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A growing field: the regulation of axonal regeneration by Wnt signaling

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Neural Regeneration Research 2018年第1期13卷 43-52页

作者： Armando L. Garcia Adanna Udeh Karthik Kalahasty abigail s. hackam Bascom Palmer Eye Institute University of Miami Miller School of Medicine Miami FL USA

The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system （CNs）. Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNs, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement.

关键词： Wnt signaling neuritogenesis retina retinal ganglion cell axonal growth regeneration spinal cord

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腹裂畸形新生儿的分娩时机影响疾病预后

世界核心医学期刊文摘（儿科学分册） 2005年第7期1卷 42-43页

作者： Ergün O. Barksdale E. Ergün F.s. D.J.hackam 宁亮 Division of Pediatric surgery Children's Hospital of Pittsburgh Pittsburgh PA 15213 United States

Background: The delayed onset of intestinal function in children with gastroschisis may be because of the injurious effects of amniotic fluid on the exposed *** has led to consideration of early delivery to minimize intestinal damage and improve outcome, although this has not been carefully *** authors hypothesized that timing of delivery influences outcome in children with gastroschisis, and sought to evaluate the relative impact of factors that predict outcome in this ***: All consecutive patients with gastroschisis (1992-2002) were divided into those delivered before (“early”) or after (“late”) 36 *** peel was described as “thin”or “thick,”based on operative *** measures were analyzed by univariate analyses (χ2/ student’s t test), and logistic regression was used to identify significant factors for the length of stay (LOs) longer than the population average of 55 ***: In 75 patients, 53.4%were “early”and 46.6%were “late.”Groups were similar with respect to maternal age, birth weight, delivery mode, sex, and associated *** of bowel peel was not affected by delivery time, yet “early”patients had significantly longer LOs and time to enteral *** predictors of LOs more than 55 days included gestational age of 36 weeks or younger, time to enteral feeds of more than 26 days, and associated *** predictors included size of the defect, thickness of bowel peel, and need for ***: Delivery before 36 weeks is associated with longer hospitalization and increased tune to attainment of full feeds compared with later *** well-being should thus be the primary determinant of delivery for gastroschisis, as opposed to considerations regarding possible injurious effects to the bowel of prolonged gestation.

关键词：分娩时机腹裂畸形疾病预后出生胎龄畸形儿肠功能显著性因素肠内营养分娩时间单变量分析

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比较儿童自发性气胸急诊手术和延期手术

世界核心医学期刊文摘（儿科学分册） 2005年第6期1卷 49-50页

作者： Qureshi F. G. sandulache V. C. Richardson W. D. J. hackam 李丹 Division of Pediatric surgery Children’s Hosp. Pittsburgh Sch. M. University of Pittsburgh Pittsburgh PA 15213 United States

Controversy exists regarding the timing of surgery for spontaneous pneumothorax (sP), which can be performed either after the first development of pneumothorax or after a recurrent spontaneous pneumothorax has occurred. Treatment after recurrence is often adopted because of the purported low recurrence of sP treated nonoperatively and the historical morbidity of open surgery. However, the effectiveness of VATs (to videoassisted bullectomy and pleurodesis) has raised the possibility of performing primary VATs (PV) in all patients. The authors therefore hypothesized that PV is safe and effective for sP and sought to perform a cost-benefit analysis of PV vs secondary VATs (sV). After institutional review board approval, consecu tive patients with sP (1991-2003) and no comorbidities were retrospectively divided into PV vs sV. Demographics, recurrent pneumothorax after VATs, length of stay, and costs were compared by student’s t test/χ2. The predicted incremental cost of PV was (cost of PV) -{[cost of nonoperative treatment ×(1 -recurrence rate)] +cost of sV ×recurrence rate}. Data are means ±sEM. There were 54 spontaneous pneumothoraces in 43 patients (11 bilateral), of whom 3 were excluded because of open thoracotomy. Of 51 pneumothoraces, nonoperative treatment was attempted in 37, of whom 20 recurred and thus required sV. Primary VATs was performed in 14. Both groups had similar age, sex, weight, height, admission heart rate, and room air oxygen saturation. Total treatment length of stay was significantly shorter for PV vs sV (7.1 ±0.96 vs 10.5 ±1.2, P =.04). However, morbidity from recurrent pneumothorax after VATs occurredmore frequently after PV than sV (4/14 vs 0/20 P sed on the observed recurrence rate of 54%, performing PV on all patients with sP would increase cost by ＄4010 per patient and require a recurrence rate of 72%or more to financially justify this approach. Contrary to the hypothesis, the increased morbidity and cost do not justify a strategy

关键词：急诊手术自发性气胸肺大泡切除术复发率胸膜固定术开胸术成本效益分析氧饱和度人口统计学于非

儿童直肠损伤时直肠镜检查和CT检查的对比分析

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世界核心医学期刊文摘（儿科学分册） 2006年第9期2卷 39-39页

作者： Leaphart C.L. Danko M. Cassidy L. D.J. hackam 刘凯 Division of Pediatric surgery Children's Hospital of PittsburghUniversity of PittsburghPittsburghPA 15213United States

Background:Current dogma suggests that the diagnosis of rectal injury can be made after physical examination and proctoscopy (PR). However,anecdotal evidence suggests that these modalities lack specificity when applied to children and that computed tomography (CT) scanning may be superior. A direct comparison between CT scanning and PR has not been performed. We therefore sought to compare CT with PR in the diagnosis of rectal injury by analyzing our large institutional experience. Methods:To assess institutional outcome,the charts of all children younger than 18 years admitted to our level I trauma center (1999-2004) were prospectively collected and retrospectively assessed. Demographics,diagnostic accuracy (PR vs CT),and outcome (length of stay,days in the intensive care unit [ICU],Injury severity score,and missed injury) were assessed. Results:There were 24 injuries (63% boys,71% blunt,100% survival),and diagnostic modality included the following:PR,37.5% ; CT,37.5% ; laparotomy alone,8% . Length of stay (PR 5.7 ± 6.2 vs CT 13.7 ± 22.2,Ns) were similar between groups. Of the missed rectal injuries,66% of patients undergoing PR hadmissed injuries that were ultimately detected by CT whereas 33% of the patients undergoing CT scan had a missed injury. Conclusion:CT is at least as accurate as PR in diagnosing pediatric rectal injury. Consideration of early scanning as opposed to PR may improve diagnosis and outcome in these patients.

关键词：直肠镜检查 CT检查直肠损伤对比分析创伤严重度评分漏诊率医疗档案诊断作用重症监护剖腹

他汀类药物降低心血管疾病患者的脓毒症风险:一项人群队列分析

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世界核心医学期刊文摘（心脏病学分册） 2006年第8期2卷 7-7页

作者： hackam D. G. Mamdani M. Li P. Redelmeier D.A. 马超(译) 杜媛(校) 不详 sunnybrook and Women's College Health sciences Centre 2075 Bayview Avenue Toronto Ont. M4N 3M5 Canada

Background: Atherosclerosis and sepsis share several pathophysiological similarities, including immune dysregulation, increased thrombogenesis, and systemic inflammation. The relation between statins and risk of sepsis in patients with atherosclerosis is unknown. Methods: We did a population-based cohort analysis through linked administrative databases in Ontario, Canada, with accrual from 1997 to 2002. We identified 141 487 patients older than 65 years who had been hospitalised for an acute coronary syndrome, ischaemic stroke, or revascularisation, who survived for at least 3 months after discharge. 46 662(33% ) were prescribed a statin within 90 days of discharge, 94 825(67% ) were not. Propensity-based matching, which accounted for each individual s likelihood of receiving a statin, yielded a cohort of 69 168 patients, of whom half(34 584) received a statin and half(34 584) did not. Findings: Incidence of sepsis was lower in patients receiving statins than in controls(71.2 vs 88.0 events per 10 000 person-years; hazard ratio [HR] 0.81; 95% CI 0.72-0.91). Adjustment for demographic characteristics, sepsis risk factors, comorbidities, and health-care use gave similar results(HR 0.81; 95% CI 0.72-0.90). The protective association between statins and sepsis persisted in high-risk subgroups,including patients with diabetes mellitus, chronic renal failure, or a history of infections. significant reductions in severe sepsis(HR 0.83; 95% CI 0.70-0.97) and fatal sepsis(0.75; 0.61-0.93) were also observed. No benefit was noted with non-statin lipid-lowering agents(0.95; 0.75-1.22). Implications: Use of statins in patients with atherosclerosis is associated with a reduced risk of subsequent sepsis. Randomised trials of statins for prevention of sepsis are warranted.

关键词：心血管疾病患者他汀类药物队列分析发生风险脓毒症急性冠状动脉综合征动脉粥样硬化病理生理特点全身炎症反应