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1.
J Infect Dis ; 227(1): 103-112, 2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36350017

RESUMO

BACKGROUND: We previously demonstrated that an intranasal dose of 108 50% tissue culture infectious dose (TCID50) M2-deficient single replication (M2SR) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection. METHODS: Serosusceptible subjects aged 18-49 years were randomized to receive 2 doses (108-109 TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines. RESULTS: The vaccine was well tolerated at all dose levels. Against Belgium2015, ≥ 2-fold increases in MN antibodies were noted among 40% (95% confidence interval [CI], 24.9%-56.7%) of subjects following a single 108 TCID50 M2SR dose and among 80.6% (95% CI, 61.4%-92.3%) after 109 dose (P < .001). A single 109 TCID50 dose of M2SR generated ≥4-fold hemagglutination inhibition antibody seroconversion against the vaccine strain in 71% (95% CI, 52.0%-85.8%) of recipients. Mucosal and cellular immune responses were also induced. CONCLUSIONS: These results indicate that M2SR may provide substantial protection against infection with highly drifted strains of H3N2 influenza. CLINICAL TRIALS REGISTRATION: NCT03999554.


In recent years, influenza A H3N2 viruses have evolved into multiple cocirculating clades, resulting in low vaccine efficacy and highlighting the need for more effective influenza vaccines. In a previous challenge study, a single intranasal dose of the investigational vaccine M2SR demonstrated protection against a highly drifted H3N2 influenza challenge virus in a subset of vaccine recipients with a signature immune response. Increasing the dose of the M2SR vaccine in this phase1b study demonstrated a statistically significant increase in the proportion of subjects with the signature immune responses seen previously. The vaccine-induced antibodies were cross-reactive with a panel of drifted H3N2 viruses from 2007 to 2019. Additionally, M2SR generated a rise in serum hemagglutination inhibition antibody titer in 71% of subjects. In contrast, the H3N2 seroresponse rate for the licensed intranasal vaccine FluMist is 10% in seronegative adults. Moreover, M2SR elicited mucosal and cell-mediated immune responses. This study demonstrates that the intranasal M2SR generates a multifaceted immune response and has the potential to provide better efficacy against vaccine-matched strains and influenza drift variants reducing the need to update the vaccine on an annual basis. This is a noteworthy step in the development of a broadly protective influenza vaccine.


Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Adulto , Vírus da Influenza A Subtipo H3N2 , Anticorpos Antivirais , Vacinação , Testes de Inibição da Hemaglutinação
2.
Eur J Orthop Surg Traumatol ; 33(7): 3037-3042, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36995391

RESUMO

PURPOSE: Various fixation techniques have been described for midshaft clavicle fractures in the literature. We hypothesized that use of the Rockwood pin for fixation of displaced midshaft clavicle fractures would result in favorable outcomes in a young active cohort. METHODS: Patients aged 10-35 years who underwent Rockwood clavicle pin fixation at a single institution were identified. Preoperative and postoperative radiographs were reviewed and assessed for fracture characteristics, postoperative alignment, and radiographic union. Postoperative outcome scores were obtained. RESULTS: A total of 39 patients (age 17.3 ± 3.9 years) with clavicle fracture treated with Rockwood pin were identified. Radiographic review demonstrated that 88% of fractures were 100%, or more, displaced, and surgery achieved near-anatomic reduction in 92% of cases. Average time to radiographic union was 2.3 ± 0.8 months, and average time to clinical union was 2.5 ± 0.3 months. One patient required revision for nonunion (3%). Complete outcome responses were obtained for 24 patients, with an average 40 ± 27.7 months of follow-up. Mean Total Clavicle Functional score was 2.75 ± 3.6 for minor patients. For adult patients, Nottingham Clavicle score was 90.7 ± 10.7, mean American Shoulder and Elbow Society score was 92.4 ± 11.2, and mean Single Assessment Numerical Evaluation score was 88.8 ± 21.5. 77% of adults reported no long-term functional limitation; 54% reported a bump at the prior fracture site, but 100% reported satisfaction with shoulder appearance. CONCLUSIONS: In our cohort of young active patients, treatment with Rockwood pin allowed for anatomic reduction, healing with a low nonunion rate, and favorable patient reported outcomes.


Assuntos
Fixação Intramedular de Fraturas , Fraturas Ósseas , Adulto , Humanos , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Consolidação da Fratura/fisiologia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas Ósseas/etiologia , Fixação Intramedular de Fraturas/efeitos adversos , Reoperação , Resultado do Tratamento , Fixação Interna de Fraturas , Estudos Retrospectivos
3.
Int J Hyperthermia ; 39(1): 733-742, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35610101

RESUMO

OBJECTIVE: To achieve a result of a large tumor ablation volume with minimal thermal damage to the surrounding blood vessels by designing a few clinically-adjustable operating parameters in radiofrequency ablation (RFA) for liver tumors abutting complex vascular structures. METHODS: Response surface method (RSM) was employed to correlate the ablated tumor volume (Ra) and thermal damage to blood vessels (Dt) based on RFA operating parameters: ablation time, electrode position, and insertion angle. A coupled electric-thermal-fluid RFA computer model was created as the testbed for RSM to simulate RFA process. Then, an optimal RFA protocol for the two conflicting goals, namely (1) large tumor ablation and (2) small thermal damage to the surrounding blood vessels, has been achieved under a specific ablation environment. RESULTS: Linear regression analysis confirmed that the RFA protocol significantly affected Ra and Dt (the adjusted coefficient of determination Radj2 = 93.61% and 95.03%, respectively). For a proposed liver tumor scenario (liver tumor with a dimension of 4×3×2.9 cm3 abutting a complex vascular structure), an optimized RFA protocol was found based on the regression results in RSM. Compared with a reference RFA protocol, in which the electrode was centered in the tumor with a 12-min ablation time, the optimized RFA protocol has increased Ra  from 98.1% to 99.6% and decreased Dt from 4.1% to 0.4%, achieving nearly the complete ablation of proposed liver tumor and ignorable thermal damages to vessels. CONCLUSION: This work showed that it is possible to design a few clinically-adjustable operating parameters of RFA for achieving a large tumor ablation volume while minimizing thermal damage to the surrounding blood vessels.


Assuntos
Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Ablação por Cateter/métodos , Protocolos Clínicos , Simulação por Computador , Computadores , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia
4.
J Biomech Eng ; 144(10)2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35445240

RESUMO

The lethal electric field (LEF) thresholds for three typical cerebral cells, including a malignant glioblastoma (GBM) cell line and two cell lines from the healthy blood-brain barrier (BBB), treated by irreversible electroporation (IRE) or high-frequency irreversible electroporation (H-FIRE) protocols were investigated in an in vitro three-dimensional (3D) cell model. A conventional IRE protocol (90 pulses, 1 Hz, and 100-µs pulse duration) and three novel H-FIRE protocols (1-3-1, 0.5-1-0.5, and 1-1-1) were used to treat the cerebral cells in both 3D single-cell and two-cell models. The electrical conductivity of the 3D cell model under different electric field strengths were characterized with the method of electrochemical impedance spectroscopy (EIS). Based on EIS, a numerical electrothermal model of electroporation was built for the determination of the LEF threshold with different protocols and temperature monitoring. Cell viability was assessed by fluorescence staining 6 h after the treatment. The results showed no thermal lethal effect on cells when these protocols were used. The LEF threshold for GBM cells was significantly lower than that of the healthy BBB cells. These results suggest the possibility of selective ablation of human cerebral GBM by IRE and H-FIRE treatments with no injury or reversible injury to healthy cells, and the potential use of IRE or H-FIRE for transient disruption of the BBB to allow chemotherapy to reach the tumor.


Assuntos
Eletroporação , Neoplasias , Sobrevivência Celular , Eletroporação/métodos , Frequência Cardíaca , Humanos
5.
HPB (Oxford) ; 24(1): 72-78, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34176743

RESUMO

BACKGROUND: Post-operative pancreatic fistula (POPF) is the most significant cause of morbidity following distal pancreatectomy. Hemopatch™ is a thin, bovine collagen-based hemostatic sealant. We hypothesized that application of Hemopatch™ to the pancreatic stump following distal pancreatectomy would decrease the incidence of clinically-significant POPF. METHODS: We conducted a prospective, single-arm, multicentre phase II study of application of Hemopatch™ to the pancreatic stump following distal pancreatectomy. The primary outcome was clinically-significant POPF within 90 days of surgery. A sample size of 52 patients was required to demonstrate a 50% relative reduction in Grade B/C POPF from a baseline incidence of 20%, with a type I error of 0.2 and power of 0.75. Secondary outcomes included incidence of POPF (all grades), 90-day mortality, 90-day morbidity, re-interventions, and length of stay. RESULTS: Adequate fixation Hemopatch™ to the pancreatic stump was successful in all cases. The rate of grade B/C POPF was 25% (95%CI: 14.0-39.0%). There was no significant difference in the incidence of grade B/C POPF compared to the historical baseline (p = 0.46). The 90-day incidence of Clavien-Dindo grade ≥3 complications was 26.9% (95%CI: 15.6-41.0%). CONCLUSION: The use of Hemopatch™ was not associated with a decreased incidence of clinically-significant POPF compared to historical rates. (NCT03410914).


Assuntos
Pancreatectomia , Fístula Pancreática , Animais , Bovinos , Humanos , Pâncreas , Pancreatectomia/efeitos adversos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos
6.
Int J Hyperthermia ; 38(1): 593-603, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33853496

RESUMO

PURPOSE: To examine the ablation zone, muscle contractions, and temperature increases in both rabbit liver and kidney models in vivo for a custom-made high-frequency irreversible electroporation (H-FIRE) generator. MATERIALS AND METHODS: A total of 18 New Zealand white rabbits were used to investigate five H-FIRE protocols (n = 3 for each protocol) and an IRE protocol (n = 3) for the performance of the designed H-FIRE device in both liver and kidney tissues. The ablation zone was determined by using histological analysis 72 h after treatment. The extent of muscle contractions and temperature change during the application of pulse energy were measured by a commercial accelerometer attached to animals and fiber optic temperature probe inserted into organs with IRE electrodes, respectively. RESULTS: All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues. The area of ablation zone generated in H-FIRE pulse protocols (e.g., 0.3-1 µs, 2000 V, and 90-195 bursts) appears similar to that of IRE protocol (100 µs, 1000 V, and 90 pulses) in both liver and kidney tissues. No significant temperature increase was noticed except for the protocol with the highest pulse energy (e.g., 1 µs, 2000 V, and 180 bursts). CONCLUSION: Our work serves to complement the current H-FIRE pulse waveforms, which can be optimized to significantly improve the quality of ablation zone in terms of precision for liver and kidney tumors in clinical setting.


Assuntos
Eletroporação , Fígado , Animais , Eletrodos , Rim/cirurgia , Fígado/cirurgia , Coelhos , Temperatura
7.
J Biomech Eng ; 143(1)2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34043747

RESUMO

Irreversible electroporation (IRE), a relatively new energy-based tumor ablation technology, has shown itself in the last decade to be able to safely ablate tumors with favorable clinical outcomes, yet little work has been done on optimizing the IRE protocol to variously sized tumors. Incomplete tumor ablation has been shown to be the main reason leading to the local recurrence and thus treatment failure. The goal of this study was to develop a general optimization approach to optimize the IRE protocol for cervical tumors in different sizes, while minimizing the damage to normal tissues. This kind of approach can lay a foundation for future personalized treatment of IRE. First, a statistical IRE cervical tumor death model was built using previous data in our group. Then, a multi-objective optimization problem model was built, in which the decision variables are five IRE-setting parameters, namely, the pulse strength (U), the length of active tip (H), the number of pulses delivered in one round between a pair of electrodes (A), the distance between electrodes (D), and the number of electrodes (N). The domains of the decision variables were determined based on the clinical experience. Finally, the problem model was solved by using nondominated sorting genetic algorithms II (NSGA-II) algorithm to give respective optimal protocol for three sizes of cervical tumors. Every protocol was assessed by the evaluation criterion established in the study to show the efficacy in a more straightforward way. The results of the study demonstrate this approach can theoretically provide the optimal IRE protocol for different sizes of tumors and may be generalizable to other types, sizes, and locations of tumors.


Assuntos
Neoplasias do Colo do Útero , Eletroporação , Feminino , Humanos , Modelos Estatísticos
8.
J Biomech Eng ; 143(10)2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33991087

RESUMO

Electroporation-based therapy (EBT), as a high-voltage-pulse technology has been prevalent with favorable clinical outcomes in the treatment of various solid tumors. This review paper aims to promote the clinical translation of EBT for brain tumors. First, we briefly introduced the mechanism of pore formation in a cell membrane activated by external electric fields using a single cell model. Then, we summarized and discussed the current in vitro and in vivo preclinical studies, in terms of (1) the safety and effectiveness of EBT for brain tumors in animal models, and (2) the blood-brain barrier (BBB) disruption induced by EBT. Two therapeutic effects could be achieved in EBT for brain tumors simultaneously, i.e., the tumor ablation induced by irreversible electroporation (IRE) and transient BBB disruption induced by reversible electroporation (RE). The BBB disruption could potentially improve the uptake of antitumor drugs thereby enhancing brain tumor treatment. The challenges that hinder the application of EBT in the treatment of human brain tumors are discussed in the review paper as well.


Assuntos
Eletroporação
9.
J Biol Chem ; 294(49): 18898-18908, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31662434

RESUMO

Bacterial membrane proteins are integrated into membranes through the concerted activities of a series of integration factors, including membrane protein integrase (MPIase). However, how MPIase activity is complemented by other integration factors during membrane protein integration is incompletely understood. Here, using inverted inner-membrane vesicle and reconstituted (proteo)liposome preparations from Escherichia coli cells, along with membrane protein integration assays and the PURE system to produce membrane proteins, we found that anti-MPIase IgG inhibits the integration of both the Sec-independent substrate 3L-Pf3 coat and the Sec-dependent substrate MtlA into E. coli membrane vesicles. MPIase-depleted membrane vesicles lacked both 3L-Pf3 coat and MtlA integration, indicating that MPIase is involved in the integration of both proteins. We developed a reconstitution system in which disordered spontaneous integration was precluded, which revealed that SecYEG, YidC, or both, are not sufficient for Sec-dependent and -independent integration. Although YidC had no effect on MPIase-dependent integration of Sec-independent substrates in the conventional assay system, YidC significantly accelerated the integration when the substrate amounts were increased in our PURE system-based assay. Similar acceleration by YidC was observed for MtlA integration. YidC mutants with amino acid substitutions in the hydrophilic cavity inside the membrane were defective in the acceleration of the Sec-independent integration. Of note, MPIase was up-regulated upon YidC depletion. These results indicate that YidC accelerates the MPIase-dependent integration of membrane proteins, suggesting that MPIase and YidC function sequentially and cooperatively during the catalytic cycle of membrane protein integration.


Assuntos
Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Lipossomos/metabolismo
10.
Proteome Sci ; 18: 3, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32336955

RESUMO

BACKGROUND: It has been previously shown that doxycycline (Doxy) protects the kidney from preservation injury by inhibition of matrix metalloproteinase. However, the precise molecular mechanism involved in this protection from injury is not known. We used a pharmaco-proteomics approach to identify potential molecular targets associated with kidney preservation injury. METHODS: Rat kidneys were cold perfused with or without doxycycline (Doxy) for 22 h. Kidneys perfusates were analyzed for the presence of injury markers such as lactate dehydrogenase (LDH), and neutrophil-gelatinase associated lipocalin (NGAL). Proteins extracted from kidney tissue were analyzed by 2-dimensional gel electrophoresis. Proteins of interest were identified by mass spectrometry. RESULTS: Triosephosphate isomerase, PGM, dihydropteridine reductase-2, pyridine nucleotide-disulfide oxidoreductase, phosphotriesterase-related protein, and aminoacylase-1A were not affected by cold perfusion. Perfusion with Doxy increased their levels. N(G),N(G)-dimethylarginine dimethylaminohydrolase and phosphoglycerate kinase 1 were decreased after cold perfusion. Perfusion with Doxy led to an increase in their levels. CONCLUSIONS: This study revealed specific metabolic enzymes involved in preservation injury and in the mechanism whereby Doxy protects the kidney against injury during cold perfusion.

11.
Dig Surg ; 37(6): 480-487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32971522

RESUMO

INTRODUCTION: Recent studies suggest that nonoperative management of appendicitis (NOMA) may be a reasonable option for managing uncomplicated acute appendicitis. We examined the Internet to see if patients are likely to find the information they need to make an informed decision between the 2 options. METHODS: A list of 29 search terms was established by a focus group and then entered into Google, resulting in 49 unique webpages, each reviewed by 3 reviewers. Consensus was obtained for bias (surgery, NOMA, or balanced), webpage type, JAMA score, reading grade, and DISCERN score, a measure of quality of written information for patients. RESULTS: Thirty of the 49 websites (61%) favored surgery, while 13 (27%) favored NOMA, and 6 sites (12%) provided balanced information. Twelve of 49 sites (24%) did not list NOMA as an option. The majority of patient-directed (11/12 = 92%) and physician-directed (7/9 = 78%) webpages favored surgery, whereas academic webpages presented a more balanced distribution. Academic and physician-directed webpages ranked higher than commercial and news webpages (median ranks 3 and 4 vs. 7.5 and 8). Only 8/49 sites (16%) mentioned that the presence of a fecalith predicts the failure of NOMA. Reading grades were almost all well above the recommended grade 8 level. CONCLUSION: Most of the webpages available on the Internet do not provide enough information, nor are they sufficiently understandable to allow most patients to make an informed decision about the current options for the management of acute appendicitis.


Assuntos
Apendicite/terapia , Informação de Saúde ao Consumidor/normas , Doença Aguda , Apendicectomia , Viés , Compreensão , Tratamento Conservador , Informação de Saúde ao Consumidor/estatística & dados numéricos , Tomada de Decisões , Humanos , Internet/estatística & dados numéricos
12.
Can Assoc Radiol J ; 70(4): 361-366, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30928202

RESUMO

INTRODUCTION: Although medical factors such as hypertension and coagulopathy have been identified that are associated with hemorrhage after renal biopsy, little is known about the role of technical factors. The purpose of our study was to examine the effects of biopsy needle direction on renal biopsy specimen adequacy and bleeding complications. METHODS: Two hundred and forty-two patients who had undergone ultrasound-guided renal biopsies were included. A printout of the ultrasound picture taken at the time of the biopsy was used to measure the biopsy angle ("angle of attack" [AOA]) and to determine if the biopsy needle was aimed at the upper or lower pole and if the medulla was targeted or avoided. RESULTS: Of the 3 groups of biopsy angle, an AOA of between 50°-70° yielded the most glomeruli per core (P = .001) and the fewest inadequate specimens (4% vs 15% for > 70°, and 9% for < 50°, P = .038). Biopsy directed at a pole vs an interpolar region resulted in fewer inadequate specimens (8% vs 23%, P = .005), while biopsies that were medulla-avoiding resulted in fewer inadequate specimens (5% vs 16%, P = .004) and markedly reduced bleeding complications (12% vs 46%, P < .001) compared to biopsies where the medulla was entered. DISCUSSION: An AOA of approximately 60°, aiming at the poles, and avoiding the medulla were each associated with fewer inadequate biopsies and bleeding complications. While biopsy of the medulla is necessary for some diagnoses, the increased bleeding risk emphasizes the need for communication between nephrologist, pathologist, and radiologist.


Assuntos
Biópsia por Agulha/métodos , Biópsia Guiada por Imagem , Nefropatias/patologia , Ultrassonografia de Intervenção , Adulto , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Transpl Int ; 30(7): 706-712, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28390094

RESUMO

Although hypothermic machine perfusion (HMP) has been shown to be beneficial to deceased donor kidneys, the effect of HMP on living donor kidneys (LDK) is unknown. LDK are subjected to minutes of normothermic ischemia at the time of recovery. Comparison of 16 LDK preserved by HMP with 16 LDK preserved by static cold storage (SCS). Outcomes of interest are resistive indices (RI), both while on HMP and postoperatively, and creatinine clearance (CrCl). Injury markers NGAL and LDH were seen in the perfusate of LDK in amounts similar to what is found for donation after neurological determination of death kidneys. Compared to SCS kidneys, CrCl was significantly higher in the HMP group from days 2 through 7 post-transplant [ie: day 7 (78.8 ± 5.4 vs. 54.0 ± 4.6 ml/min, P = 0.005)]. CrCl at 1 year was higher in the HMP group (81.2 ± 5.8 vs. 70.0 ± 5.3 ml/min, P = 0.03). Early post-transplant RI was significantly lower in the HMP group (0.61 ± 0.02 vs. 0.71 ± 0.02, P < 0.0001). Our data support the assertion that injury does occur during LDK procurement and suggest that some of this injury may be reversed with HMP, resulting in more favorable early RI and graft function compared to SCS kidneys.


Assuntos
Transplante de Rim/métodos , Rim , Doadores Vivos , Preservação de Órgãos/métodos , Adulto , Isquemia Fria , Temperatura Baixa , Creatinina/sangue , Feminino , Humanos , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Perfusão/instrumentação , Perfusão/métodos , Estudos Retrospectivos , Isquemia Quente
14.
Int J Hyperthermia ; 33(4): 367-377, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27868461

RESUMO

AIM: The aim of this study was to investigate the feasibility of achieving relatively large coagulation zones (i.e. ≥3 cm in diameter) with radiofrequency ablation (RFA) by using a broad control system. MATERIALS AND METHODS: A broad control system consists of information such as (i) the area of the tumour tissue for feedback control, (ii) the set-point temperature and (iii) the control law. The proposed approach has advanced knowledge in (i) and (ii) in particular. RFA is known to be limited by tissue dehydration that occurs around the electrode, which results in impedance such that no further energy can be delivered to the tissues. We proposed the notion of "energy gate", an area on the electrode, which is not covered by the dehydrated tissue and through which energy can still be delivered to the surrounding tissues. Given a specific size of energy gate, both (i) the area of the tissue in which the temperature is monitored and (ii) the set-point temperature were determined. A reliable finite element model or simulator for a commercially available electrode was used and the tissue surrounding the RFA electrode was divided into three areas for a comprehensive study of the issues (i) and (ii). Porcine liver tissue (30 specimens in total) and a custom-made RFA device with a RF power generator (100 W and 460 ± 30 kHz) and a Covidien cool-tip electrode (17 gauge and 30 mm exposure) were used to validate the findings regarding the area of the tissue for feedback control and the set-point temperature. RESULTS: The size of coagulation zone achieved was maximised when the area of tissue surrounding the middle part of the active tip (i.e. Point 7) was used for feedback control and when the set-point temperature was set to 90 ^ C (this temperature is determined based on the energy gate through a trial-and-error procedure). At both 80 and 90 ^ C, the coagulation zones generated using Area II were significantly larger than that generated using Area I (p = 0.0028 and 0.0003, respectively) and Area III (P = 0.0010 and < 0.0001, respectively). A similar finding regarding the control area and set-point temperature was confirmed by the in-vitro experiment. When compared with Point a (p < 0.0001) and Point c (p < 0.0001), the largest coagulation zone (1066.7 ± 36.1 mm2) was achieved by controlling the temperature of the tissue area surrounding the middle part of the active tip (i.e. Point b) at 90 ^ C. CONCLUSION: The judicious selection of the control area within the biological tissue for temperature monitoring and the set-point temperature for feedback control is critical in increasing the size of the coagulation zone in the treatment of RFA.

16.
Clin Transplant ; 30(8): 934-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27218443

RESUMO

INTRODUCTION: The purpose of this study is to determine what information about donation after circulatory death (DCD) is available on the Internet and to document the common statements for and against DCD. METHODS: The search terms non-heart-beating donor, donation after cardiac death, DCD, deceased donor, organ donation, and organ harvesting were entered into the four most-accessed English-language Internet search engines. The top 10 webpages from each search (240 webpages) yielded 116 unique sites. Three reviewers reviewed each webpage and recorded statements for and against DCD as well as site type, tone, and mention of DCD. RESULTS: While 59 (50.9%) of the overall 116 sites included DCD information, only 10% of sites found with the term "organ donation" mentioned DCD at all. The sites that did include DCD were mostly (78%) of the type "medical journal" or "hospital or university webpage" and 89% of these had a positive or neutral tone. Nine positive and nine negative tropes were defined using the Grounded Theory Method. CONCLUSION: This study reveals the lack of information regarding DCD in organ donation webpages. Thoughtful responses to these statements should be considered in family discussions and in the design of future webpages.


Assuntos
Internet , Transplante de Órgãos/psicologia , Doadores de Tecidos/psicologia , Coleta de Tecidos e Órgãos/psicologia , Obtenção de Tecidos e Órgãos/organização & administração , Suspensão de Tratamento , Morte Encefálica , Feminino , Humanos , Masculino
17.
Proc Natl Acad Sci U S A ; 110(24): 9734-9, 2013 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-23716687

RESUMO

Presecretory proteins are translocated across biological membranes through protein-conducting channels such as Sec61 (eukaryotes) and SecYEG (bacteria). SecA, a translocation ATPase, pushes preproteins out with dynamic structural changes through SecYEG. SecG, a subunit of the SecYEG channel possessing two transmembrane stretches (TMs), undergoes topology inversion coupled with SecA-dependent translocation. Recently, we characterized membrane protein integrase (MPIase), a glycolipozyme involved in not only protein integration into membranes but also preprotein translocation. We report here that SecG inversion occurs only when MPIase associates with SecYEG. We also found that MPIase modulates the dimer orientation of SecYEG. Cysteine-scanning mutagenesis mapped SecG TM 2 to a relatively hydrophilic environment. The dimer formation of SecG, crosslinked at TM 2, was not observed on SecG inversion, indicating that SecYEG undergoes a dynamic structural change during preprotein translocation.


Assuntos
Proteínas de Escherichia coli/metabolismo , Integrases/metabolismo , Proteínas de Membrana/metabolismo , Precursores de Proteínas/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Sítios de Ligação/genética , Membrana Celular/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Immunoblotting , Integrases/química , Integrases/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Modelos Moleculares , Mutação , Ligação Proteica , Multimerização Proteica , Estrutura Terciária de Proteína , Transporte Proteico , Canais de Translocação SEC
19.
Bioorg Med Chem Lett ; 25(19): 4114-7, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26318995

RESUMO

Tris(3-hydroxypropyl)phosphine (THPP) is demonstrated to be a versatile, water-soluble and air-stable reducing agent, allowing for the rapid, irreversible reductive cleavage of disulfide bonds in both aqueous and buffered aqueous-organic media. The reagent shows exceptional stability at biological pH under which condition it permits the rapid reduction of a wide range of differentially functionalized small-molecule disulfides.


Assuntos
Ar , Dissulfetos/química , Fosfinas/química , Concentração de Íons de Hidrogênio , Indicadores e Reagentes/química , Estrutura Molecular , Oxirredução/efeitos dos fármacos , Fosfinas/farmacologia
20.
Surg Endosc ; 29(2): 381-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24986020

RESUMO

INTRODUCTION: Athletic pubalgia is a syndrome of chronic lower abdomen and groin pain that occurs in athletes. It is the direct result of stress and microtears of the rectus abdominis inserting on the pubis from the antagonizing adductor longus muscles, and weakness of the posterior transversalis fascia and bulging of the inguinal floor. METHODS: Under IRB approval, we conducted a retrospective review of our prospectively competitive athlete patients with athletic pubalgia from 2007 to 2013. RESULTS: A cohort of 54 patients was examined. Mean age was 22.4 years. Most patients were football players (n = 23), triathlon (n = 11), track and field (n = 6), soccer players (n = 5), baseball players (n = 4), swimmers (n = 3), golfer (n = 1), and tennis player (n = 1). Fifty one were males and three were females. All patients failed medical therapy with physiotherapy prior to surgery. 76 % of patients had an MRI performed with 26 % having a right rectus abdominis stripping injury with concomitant strain at the adductor longus musculotendinous junction. 7 % of patients had mild nonspecific edema in the distal bilateral rectus abdominis muscles without evidence of a tear. Twenty patients had no findings on their preoperative MRI, and only one patient was noted to have an inguinal hernia on MRI. All patients underwent laparoscopic totally extraperitoneal inguinal hernia repair with synthetic mesh and ipsilateral adductor longus tenotomy. All patients were able to return to full sports-related activity in 24 days (range 21-28 days). One patient experienced urinary retention and another sustained an adductor brevis hematoma 3 months after completion of rehabilitation and surgical intervention. Mean follow up was 18 months. CONCLUSION: Athletic pubalgia is a disease with a multifactorial etiology that can be treated surgically by a laparoscopic totally extraperitoneal hernia repair with synthetic mesh accompanied with an ipsilateral adductor longus tenotomy allowing patients to return to sports-related activity early with minimal complications.


Assuntos
Traumatismos em Atletas/cirurgia , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Laparoscopia , Reto do Abdome/lesões , Tenotomia , Adulto , Feminino , Hérnia Inguinal/complicações , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Dor/etiologia , Reto do Abdome/cirurgia , Estudos Retrospectivos , Tenotomia/métodos , Adulto Jovem
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