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1.
Immunity ; 55(9): 1645-1662.e7, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-35882236

RESUMO

Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a/b. Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion of Staphylococcus species. Defensins and Mrgpra2 were critical for combating S. aureus infections and the formation of neutrophil abscesses, a hallmark of antibacterial immunity. Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1ß and CXCL2 which are vital for proper amplification and propagation of the antibacterial immune response. This study demonstrated the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.


Assuntos
Infecções Bacterianas , Neutrófilos , Receptores Acoplados a Proteínas G , Animais , Camundongos , Antibacterianos , Proteínas de Transporte , Defensinas/genética , Disbiose , Queratinócitos , Receptores Acoplados a Proteínas G/metabolismo , Staphylococcus aureus
2.
J Med Virol ; 94(10): 4689-4695, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35644902

RESUMO

The massive sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global genomic surveillance strategies allowed the detection of many variants of concern and interest. The variant of interest Lambda (C.37), which originated in South America, has been the most prevalent in Peru and Chile, but its dispersion in other continents still remains unknown. The current study aims to determine the phylogenetic relationship among C.37 isolates worldwide, focusing on spike mutations to understand the spread of Lambda in pandemics. A total of 7441 sequences identified as C.37 were downloaded from the GISAID database; local analysis was carried out to identify spike mutations and phylogenetic analysis was carried out to determine the rate of spread of the virus. Our results showed some spike mutations of Lambda that allowed us to detect small local outbreaks in different countries that occurred in the past and identify several clades that have not yet been designated. Although the lineage C.37 is not epidemiologically relevant in Europe or North America, the endemic behavior of this variant in Peru had a major impact on the second SARS-CoV-2 wave.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Chile , Genoma Viral , Genômica , Humanos , Mutação , Filogenia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
3.
Proc Natl Acad Sci U S A ; 116(22): 10917-10926, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31088972

RESUMO

T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1ß, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4 However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.


Assuntos
Interleucina-17/fisiologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/patogenicidade , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Animais , Modelos Animais de Doenças , Humanos , Linfonodos/imunologia , Camundongos , Infecções Estafilocócicas/microbiologia
4.
Clin J Sport Med ; 32(3): e288-e292, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34320568

RESUMO

OBJECTIVE: To characterize recurrent instability, return to sport (RTS), and patient-reported outcomes (PROs) after arthroscopic Bankart repair for acute traumatic anterior shoulder instability in National Collegiate Athletic Association (NCAA) and National Football League (NFL) football players. DESIGN: Case series. SETTING: Orthopaedic and sports medicine clinic. PARTICIPANTS: National Collegiate Athletic Association and NFL football athletes with traumatic anterior shoulder instability who underwent arthroscopic shoulder stabilization at a single institution with at least 2-year follow-up. INTERVENTIONS OR ASSESSMENT OF RISK FACTORS OR INDEPENDENT VARIABLES: Arthroscopic Bankart repair. MAIN OUTCOME MEASURES: Recurrent instability, RTS, patient satisfaction, the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score. RESULTS: Thirty-three players were included with a mean age of 23.8 years (range, 18-33 years) and a mean follow-up of 6.3 years (range, 4.1-9.3 years). One shoulder (3.0%) had a postoperative subluxation event, and 1 shoulder (3.0%) required revision surgery for issues other than instability; 93.3% of players were able to RTS at the same level or higher for at least 1 season. Mean satisfaction was 8.9 ± 2.3. Mean VAS was 1.0 ± 1.7, and mean ASES and Rowe scores were 90.7 ± 18.5 and 89.7 ± 15.2, respectively. CONCLUSION: Arthroscopic Bankart repair is an effective surgical intervention for traumatic anterior shoulder instability in NCAA and NFL football players. At a mean 6-year follow-up, surgery restored stability in 97% of cases and 93.3% returned to their preinjury level of sport.


Assuntos
Futebol Americano , Instabilidade Articular , Articulação do Ombro , Adulto , Artroscopia , Futebol Americano/lesões , Humanos , Instabilidade Articular/cirurgia , Volta ao Esporte , Articulação do Ombro/cirurgia , Estados Unidos , Adulto Jovem
5.
J Appl Biomech ; 37(1): 6-12, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33022654

RESUMO

Auditory feedback is a simple, low-cost training solution that can be used in rehabilitation, motor learning, and performance development. The use has been limited to the instruction of a single kinematic or kinetic target. The goal of this study was to determine if auditory feedback could be used to simultaneously train 2 lower-extremity parameters to perform a bodyweight back squat. A total of 42 healthy, young, recreationally active males participated in a 4-week training program to improve squat biomechanics. The Trained group (n = 22) received 4 weeks of auditory feedback. Feedback focused on knee flexion angle and center of pressure under the foot at maximum squat depth. The Control group (n = 20) performed squats without feedback. Subjects were tested pre, post, and 1 week after training. The Trained group achieved average target knee flexion angle within 1.73 (1.31) deg (P < .001) after training and 5.36 (3.29) deg (P < .01) at retention. While achieving target knee flexion angle, the Trained group maintained target center of pressure (P < .001). The Control group improved knee range of motion, but were not able to achieve both parameter targets at maximum squat depth (P < .90). Results from this study demonstrate that auditory feedback is an effective way to train 2 independent biomechanical targets simultaneously.


Assuntos
Percepção Auditiva , Retroalimentação Sensorial , Articulação do Joelho , Postura , Amplitude de Movimento Articular , Humanos , Masculino , Adulto Jovem
6.
Hum Reprod ; 35(12): 2755-2762, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33083823

RESUMO

STUDY QUESTION: How does a history of dramatic weight loss linked to bariatric surgery impact IVF outcomes? SUMMARY ANSWER: Women with a history of bariatric surgery who had undergone IVF had a comparable cumulative live birth rate (CLBR) to non-operated patients of the same BMI after the first IVF cycle. WHAT IS KNOWN ALREADY: In the current context of increasing prevalence of obesity in women of reproductive age, weight loss induced by bariatric surgery has been shown to improve spontaneous fertility in obese women. However, little is known on the clinical benefit of bariatric surgery in obese infertile women undergoing IVF. STUDY DESIGN, SIZE, DURATION: This exploratory retrospective multicenter cohort study was conducted in 10 287 IVF/ICSI cycles performed between 2012 and 2016. We compared the outcome of the first IVF cycle in women with a history of bariatric surgery to two age-matched groups composed of non-operated women matched on the post-operative BMI of cases, and non-operated severely obese women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The three exposure groups of age-matched women undergoing their first IVF cycle were compared: Group 1: 83 women with a history of bariatric surgery (exposure, mean BMI 28.9 kg/m2); Group 2: 166 non-operated women (non-exposed to bariatric surgery, mean BMI = 28.8 kg/m2) with a similar BMI to Group 1 at the time of IVF treatment; and Group 3: 83 non-operated severely obese women (non-exposed to bariatric surgery, mean BMI = 37.7 kg/m2). The main outcome measure was the CLBR. Secondary outcomes were the number of mature oocytes retrieved and embryos obtained, implantation and miscarriage rates, live birth rate per transfer as well as birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: No significant difference in CLBR between the operated Group 1 patients and the two non-operated Groups 2 and 3 was observed (22.9%, 25.9%, and 12.0%, in Groups 1, 2 and 3, respectively). No significant difference in average number of mature oocytes and embryos obtained was observed among the three groups. The implantation rates were not different between Groups 1 and 2 (13.8% versus 13.7%), and although lower (6.9%) in obese women of Group 3, this difference was not statistically significant. Miscarriage rates in Groups 1, 2 and 3 were 38.7%, 35.8% and 56.5%, respectively (P = 0.256). Live birth rate per transfer in obese patients was significantly lower compared to the other two groups (20%, 18%, 9.3%, respectively, in Groups 1, 2 and 3, P = 0.0167). Multivariate analysis revealed that a 1-unit lower BMI increased the chances of live birth by 9%. In operated women, a significantly smaller weight for gestational age was observed in newborns of Group 1 compared to Group 3 (P = 0.04). LIMITATIONS, REASONS FOR CAUTION: This study was conducted in France and nearly all patients were Caucasian, questioning the generalizability of the results in other countries and ethnicities. Moreover, 950 women per group would be needed to achieve a properly powered study in order to detect a significant improvement in live birth rate after bariatric surgery as compared to infertile obese women. WIDER IMPLICATIONS OF THE FINDINGS: These data fuel the debate on the importance of pluridisciplinary care of infertile obese women, and advocate for further discussion on whether bariatric surgery should be proposed in severely obese infertile women before IVF. However, in light of the present results, infertile women with a history of bariatric surgery can be reassured that surgery-induced dramatic weight loss has no significant impact on IVF prognosis. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by unrestricted grants from FINOX-Gédéon Richter and FERRING Pharmaceuticals awarded to the ART center of the Clinique Mathilde to fund the data collection and the statistical analysis. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT02884258.


Assuntos
Cirurgia Bariátrica , Infertilidade Feminina , Coeficiente de Natalidade , Estudos de Coortes , Feminino , Fertilização in vitro , França , Humanos , Recém-Nascido , Infertilidade Feminina/terapia , Nascido Vivo , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas
7.
Proc Natl Acad Sci U S A ; 114(26): E5094-E5102, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28607050

RESUMO

Infection is a major complication of implantable medical devices, which provide a scaffold for biofilm formation, thereby reducing susceptibility to antibiotics and complicating treatment. Hematogenous implant-related infections following bacteremia are particularly problematic because they can occur at any time in a previously stable implant. Herein, we developed a model of hematogenous infection in which an orthopedic titanium implant was surgically placed in the legs of mice followed 3 wk later by an i.v. exposure to Staphylococcus aureus This procedure resulted in a marked propensity for a hematogenous implant-related infection comprised of septic arthritis, osteomyelitis, and biofilm formation on the implants in the surgical legs compared with sham-operated surgical legs without implant placement and with contralateral nonoperated normal legs. Neutralizing human monoclonal antibodies against α-toxin (AT) and clumping factor A (ClfA), especially in combination, inhibited biofilm formation in vitro and the hematogenous implant-related infection in vivo. Our findings suggest that AT and ClfA are pathogenic factors that could be therapeutically targeted against Saureus hematogenous implant-related infections.


Assuntos
Anticorpos Antibacterianos/farmacologia , Anticorpos Neutralizantes/farmacologia , Artrite Infecciosa , Biofilmes/efeitos dos fármacos , Implantes Experimentais/microbiologia , Osteomielite , Infecções Estafilocócicas , Staphylococcus aureus/fisiologia , Animais , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/etiologia , Artrite Infecciosa/microbiologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Osteomielite/tratamento farmacológico , Osteomielite/etiologia , Osteomielite/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Titânio
8.
J Allergy Clin Immunol ; 143(4): 1426-1443.e6, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30240702

RESUMO

BACKGROUND: Atopic dermatitis (AD) is associated with epidermal barrier defects, dysbiosis, and skin injury caused by scratching. In particular, the barrier-defective epidermis in patients with AD with loss-of-function filaggrin mutations has increased IL-1α and IL-1ß levels, but the mechanisms by which IL-1α, IL-1ß, or both are induced and whether they contribute to the aberrant skin inflammation in patients with AD is unknown. OBJECTIVE: We sought to determine the mechanisms through which skin injury, dysbiosis, and increased epidermal IL-1α and IL-1ß levels contribute to development of skin inflammation in a mouse model of injury-induced skin inflammation in filaggrin-deficient mice without the matted mutation (ft/ft mice). METHODS: Skin injury of wild-type, ft/ft, and myeloid differentiation primary response gene-88-deficient ft/ft mice was performed, and ensuing skin inflammation was evaluated by using digital photography, histologic analysis, and flow cytometry. IL-1α and IL-1ß protein expression was measured by means of ELISA and visualized by using immunofluorescence and immunoelectron microscopy. Composition of the skin microbiome was determined by using 16S rDNA sequencing. RESULTS: Skin injury of ft/ft mice induced chronic skin inflammation involving dysbiosis-driven intracellular IL-1α release from keratinocytes. IL-1α was necessary and sufficient for skin inflammation in vivo and secreted from keratinocytes by various stimuli in vitro. Topical antibiotics or cohousing of ft/ft mice with unaffected wild-type mice to alter or intermix skin microbiota, respectively, resolved the skin inflammation and restored keratinocyte intracellular IL-1α localization. CONCLUSIONS: Taken together, skin injury, dysbiosis, and filaggrin deficiency triggered keratinocyte intracellular IL-1α release that was sufficient to drive chronic skin inflammation, which has implications for AD pathogenesis and potential therapeutic targets.


Assuntos
Dermatite Atópica/metabolismo , Inflamação/metabolismo , Interleucina-1alfa/metabolismo , Proteínas de Filamentos Intermediários/deficiência , Queratinócitos/metabolismo , Animais , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Disbiose/imunologia , Disbiose/metabolismo , Proteínas Filagrinas , Inflamação/imunologia , Inflamação/microbiologia , Interleucina-1alfa/imunologia , Queratinócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout
9.
Artigo em Inglês | MEDLINE | ID: mdl-31138566

RESUMO

Surgical site infections (SSIs) are commonly caused by Staphylococcus aureus We report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus alpha-toxin, clumping factor A, and four leukocidins (LukSF, LukED, HlgAB, and HlgCB) plus vancomycin had enhanced efficacy compared with control antibody plus vancomycin in two mouse models of S. aureus SSI. Therefore, monoclonal antibody-based neutralization of multiple S. aureus virulence factors may provide an adjunctive perioperative approach to combat S. aureus SSIs.


Assuntos
Antibacterianos/farmacologia , Anticorpos Monoclonais/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Proteínas de Bactérias/imunologia , Anticorpos Amplamente Neutralizantes/farmacologia , Coagulase/imunologia , Leucocidinas/imunologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Infecções Estafilocócicas/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Vancomicina/farmacologia
10.
Trop Med Int Health ; 24(3): 328-338, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30589977

RESUMO

OBJECTIVE: To estimate the prevalence of self-reported tuberculosis TB diagnosed at Peruvian correctional facilities (CFs), and their associated factors. METHODS: Cross-sectional study based on secondary analysis of the National Census held in all Peruvian CFs in 2016. Outcome was defined as self-reported TB diagnosed by a healthcare professional intra-penitentiary. A descriptive bivariate analysis was carried out, followed by multivariate analysis using Poisson regression in order to calculate the adjusted prevalence ratios (PRa). Additionally, a mixed effects multilevel model adjusted by CFs as clusters was performed. RESULTS: Of 77 086 prison inmates in 66 CFs participated in the original census, of which 69 890 were included. Of these, 1754 self-reported TB diagnosed intra-penitentiary, yielding a prevalence of 2510/100 000 PDL. In the final model, self-reported TB was associated with younger age, male gender, lower educational level, not having a stable partner, having prison readmissions and having relatives in prison. There was also strong association with HIV/AIDS (PRa 2.77; 1.84-4.18), STIs (PRa 2.13; 1.46-3.10), DM (PRa 1.99; 1.59-2.50) and recreational drugs use (PRa 1.41; 1.23-1.61). The mixed model showed significant variance for belonging to different CFs (2.13; 1.02-4.44) and CF overcrowding (3.25; 1.37-7.71). CONCLUSIONS: Self-reported TB prevalence found was higher than reported by other lower/lower-middle income countries. Demographic factors, individual clinical features and overcrowding increases the likelihood of self-reported TB.


OBJECTIF: Estimer la prévalence de la tuberculose (TB) auto-déclarée, diagnostiquée dans des établissements pénitentiaires (EP) péruviens et les facteurs associés. MÉTHODES: Etude transversale basée sur une analyse secondaire du recensement national réalisée dans tous les EP péruviens en 2016. Le résultat était défini comme une TB auto-déclarée diagnostiquée par un professionnel de la santé intra-pénitentiaire. Une analyse descriptive à deux variables a été réalisée, suivie d'une analyse à plusieurs variables en utilisant une régression de Poisson afin de calculer les ratios de prévalence ajustés (PRa). En outre, un modèle multiniveau à effets mixtes ajusté selon les EP comme grappes a été réalisé. RÉSULTATS: 77.086 détenus de 66 EP ont participé au recensement initial, dont 69.890 ont été inclus. Parmi ceux-ci, 1.754 cas de TB auto-déclarée ont été diagnostiqués au sein des pénitenciers, soit une prévalence de 2.510/100.000 PDL. Dans le dernier modèle, la TB auto-déclarée était associée à un âge plus jeune, au sexe masculin, à un niveau d'éducation plus faible, à l'absence de partenaire stable, à la réadmission en prison et avoir des parents en prison. Il existait également une forte association avec le VIH/SIDA (PRa: 2,77; 1,84 - 4,18), les IST (PRa: 2,13; 1,46 - 3,10), le diabète (PRa: 1,99; 1,59 - 2,50) et la consommation de drogues à des fins récréatives (PRa: 1,41; 1,23 - 1,61). Le modèle mixte a montré une variance significative pour l'appartenance à différents EP (2,13; 1,02 - 4,44) et au surpeuplement des EP (3,25; 1,37 à 7,71). CONCLUSIONS: La prévalence auto-déclarée de la TB était plus élevée que celle rapportée par d'autres pays à revenu inférieur/moyen-inférieur. Les facteurs démographiques, les caractéristiques cliniques individuelles et le surpeuplement augmentent le risque de TB auto-déclarée.


Assuntos
Tuberculose/epidemiologia , Adulto , Distribuição por Idade , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Prevalência , Fatores de Risco , Autorrelato , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
11.
J Shoulder Elbow Surg ; 28(6): 1154-1158, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30770313

RESUMO

BACKGROUND: The ulnar collateral ligament (UCL), consisting of 3 bundles, is the primary medial restraint in the elbow. Recent research has demonstrated that ultrasound is an effective modality to evaluate the medial elbow, whereas stress radiography is standard practice in the measurement of medial elbow laxity. This study (1) compared dynamic ultrasound (USD) with stress radiography in the evaluation of UCL insufficiency and (2) further evaluated the contribution of the anterior bundle of the UCL to medial elbow stability. METHODS: Stress radiographs and USD were used to obtain coronal plane measurements of the medial joint space of 16 cadaveric elbows before and after USD-guided isolated transection of the anterior bundle of the UCL. Measurements were performed with and without a valgus stress applied to the elbows, and gapping of the ulnohumeral joint space was documented. RESULTS: Transection of the anterior bundle of the UCL resulted in 1.5 mm and 1.7 mm of additional gapping in the ulnohumeral joint as measured with stress radiographs and USD, respectively. No differences were recorded in the ulnohumeral gapping measurements between stress radiography and USD. CONCLUSIONS: The lack of difference between measurements reveals USD is as reliable as stress radiography in evaluating the medial ulnohumeral joint space and continuity of the UCL while eliminating radiation exposure and minimizing cost of the diagnostic examination. The increase in ulnohumeral gapping with isolated transection of the anterior bundle of the UCL demonstrates its significant contribution to medial elbow stability.


Assuntos
Ligamento Colateral Ulnar/diagnóstico por imagem , Ligamento Colateral Ulnar/cirurgia , Articulação do Cotovelo/diagnóstico por imagem , Instabilidade Articular/diagnóstico por imagem , Ultrassonografia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Humanos , Masculino , Radiografia/métodos
12.
J Craniofac Surg ; 30(5): e453-e454, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31299812

RESUMO

Protuberant fibro-osseous lesion of the temporal bone, otherwise known as "Bullough's lesion", is a rare, benign exophytic fibro-osseous tumor. In this brief report, we present a case of a 61-year-old woman with a history of a right-sided skull mass that had been increasing in size for approximately 6 years before presentation. Clinical, radiological and histological features are examined and discussed. We achieved excellent results with surgical resection, with no evidence of recurrence.


Assuntos
Neoplasias Ósseas/cirurgia , Osso Temporal/cirurgia , Cartilagem Articular/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-29311091

RESUMO

Staphylococcus aureus wound infections delay healing and result in invasive complications such as osteomyelitis, especially in the setting of diabetic foot ulcers. In preclinical animal models of S. aureus skin infection, antibody neutralization of alpha-toxin (AT), an S. aureus-secreted pore-forming cytolytic toxin, reduces disease severity by inhibiting skin necrosis and restoring effective host immune responses. However, whether therapeutic neutralization of alpha-toxin is effective against S. aureus-infected wounds is unclear. Herein, the efficacy of prophylactic treatment with a human neutralizing anti-AT monoclonal antibody (MAb) was evaluated in an S. aureus skin wound infection model in nondiabetic and diabetic mice. In both nondiabetic and diabetic mice, anti-AT MAb treatment decreased wound size and bacterial burden and enhanced reepithelialization and wound resolution compared to control MAb treatment. Anti-AT MAb had distinctive effects on the host immune response, including decreased neutrophil and increased monocyte and macrophage infiltrates in nondiabetic mice and decreased neutrophil extracellular traps (NETs) in diabetic mice. Similar therapeutic efficacy was achieved with an active vaccine targeting AT. Taken together, neutralization of AT had a therapeutic effect against S. aureus-infected wounds in both nondiabetic and diabetic mice that was associated with differential effects on the host immune response.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Diabetes Mellitus Experimental/imunologia , Proteínas Hemolisinas/antagonistas & inibidores , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Carga Bacteriana/efeitos dos fármacos , Toxinas Bacterianas/imunologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/microbiologia , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/microbiologia , Proteínas Hemolisinas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/efeitos dos fármacos , Monócitos/microbiologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/microbiologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/complicações , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/microbiologia , Vacinas Antiestafilocócicas/farmacologia , Cicatrização/imunologia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/imunologia , Ferimentos não Penetrantes/microbiologia
14.
Breast Cancer Res Treat ; 168(2): 577-578, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29270699

RESUMO

We would like to express our opinion regarding a Parise and Caggiano paper recently published in your journal. We certainly believe this is a great contribution, since it found that node-negative HER2 (+) breast cancer patients have better survival contrary to the common knowledge. This finding could reflect the consequences of targeted therapies that are changing the natural history of the disease. However, we think that such an interesting analysis could also have been done with stage III and IV patients, since this group of people could benefit greatly from these findings. In fact, new guidelines now recommend the use of HER2-specific therapy for stage IV patients with positive markers, even for life if they do not show signs of progression. Additionally, we would like to discuss the value of adding the Ki-67 marker to the classification proposed by the authors, because several papers consider it an important prognostic factor.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico
15.
J Biomech Eng ; 139(12)2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28877307

RESUMO

Advancements in computational musculoskeletal biomechanics are constrained by a lack of experimental measurement under real-time physiological loading conditions. This paper presents the design, configuration, capabilities, accuracy, and repeatability of The University of Texas at El Paso Joint Load Simulator (UTJLS) by testing four cadaver knee specimens with 47 real-time tests including heel and toe squat maneuvers with and without musculotendon forces. The UTJLS is a musculoskeletal simulator consisting of two robotic manipulators and eight musculotendon actuators. Sensors include eight tension load cells, two force/torque systems, nine absolute encoders, and eight incremental encoders. A custom control system determines command output for position, force, and hybrid control and collects data at 2000 Hz. Controller configuration performed forward-dynamic control for all knee degrees-of-freedom (DOFs) except knee flexion. Actuator placement and specimen potting techniques uniquely replicate muscle paths. Accuracy and repeatability standard deviations across specimen during squat simulations were equal or less than 8 N and 5 N for musculotendon actuators, 30 N and 13 N for ground reaction forces (GRFs), and 4.4 N·m and 1.9 N·m for ground reaction moments. The UTJLS is the first of its design type. Controller flexibility and physical design support axis constraints to match traditional testing rigs, absolute motion, and synchronous real-time simulation of multiplanar kinematics, GRFs, and musculotendon forces. System DOFs, range of motion, and speed support future testing of faster maneuvers, various joints, and kinetic chains of two connected joints.


Assuntos
Fenômenos Mecânicos , Movimento , Músculos/fisiologia , Tendões/fisiologia , Adulto , Fenômenos Biomecânicos , Humanos , Joelho/fisiologia , Masculino , Teste de Materiais , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Fatores de Tempo , Adulto Jovem
16.
Arthroscopy ; 33(6): 1225-1232.e1, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28216289

RESUMO

PURPOSE: To compare the displacement, stiffness, and ultimate failure load of a fixed-loop cortical suspensory device with 2 adjustable-loop devices when positioned on metaphyseal bone. METHODS: Thirty devices (10 of each device) were positioned on the metaphyseal cortex of 30 porcine femora simulating anatomic anterior cruciate ligament femoral tunnel placement. Bovine tendons were used for soft tissue grafts, and the constructs were then cycled 1,000 times and pulled to failure, measuring displacement, stiffness, and failure load. RESULTS: Initial displacement, cyclic displacement, and total displacement were 2.98 mm, 2.09 mm, and 5.08 mm for the Endobutton CL (ECL), 2.82 mm, 2.27 mm, and 5.09 mm for the Tightrope (TRT), and 4.25 mm, 3.19 mm, and 7.44 mm for the adjustable-loop ToggleLoc Inline with Ziploop (TLZ), respectively. There was no difference between the ECL and the TRT on any measured outcome. Differences between the TLZ and ECL were statistically significant (initial displacement P = .024, cyclic displacement P < .001, and total displacement P < .001), as were those between the TLZ and TRT (initial displacement P = .010, cyclic displacement P = .001, and total displacement P < .001). Failure loads were 804 N, 801 N, and 682 N for the TRT, ECL, and TLZ, respectively, with no statistically significant difference. CONCLUSIONS: When positioned on the metaphyseal cortex, there was no difference in the biomechanical performance of the fixed-loop ECL and adjustable-loop TRT, and no lengthening of the TRTs was observed during cycling. However, the TLZ showed statistically significantly lower stiffness and more displacement during cycling with lengthening of the adjustable loop, the clinical significance of which is unknown. CLINICAL RELEVANCE: When used for femoral-sided soft tissue graft fixation in an anatomically placed femoral tunnel, the adjustable-loop TRT was biomechanically equivalent to the fixed-loop ECL. However, the adjustable-loop TLZ showed displacement during biomechanical testing that could potentially contribute to clinical failure after anterior cruciate ligament reconstruction. However, the clinical significance was not directly tested.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/instrumentação , Ligamento Cruzado Anterior/cirurgia , Fêmur/cirurgia , Fixadores Internos , Tendões/transplante , Animais , Fenômenos Biomecânicos , Bovinos , Modelos Animais , Suínos
17.
Am J Obstet Gynecol ; 214(2): 172-191, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26548710

RESUMO

The mechanisms responsible for twinning and disorders of twin gestations have been the subject of considerable interest by physicians and scientists, and cases of atypical twinning have called for a reexamination of the fundamental theories invoked to explain twin gestations. This article presents a review of the literature focusing on twinning and atypical twinning with an emphasis on the phenomena of chimeric twins, phenotypically discordant monozygotic twins, mirror-image twins, polar body twins, complete hydatidiform mole with a coexistent twin, vanishing twins, fetus papyraceus, fetus in fetu, superfetation, and superfecundation. The traditional models attributing monozygotic twinning to a fission event, and more recent models describing monozygotic twinning as a fusion event, are critically reviewed. Ethical restrictions on scientific experimentation with human embryos and the rarity of cases of atypical twinning have limited opportunities to elucidate the exact mechanisms by which these phenomena occur. Refinements in the modeling of early embryonic development in twin pregnancies may have significant clinical implications. The article includes a series of figures to illustrate the phenomena described.


Assuntos
Âmnio/embriologia , Córion/embriologia , Mórula , Gravidez de Gêmeos/fisiologia , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Desenvolvimento Embrionário , Feminino , Feto , Humanos , Mola Hidatiforme , Gravidez , Complicações na Gravidez , Técnicas de Reprodução Assistida , Superfetação , Neoplasias Uterinas
18.
Proc Natl Acad Sci U S A ; 110(8): 2729-34, 2013 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-23382231

RESUMO

Photochemically produced aerosols are common among the atmospheres of our solar system and beyond. Observations and models have shown that photochemical aerosols have direct consequences on atmospheric properties as well as important astrobiological ramifications, but the mechanisms involved in their formation remain unclear. Here we show that the formation of aerosols in Titan's upper atmosphere is directly related to ion processes, and we provide a complete interpretation of observed mass spectra by the Cassini instruments from small to large masses. Because all planetary atmospheres possess ionospheres, we anticipate that the mechanisms identified here will be efficient in other environments as well, modulated by the chemical complexity of each atmosphere.

19.
Arthroscopy ; 32(7): 1384-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27085852

RESUMO

PURPOSE: The purpose of this ex vivo biomechanical study was to evaluate the tensile mechanical properties of 2 modified suture-graft constructs regarding elongation after pre-tensioning and cyclic loading as well as load to failure. METHODS: Thirty fresh-frozen porcine Achilles tendons were randomly divided into 2 groups of 15 specimens to assess elongation of the suture-graft construct across 2 different tendon-grasping techniques: a modified locking SpeedWhip (MLS) stitch and a modified Krackow (MK) stitch. Each tendon was pre-tensioned to 89 N for 10 minutes and then cyclically loaded to 200 N for 200 cycles. Finally, each tendon was loaded to failure. RESULTS: After being pre-tensioned, the MK group elongated significantly more than the MLS group (7.12 ± 0.95 mm v 6.26 ± 0.94 mm, P = .02). Elongation after cyclic loading for the MK and MLS groups was not significantly different (3.39 ± 0.95 mm and 3.21 ± 0.93 mm, respectively; P > .05). The MK group showed a significantly larger load to failure compared with the MLS group (689 ± 61 N v 604 ± 46 N, P = .000024). The mean tendon cross-sectional area was larger in the MK group (399 ± 5 mm(2)v 393 ± 8 mm(2), P = .02), but this difference did not relate to the amount of elongation or load to failure. All but 1 specimen failed by suture breakage at the square knot. CONCLUSIONS: The MLS and MK stitches, pre-tensioned to 89 N for 10 minutes, both effectively minimized suture-graft construct elongation after cyclic loading. Consequently, both suture patterns are recommended for soft-tissue graft fixation. CLINICAL RELEVANCE: The MLS and MK suture configurations may provide sufficient biomechanical fixation of the tendon graft in the clinical setting of soft-tissue fixation without an interference screw.


Assuntos
Tendão do Calcâneo/cirurgia , Técnicas de Sutura , Tendão do Calcâneo/fisiologia , Animais , Fenômenos Biomecânicos/fisiologia , Suínos , Resistência à Tração/fisiologia
20.
Arthroscopy ; 32(7): 1263-70, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27039965

RESUMO

PURPOSE: To report a large number of highly active patients who underwent arthroscopic Bankart repair at our institution over the last decade. METHODS: A retrospective analysis of patients who underwent primary and revision arthroscopic Bankart repairs using bioabsorbable anchors was performed. Outcome measures included recurrence of dislocation, American Shoulder and Elbow Scores (ASES), Rowe, visual analog scale (VAS), return to sports, and satisfaction scores. RESULTS: A total of 94 shoulders met the inclusion criteria. The recurrence rate was 6/94 (6.4%) at a mean follow-up of 5 years (range, 3 to 8.3). The mean postoperative scores were as follows: ASES = 91.5/100; Rowe = 84.3/100; VAS = 0.8/10; satisfaction = 8.8/10. In those who attempted to return to sports, 82.5% were able to return to the same level of competition. Statistical analyses revealed a significant increase in risk of recurrence among high school and recreational athletes. No recurrences were observed among professional or college-level athletes. No significant difference in recurrence rates was observed in regards to age, time to surgery, type of athlete (collision v limited contact), repair of SLAP lesion, number of anchors, or revision surgery. CONCLUSIONS: Although several repair techniques exist for traumatic anterior shoulder instability, arthroscopic repair remains a viable option even in a highly active patient population. This study uniquely identified high school and recreational athletes at higher risk for recurrence. This is perhaps due to inferior shoulder development and technique as well as to limited access to postoperative physical therapy. LEVEL OF EVIDENCE: Level IV, therapeutic case series.


Assuntos
Artroscopia , Traumatismos em Atletas/cirurgia , Lesões de Bankart/cirurgia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Satisfação do Paciente , Recidiva , Estudos Retrospectivos , Volta ao Esporte , Adulto Jovem
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