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1.
J Clin Microbiol ; 62(7): e0020324, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38934681

RESUMEN

In this study, we investigated the genomic changes in a major methicillin-resistant Staphylococcus aureus (MRSA) clone following a significant outbreak at a hospital. Whole-genome sequencing of MRSA isolates was utilized to explore the genomic evolution of post-outbreak MRSA strains. The epidemicity of the clone declined over time, coinciding with the introduction of multimodal infection control measures. A genome-wide association study (GWAS) identified multiple genes significantly associated with either high or low epidemic success, indicating alterations in mobilome, virulence, and defense mechanisms. Random Forest models pinpointed a gene related to fibrinogen binding as the most influential predictor of epidemicity. The decline of the MRSA clone may be attributed to various factors, including the implementation of new infection control measures, single nucleotide polymorphisms accumulation, and the genetic drift of a given clone. This research underscores the complex dynamics of MRSA clones, emphasizing the multifactorial nature of their evolution. The decline in epidemicity seems linked to alterations in the clone's genetic profile, with a probable shift towards decreased virulence and adaptation to long-term carriage. Understanding the genomic basis for the decline of epidemic clones is crucial to develop effective strategies for their surveillance and management, as well as to gain insights into the evolutionary dynamics of pathogen genomes.


Asunto(s)
Infección Hospitalaria , Brotes de Enfermedades , Evolución Molecular , Genoma Bacteriano , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Secuenciación Completa del Genoma , Humanos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/clasificación , Genoma Bacteriano/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Epidemiología Molecular
2.
J Inherit Metab Dis ; 47(3): 494-508, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38196161

RESUMEN

Proteostatic regulation of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis, is crucial for maintaining proper brain neurotransmitter homeostasis. Variants of the TH gene are associated with tyrosine hydroxylase deficiency (THD), a rare disorder with a wide phenotypic spectrum and variable response to treatment, which affects protein stability and may lead to accelerated degradation, loss of TH function and catecholamine deficiency. In this study, we investigated the effects of the TH cofactor tetrahydrobiopterin (BH4) on the stability of TH in isolated protein and in DAn- differentiated from iPSCs from a human healthy subject, as well as from THD patients with the R233H variant in homozygosity (THDA) and R328W and T399M variants in heterozygosity (THDB). We report an increase in TH and dopamine levels, and an increase in the number of TH+ cells in control and THDA cells. To translate this in vitro effect, we treated with BH4 a knock-in THD mouse model with Th variant corresponding to R233H in patients. Importantly, treatment with BH4 significantly improved motor function in these mice, as demonstrated by increased latency on the rotarod test and improved horizontal activity (catalepsy). In conclusion, our study demonstrates the stabilizing effects of BH4 on TH protein levels and function in THD neurons and mice, rescuing disease phenotypes and improving motor outcomes. These findings highlight the therapeutic potential of BH4 as a treatment option for THDA patients with specific variants and provide insights into the modulation of TH stability and its implications for THD management.


Asunto(s)
Biopterinas , Modelos Animales de Enfermedad , Neuronas , Fenotipo , Tirosina 3-Monooxigenasa , Biopterinas/análogos & derivados , Animales , Humanos , Tirosina 3-Monooxigenasa/metabolismo , Ratones , Neuronas/metabolismo , Dopamina/metabolismo , Masculino , Fenilcetonurias/tratamiento farmacológico , Fenilcetonurias/genética , Fenilcetonurias/metabolismo , Femenino , Técnicas de Sustitución del Gen
3.
BMC Pediatr ; 24(1): 515, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127623

RESUMEN

BACKGROUND: The remarkable advancements in surgical techniques over recent years have shifted the clinical focus from merely reducing mortality to enhancing the quality of postoperative recovery. The duration of a patient's hospital stay serves as a crucial indicator in evaluating postoperative recovery and surgical outcomes. This study aims to identify predictors of the length of hospital stay for children who have undergone corrective surgery for Ebstein Anomaly (EA). METHODS: We conducted a retrospective cohort study on children (under 18 years of age) diagnosed with EA who were admitted for corrective surgery between January 2009 and November 2021 at Fuwai Hospital. The primary outcome was the Time to Hospital Discharge (THD). Cox proportional hazard models were utilized to identify predictors of THD. In the context of time-to-event analysis, discharge was considered an event. In cases where death occurred before discharge, it was defined as an extended THD, input as 100 days (exceeding the longest observed THD), and considered as a non-event. RESULTS: A total of 270 children were included in this study, out of which three died in the hospital. Following the Cox proportional hazard analysis, six predictors of THD were identified. The hazard ratios and corresponding 95% confidence intervals were as follows: age, 1.030(1.005,1.055); C/R > 0.65, 0.507(0.364,0.707); Carpentier type C or D, 0.578(0.429,0.779); CPB time, 0.995(0.991,0.998); dexamethasone, 1.373(1.051,1.795); and transfusion, 0.680(0.529,0.875). The children were categorized into three groups based on the quartile of THD. Compared to children in the ≤ 6 days group, those in the ≥ 11 days group were associated with a higher incidence of adverse outcomes. Additionally, the duration of mechanical ventilation and ICU stay, as well as hospital costs, were significantly higher in this group. CONCLUSION: We identified six predictors of THD for children undergoing corrective surgery for EA. Clinicians can utilize these variables to optimize perioperative management strategies, reduce adverse complications, improve postoperative recovery, and reduce unnecessary medical expenses.


Asunto(s)
Anomalía de Ebstein , Tiempo de Internación , Humanos , Estudios Retrospectivos , Tiempo de Internación/estadística & datos numéricos , Femenino , Masculino , Anomalía de Ebstein/cirugía , Preescolar , Lactante , Niño , Modelos de Riesgos Proporcionales , Adolescente , Factores de Riesgo , Alta del Paciente
4.
Sensors (Basel) ; 22(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36298118

RESUMEN

Different methods for galvanically isolated monitoring of the mains voltage waveform were evaluated. The aim was to determine the level of distortion of the output signal relative to the input signal and the suitability of each method for calculating active power values. Six fixtures were tested: two voltage transformers, an electronic circuit with a current transformer, a standalone current transformer, a simple circuit with optocouplers, and a circuit with an A/D-D/A converter with capacitive coupling. The input and output waveforms were mathematically analyzed by three methods: (1) calculating the spectral components of waveforms and the relative changes in their THD (total harmonic distortion) values, (2) determining the similarity of waveforms according to the size of the area bounded by the input and output waveform curves, and (3) determining the accuracy of the active power calculation based on the output waveform. The time difference in the zero crossing of the input and output signals was measured, and further calculations for the second and third method were performed on the zero-crossing time shift-corrected waveforms. Other aspects of selecting the appropriate type of monitoring element, such as power consumption or overall circuit complexity, were also evaluated.


Asunto(s)
Suministros de Energía Eléctrica , Electrónica
5.
Sensors (Basel) ; 22(1)2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-35009894

RESUMEN

For the optimization of three-phase hybrid stepper motors with complex electromagnetic structures, an optimization method is presented in this paper. The method is a combination of 3D-FEM and the Taguchi optimization method intended to reduce the dependence on FEM results during the optimization calculation. In this paper, the optimization method is used in the optimization of the tooth shape of the three-phase hybrid stepper motor, and the objective is to reduce the noise caused by harmonics in the "torque-angle characteristic" of the motor. It is clear that traditional optimization methods make it very difficult to carry out such an optimization calculation as a large number of finite element calculations have to be used in the optimization process, and the required computation time is extremely long. Using the optimization method presented in the paper, the optimization becomes feasible because the number of finite element calculations is greatly reduced and the computation time is thus greatly reduced. In order to check the effectiveness of the optimization, the waterfall diagram for noise analysis and its application to check torque ripple are also presented in the paper. Both simulation and test results show that the optimized structure can significantly reduce the motor noise caused by torque ripple. Therefore, the optimization method proposed in this paper can be an effective tool for the optimal design of high-performance motors, including stepper motors.

6.
Sensors (Basel) ; 22(17)2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36080886

RESUMEN

This paper presents the design and simulation of a mass sensitive Lamb wave microsensor with CMOS technology provided by SilTerra. In this work, the effects of the metalization ratio variation on the transmission gain, total harmonic distortion (THD), and two different resonant modes (around 66 MHz and 86 MHz) are shown. It has been found that the metalization ratio can be adjusted in order to obtain a compromise between transmission gain and sensitivity, depending on the design criteria. By adding a Si3N4 layer on top of the device, a five-fold improvement in transmission gain is reached. It was also shown that the transmission of the input differential IDT configuration is 20% more efficient than a single terminal. With this combination, the mass sensitivity is about 114 [cm2/gr].


Asunto(s)
Acústica , Simulación por Computador , Electrodos
7.
Eur Spine J ; 30(8): 2211-2220, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33389202

RESUMEN

PURPOSE: To analyze the clinical and radiographic characteristics of thoracic disk disease associated with myelopathy (TDM). METHODS: This is a retrospective clinical review of prospectively collected imaging data based at a single institute. Based on preoperative CT and MRI, we classified TDM as thoracic disk herniation (TDH), THD with ossification (THDO), TDH with posterior bony avulsions of the vertebrae (TDH with PBA), TDH with posterior vertebral osteophytes (TDH with PVO), giant thoracic osteophyte and calcific discitis with herniation (CDH). Patient characteristics and radiographic data were compared between different types of TDM. RESULTS: Among the 257 patients included, 12.06% of patients presented with symptoms after traumatic events. The most frequent complaint at onset and preoperative was back pain (29.2%) and subjective lower limb weakness (75.5%), respectively. All TDH with PBA is distributed at the lower thoracic segments, while CDH predominantly in the middle and lower thoracic segments. TDH with PBA was more frequent in men than TDH and CDH. Compared with TDH, TDHO, and TDH with PVO, TDH with PBA was younger in surgery age, and TDH and CDH had lower preoperative JOA scores than TDH with PBA. CDH had a larger ventral occupying ratio than TDH, TDHO, and TDH with PBA. CONCLUSIONS: The onset of TDM was generally insidious but may be triggered acutely by apparently trivial events. With a low prevalence, TDM varied clinical symptoms. Different types of TDM had various clinical features, which might indicate different pathological mechanisms.


Asunto(s)
Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Enfermedades de la Médula Espinal , Humanos , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Masculino , Estudios Retrospectivos , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Resultado del Tratamiento
8.
Surgeon ; 19(2): 72-76, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32223930

RESUMEN

BACKGROUND: Although conventional open haemorrhoidectomy and stapled haemorrhoidectomy are effective procedures, they can lead to significant post-operative pain with risks to continence. Current evidence favours transanal haemorrhoidal dearterialisation (THD) and targeted mucopexy to be an efficacious alternative to conventional modalities. Our aim was to assess the midterm outcomes following THD. METHODS: Prospective data was collected for patients undergoing day case THD under a single consultant over a 9-year period (March 2009 to February 2018). Data collected included: intra-operative findings, post-operative pain (defined as requirement of analgesia in recovery), post-operative complications and requirement of further procedures. RESULTS: Over this time period, 271 patients underwent THD, with 203 (74.9%) patients also undergoing targeted mucopexy for 2nd to 4th degree haemorrhoids. Only 4 (1.5%) patients suffered from post-operative complications, including significant bleeding (n = 1), urinary retention (n = 1) and constipation (n = 2). Post-operative pain was identified in only 10 (3.7%) patients; eight of which had simultaneously undergone an additional procedure (e.g. excision of anal polyps and skin tags). Only 5 (1.8%) patients were identified that required further haemorrhoidal invasive intervention subsequently. CONCLUSIONS: These results are comparable with national data and demonstrate that THD is a safe procedure for symptomatic haemorrhoids with minimal morbidity.


Asunto(s)
Canal Anal/irrigación sanguínea , Hemorroides/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/cirugía , Femenino , Humanos , Mucosa Intestinal/cirugía , Ligadura , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Vasculares
9.
Int J Colorectal Dis ; 35(3): 481-490, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31912268

RESUMEN

PURPOSE: To compare the results of laser hemorrhoidoplasty (LHP), excisional hemorrhoidectomy (EH), and sutured mucopexy (MP). METHODS: A randomized, parallel-group, double-blinded, single-center prospective study. PATIENTS: Symptomatic 2nd- or 3rd-degree hemorrhoids patients. INTERVENTIONS: Computer randomization sequence, patient blinding, operating surgeon blinding, and surgeon-evaluator blinding. LHP was performed using a 1470 nm diode laser. Up to 250 J of energy delivered per 1 hemorrhoid. The procedure was performed circumferentially. MP ligations were placed in the area of visible hemorrhoidal tissue. Standard EH was performed up to the level of the hemorrhoidal pedicle. Follow-up at 1 and 6 weeks and 1 year. OUTCOME MEASURES: Recurrence of symptoms requiring treatment, intensity, and duration of pain after the operation, patients' quality of life, fecal incontinence, and patients' evaluation of treatment. RESULTS: A total of 121 patients. Groups were even preoperatively. LHP took 15 min (SD 5.6), MP took 16 min (SD 5.58), and EH took 29 min (SD 10.3). Recurrence requiring treatment rate was 0% after EH, 10% after LHP, and 22% after MP, p = 0.004. LHP and MP were less painful than EH, p < 0.001. Patients after LHP returned to regular activity after 15 days, after MP after 22 days, and after EH after 30 days, p < 0.001. SF-36 scores were better after EH. Symptoms of fecal incontinence improved in all the groups. Patients evaluate LHP better than EH and MP. LIMITATIONS: Single-center study. CONCLUSIONS: Laser hemorrhoidoplasty is a safe, minimally invasive option for hemorrhoids, more effective than MP and less effective than EH. Patients evaluate this technique better than the other two.


Asunto(s)
Hemorreoidectomía , Hemorroides/cirugía , Rayos Láser , Suturas , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Dimensión del Dolor , Resultado del Tratamiento
10.
Sensors (Basel) ; 20(6)2020 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-32214049

RESUMEN

Power quality is a wide-ranging and current topic that involves a huge effort from the scientific community. Power quality issues have to be avoided or solved in order to preserve the integrity of the network and its assets. To this purpose, several power quality indexes and measurement techniques have been developed and used by experts. This paper aims at solving the issue of having an uncertainty associated to the total harmonic distortion (THD) measurements. The idea is to obtain a close-form expression, which only requires the knowledge of the instrument transformer accuracy class, to estimate the mean value and the variance of THD. After the development of such an expression, it has been tested and stressed to confirm its effectiveness and applicability in a variety of conditions, and for harmonics up to 25th (of 50 Hz), defined by the standards.

11.
Biosci Biotechnol Biochem ; 82(4): 600-610, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29504827

RESUMEN

Several dietary flavonoids exhibit anti-oxidative, anti-inflammatory, and anti-osteoporotic activities relevant to prevention of chronic diseases, including lifestyle-related diseases. Dietary flavonoids (glycoside forms) are enzymatically hydrolyzed and absorbed in the intestine, and are conjugated to their glucuronide/sulfate forms by phase II enzymes in epithelial cells and the liver. The intestinal microbiota plays an important role in the metabolism of flavonoids found in foods. Some specific products of bacterial transformation, such as ring-fission products and reduced metabolites, exhibit enhanced properties. Studies on the metabolism of flavonoids by the intestinal microbiota are crucial for understanding the role of these compounds and their impact on our health. This review focused on the metabolic pathways, bioavailability, and physiological role of flavonoids, especially metabolites of quercetin and isoflavone produced by the intestinal microbiota.


Asunto(s)
Dieta , Flavonoides/metabolismo , Microbioma Gastrointestinal , Disponibilidad Biológica , Flavonoides/administración & dosificación , Humanos , Absorción Intestinal , Mucosa Intestinal/metabolismo , Isoflavonas/administración & dosificación , Isoflavonas/metabolismo , Hígado/metabolismo , Polifenoles/metabolismo , Quercetina/administración & dosificación , Quercetina/metabolismo
12.
Surg Innov ; 25(3): 236-241, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29504471

RESUMEN

AIM: This study aims to compare the early and late outcomes of transanal hemorrhoidal dearterialization (THD) versus stapled hemorrhoidopexy (SH) for the treatment of hemorrhoidal disease. METHODS: From January 2013 to December 2014, 100 patients-50 patients on each arm-were randomly allocated to THD or SH groups. The inclusion criteria were grade III and IV hemorrhoids diagnosed by clinical examination and proctoscopy. The primary outcome was to compare the recurrence rate with a minimum follow-up of 2 years, and the secondary outcome was to compare complications rate, time to return to work postsurgery, procedure length, and patient's satisfaction between the 2 techniques. RESULTS: The mean follow-up period was 33.7 ± 7.6. The recurrence rate was 4% in the SH group and 16% in the THD group ( P = .04). There was no difference in the intraoperative and postoperative complications rate; the pain score was significantly higher in the THD group. The mean operative time was significantly shorter in the SH group compared with the THD group. Patients in the THD group returned to work or routine activities significantly later compared with patients in the SH group. The overall satisfaction rate was also higher in the SH group. CONCLUSION: Both procedures are simple and easy to perform for the treatment of grade III and IV hemorrhoids. SH showed better results in terms of lower rate of recurrence, lower postoperative pain, quicker return to work, and higher patient satisfaction.


Asunto(s)
Hemorreoidectomía , Hemorroides/epidemiología , Hemorroides/cirugía , Anciano , Femenino , Estudios de Seguimiento , Hemorreoidectomía/efectos adversos , Hemorreoidectomía/métodos , Hemorreoidectomía/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Recto/cirugía , Grapado Quirúrgico , Resultado del Tratamiento
13.
Tech Coloproctol ; 21(5): 337-344, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28451767

RESUMEN

BACKGROUND: Distal Doppler-guided transanal hemorrhoidal dearterialization with mucopexy (Doppler-guided THD) seems to be associated with better short-term outcomes than conventional hemorrhoidectomy, but there are little data about long-term recurrence. The aim of this study was to compare Doppler-guided THD for grade III-IV hemorrhoids with conventional hemorrhoidectomy with regard to long-term postoperative morbidity and recurrence. METHODS: This was a single-center longitudinal and comparative study of a cohort of patients who underwent either distal Doppler-guided THD with low ligation of the hemorrhoidal artery and mucopexy or conventional excisional hemorrhoidectomy (Milligan and Morgan or Ferguson) for grade III and IV hemorrhoids. Short- and long-term postoperative morbidity was recorded. Severity of hemorrhoid symptoms (bleeding, prolapse, manual reduction, discomfort or pain and impact on quality of life) and fecal continence status (Vaizey score) were evaluated before surgery and at minimum of 1 year after surgery. RESULTS: Eighty-three patients were included in the study. Forty-nine patients (59%) underwent Doppler-guided THD, and 34 (41%) patients underwent conventional hemorrhoidectomy. The 30-day postoperative surgical morbidity was 26.5% in the Doppler-guided THD group and 8.82% in the conventional hemorrhoidectomy group (p = 0.085). No significant differences between the groups were observed in terms of persistence of bleeding, prolapse, need for manual reduction in prolapse and pain. One (2%) patient in the THD group and 2 (5.4%) patients in the conventional hemorrhoidectomy group needed further surgical procedures. Minor fecal incontinence occurred only after conventional hemorrhoidectomy in 2 (5.4%) patients. CONCLUSIONS: Our results showed that Doppler-guided THD is not inferior to conventional excisional hemorrhoidectomy for advanced hemorrhoidal disease in terms of postoperative complications and long-term recurrence of symptoms.


Asunto(s)
Canal Anal/cirugía , Hemorreoidectomía/métodos , Hemorroides/cirugía , Ligadura/métodos , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Arterias/cirugía , Femenino , Hemorroides/patología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Recurrencia , Resultado del Tratamiento
14.
Scand J Gastroenterol ; 51(12): 1429-1432, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27687850

RESUMEN

PURPOSE: Real-time polymerase chain reaction (RT-PCR) is a widely used technique for bacterial and viral infection diagnosis. Herein, we report our preliminary experience in retrieving H. pylori genetic sequences in stools and analyzing genotypic clarithromycin resistance by RT-PCR (noninvasive), with the aim of comparing this procedure with that performed on biopsy samples (invasive). MATERIALS AND METHODS: After 'in vitro' demonstration of H. pylori DNA detection from pure and stool-mixed bacteria, 52 consecutive patients at the first diagnosis of infection were investigated. DNA was extracted from biopsy tissue and stool samples (THD® Fecal Test, Italy). RT-PCR was performed to detect 23S rRNA encoding bacterial subunit gene and search A2143G, A2142C, A2142G point mutations for clarithromycin resistance assessment. RESULTS: RT-PCR showed H. pylori positive DNA in all infected patients with full concordance between tissue and stool detection (100%). We found A2143G mutation in 10 (19.2%), A2142G in 4 (7.7%) and A2142C in 5 (9.6%) patients; there was a full agreement between biopsy and fecal samples. A2143G was found in all the four A2142G positive cases and in three out of the five A2142C positive strains. Overall clarithromycin resistance rate in our series was 23%. CONCLUSIONS: Despite the need of confirmation on large sample, stool RT-PCR analysis could represent a feasible tool to detect H. pylori DNA sequences and antibiotic resistance point mutations. As compared to tissue molecular analysis, this technique is noninvasive, with potential advantages such as improvement of patient compliance, reduction of diagnostic procedure time/cost and improvement of therapeutic outcome.


Asunto(s)
Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , ADN Bacteriano/aislamiento & purificación , Farmacorresistencia Bacteriana/genética , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Heces/microbiología , Femenino , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Italia , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación Puntual , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto Joven
15.
Tech Coloproctol ; 20(7): 461-6, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27170327

RESUMEN

BACKGROUND: Approximately one in five persons living in the USA is maintained on oral anticoagulation. It has typically been recommended that anticoagulation be withheld prior to hemorrhoidal procedures. Transanal hemorrhoidal dearterialization (THD) is a minimally invasive treatment for symptomatic hemorrhoids, and outcomes with patients on anticoagulation who have undergone this procedure have not been previously reported. Here, we report our preliminary results of patients who underwent THD while on anticoagulation. METHODS: During a 53-month period (February 2009-July 2015), patients with symptomatic hemorrhoids refractory to medical management who underwent surgical treatment with THD were retrospectively reviewed. The subset of patients who underwent THD while anticoagulated was compared to a cohort of patient who were not taking anticoagulation and who otherwise demonstrated normal coagulation profiles and who did not have a known predisposition to bleeding or inherited coagulopathy. The primary study endpoint was to assess postoperative bleeding in patients who were maintained on anticoagulation before and after surgery. RESULTS: During the 53-month study period, 106 patients underwent the THD procedure for symptomatic hemorrhoids. Of these, seventy patients underwent THD without anticoagulation therapy, while 36 patients underwent THD while taking one or more oral anticoagulants. The postoperative morbidity between the two cohorts was similar, and specifically there was no statistical difference in the rate of postoperative hemorrhage (19.4 vs. 15.7 %; odds ratio 1.295, 95 % CI 0.455-3.688, p = 0.785). No patient, in either cohort, required re-intervention for any reason during the study period. Patients who underwent THD while on anticoagulation were less likely to have recurrent hemorrhoidal disease during the study's 6-month median follow-up period (2.8 vs. 7.1 %, p = 0.049). CONCLUSIONS: These preliminary data reveal that THD can be performed on anticoagulated patients without cessation of oral agents without increasing morbidity from postoperative bleeding.


Asunto(s)
Anticoagulantes/uso terapéutico , Hemorreoidectomía/métodos , Hemorroides/cirugía , Hemorragia Posoperatoria/etiología , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Femenino , Hemorreoidectomía/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Recurrencia , Estudios Retrospectivos , Cirugía Endoscópica Transanal/efectos adversos
16.
Bioorg Med Chem ; 23(17): 5459-65, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26264841

RESUMEN

CYP2D6, a cytochrome P450 isoform, significantly contributes to the metabolism of many clinically important drugs. Thioridazine (THD) is one of the phenothiazine-type antipsychotics, which exhibit dopamine D2 antagonistic activity. THD shows characteristic metabolic profiles compared to other phenothiazine-type antipsychotics such as chlorpromazine. The sulfur atom attached to the phenothiazine ring is preferentially oxidized mainly by CYP2D6, that is, the 2-sulfoxide is a major metabolite, and interestingly this metabolite shows more potent activity against dopamine D2 receptors than THD. On the other hand, the formation of this metabolite causes many serious problems for its clinical use. Wójcikowski et al. (Drug Metab. Dispos. 2006, 34, 471) reported a kinetic study of THD formed by CYP2D6. Recently, Wang et al. (J. Biol. Chem. 2012, 287, 10834 and J. Biol. Chem. 2015, 290, 5092) revealed the crystallographic structure of THD with CYP2D6. In the current study, the binding and reaction mechanisms at the atomic and electronic levels were computationally examined based on the assumption as to whether or not the different crystallographic binding poses correspond to the different metabolites. The binding and oxidative reaction steps in the whole metabolic process were investigated using molecular dynamics and density functional theory calculations, respectively. The current study demonstrated the essential importance of the orientation of the substrate in the reaction center of CYP2D6 for the metabolic reaction.


Asunto(s)
Antipsicóticos/metabolismo , Tioridazina/metabolismo , Antipsicóticos/farmacología , Citocromo P-450 CYP2D6/metabolismo , Humanos , Simulación de Dinámica Molecular , Tioridazina/farmacología
17.
Molecules ; 20(12): 22546-52, 2015 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-26694338

RESUMEN

Cornaceae plants are known for their edible berries, and their leaves are used as tea. In the present study aqueous leaf extracts from Cornus mas (CM), C. alba (CA), C. flaviramea (CF), C. kousa (CK), and C. officinalis (CO) were tested for their antiproliferative activity in human breast cancer cells (MCF-7). Dose- (50-750 µg/mL) and time (24, 48, 72 h)-dependent antiproliferative effects were measured by WST-1, and correlated with the content of flavonoids (FL), total hydroxycinnamic derivatives (THD), total polyphenols (TP) and tannins (T). Extracts induced time dependent decreases in cell survival; CA, CO and CM were the most effective (11.2%, 10.3% and 11.1%, after 72 h). The ED50 (effective dose) values were similar for all extracts and times tested. The THD and TP were identical in all samples, while a two-fold higher T content was present in CK and CO, and of FL in CF. The maximal effects (% of surviving cells) negatively correlated with the T and TP levels, and positively with FL and THD. The results demonstrate the significant antiproliferative effects of the tested water extracts in MCF-7 cells, in which CA, CO and CM are the most effective; and the effectiveness is related to the T and TP contents.


Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Cornus/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Antineoplásicos Fitogénicos/farmacología , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Células HT29 , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Extractos Vegetales/farmacología , Solventes/química , Agua/química
18.
Hum Mutat ; 35(7): 880-90, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24753243

RESUMEN

Congenital tyrosine hydroxylase deficiency (THD) is found in autosomal-recessive Dopa-responsive dystonia and related neurological syndromes. The clinical manifestations of THD are variable, ranging from early-onset lethal disease to mild Parkinson disease-like symptoms appearing in adolescence. Until 2014, approximately 70 THD patients with a total of 40 different disease-related missense mutations, five nonsense mutations, and three mutations in the promoter region of the tyrosine hydroxylase (TH) gene have been reported. We collected clinical and biochemical data in the literature for all variants, and also generated mutant forms of TH variants previously not studied (N = 23). We compared the in vitro solubility, thermal stability, and kinetic properties of the TH variants to determine the cause(s) of their impaired enzyme activity, and found great heterogeneity in all these properties among the mutated forms. Some TH variants had specific kinetic anomalies and phenylalanine hydroxylase, and Dopa oxidase activities were measured for variants that showed signs of altered substrate binding. p.Arg233His, p.Gly247Ser, and p.Phe375Leu had shifted substrate specificity from tyrosine to phenylalanine and Dopa, whereas p.Cys359Phe had an impaired activity toward these substrates. The new data about pathogenic mechanisms presented are expected to contribute to develop individualized therapy for THD patients.


Asunto(s)
Trastornos Distónicos/genética , Mutación Missense , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismo , Progresión de la Enfermedad , Trastornos Distónicos/diagnóstico , Activación Enzimática , Estabilidad de Enzimas , Expresión Génica , Humanos , Modelos Moleculares , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Solubilidad , Especificidad por Sustrato , Tirosina 3-Monooxigenasa/química
19.
Sci Rep ; 14(1): 17860, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090223

RESUMEN

This study aimed to analyse the treatment and outcomes of traumatic hip dislocation (THD) in children. Clinical data of children with THD were collected at our clinical centre from 1 June 2012 to 1 January 2023. Demographic data, injury mechanism, type of dislocation, combined injuries, reduction time, reduction method, and radiographs were analysed. The Merle d'Aubigné-Postel hip score was used to evaluate hip function and complications at the final follow-up. A total of 19 children with THD were enrolled, including 12 male and seven female patients, with an average age of 8.28 ± 0.99 years. Posterior dislocation was the main type of dislocation (89.47%). Fifteen patients (78.95%) had experienced high-energy injuries and traffic accidents were the main causes of injury (47.37%). Closed reduction was performed as soon as possible, and open reduction was performed if necessary. The hip scores of 18 patients (94.74%) were excellent. One patient had osteonecrosis of the femoral head, with a hip function score of 10 (moderate). High-energy injuries, such as traffic accidents, have gradually become the main cause of injury. The prognosis for THD in children is generally good.


Asunto(s)
Luxación de la Cadera , Humanos , Masculino , Femenino , Niño , Luxación de la Cadera/terapia , Luxación de la Cadera/etiología , Estudios Retrospectivos , Accidentes de Tránsito , Resultado del Tratamiento , Preescolar
20.
Heliyon ; 10(12): e33008, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38988544

RESUMEN

This paper presents a new energy-efficient space vector pulse width modulation (SVPWM) for controlling the switches of a New three-phase inverter (NTPI) for photovoltaic (PV) applications to reduce switching losses, the peak value, and the dv/dt of the common mode voltage (CMV) with fewer number of switches. The proposed system offers a reliable operation in PV energy system with less leakage current and increased efficiency because of the reduction of the CMV, the source of leakage current in PV inverter-based application. Moreover, this also optimizes the operation of electric vehicle application with lower bearing failure. The performance of the proposed system with the new SVPWM is evaluated to the existing PWM in the literature, as well as the active zero state pulse width modulation (AZSPWM) of the two-level inverter introduced under identical conditions. Experiments and MATLAB simulations have both been used in this study.

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