea/efectos adversos , Paridad , Adulto Joven
7.
J Am Chem Soc ; 145(18): 10015-10021, 2023 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-37104712

RESUMEN

Caspases are a family of cysteine-dependent proteases with important cellular functions in inflammation and apoptosis, while also implicated in human diseases. Classical chemical tools to study caspase functions lack selectivity for specific caspase family members due to highly conserved active sites and catalytic machinery. To overcome this limitation, we targeted a non-catalytic cysteine residue (C264) unique to caspase-6 (C6), an enigmatic and understudied caspase isoform. Starting from disulfide ligands identified in a cysteine trapping screen, we used a structure-informed covalent ligand design to produce potent, irreversible inhibitors (3a) and chemoproteomic probes (13-t) of C6 that exhibit unprecedented selectivity over other caspase family members and high proteome selectivity. This approach and the new tools described will enable rigorous interrogation of the role of caspase-6 in developmental biology and in inflammatory and neurodegenerative diseases.


Asunto(s)
Caspasas , Cisteína , Humanos , Caspasa 6 , Apoptosis , Inhibidores de Cisteína Proteinasa/farmacología
8.
Niger J Clin Pract ; 26(9): 1309-1318, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37794544

RESUMEN

Background: Pelvic floor muscle (PFM) training varies according to the functional status of PFM. It is used to strengthen underactive PFM and relax overactive PFM. Aim: This study aimed to determine the appropriate PFM training positions according to the functional status of the PFM in women with pelvic floor dysfunction. Materials and Methods: Seventy-six women diagnosed with pelvic floor dysfunction were included. After the digital palpation, participants were divided into four groups according to the functional status of PFM: normal, overactive, underactive, and nonfunctional. Participants' PFM and abdominal muscle functions were assessed with superficial electromyography in three positions (modified butterfly pose-P1, modified child pose-P2, and modified deep squat with block pose-P3). Friedman's analysis of variance and the Kruskal-Wallis test were used to assess whether the function of the muscles differed according to the functional status of the PFM and training positions. Results: Normal PFM maximally contracted and relaxed in P1, whereas nonfunctional PFM was in P3 (P > 0.05). Overactive and underactive PFM was most contracted in P2 (P > 0.05) and relaxed in P1 (P < 0.001). In each functional state of the PFM, all abdominal muscles were most relaxed in P1, while their most contracted positions varied (P < 0.05). Conclusion: This study showed that the positions in which the PFM relaxes and contracts the most may vary according to the functional status of the PFM. Therefore, different PFM training positions may be preferred according to the functional status of the PFM in women with pelvic floor dysfunction. However, more study needs to be done in this subject.


Asunto(s)
Contracción Muscular , Diafragma Pélvico , Femenino , Humanos , Electromiografía , Estado Funcional , Contracción Muscular/fisiología , Diafragma Pélvico/fisiología , Postura/fisiología
9.
BMC Emerg Med ; 21(1): 111, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620117

RESUMEN

BACKGROUND: Limited research regarding administration of timed medication infusions in the prehospital environment has identified wide variability with accuracy, timing, and overall feasibility. This study was a quality improvement project that utilized a randomized, controlled, crossover study design to compare two different educational techniques for medication infusion administration. We hypothesized that the use of a metronome-based technique would decrease medication dosage errors and reduce time to administration for intravenous medication infusions. METHODS: Forty-two nationally registered paramedics were randomized to either a metronome-based technique versus a standard stopwatch-based technique. Each subject served as a control. Subjects were asked to establish an infusion of amiodarone at a dose of 150 mg administered over 10 min, simulating treatment of a hemodynamically stable patient with sustained monomorphic ventricular tachycardia. Descriptive statistics and a repeated measures mixed linear regression model were used for data analysis. RESULTS: When compared to a standard stopwatch-based technique, a metronome-based technique was associated with faster time to goal (median 34 s [IQR, 22-54] vs 50 s; [IQR 38-61 s], P = 0.006) and fewer mid-infusion adjustments. Ease of use was reported to be significantly higher for the metronome group (median ranking 5, IQR 4-5) compared to the standard group (median ranking 2, IQR 2-3; P < 0.001). CONCLUSIONS: Knowledge regarding a metronome technique may help EMS clinicians provide safe and effective IV infusions. Such a technique may be beneficial for learners and educators alike.


Asunto(s)
Servicios Médicos de Urgencia , Auxiliares de Urgencia , Infusiones Intravenosas/métodos , Errores de Medicación , Técnicos Medios en Salud , Estudios Cruzados , Humanos , Errores de Medicación/prevención & control
10.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-34576237

RESUMEN

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.


Asunto(s)
Antivirales/farmacología , Heparina/farmacología , Cloruro de Magnesio/farmacología , Aciclovir/farmacología , Adenovirus Humanos/efectos de los fármacos , Adenovirus Humanos/fisiología , Animales , Antivirales/química , Células CHO , Línea Celular Tumoral , Chlorocebus aethiops , Cricetulus , Evaluación Preclínica de Medicamentos , Fibroblastos , Heparina/química , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/fisiología , Humanos , Cloruro de Magnesio/química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Cultivo Primario de Células , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/fisiología , Relación Estructura-Actividad , Células Vero , Carga Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacos
11.
Balkan J Med Genet ; 24(1): 67-72, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34447661

RESUMEN

Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

12.
Niger J Clin Pract ; 24(11): 1706-1711, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34782512

RESUMEN

BACKGROUND: The aim of our study is to evaluate whether the CURB-65 or expanded-CURB-65 score can be used in healthcare-associated pneumonia (HCAP) and subgroups of HCAP patients at the same efficiency. Thirty and 90-day mortality rates of the patients and predictive values of CURB-65 and E-CURB-65 scores were compared. PATIENTS AND METHODS: This is a retrospective study of patients who presented to the Emergency Department between January 2015 and January 2016. All patient charts above 18 years of age were evaluated according to American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA) pneumonia diagnostic criteria and pneumonia diagnoses were confirmed. RESULTS: 167 pneumonia patients (27.8%) of all pneumonia cases were grouped as HCAP and 433 (54.4%) were grouped as community-acquired pneumonia (CAP). 43% (n = 72) of HCAP patients were classified as nursing home-associated pneumonia (NHAP) and 57% (n = 95) were classified as HCAP (except NHAP) group. NHAP patients were older than the other groups. HCAP (except NHAP) group had somehow more comorbid diseases when compared with the other groups. However, the NHAP group had more unstable vital signs and confusion rates. Hospital and ICU admissions, 30-90-day mortality rates were all significantly higher in NHAP group E-CURB-65 was found to have better predictive values than CURB-65 for 30-day and 90-day mortalities overall. CONCLUSION: According to our results, commonly used scoring systems, CURB 65 and E-CURB 65, are not suitable for HCAP, NHAP, and HCAP (except NHAP) patients. NHAP patients have significant worse prognosis compared with CAP and HCAP (except NHAP) in terms of admission to intensive care and 30 and 90-day mortality rates.


Asunto(s)
Infecciones Comunitarias Adquiridas , Infección Hospitalaria , Neumonía Asociada a la Atención Médica , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/epidemiología , Mortalidad Hospitalaria , Humanos , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
13.
Curr Opin Cardiol ; 35(3): 308-311, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32109927

RESUMEN

PURPOSE OF REVIEW: Orthotopic heart transplantation (OHT) significantly improves morbidity and mortality in patients with end-stage heart disease. Despite advances in surgical technique, immunosuppressive therapies, and patient monitoring, long-term risk of arrhythmias and sudden cardiac death (SCD) in the denervated heart remains unchanged. RECENT FINDINGS: SCD is responsible for approximately 10% of all posttransplant deaths with a pooled incidence rate of 1.30 per 100 person years and is strongly associated with cardiac allograft vasculopathy (CAV). Risk factors for SCD and CAV include higher donor age, younger recipient age, and reduced left ventricular ejection fraction. Little is known about the time course between CAV and SCD. Although some registry data establish ventricular fibrillation as a documented terminal rhythm, the arrhythmia may not be the mechanism of SCD. SUMMARY: In this review, we identify risk factors and general independent predictors of arrhythmia and SCD and discuss the utility of implantable cardiac defibrillators in post-cardiac transplant patients.


Asunto(s)
Desfibriladores Implantables , Trasplante de Corazón , Arritmias Cardíacas/etiología , Muerte Súbita Cardíaca/prevención & control , Humanos , Factores de Riesgo , Volumen Sistólico , Función Ventricular Izquierda
14.
BMC Cancer ; 20(1): 446, 2020 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-32430004

RESUMEN

BACKGROUND: Several physiological (fertilization, placentation, wound healing) and pathophysiological processes (infection with enveloped viruses, cancer) depend on cell fusion. In cancer it was postulated that the fusion of cancer cells with normal cells such as macrophages or stem cells may not only give rise to hybrid cells exhibiting novel properties, such as an increased metastatic capacity and drug resistance, but possibly also cancer stem/ initiating cell properties. Hence, hybrid clone cells (M13HS, M13MDA435 and M13MDA231) that were derived from spontaneous fusion events of human M13SV1-EGFP-Neo breast epithelial cells and HS578T-Hyg, MDA-MB-435-Hyg and MDA-MB-231-Hyg cancer cells were investigated regarding potential in vitro cancer stem/ initiating cell properties. METHODS: CD44/CD24 expression pattern and ALDH1 activity of parental cells and hybrid clones was determined by flow cytometry. A colony formation and mammosphere formation assay was applied to determine the cells' capability to form colonies and mammospheres. Sox9, Slug and Snail expression levels were determined by Western blot analysis. RESULTS: Flow cytometry revealed that all hybrid clone cells were CD44+/CD24-/low, but differed markedly among each other regarding ALDH1 activity. Likewise, each hybrid clone possessed a unique colony formation and mammosphere capacity as well as unique Snail, Slug and Sox9 expression patterns. Nonetheless, comparison of hybrid clones revealed that M13HS hybrids exhibited more in vitro cancer stem/ initiating cell properties than M13MDA231 and M13MDA435 hybrids, such as more ALDH1 positive cells or an increased capacity to form colonies and mammospheres. CONCLUSION: The fate whether cancer stem/ initiating cells may originate from cell fusion events likely depends on the specific characteristics of the parental cells.


Asunto(s)
Neoplasias de la Mama/patología , Células Epiteliales/patología , Células Híbridas/patología , Neoplasias/patología , Células Madre Neoplásicas/patología , Neoplasias de la Mama/metabolismo , Antígeno CD24/metabolismo , Fusión Celular , Movimiento Celular , Células Epiteliales/metabolismo , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Células Híbridas/metabolismo , Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Factor de Transcripción SOX9/metabolismo , Células Tumorales Cultivadas
15.
Pacing Clin Electrophysiol ; 43(1): 21-29, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31682283

RESUMEN

Variant accessory pathways include atriofascicular, nodofascicular, nodoventricular, atrio-Hisian, and fasciculoventricular pathways. Atriofascicular pathways are the most common with others occurring rarely. The anatomical descriptions, electrocardiographic findings, electrophysiologic findings, and clincial manifestations are discussed.


Asunto(s)
Trastorno del Sistema de Conducción Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/anatomía & histología , Sistema de Conducción Cardíaco/fisiopatología , Variación Anatómica , Electrofisiología Cardíaca , Electrocardiografía , Humanos
16.
Pacing Clin Electrophysiol ; 43(6): 542-550, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32297348

RESUMEN

BACKGROUND: Atrial fibrillation (AF) is frequently present in patients with heart failure (HF) and an implantable cardioverter-defibrillator (ICD). This study aims to identify clinical factors associated with a baseline history of AF in ICD recipients, and compares subsequent clinical outcomes in those with and without a baseline history of AF. METHODS: We studied 566 consecutive first-time ICD recipients at an academic center between 2011 and 2018. Logistic regression multivariable analyses were used to identify clinical factors associated with a baseline history of AF at the time of ICD implant. Cox-proportional hazard regression models were constructed for multivariate analysis to examine associations between a baseline history of AF with subsequent clinical outcomes, including ICD therapies, HF readmission, and all-cause mortality. RESULTS: Of all patients, 201 (36%) had a baseline history of AF at the time of ICD implant. In multivariate analyses, clinical factors associated with a baseline history of AF included hypertension, valvular heart disease, body weight, PR interval, and serum creatinine level. After multivariate adjustment for potential confounders, a baseline history of AF was associated with an increased risk of anti-tachycardia pacing (HR = 1.84, 95% CI = 1.19-2.85, P = .006), appropriate ICD shocks (HR = 1.80, 95% CI = 1.05-3.09, P = .032), and inappropriate ICD shocks (HR = 3.72, 95% CI = 1.7-7.77, P = .0001), but not other adverse outcomes. CONCLUSION: Among first-time ICD recipients, specific clinical characteristics were associated with a baseline history of AF at the time of ICD implant. After adjustment for potential confounders, a baseline history of AF was associated with a higher risk of all ICD therapies in follow-up.


Asunto(s)
Fibrilación Atrial/terapia , Desfibriladores Implantables , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
17.
Nature ; 511(7509): 319-25, 2014 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-25030168

RESUMEN

Malignancy is associated with altered expression of glycans and glycoproteins that contribute to the cellular glycocalyx. We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. We tested this prediction by investigating whether bulky glycoproteins in the glycocalyx promote a tumour phenotype in human cells by increasing integrin adhesion and signalling. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumour-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent growth factor signalling to support cell growth and survival. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Thus, a bulky glycocalyx is a feature of tumour cells that could foster metastasis by mechanically enhancing cell-surface receptor function.


Asunto(s)
Glicocálix/metabolismo , Glicoproteínas/metabolismo , Integrinas/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Animales , Mama/citología , Mama/metabolismo , Mama/patología , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Fibroblastos , Glicocálix/química , Humanos , Proteínas Inmovilizadas/química , Proteínas Inmovilizadas/metabolismo , Integrinas/química , Ratones , Terapia Molecular Dirigida , Mucina-1/metabolismo , Metástasis de la Neoplasia/patología , Células Neoplásicas Circulantes , Unión Proteica , Receptores de Superficie Celular
18.
Mediators Inflamm ; 2020: 2929163, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32508523

RESUMEN

Relieving Sore Throat Formula (RSTF) is a formula approved by the China Food and Drug Administration and has been used for the treatment of pharyngitis in clinic for many years. However, the potential pharmacological mechanism still remains unknown. We combined multiple methods including bioinformatics data digging, network pharmacology analysis, and pathway analysis to predict the potential target of RSTF. We verified our in silico prediction results with an in vivo/vitro antibacterial effect test, mouse phagocytic index test, proliferation, transformation, and migration of mouse spleen lymphocytes. Alteration of NF-κB pathway was determined by Western blotting, immunofluorescence, and PCR. The in vivo experiments demonstrated that the RSTF could significantly relieve the symptoms of pharyngitis. A rat saliva secretion test showed that RSTF can effectively relieve the xerostomia symptom. A phenol red excretion test showed that RSTF has an eliminating phlegm effect. A hot plate method and granuloma experiment proved that RSTF also have analgesic and anti-inflammatory effects. In silico prediction demonstrates that 70 active compounds of RSTF were filtered out through ADME screening and 84 putative targets correlated with different diseases. Pathway enrichment analysis showed that the candidate targets were mostly related to the response to bacteria and immunity signalling pathways, which are known contributors to pharyngitis. Experimental results confirmed that RSTF exerted therapeutic effects on pharyngitis mainly by antibacterial effect and downregulation of NF-κB activities. It is demonstrated both in silico and in vivo/vitro that RSTF exerted therapeutic effects on pharyngitis mainly through an antibiotic effect and downregulation of NF-κB signalling pathway.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , FN-kappa B/metabolismo , Faringitis/tratamiento farmacológico , Animales , Antibacterianos/uso terapéutico , Movimiento Celular , Proliferación Celular , Celulosa/química , Biología Computacional , Simulación por Computador , Regulación hacia Abajo , Granuloma/metabolismo , Proteínas Hemolisinas/sangre , Sistema Inmunológico , Inmunidad Innata , Masculino , Ratones , Ratones Endogámicos ICR , Ácido N-Acetilneuramínico/metabolismo , Fagocitosis , Fenolsulfonftaleína/química , Extractos Vegetales/uso terapéutico , Ratas , Saliva/metabolismo , Transducción de Señal , Bazo/metabolismo , Temperatura , Xerostomía/terapia
19.
Subst Use Misuse ; 55(11): 1733-1745, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32441179

RESUMEN

Aim: A range of nations, including countries of the European Union, Australia, and the Americas have recently implemented or proposed reforms to how they control cannabis use, thereby departing from traditional approaches of criminal prohibition that have dominated throughout most of the twentieth century. Given these policy developments and the widespread global use of cannabis, it is critically important to understand the possible risks associated with cannabis use in relation to major societal harms. Methods: This systematic review investigates the potential link between cannabis use and occupational injury. Consequently, it appraises all available current literature from five databases, following Cochrane and PRISMA guidelines. Results: Seven of the 16 reviewed studies show evidence supporting a positive association between cannabis use and occupational injury. One study shows evidence supporting a negative association and the remaining eight studies show no evidence of a significant relation. None of the studies assessed cannabis-related impairment. Only three of the reviewed studies show clear evidence that cannabis use preceded the occupational-injury event. Conclusion: The current body of evidence does not provide sufficient evidence to support the position that cannabis users are at increased risk of occupational injury. Further, the study quality assessment suggests significant biases in the extant literature are present due to potential confounding variables, selection of participants, and measurement of exposures and outcomes. Future high-quality evidence will be needed to elucidate the relation between cannabis use and occupational injury.


Asunto(s)
Cannabis , Traumatismos Ocupacionales , Australia , Cannabis/efectos adversos , Humanos , Formulación de Políticas
20.
J Hand Surg Am ; 45(11): 1091.e1-1091.e4, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32238279

RESUMEN

Aeromonas veronii, a bacterium found in freshwater, is an unusual pathogen in healthy patients. We present a case report of a rare, aggressive subtype in a young, immunocompetent individual. History of injury in an aquatic environment and culture data are key for identification of the causal agent and should dictate acute clinical management and antibiotic therapy. Coverage should include cephalosporins, quinolones, or sulfas if Aeromonas is suspected, and adjusted depending on culture and sensitivity. Early surgical exploration, incision and drainage, and appropriate antimicrobial therapy are the cornerstones for successful treatment of these aggressive, sometimes life-threatening infections.


Asunto(s)
Aeromonas , Infecciones por Bacterias Gramnegativas , Infecciones de los Tejidos Blandos , Aeromonas veronii , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Extremidad Superior
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