Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 141
Filtrar
1.
J Virol ; 97(5): e0171822, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37125912

RESUMO

Human cytomegalovirus (HCMV) is a leading cause of birth defects in humans. These birth defects include microcephaly, sensorineural hearing loss, vision loss, and cognitive impairment. The process by which the developing fetus incurs these neurological defects is poorly understood. To elucidate some of these mechanisms, we have utilized HCMV-infected induced pluripotent stem cells (iPSCs) to generate in vitro brain organoids, modeling the first trimester of fetal brain development. Early during culturing, brain organoids generate neural rosettes. These structures are believed to model neural tube formation. Rosette formation was analyzed in HCMV-infected and mock-infected brain organoids at 17, 24, and 31 days postinfection. Histological analysis revealed fewer neural rosettes in HCMV-infected compared to mock-infected organoids. HCMV-infected organoid rosettes incurred multiple structural deficits, including increased lumen area, decreased ventricular zone depth, and decreased cell count. Immunofluorescent (IF) analysis found that nidogen-1 (NID1) protein expression in the basement membrane surrounding neural rosettes was greatly reduced by virus infection. IF analysis also identified a similar downregulation of laminin in basement membranes of HCMV-infected organoid rosettes. Knockdown of NID1 alone in brain organoids impaired their development, leading to the production of rosettes with increased lumen area, decreased structural integrity, and reduced laminin localization in the basement membrane, paralleling observations in HCMV-infected organoids. Our data strongly suggest that HCMV-induced downregulation of NID1 impairs neural rosette formation and integrity, likely contributing to many of HCMV's most severe birth defects. IMPORTANCE HCMV infection in pregnant women continues to be the leading cause of virus-induced neurologic birth defects. The mechanism through which congenital HCMV (cCMV) infection induces pathological changes to the developing fetal central nervous system (CNS) remains unclear. Our lab previously reproduced identified clinical defects in HCMV-infected infants using a three dimensional (3D) brain organoid model. In this new study, we have striven to discover very early HCMV-induced changes in developing brain organoids. We investigated the development of neural tube-like structures, neural rosettes. HCMV-infected rosettes displayed multiple structural abnormalities and cell loss. HCMV-infected rosettes displayed reduced expression of the key basement membrane protein, NID1. We previously found NID1 to be specifically targeted in HCMV-infected fibroblasts and endothelial cells. Brain organoids generated from NID1 knockdown iPSCs recapitulated the structural defects observed in HCMV-infected rosettes. Findings in this study revealed HCMV infection induced early and dramatic structural changes in 3D brain organoids. We believe our results suggest a major role for infection-induced NID1 downregulation in HCMV-induced CNS birth defects.


Assuntos
Encéfalo , Glicoproteínas de Membrana , Feminino , Humanos , Lactente , Gravidez , Encéfalo/metabolismo , Encéfalo/virologia , Citomegalovirus/fisiologia , Células Endoteliais/metabolismo , Laminina/metabolismo , Organoides , Formação de Roseta
2.
J Virol ; 96(20): e0133622, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36218358

RESUMO

Nidogen 1 (NID1) is an important basement membrane protein secreted by many cell types. We previously found that human cytomegalovirus (HCMV) infection rapidly induced chromosome 1 breaks and that the basement membrane protein NID1, encoded near the 1q42 break site, was downregulated. We have now determined that the specific breaks in and of themselves did not regulate NID1, rather interactions between several viral proteins and the cellular machinery and DNA regulated NID1. We screened a battery of viral proteins present by 24 hours postinfection (hpi) when regulation was induced, including components of the incoming virion and immediate early (IE) proteins. Adenovirus (Ad) delivery of the tegument proteins pp71 and UL35 and the IE protein IE1 influenced steady-state (ss) NID1 levels. IE1's mechanism of regulation was unclear, while UL35 influenced proteasomal regulation of ss NID1. Real-time quantitative PCR (RT-qPCR) experiments determined that pp71 downregulated NID1 transcription. Surprisingly, WF28-71, a fibroblast clone that expresses minute quantities of pp71, suppressed NID1 transcription as efficiently as HCMV infection, resulting in the near absence of ss NID1. Sequence analysis of the region surrounding the 1q42 break sites and NID1 promoter revealed CCCTC-binding factor (CTCF) binding sites. Chromatin immunoprecipitation experiments determined that pp71 and CTCF were both bound at these two sites during HCMV infection. Expression of pp71 alone replicated this binding. Binding was observed as early as 1 hpi, and colocalization of pp71 and CTCF occurred as quickly as 15 min postinfection (pi) in infected cell nuclei. In fibroblasts where CTCF was knocked down, Adpp71 infection did not decrease NID1 transcription nor ss NID1 protein levels. Our results emphasize another aspect of pp71 activity during infection and identify this viral protein as a key contributor to HCMV's efforts to eliminate NID1. Further, we show, for the first time, direct interaction between pp71 and the cellular genome. IMPORTANCE We have found that human cytomegalovirus (HCMV) utilizes multiple viral proteins in multiple pathways to regulate a ubiquitous cellular basement membrane protein, nidogen-1 (NID1). The extent of the resources and the redundant methods that the virus has evolved to affect this control strongly suggest that its removal provides a life cycle advantage to HCMV. Our discoveries that one of the proteins that HCMV uses to control NID1, pp71, binds directly to the cellular DNA and can exert control when present in vanishingly small quantities may have broad implications in a wide range of infection scenarios. Dysregulation of NID1 in an immunocompetent host is not known to manifest complications during infection; however, in the naive immune system of a developing fetus, disruption of this developmentally critical protein could initiate catastrophic HCMV-induced birth defects.


Assuntos
Citomegalovirus , Proteínas Imediatamente Precoces , Humanos , Citomegalovirus/fisiologia , Proteínas Virais/metabolismo , Fator de Ligação a CCCTC/genética , Regulação Viral da Expressão Gênica , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Membrana Basal/metabolismo
3.
J Virol ; 95(3)2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33177203

RESUMO

In 2000, we reported that human cytomegalovirus (HCMV) induced specific damage on chromosome 1. The capacity of the virus to induce DNA breaks indicated potent interaction between viral proteins and these loci. We have fine mapped the 1q42 breaksite. Transcriptional analysis of genes encoded in close proximity revealed virus-induced downregulation of a single gene, nidogen 1 (NID1). Beginning between 12 and 24 hours postinfection (hpi) and continuing throughout infection, steady-state (ss) NID1 protein levels were decreased in whole-cell lysates and secreted supernatants of human foreskin fibroblasts. Addition of the proteasomal inhibitor MG132 to culture medium stabilized NID1 in virus-infected cells, implicating infection-activated proteasomal degradation of NID1. Targeting of NID1 via two separate pathways highlighted the virus' emphasis on NID1 elimination. NID1 is an important basement membrane protein secreted by many cell types, including the endothelial cells (ECs) lining the vasculature. We found that ss NID1 was also reduced in infected ECs and hypothesized that virus-induced removal of NID1 might offer HCMV a means of increased distribution throughout the host. Supporting this idea, transmigration assays of THP-1 cells seeded onto NID1-knockout (KO) EC monolayers demonstrated increased transmigration. NID1 is expressed widely in the developing fetal central and peripheral nervous systems (CNS and PNS) and is important for neuronal migration and neural network excitability and plasticity and regulates Schwann cell proliferation, migration, and myelin production. We found that NID1 expression was dramatically decreased in clinical samples of infected temporal bones. While potentially beneficial for virus dissemination, HCMV-induced elimination of NID1 may underlie negative ramifications to the infected fetus.IMPORTANCE We have found that HCMV infection promotes the elimination of the developmentally important basement membrane protein nidogen 1 (NID1) from its host. The virus both decreased transcription and induced degradation of expressed protein. Endothelial cell (EC) secretion of basement membrane proteins is critical for vascular wall integrity, and infection equivalently affected NID1 protein levels in these cells. We found that the absence of NID1 in an EC monolayer allowed increased transmigration of monocytes equivalent to that observed after infection of ECs. The importance of NID1 in development has been well documented. We found that NID1 protein was dramatically reduced in infected inner ear clinical samples. We believe that HCMV's attack on host NID1 favors viral dissemination at the cost of negative developmental ramifications in the infected fetus.


Assuntos
Membrana Basal/metabolismo , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/virologia , Citomegalovirus/fisiologia , Endotélio Vascular/metabolismo , Fibroblastos/metabolismo , Glicoproteínas de Membrana/metabolismo , Movimento Celular , Infecções por Citomegalovirus/patologia , Endotélio Vascular/virologia , Fibroblastos/virologia , Humanos , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Transdução de Sinais , Internalização do Vírus
4.
Hum Factors ; : 187208221113625, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35815866

RESUMO

OBJECTIVE: This study examined the interaction of gait-synchronized vibrotactile cues with an active ankle exoskeleton that provides plantarflexion assistance. BACKGROUND: An exoskeleton that augments gait may support collaboration through feedback to the user about the state of the exoskeleton or characteristics of the task. METHODS: Participants (N = 16) were provided combinations of torque assistance and vibrotactile cues at pre-specified time points in late swing and early stance while walking on a self-paced treadmill. Participants were either given explicit instructions (N = 8) or were allowed to freely interpret (N=8) how to coordinate with cues. RESULTS: For the free interpretation group, the data support an 8% increase in stride length and 14% increase in speed with exoskeleton torque across cue timing, as well as a 5% increase in stride length and 7% increase in speed with only vibrotactile cues. When given explicit instructions, participants modulated speed according to cue timing-increasing speed by 17% at cues in late swing and decreasing speed 11% at cues in early stance compared to no cue when exoskeleton torque was off. When torque was on, participants with explicit instructions had reduced changes in speed. CONCLUSION: These findings support that the presence of torque mitigates how cues were used and highlights the importance of explicit instructions for haptic cuing. Interpreting cues while walking with an exoskeleton may increase cognitive load, influencing overall human-exoskeleton performance for novice users. APPLICATION: Interactions between haptic feedback and exoskeleton use during gait can inform future feedback designs to support coordination between users and exoskeletons.

5.
BMC Public Health ; 21(1): 815, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910532

RESUMO

BACKGROUND: Studies have demonstrated that noise is associated with various health problems, such as obesity and hypertension. Although the evidence of the associations of noise with obesity and hypertension is inconsistent, there seems to be a stronger association of the latter. This study aimed to investigate the associations of noise with body mass index (BMI) and blood pressure in adults living in multi-story residential buildings. METHODS: A cross-sectional study was conducted in Hong Kong from February 2018 to September 2019. The Weinstein Noise Sensitivity Scale, Pittsburgh Sleep Quality Index, ENRICHD Social Support Instrument, Patient Health Questionnaire, Perceived Stress Scale, and Hospital Anxiety and Depression Scale were administered to the participants. BMI and blood pressure were assessed. Nocturnal noise exposure and total sleep duration were measured for a week. RESULTS: Five hundred adults (66.4% female), with an average age of 39 years (range: 18-80), completed the study. The average levels of nocturnal noise, BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 51.3 dBA, 22.2 kg/m2, 116.0 mmHg, and 75.4 mmHg, respectively. After adjusting for sociodemographic characteristics, nocturnal noise was associated with BMI (b = 0.54, 95% CI: 0.01 to 1.06, p = 0.045) and SBP (b = 2.90, 95% CI: 1.12 to 4.68, p = 0.001). No association was detected between nocturnal noise and DBP (b = 0.79, 95% CI: - 0.56 to 2.13, p = 0.253). Specifically, higher nocturnal noise was associated with higher BMI (b = 0.72, 95% CI: 0.07 to 1.38, p = 0.031) and SBP (b = 3.91, 95% CI: 2.51 to 5.31, p < 0.001) in females but only higher SBP (b = 3.13, 95% CI: 1.35 to 4.92, p < 0.001) in males. The association between noise and SBP remained significant (b = 2.41, 95% CI: 0.62 to 4.20, p = 0.008) after additionally adjusting for lifestyle, diagnosis of hypertension, psychometric constructs, and sleep. CONCLUSIONS: Indoor nocturnal noise was associated with BMI and blood pressure in females but only blood pressure in males. It is important to control nocturnal noise or use soundproofing materials in buildings to reduce noise exposure.


Assuntos
Hipertensão , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Feminino , Hong Kong/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Masculino
7.
Surg Endosc ; 29(3): 673-85, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25030478

RESUMO

BACKGROUND: We have previously reported that laparoscopic approach improved short-term postoperative courses even for advanced gastric adenocarcinoma, but not morbidity, in comparison with open approach. The objective of this study was to determine the impact of the use of the surgical robot, da Vinci Surgical System, in minimally invasive radical gastrectomy on short-term outcomes. METHODS: A single institutional retrospective cohort study was performed (UMIN000011749). Five hundred twenty-six patients who underwent radical gastrectomy were enrolled. Eighty-eight patients who agreed to uninsured use of the surgical robot underwent robotic gastrectomy, whereas the remaining 438 patients who wished for laparoscopic (lap) approach with health insurance coverage underwent conventional laparoscopic gastrectomy. RESULTS: In the robotic group, morbidity (robotic vs lap 2.3 vs 11.4 %, p = 0.009) and hospital stay following surgery (robotic vs lap 14 [2-31] vs 15 [8-136] days, p = 0.021) were significantly improved, even though operative time (p = 0.003) and estimated blood loss (p = 0.026) were slightly greater. In particular, local (robotic vs lap 1.1 vs 9.8 %, p = 0.007) rather than systemic (robotic vs lap 1.1 vs 2.5 %, p = 0.376) complication rates were attenuated using the surgical robot. Multivariate analyses revealed that non-use of the surgical robot (OR 6.174 [1.454-26.224], p = 0.014), total gastrectomy (OR 4.670 [2.503-8.713], p < 0.001), and D2 lymphadenectomy (OR 2.095 [1.124-3.903], p = 0.020) were the significant independent risk factors determining postoperative complications. CONCLUSIONS: The use of the surgical robot might reduce surgery-related complications, leading to further improvement in short-term postoperative courses following minimally invasive radical gastrectomy.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Laparoscopia/métodos , Robótica/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
Surg Endosc ; 29(11): 3304-12, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25732753

RESUMO

BACKGROUND: A delta-shaped anastomosis in totally laparoscopic Billroth I gastrectomy could be performed easily and sufficiently using only laparoscopic linear staplers. However, the restricted maneuverability and severe blurring of these staplers along with their limited hemostability induced strain. In this study, we determined the feasibility and safety of performing delta-shaped anastomosis using the Endo GIA™ Reloads with Tri-Staple™ Technology combined with Endo GIA™ Ultra Universal stapler (Tri-Staple) with a particular focus on short-term surgical outcomes. METHODS: We performed a single-institutional prospective interventional study (UMIN 000008014). The Tri-Staple was prospectively used on 23 consecutive patients who underwent a curative totally laparoscopic Billroth I gastrectomy with delta-shaped anastomosis. These patients were matched with the 19 patients previously treated using the ENDOPATH(®) ETS Articulating Linear Cutters (ETS) on clinical and demographic characteristics. RESULTS: There were no differences between the groups in anastomosis-related local complications, morbidity, non-anastomosis-related local complications, total systemic complications, and short-term outcomes with the exception of significantly reduced blood loss in the Tri-Staple group (ETS vs. Tri-Staple: 37 [10-306] vs. 15 [5-210] mL, p = 0.02). Intraoperative bleeding from the staple line was significantly reduced in the Tri-Staple group. The postoperative drain indwelling period (ETS vs. Tri-Staple, 6 [4-10] vs. 4 [2-43] days, p = 0.032), fasting period (5 [3-7] vs. 3 [3-24] days, p = 0.022), and hospital stay (14 [10-47] vs. 11 [6-58] days, p = 0.025) were significantly shorter in the Tri-Staple group. There was no mortality in this series. Acceleration assessed as indices of blurring of stapler tip might have a significant adverse influence on staple-line bleeding at stapling sites. CONCLUSION: Totally laparoscopic Billroth I distal gastrectomy using Tri-Staple was feasible and safe with favorable short-term surgical outcomes. Reduced blurring while stapling may be a novel endpoint which newly developed stapling devices should target.


Assuntos
Gastrectomia/métodos , Gastroenterostomia/instrumentação , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Grampeadores Cirúrgicos , Grampeamento Cirúrgico/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia/instrumentação , Gastroenterostomia/métodos , Humanos , Laparoscopia/instrumentação , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Grampeamento Cirúrgico/métodos , Resultado do Tratamento
9.
Eur J Clin Microbiol Infect Dis ; 32(8): 1023-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23443473

RESUMO

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has emerged in a wide variety of animal species, including poultry. The objective of this study was to evaluate three different chromogenic media for MRSA clonal complex (CC) 398 detection in broilers. On three Belgian poultry farms, 50 broiler chickens were sampled per farm from both nose shell and cloaca. All swab specimens were enriched and inoculated the following day on three chromogenic media: chromID MRSA (bioMérieux), Brilliance MRSA 2 Agar (Oxoid) and MRSASelect (Bio-Rad). ChromID had the highest isolation rates, yet, Brilliance MRSA 2 Agar demonstrated the highest relative sensitivity, while MRSASelect and Brilliance MRSA 2 Agar showed the highest relative specificity. A subset of MRSA isolates was confirmed to be CC398 by the polymerase chain reaction (PCR) targeting sau1-hsdS1. In conclusion, Brilliance MRSA 2 Agar outperformed MRSASelect and chromID MRSA for the detection of MRSA in broilers.


Assuntos
Técnicas Bacteriológicas/métodos , Galinhas/microbiologia , Compostos Cromogênicos/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Doenças das Aves Domésticas/microbiologia , Infecções Estafilocócicas/veterinária , Animais , Bélgica , Meios de Cultura , Staphylococcus aureus Resistente à Meticilina/classificação , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia
10.
Gastric Cancer ; 16(1): 56-66, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22382930

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) has come to be widely performed for reduced invasiveness; however, its safety in patients with co-morbidities is not fully examined. We aimed to evaluate the safety and efficacy of gastric ESD with co-morbidities categorized according to ASA Physical Status Classification. METHODS: Two hundred and forty patients of ASA 1 (no co-morbidities), 268 of ASA 2 (mild), and 19 of ASA 3 (severe) were treated by ESD for gastric neoplasms. We retrospectively compared clinicopathological features and treatment results of these three groups. RESULTS: Cases (by percent) treated with anticoagulant/platelet agents were more common in the higher ASA grades (ASA 1, 5.8%; ASA 2, 29.1%; ASA 3, 31.6%; P < 0.0001). There were no significant differences in case numbers treated under guideline criteria, curative resection (ASA 1, 79.6%; ASA 2, 79.9%; ASA 3, 78.9%), or complications related to the ESD procedure (e.g., postoperative bleeding, perforation, thermal injury). By a patient risk prediction model on surgery, i.e., P-POSSUM, morbidity was halved, and no patients died compared to a predicted death rate of 0.5-2%; however, total and complications unrelated to ESD procedure (e.g., aspiration pneumonia, ischemic heat attack) were more common in higher ASA grades (ASA 1, ASA 2, ASA 3: 15.4, 23.9, 26.3%, respectively, P = 0.014; 0.4, 7.1, 0%, respectively, P = 0.00087). Deviation rates from clinical pathway were more frequent and hospital stay (days) longer in higher ASA grades (ASA 1, ASA 2, ASA 3: 11.3, 17.9, 26.3%, respectively, P = 0.014; 8, 8, 9%, respectively, P = 0.0053). CONCLUSIONS: ESD is an efficient treatment for gastric neoplasms with co-morbidities. However, additional caution is required because co-morbidity is a risk factor for both total complications and complications unrelated to the ESD procedure, and may cause deviations in the clinical course and prolonged hospital stay.


Assuntos
Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Mucosa Gástrica/patologia , Gastroscopia/efeitos adversos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Resultado do Tratamento
11.
J Appl Microbiol ; 114(6): 1634-41, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23551524

RESUMO

AIMS: To assess, in a cleaned and disinfected barn environment, the efficacy of an animal disinfection strategy to reduce the livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) prevalence in sows, their offspring and the barn environment. METHODS AND RESULTS: On each farm, six sow rounds were sampled; sows were divided into either a test or control group. Per round, 20 sows and 40 of their piglets were sampled at different time points together with the barn environment. The disinfection strategy of the test groups consisted of washing the sows with a shampoo followed by disinfection of the skin with a solution containing chlorhexidine digluconate and isopropanol. On the first day of disinfection and 6 days after stopping the disinfection, a significant decrease (P < 0·01) of on average 68 and 66% in sow MRSA prevalence was observed on both farms, whereas no decrease was seen in the control groups. Just before weaning, 21-28 days after the end of the disinfection strategy, the difference in MRSA prevalence between both groups was reduced to 4% and no longer significant (P = 0·20). The MRSA prevalence of the piglets in the test groups was significantly lower (26%; P < 0·01) 6 days after the end of disinfection. Just before weaning, this difference was reduced to 5% but still significant (P < 0·01). In the swine nursery unit, no significant difference (P = 0·99) was seen between both groups. Based on semi-quantitative counts, a relationship (r(2)  > 0·6; P < 0·01) was seen between MRSA contamination in the barn environment and the MRSA prevalence in pigs. CONCLUSION: Results show that the tested disinfection strategy reduces temporarily the sow and piglet MRSA status, but does not result in a final reduction in MRSA at weaning or in the nursery unit. SIGNIFICANCE AND IMPACT OF THE STUDY: First report on the efficacy of an animal disinfection strategy to reduce LA-MRSA prevalence in sows, their offspring and the barn environment.


Assuntos
Desinfecção/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Suínos/microbiologia , Animais , Meio Ambiente , Suínos/crescimento & desenvolvimento , Desmame
12.
Surg Endosc ; 27(3): 1000-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23052530

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) enables en bloc resection of early gastrointestinal neoplasms; however, most ESD articles report small series, with short-term outcomes performed by multiple operators on single organ. We assessed short- and long-term treatment outcomes following ESD for early neoplasms throughout the gastrointestinal tract. METHODS: We performed a longitudinal cohort study in single tertiary care referral center. A total of 1,635 early gastrointestinal neoplasms (stomach 1,136; esophagus 138; colorectum 361) were treated by ESD by single operator. Outcomes were complication rates, en bloc R0 resection rates, and long-term overall and disease-specific survival rates at 3 and 5 years for both guideline and expanded criteria for ESD. RESULTS: En bloc R0 resection rates were: stomach: 97.1 %; esophagus: 95.7 %; colorectum: 98.3 %. Postoperative bleeding and perforation rates respectively were: stomach: 3.6 and 1.8 %; esophagus: 0 and 0 %; colorectum: 1.7 and 1.9 %. Intra criteria resection rates were: stomach: 84.9 %; esophagus: 81.2 %; colorectum: 88.6 %. Three-year survival rates for lesions meeting Japanese ESD guideline/expanded criteria were for all organ-combined: 93.4/92.7 %. Five-year rates were: stomach: 88.1/84.6 %; esophagus: 81.6/57.3 %; colorectum: 94.3/100 %. Median follow-up period was 53.4 (range, 0.07-98.6) months. Follow-up rate was 94 % (1,020/1,085). There was no recurrence or disease-related death. CONCLUSIONS: In this large series by single operator, ESD was associated with high curative resection rates and low complication rates across the gastrointestinal tract. Disease-specific and overall long-term prognosis for patients with lesions within intra criteria after curative resection appeared to be excellent.


Assuntos
Endoscopia Gastrointestinal/efeitos adversos , Mucosa Gástrica/cirurgia , Neoplasias Gastrointestinais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/estatística & dados numéricos , Feminino , Neoplasias Gastrointestinais/mortalidade , Humanos , Perfuração Intestinal/etiologia , Perfuração Intestinal/mortalidade , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 1809-1813, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086362

RESUMO

In operational settings, lower-limb active exoskeletons may experience errors, where an actuation that should be present is missed. These missed actuations may impact users' trust in the system and the adapted human-exoskeleton coordination strategies. In this study, we introduced pseudorandom catch trials, in which an assistive exoskeleton torque was not applied, to understand the immediate responses to missed actuations and how users' internal models to an exoskeleton adapt upon repeated exposure to missed actuations. Participants (N = 15) were instructed to complete a stepping task while wearing a bilateral powered ankle exoskeleton. Human-exoskeleton coordination and trust were inferred from task performance (step accuracy), step characteristics (step length and width), and joint kinematics at selected peak locations of the lower limb. Step characteristics and task accuracy were not impacted by the loss of exoskeleton torque as hip flexion was modulated to support completing the stepping task during catch trials, which supports an impacted human-exoskeleton coordination. Reductions in ankle plantarflexion during catch trials suggest user adaptation to the exoskeleton. Trust was not impacted by catch trials, as there were no significant differences in task performance or gait characteristics between earlier and later strides. Understanding the interactions between human-exoskeleton coordination, task accuracy, and step characteristics will support development of exoskeleton controllers for non-ideal operational settings.


Assuntos
Exoesqueleto Energizado , Tornozelo/fisiologia , Fenômenos Biomecânicos/fisiologia , Marcha/fisiologia , Humanos , Caminhada/fisiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-35333715

RESUMO

Robotic ankle exoskeletons have the potential to extend human ability, and actuation timing serves as one of the critical parameters in its controller design. While many experiments have investigated the optimal actuation timing values to achieve different objective functions (e.g. minimizing metabolic cost), studies on users' perception of control parameters are gaining interest as it gives information on people's comfort, coordination, and trust in using devices, as well as providing foundations on how the sensorimotor system detects the exoskeleton behavior changes. The purpose of this study was to evaluate people's sensitivity to changes in exoskeleton actuation timing and its associated exoskeleton ankle angle changes during walking. Participants (n =15) with little or no prior experience with ankle exoskeletons were recruited and performed a psychophysical experiment to characterize their just-noticeable difference (JND) thresholds for actuation timing. Participants wore a bilateral active ankle exoskeleton and compared pairs of torque profiles with different actuation timings and low peak torque (0.225 Nm/kg) while walking on the treadmill. The mean timing JND across participants was 2.8±0.6% stride period. Individuals exhibited different sensitivity towards actuation timing, and their associated exoskeleton ankle angle changes also varied. The variance in ankle angle changes might be explained by their differences in ankle stiffness and different ankle torques provided during walking. The results provide insights into how people perceive the changes in exoskeleton control parameters and show individual differences in exoskeleton usage. The actuation timing JND found in this study can also help determine the necessary controller precision.


Assuntos
Exoesqueleto Energizado , Tornozelo , Articulação do Tornozelo , Fenômenos Biomecânicos , Marcha , Humanos , Percepção , Caminhada
16.
Med Dosim ; 47(3): 288-294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35641365

RESUMO

To evaluate the dosimetric advantages of incorporating the deep inspiration breath hold (DIBH) technique into left breast cancer volumetric modulated arc therapy (VMAT) treatment under Halcyon Linac and to investigate the correlation between mean heart dose (MHD) and distance from the heart to target volumes in left breast cancer VMAT treatment. Fifteen Post-lumpectomy, left-sided breast patients treated between January 2017 and October 2020 were selected. Two plans were generated for each patient using Eclipse treatment planning system (TPS) with the prescription of 50.4 Gy to planning target volume (PTV) breast and 58.8 Gy to PTV boost in 28 fractions. For each patient, DIBH and free breathing (FB) VMAT treatment plans under Halcyon Linac were generated. Dosimetric parameters, monitor unit and beam-on time of both DIBH and FB groups were compared. Three-dimensional distances from heart surface to each target volume were measured on computed tomography images using the TPS contouring tool and their correlation with MHD was evaluated by Pearson's correlation coefficient (r). Comparable target coverage was shown in both groups. Mean dose to heart, left anterior descending artery, and left ventricle in Halcyon-DIBH-VMAT group were significantly reduced by 0.49 Gy, 1.19 Gy, and 0.57 Gy, respectively, compared to Halcyon-FB-VMAT (p < 0.001). A significant lung dose reduction was also achieved in Halcyon-DIBH-VMAT group. There was also a strong negative correlation between MHD and distance from heart surface to PTV boost in both FB and DIBH group (r = -0.741, p < 0.001), but not observed for distance from heart surface to PTV breast. Incorporating DIBH into left breast cancer VMAT treatment under Halcyon Linac demonstrated significant cardiac and lung dose reduction. It was also demonstrated that MHD had a strong negative correlation with distance from heart surface to PTV boost but relatively independent of distance from heart surface to PTV breast. Recognizing the distance from the heart surface to PTV boost as the main factor in affecting MHD could potentially facilitate clinical treatment planning workflow and decision.


Assuntos
Neoplasias da Mama , Radioterapia de Intensidade Modulada , Neoplasias Unilaterais da Mama , Neoplasias da Mama/radioterapia , Suspensão da Respiração , Feminino , Coração , Humanos , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia
17.
J Orthop Res ; 40(6): 1338-1348, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34370873

RESUMO

The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present a novel arthroscopic Raman probe that can "optically biopsy" cartilage and quantify key extracellular matrix (ECM) biomarkers for determining cartilage composition, structure, and material properties in health and disease. Technological and analytical innovations to optimize Raman analysis include (1) multivariate decomposition of cartilage Raman spectra into ECM-constituent-specific biomarkers (glycosaminoglycan [GAG], collagen [COL], water [H2 O] scores), and (2) multiplexed polarized Raman spectroscopy to quantify superficial zone (SZ) COL anisotropy via a partial least squares-discriminant analysis-derived Raman collagen alignment factor (RCAF). Raman measurements were performed on a series of ex vivo cartilage models: (1) chemically GAG-depleted bovine cartilage explants (n = 40), (2) mechanically abraded bovine cartilage explants (n = 30), (3) aging human cartilage explants (n = 14), and (4) anatomical-site-varied ovine osteochondral explants (n = 6). Derived Raman GAG score biomarkers predicted 95%, 66%, and 96% of the variation in GAG content of GAG-depleted bovine explants, human explants, and ovine explants, respectively (p < 0.001). RCAF values were significantly different for explants with abrasion-induced SZ COL loss (p < 0.001). The multivariate linear regression of Raman-derived ECM biomarkers (GAG and H2 O scores) predicted 94% of the variation in elastic modulus of ovine explants (p < 0.001). Finally, we demonstrated the first in vivo Raman arthroscopy assessment of an ovine femoral condyle through intraarticular entry into the synovial capsule. This study advances Raman arthroscopy toward a transformative low-cost, minimally invasive diagnostic platform for objective monitoring of treatment outcomes from emerging OA therapies.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Artroscopia , Cartilagem Articular/química , Bovinos , Colágeno/análise , Glicosaminoglicanos/análise , Humanos , Ovinos
18.
Pathobiology ; 78(6): 328-33, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22104204

RESUMO

OBJECTIVE: The robot-assisted surgical system was developed for minimally invasive surgery and is thought to have the potential to overcome the shortcomings of laparoscopic surgery. We introduced this system for the treatment of gastric cancer in 2008. Here we report our initial experiences of robot-assisted surgery using the da Vinci system. METHODS: A retrospective review of robot-assisted gastrectomy for gastric cancer patients was performed in our institute. The clinicopathological features and surgical outcomes were analyzed. Whereas the procedures of the gastrectomy were similar to those of the usual laparoscopic surgery, several aspects such as the port placement and the role of the assistant were modified from those for conventional laparoscopic surgery. RESULTS: From January 2008 to December 2010, 61 patients with gastric cancer underwent robot-assisted surgery. Gastrectomy was distal in 46 patients, total in 14, proximal in 1 and no operation was converted to the open procedure. D2 lymph node dissection was performed on 28 patients in the distal gastrectomy group and on 11 in the total gastrectomy group. Complications occurred in 2 cases (4%): these consisted of ruptured sutures and hemorrhage from the anastomotic site. CONCLUSIONS: This study demonstrated that robot-assisted gastrectomy using the da Vinci system can be applied safely and effectively for patients with gastric cancer.


Assuntos
Gastrectomia/métodos , Laparoscopia , Robótica , Neoplasias Gástricas/cirurgia , Cirurgia Assistida por Computador , Adulto , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/instrumentação , Humanos , Japão , Laparoscopia/efeitos adversos , Laparoscopia/instrumentação , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Robótica/instrumentação , Neoplasias Gástricas/patologia , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/instrumentação , Resultado do Tratamento
19.
J Chem Phys ; 134(24): 244509, 2011 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-21721645

RESUMO

Versatile Brønsted-Evans-Polanyi (BEP) relations are found from density functional theory for a wide range of transition metal oxides including rutiles and perovskites. For oxides, the relation depends on the type of oxide, the active site, and the dissociating molecule. The slope of the BEP relation is strongly coupled to the adsorbate geometry in the transition state. If it is final state-like the dissociative chemisorption energy can be considered as a descriptor for the dissociation. If it is initial state-like, on the other hand, the dissociative chemisorption energy is not suitable as descriptor for the dissociation. Dissociation of molecules with strong intramolecular bonds belong to the former and molecules with weak intramolecular bonds to the latter group. We show, for the prototype system La-perovskites, that there is a "cyclic" behavior in the transition state characteristics upon change of the active transition metal of the oxide.

20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 4654-4657, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34892251

RESUMO

Actuation timing is an important parameter in powered ankle exoskeleton control that can significantly influence user experience and human-system performance. Previous studies have investigated the actuation timing through optimization under different objective functions, such as minimizing metabolic cost. However, little is known about people's psychological sense of actuation timing. This pilot study measured two subjects' sensitivity to small changes in actuation timing during walking. The just-noticeable difference (JND) threshold was determined via a fitted psychometric function, which quantified subjects' performance in discriminating between a pair of actuation timings. Subjects could detect changes of 3.6% and 6.8% stride period in actuation timing respectively, showing the difference in perception between individuals. The results from this pilot study provide a preliminary understanding of human perception towards exoskeleton control parameters, which offers insight on individual differences in exoskeleton usage and informs exoskeleton precision requirements to minimize undesired human-system interaction.


Assuntos
Exoesqueleto Energizado , Tornozelo , Fenômenos Biomecânicos , Marcha , Humanos , Percepção , Projetos Piloto , Caminhada
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa