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Molybdenum cofactor (Moco) deficiency (MoCD) is characterized by neonatal-onset myoclonic epileptic encephalopathy and dystonia with cerebral MRI changes similar to hypoxic-ischemic lesions. The molecular cause of the disease is the loss of sulfite oxidase (SOX) activity, one of four Moco-dependent enzymes in men. Accumulating toxic sulfite causes a secondary increase of metabolites such as S-sulfocysteine and thiosulfate as well as a decrease in cysteine and its oxidized form, cystine. Moco is synthesized by a three-step biosynthetic pathway that involves the gene products of MOCS1, MOCS2, MOCS3, and GPHN. Depending on which synthetic step is impaired, MoCD is classified as type A, B, or C. This distinction is relevant for patient management because the metabolic block in MoCD type A can be circumvented by administering cyclic pyranopterin monophosphate (cPMP). Substitution therapy with cPMP is highly effective in reducing sulfite toxicity and restoring biochemical homeostasis, while the clinical outcome critically depends on the degree of brain injury prior to the start of treatment. In the absence of a specific treatment for MoCD type B/C and SOX deficiency, we summarize recent progress in our understanding of the underlying metabolic changes in cysteine homeostasis and propose novel therapeutic interventions to circumvent those pathological changes.
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Encefalopatías , Metaloproteínas , Sulfito-Oxidasa , Masculino , Recién Nacido , Humanos , Cisteína , Tiosulfatos , Cistina , Coenzimas/metabolismo , Metaloproteínas/metabolismo , Sulfito-Oxidasa/genética , Sulfitos , Cofactores de Molibdeno , MolibdenoRESUMEN
BACKGROUND: Continuing medical education (CME) is an effective way for practicing physicians to acquire up-to-date clinical information. MATERIALS AND METHODS: We conducted four CME seminars in 2007-2010 endorsed by the Chinese Medical Association Council on Medical Education. Overseas telelectures and live case demonstrations were introduced in each seminar via telemedicine based on a digital video transport system. Network stability and packet loss were recorded. An anonymous mini-questionnaire was conducted to evaluate the satisfaction of attendees regarding the image and sound quality, content selection, and overall evaluation. RESULTS: Four telelectures and five live case demonstrations were successfully conducted. Stability of the network was maintained during each videoconference. High-quality videos of 720 × 480 pixels at the rate of 30 frames per second were shown to the entire group of attendees. The time delay between Shanghai and Fukuoka, Japan, was only 0.3 s, and the packet loss was 0%. We obtained 129 valid responses to the mini-questionnaire from a total of 146 attendees. The majority of the attendees were satisfied with the quality of transmitted images and voices and with the selected contents. The overall evaluation was ranked as excellent or good. CONCLUSIONS: Videoconferences are excellent channels for CME programs associated with laparoscopic training.
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Educación Médica Continua/métodos , Laparoscopía/educación , Comunicación por Videoconferencia , China , Humanos , Japón , Control de Calidad , Factores de TiempoRESUMEN
Breast cancer is a significant public health problem globally and prevention strategies have become of great interest as its incidence rises. Exploring the connection between dietary patterns and the reduction of breast cancer risk is considered a promising approach. High levels of fiber, phytochemicals, a good antioxidant profile, and a composition of advantageous fatty acids are characteristics of healthy dietary programs such as the Mediterranean diet. This review summarized and discussed the active compounds that are considered important in preventing breast cancer, including dietary components from recent related reports. These include polyunsaturated fatty acids, fiber, phytochemicals, and alcohol. Although the exact mechanism for preventing breast cancer using these dietary factors is not well understood, the combination of all the elements in a healthy diet plays a role in reducing breast cancer risk. Considering the elevated probability of breast cancer relapse and mortality, it is crucial to investigate the correlation between a nutritious dietary pattern and breast cancer, while identifying bioactive components that have the potential to mitigate the risk of breast cancer incidence.
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Dieta Mediterránea , Neoplasias , Investigación , Antioxidantes , Dieta Saludable , EtanolRESUMEN
The aims of the present study were to examine whether and how frailty impacts the outcomes of breast cancer. Data of women with breast cancer hospitalized during 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS) database. Frailty was identified using a novel algorithm, Hospital Frailty Risk Score (HFRS). Propensity-score (PS) matching was utilized to balance the baseline characteristics between frail and non-frail groups. In-hospital mortality, unfavorable discharge, prolonged length of stay (LOS), and total hospital cost were compared using univariate and multivariable logistic regression analyses. A total of 19,522 patients with metastatic (frailty n = 9,906; no frailty n = 9,716) and 135,200 with non-metastatic breast cancer (frailty n = 30,235; no frailty n = 104,965) were included. After adjustment, frailty was significantly and independently associated with higher risk for in-hospital mortality, unfavorable discharge, prolonged LOS, and greater hospital cost in both metastatic and non-metastatic diseases, in which the impacts of frailty was greater in women with non-metastatic disease. In stratified analysis, frailty had the greatest impact on in-hospital mortality among women had had non-metastatic disease and aged <50 years (aOR = 3.88; 95% CI: 1.95-7.73). In conclusion, frailty is associated with worse outcomes in women with breast cancer, and the effects are greater in non-metastatic disease and younger patients.
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Therapies to accelerate vascular repair are currently lacking. Pre-clinical studies suggest that hydrogen sulfide (H2S), an endogenous gasotransmitter, promotes angiogenesis. Here, we hypothesized that sodium thiosulfate (STS), a clinically relevant source of H2S, would stimulate angiogenesis and vascular repair. STS stimulated neovascularization in WT and LDLR receptor knockout mice following hindlimb ischemia as evidenced by increased leg perfusion assessed by laser Doppler imaging, and capillary density in the gastrocnemius muscle. STS also promoted VEGF-dependent angiogenesis in matrigel plugs in vivo and in the chorioallantoic membrane of chick embryos. In vitro, STS and NaHS stimulated human umbilical vein endothelial cell (HUVEC) migration and proliferation. Seahorse experiments further revealed that STS inhibited mitochondrial respiration and promoted glycolysis in HUVEC. The effect of STS on migration and proliferation was glycolysis-dependent. STS probably acts through metabolic reprogramming of endothelial cells toward a more proliferative glycolytic state. These findings may hold broad clinical implications for patients suffering from vascular occlusive diseases.
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Caloric Restriction (CR) extends lifespan and augments cellular stress-resistance from yeast to primates, making CR an attractive strategy for organ protection in the clinic. Translation of CR to patients is complex, due to problems regarding adherence, feasibility, and safety concerns in frail patients. Novel tailored dietary regimens, which modulate the dietary composition of macro- and micronutrients rather than reducing calorie intake promise similar protective effects and increased translatability. However, a direct head-to-head comparison to identify the most potent approach for organ protection, as well as overlapping metabolic consequences have not been performed. We systematically analyzed six dietary preconditioning protocols - fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chained amino acids (BCAA), two dietary regimens restricting sulfur-containing amino acids (SR80/100) and CR - in a rodent model of renal ischemia-reperfusion injury (IRI) to quantify diet-induced resilience in kidneys. Of the administered diets, FMD, SR80/100 and CR efficiently protect from kidney damage after IRI. Interestingly, these approaches show overlapping changes in oxidative and hydrogen sulfide (H2S)-dependent cysteine catabolism as a potential common mechanism of organ protection.
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Cisteína , Daño por Reperfusión , Animales , Restricción Calórica , Dieta , Humanos , LongevidadRESUMEN
Glioblastoma multiforme (GBM) is the most common form of malignant brain tumor, with poor prognosis; the efficacy of current standard therapy for GBM remains unsatisfactory. Magnolol, an herbal medicine from Magnolia officinalis, exhibited anticancer properties against many types of cancers. However, whether magnolol suppresses GBM progression as well as its underlying mechanism awaits further investigation. In this study, we used the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay, apoptosis marker analysis, transwell invasion and wound-healing assays to identify the effects of magnolol on GBM cells. We also validated the potential targets of magnolol on GBM with the GEPIA (Gene Expression Profiling Interactive Analysis) and Western blotting assay. Magnolol was found to trigger cytotoxicity and activate extrinsic/intrinsic apoptosis pathways in GBM cells. Both caspase-8 and caspase-9 were activated by magnolol. In addition, GEPIA data indicated the PKCδ (Protein kinase C delta)/STAT3 (Signal transducer and activator of transcription 3) signaling pathway as a potential target of GBM. Magnolol effectively suppressed the phosphorylation and nuclear translocation of STAT3 in GBM cells. Meanwhile, tumor invasion and migration ability and the associated genes, including MMP-9 (Matrix metalloproteinase-9) and uPA (Urokinase-type plasminogen activator), were all diminished by treatment with magnolol. Taken together, our results suggest that magnolol-induced anti-GBM effect may be associated with the inactivation of PKCδ/STAT3 signaling transduction.
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This study aimed to determine the rates of overall survival and recurrence-free survival among elderly Taiwanese women (>65 years old) according to breast cancer subtype and lymph node status. We identified 554 eligible patients who were >65 years old and had been treated based on international recommendations at our center between June 2005 and June 2015. Patients with the luminal A subtype had the highest rates of overall survival (90.6%) and recurrence-free survival (97.0%), while the lowest overall survival rate was observed in those with the triple-negative subtype (81.3%) and the lowest recurrence-free survival rate was observed in those with the luminal B subtype (84.0%). Multivariate Cox proportional hazard analysis, using the luminal A subtype as the reference, revealed significant differences in recurrence-free survival among luminal B patients according to lymph node status. Among elderly Taiwanese women with breast cancer, the breast cancer subtype might help predict survival outcomes. The luminal B subtype was associated with poor recurrence-free survival, and lymph node status was useful for predicting recurrence-free survival in this subset of patients.
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Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Análisis Multivariante , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Análisis de Supervivencia , TaiwánRESUMEN
BACKGROUND: Various types of incisions have been applied in simultaneous resections of colorectal cancer and synchronous liver metastases. We describe our experience with the reversed L-shaped incision for simultaneous right hemicolectomy and liver resection. METHODS: We applied the reversed L-shaped incision in nine patients who underwent simultaneous right hemicolectomy and right liver resection or left hepatectomy. A reversed L-shaped incision of the abdomen was consisted of midline and transverse incisions with the junction of the umbilicus. The operative field was kept open using Kent retractors. First, right colon mobilization was performed easily and right hemicolectomy was performed. Subsequently, liver mobilization with identification of hepatic vessels was achieved and right liver resection or left hepatectomy was performed. RESULTS: The reversed L-shaped incision successfully provided a good and rapid exposure in nine patients. There were no complications, such as wound infection, lung atelectasis/pneumonia, or incisional hernia, in patients with the reversed L-shaped incision. CONCLUSIONS: Our preliminary experience demonstrated that the reversed L-shaped incision might be a good choice in a subset of patients with simultaneous right hemicolectomy and right liver resection or left hepatectomy. However, a large, prospective, controlled study comparing different incision types in the same procedure with variables, such as operating time, postoperative pain scores, patient's satisfaction, and postoperative complication, is needed to support the benefit of the reversed L-shaped incision.
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Colectomía/métodos , Neoplasias Colorrectales/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Traditional narrowband telemedicine cannot provide quality dynamic images. We conducted videoconferences of laparoscopic and endoscopic operations via an uncompressed video transmission technique. A superfast broadband Internet link was set up between Shanghai in the People's Republic of China and Fukuoka in Japan. Uncompressed dynamic video images of laparoscopic and endoscopic operations were transmitted by a digital video transfer system (DVTS). Seven teleconferences were conducted between June 2005 and June 2007. Of the 7 teleconferences, 5 were live surgical demonstrations and 3 were recorded video teleconsultations. Smoothness of the motion picture, sharpness of images, and clarity of sound were benefited by this form of telemedicine based upon DVTS. Telemedicine based upon DVTS is a superior choice for laparoscopic and endoscopic skill training across the borders.
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Compresión de Datos , Endoscopía , Laparoscopía , Telemedicina , Cirugía Asistida por Video , Asia Oriental , Humanos , Médicos , Encuestas y Cuestionarios , Comunicación por VideoconferenciaRESUMEN
Gallbladder torsion is a rare, acute abdominal disease. It was first reported by Wendell in 1898. Since then, only 500 cases have been reported. Gallbladder torsion occurs in all age groups, although it usually appears in the latter stages of life. The occurrence ratio between women and men is 3:1. Most cases are diagnosed during surgery. The main treatment is surgical detorsion and cholecystectomy. Despite progress in radiologic imaging diagnosis, it is not easy to obtain a precise preoperative diagnosis of gallbladder torsion. In previous reports, only 9.8% of all gallbladder torsion cases were diagnosed preoperatively. We present a case of acute body-neck gallbladder torsion in an elderly man, and we review the radiologic findings of magnetic resonance imaging, computed tomography, and ultrasonography. The radiologic findings in the present case were helpful in obtaining a preoperative diagnosis of gallbladder torsion. The diagnosis was confirmed by T2-weighted magnetic resonance images, which showed an intra-gallbladder segment located between the body and neck of the gallbladder, with a notable crease within this segment.
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Enfermedades de la Vesícula Biliar , Anomalía Torsional , Anciano , Colecistectomía Laparoscópica , Colecistitis/etiología , Diagnóstico Precoz , Enfermedades de la Vesícula Biliar/complicaciones , Enfermedades de la Vesícula Biliar/diagnóstico , Enfermedades de la Vesícula Biliar/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Anomalía Torsional/complicaciones , Anomalía Torsional/diagnóstico , Anomalía Torsional/cirugíaRESUMEN
BACKGROUND: Warm water sitz bath is advised for a variety of anorectal disorders. However, preparation of the sitz bath is sometimes difficult for patients. As an alternative to the sitz bath, we have adapted a water spray method. A randomized, controlled study was conducted to determine if the water spray method has similar effects to the sitz bath in the post-hemorrhoidectomy period and it is easy to carry out. METHODS: A total of 120 patients were randomly assigned to water spray or sitz bath groups. All patients received analgesics and a fiber-rich diet after hemorrhoidectomy. Clinical parameters including pain, irritation (burning or itching sensations), hygiene, convenience, and overall satisfaction were evaluated by a visual analog scale to assess treatment outcome in both groups. RESULTS: There was no obvious difference in age, gender distribution, body mass index, or duration of disease between groups. There were no significant difference in scores for postoperative pain (p = 0.23), irritation (p = 0.48), or hygiene (p = 0.725) between groups. However, the water spray group reported significantly greater convenience (p < 0.05) and higher overall satisfaction (p < 0.05) compared with the sitz bath group. At the end of the 4-week postoperative follow-up period, 90% of patients in the watery spray group and 93% of patients in the sitz bath group showed complete wound healing. There were no significant differences in postoperative complications between groups. CONCLUSION: Our results demonstrate that the water spray method could provide a safe and reliable alternative to the sitz bath for post-hemorrhoidectomy care. Furthermore, the water spray method could be used instead of the sitz bath as a more convenient and satisfactory form of treatment.
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Hemorroides/cirugía , Hidroterapia/métodos , Dolor Postoperatorio/terapia , Agua/farmacología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Hemorroides/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Cuidados Posoperatorios/métodos , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
Internal abdominal herniations are rare. A 34-year-old healthy man was seen in the emergency room because of severe lower abdominal pain and episodic vomiting. Pericecal internal herniation of the inferior ileocecal recess was suspected by abdominal CT study and confirmed by exploratory laparotomy. Finally, the herniated ileal loops were reduced, and the redundant peritoneum was resected. In the present case, CT demonstrates the precise anatomic diagnosis and shows acute complications that should be recommended preoperatively. Urgent surgical intervention is necessary to prevent strangulation, which is responsible for high mortality. Early diagnosis and treatment had a good outcome.