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1.
PLoS Pathog ; 13(11): e1006729, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29155899

RESUMO

Type VI secretion systems (T6SS) function to deliver lethal payloads into target cells. Many studies have shown that protection against a single, lethal T6SS effector protein requires a cognate antidote immunity protein, both of which are often encoded together in a two-gene operon. The T6SS and an effector-immunity pair is sufficient for both killing and immunity. HereIn this paper we describe a T6SS effector operon that differs from conventional effector-immunity pairs in that eight genes are necessary for lethal effector function, yet can be countered by a single immunity protein. In this study, we investigated the role that the PefE T6SS immunity protein plays in recognition between two strains harboring nearly identical effector operons. Interestingly, despite containing seven of eight identical effector proteins, the less conserved immunity proteins only provided protection against their native effectors, suggesting that specificity and recognition could be dependent on variation within an immunity protein and one effector gene product. The variable effector gene product, PefD, is encoded upstream from pefE, and displays toxic activity that can be countered by PefE independent of T6SS-activity. Interestingly, while the entire pef operon was necessary to exert toxic activity via the T6SS in P. mirabilis, production of PefD and PefE alone was unable to exert this effector activity. Chimeric PefE proteins constructed from two P. mirabilis strains were used to localize immunity function to three amino acids. A promiscuous immunity protein was created using site-directed mutagenesis to change these residues from one variant to another. These findings support the notion that subtle differences between conserved effectors are sufficient for T6SS-mediated kin discrimination and that PefD requires additional factors to function as a T6SS-dependent effector.


Assuntos
Óperon , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/imunologia , Vibrio cholerae/genética , Proteínas de Bactérias/metabolismo , Escherichia coli/metabolismo , Mutagênese Sítio-Dirigida/métodos , Proteus mirabilis/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sistemas de Secreção Tipo VI/metabolismo , Vibrio cholerae/imunologia
2.
Urol Case Rep ; 34: 101500, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33304819

RESUMO

We highlight the case of a 12 year old male who presented after sustaining a gunshot injury to the scrotum resulting in testicular, prostatic, and urethral transection in addition to pelvic fracture, extra peritoneal bladder injury, and transmural injury to recto sigmoid and ileum. The patient underwent a left orchiectomy, primary repair of the bladder and urethra, placement of universal plate on superior pubic rami, and segmental rectosigmoid and ileum resection. These findings illustrate the collaborative efforts of trauma surgery and urology to treat complex lower genitourinary (GU) injuries and how the direct prioritization of surgical efforts provides acceptable outcomes.

3.
J Pediatr Surg ; 55(1): 169-175, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31706614

RESUMO

PURPOSE: Chest tube (CT) management for pediatric primary spontaneous pneumothorax (PSP) is associated with long hospital stays and high recurrence rates. To streamline management, we explored simple aspiration as a test to predict need for surgery. METHODS: A multi-institution, prospective pilot study of patients with first presentation for PSP at 9 children's hospitals was performed. Aspiration was performed through a pigtail catheter, followed by 6 h observation with CT clamped. If pneumothorax recurred during observation, the aspiration test failed and subsequent management was per surgeon discretion. RESULTS: Thirty-three patients were managed with simple aspiration. Aspiration was successful in 16 of 33 (48%), while 17 (52%) failed the aspiration test and required hospitalization. Twelve who failed aspiration underwent CT management, of which 10 (83%) failed CT management owing to either persistent air leak requiring VATS or subsequent PSP recurrence. Recurrence rate was significantly greater in the group that failed aspiration compared to the group that passed aspiration [10/12 (83%) vs 7/16 (44%), respectively, P=0.028]. CONCLUSION: Simple aspiration test upon presentation with PSP predicts chest tube failure with 83% positive predictive value. We recommend changing the PSP management algorithm to include an initial simple aspiration test, and if that fails, proceed directly to VATS. TYPE OF STUDY: Prospective pilot study LEVEL OF EVIDENCE: Level III.


Assuntos
Tubos Torácicos , Pneumotórax/cirurgia , Toracentese , Adolescente , Criança , Feminino , Humanos , Masculino , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Cirurgia Torácica Vídeoassistida , Falha de Tratamento
4.
J Pediatr Surg ; 53(6): 1092-1097, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29576400

RESUMO

INTRODUCTION: The purpose of this study was to evaluate clinical outcomes in children with asymptomatic congenital lung malformations (CLM) who were initially managed nonoperatively. METHODS: An IRB-approved retrospective review was performed on all CLMs at a single tertiary care referral center (Jan 2006-Dec 2016, n=140). Asymptomatic cases that did not undergo elective resection were evaluated for subsequent CLM-related complications based on clinical records and a telephone quality of life survey. RESULTS: Out of 39 (27.9%) who were initially managed nonoperatively, 13 (33%) developed CLM-related symptoms and underwent surgical intervention at a median age of 6.8years (range, 0.7-19.8years). The most common indication for conversion to operative management was pneumonia (78%). Larger lesions, as measured by CT scan, were significantly associated with the need for subsequent surgical intervention (mean maximal diameter, 5.7 vs. 2.9cm; p=0.005). Based on survey data with a median follow up of 3.9years (range, 0.2-13.2years), 17% developed chronic pulmonary symptoms, including cough (11%) and asthma requiring bronchodilators (12%). CONCLUSION: Although these data support nonoperative management as a viable alternative to surgical resection, at least one-third of CLM children eventually develop pneumonia or other pulmonary symptoms. Larger lesions are correlated with an increased risk for eventual surgical resection. LEVEL OF EVIDENCE: Level IV.


Assuntos
Tratamento Conservador , Pneumopatias/congênito , Pneumopatias/terapia , Pulmão/anormalidades , Anormalidades do Sistema Respiratório/terapia , Adolescente , Adulto , Doenças Assintomáticas , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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