BACKGROUND: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of Erα. These findings demonstrated that TrkB activation in the presence of Erα comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of Erα-dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period. METHODS: In this study, we used a unilateral hypoxic ischemic (HI) mouse model. Erα+/+ or Erα-/- mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for 7 days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety-like behavior. The brains were then assessed for tissue damage using immunohistochemistry. RESULTS: Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking Erα. The female-specific improved recognition and location memory outcomes in adulthood conferred by DHF therapy after neonatal HI tended to be or were Erα-dependent, respectively. Interestingly, DHF triggered anxiety-like behavior in both sexes only in the mice that lacked Erα. When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of Erα significantly reduced overall HI-associated mortality in both sexes. CONCLUSIONS: These observations provide evidence for a therapeutic role for DHF in which TrkB-mediated sustained recovery of recognition and location memories in females are Erα-associated and dependent, respectively. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner.
Periods of low oxygen delivery and blood flow to the brains of newborns are known to cause life-long impairments to their cognitive ability as adults. Interestingly, male newborns are more susceptible to this injury than females. The mechanisms causing this sex difference are poorly understood. Here we test the role of the nerve growth factor receptor tyrosine kinase B (TrkB) in providing long-term neuroprotection following neonatal hypoxiaischemia (HI) in mice. We have previously shown that when mice are treated with the TrkB agonist 7,8-dihydroxyflavone (DHF) in the days following neonatal HI, the result is short-term neuroprotection only in females and this protection is dependent on the presence of the estrogen receptor alpha receptor ([Formula: see text]). In this study, we extend these observations by subjecting mice either with or without [Formula: see text] to HI. Some of the mice were then treated with DHF immediately after HI. As adults, we performed tests to assess the mice's memory and anxiety-like behavior. At the end of these tests, we assessed the brains for tissue loss. Our results show that as adults the DHF treatment following HI in neonatal mice preserved memory only in females and this effect was dependent on the presence of [Formula: see text]. In addition, DHF therapy triggered anxiety-like behavior in mice lacking [Formula: see text]. We also show that this neuroprotection is not dependent on preservation of brain tissue following the injury. These results provide insight into the mechanisms behind the female resistance to hypoxic ischemic episodes as newborns.
Hypoxia-Ischemia, Brain , Receptor Protein-Tyrosine Kinases , Animals , Mice , Male , Female , Receptor Protein-Tyrosine Kinases/therapeutic use , Neuroprotection , Hypoxia-Ischemia, Brain/drug therapy , Hypoxia-Ischemia, Brain/metabolism , Ischemia , Hypoxia
Objectives: Laparoscopic totally extraperitoneal inguinal hernia repair (TEP) surgery technique includes three key steps: reaching the preperitoneal space, reducing hernias, and placement of mesh. However, reaching the preperitoneal space can be complicated in patients with previous lower abdominal surgeries. This study aimed to assess the feasibility of laparoscopic inguinal TEP in patients with previous prostatectomies. Material and Methods: Inguinal hernia patients who underwent laparoscopic TEP between January 2015 and February 2021 at Koç University Faculty of Medicine, Department of General Surgery, were included in this retrospective study. The operations were performed by five senior surgeons experienced in laparoscopy. Patients were divided into two study groups, as the radical prostatectomy (RP) group which included patients with previous prostatectomy non-RP which included patients without previous radical prostatectomy. Operative time (OT), length of hospital stay (LOS), and postoperative complications were compared within two groups. Results: Three hundred and forty-nine patients underwent laparoscopic TEP, and 27 had previous prostatectomies. Among them, 190 patients had unilateral inguinal hernias, and 159 had bilateral inguinal hernias. Mean age of the patients in the non-RP and RP groups was 58.1 ± 14.7 and 73.9 ± 9.6 years, respectively. Only one (3.7%) case was complicated with urinary tract infection in the RP group, and 10 (3.1%) were complicated in the non-RP group. Complications for the non-RP group include hematomas in six cases, urinary tract infection in three cases, and urinary retention in one case. No significant difference in mean operative time was seen between non-RP and RP groups (p= 0.43). There was no significant difference in the means of the length of hospital stay between the two groups (p= 0.7). Conclusion: Laparoscopic TEP in patients with a previous prostatectomy can be performed safely without prolonging the operative time and increasing the length of hospital stay.
Background: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of life-long neurological morbidities that result in learning and memory impairments. Evidence suggests that male neonates are more susceptible to the detrimental effects of HI, yet the mechanisms mediating these sex-specific responses to neural injury in neonates remain poorly understood. We previously tested the effects of treatment with a small molecule agonist of the tyrosine kinase B receptor (TrkB), 7,8-dihydroxyflavone (DHF) following neonatal HI and determined that females, but not males exhibit increased phosphorylation of TrkB and reduced apoptosis in their hippocampi. Moreover, these female-specific effects of the TrkB agonist were found to be dependent upon the expression of ERα. These findings demonstrated that TrkB activation in the presence of ERα comprises one pathway by which neuroprotection may be conferred in a female-specific manner. The goal of this study was to determine the role of ERα-dependent TrkB-mediated neuroprotection in memory and anxiety in young adult mice exposed to HI during the neonatal period. Methods: In this study we used a unilateral hypoxic ischemic (HI) mouse model. ERα+/+ or ERα-/- mice were subjected to HI on postnatal day (P) 9 and mice were treated with either vehicle control or the TrkB agonist, DHF, for seven days following HI. When mice reached young adulthood, we used the novel object recognition, novel object location and open field tests to assess long-term memory and anxiety like behavior. The brains were then assessed for tissue damage using immunohistochemistry. Results: Neonatal DHF treatment prevented HI-induced decrements in recognition and location memory in adulthood in females, but not in males. This protective effect was absent in female mice lacking ERα. Thus, the female-specific and ERα-dependent neuroprotection conferred by DHF therapy after neonatal HI was associated with improved learning and memory outcomes in adulthood. Interestingly, DHF triggered anxiety like behavior in both sexes only in the mice that lacked ERα. When we assessed the severity of injury, we found that DHF therapy did not decrease the percent tissue loss in proportion to functional recovery. We additionally observed that the presence of ERα significantly reduced overall HI-associated mortality in both sexes. Conclusions: These observations provide evidence for a therapeutic role for DHF in which sustained recovery of memory in females is TrkB-mediated and ERα-dependent. However, the beneficial effects of DHF therapy did not include reduction of gross tissue loss but may be derived from the enhanced functioning of residual tissues in a cell-specific manner.
Background: Anastomotic leakage is a major complication in colorectal surgery, resulting in significant morbidity and mortality rates. Despite substantial progress in surgical technique, anastomotic leakage rates remain stable. An early diagnosis of anastomotic leaks was proven to reduce adverse outcomes and improve survival. Objective: This study aims to find a novel scoring system for detecting anastomotic leaks using inflammatory and nutritional indicators after colorectal surgery. Our purpose was to analyze the diagnostic accuracy of leak scores ((CRPPOD3)(CRPPOD1)∗preoperativealbuminlevel) in predicting postoperative complications. Design: The study included colorectal cancer patients who underwent curative surgery at Koc University Hospital between 2014 and 2018. Patients were categorized into two groups depending on the presence of anastomotic leaks and compared in terms of preoperative albumin levels, CRP levels in postoperative days 1 and 3, anastomotic leakage rates, length of hospital stay, and CRP quotient, which was calculated by dividing POD 3 CRP level to POD 1 CRP level. The bedside leak score is calculated by dividing the CRP quotient by the preoperative albumin level. The predictive value of bedside leak score, CRP quotient, and preoperative albumin levels in estimating anastomotic leakage was analyzed, and a cutoff value for the leak score was calculated. Results: A total of 184 patients were included in the study. The leak score, CRP POD 3-1 ratio, and preoperative albumin levels were found to successfully detect anastomotic leakage. The area under the curve for the leak score was calculated as 0.78. The optimal cutoff value was found to be 50.3 for the bedside leak score, which shows 90.9% sensitivity and 59.3% specificity. Conclusion: The leak score may represent a valuable diagnostic tool for detecting patients at risk for anastomotic leakage after colorectal surgery and planning a better strategy to reduce morbidity and mortality rates and associated costs. However, further multicenter studies with large cohorts are necessary to confirm these results.
