Prenatal exposure of citalopram elicits depression-like and anxiety-like behaviors and alteration of morphology and protein expression of medial prefrontal cortex in young adult mice.

BACKGROUND: Treatment of major depression disorder with Selective serotonin reuptake inhibitors (SSRIs), such as citalopram (CTM), during pregnancy effects on the neurological trajectory of the offspring and induces enduring consequences, notably emotional and cognitive impairment. The associations between prenatal exposure to SSRIs and neurological underpinnings of these atypical behaviors in offspring are contentious and poorly understood. METHODS: We examined modifications in physiological, morphological, and biochemical characteristics in male and female offspring of C57BL/6 exposed to CTM during the third trimester of gestation. We utilized different behavior procedures to observe depression and anxiety-like behavior in 1~2 month old CTM-exposed mouse offspring. We employed Golgi-Cox staining to examine the neuronal structure of medial prefrontal cortex (mPFC) in CTM-exposed mice following protein expression levels by utilizing biochemical techniques. RESULTS: Our results indicate an impaired behavior such as anxiety and altered locomotion along with the substantial reduction in dendritic length and the number of dendritic branches in CTM-exposed mice. We observed differentially increase c-Fos expression in the mPFC following altered protein expression levels relative to controls. CONCLUSIONS: Our finding supports the function of CTM as a prenatal modulator of susceptibility to depressive-like behavior in offspring. We indicate that prenatal CTM exposure elicits a negative impact on the central nervous system, especially those regions involved in cognition and drug reinforcement. Furthermore, genetic, chemo-genetic, and optogenetic methods should be used to explain the function of SSRIs such as CTM during pregnancy in the regulation of mood and emotion-related behaviors in children.

Perception of training in hepatopancreatobiliary surgery among general surgery residents in the Americas.

BACKGROUND: Hepatopancreatobiliary (HPB) surgery experience during residency in the Americas is limited. Residents interested in HPB surgery have different options available for further training. This study evaluated training in HPB surgery received during general surgery (GS) residency, and sought to determine the perception of fellowship training in HPB surgery. METHODS: An anonymous survey was distributed to all 259 GS residency programs in the United States. Questions evaluated demographics, program structure, overall training & HPB experience in particular during residency, plans for fellowship training and understanding of training in HPB surgery. RESULTS: Of the 340 respondents, 162 (48%) were from university programs, 145 (43%) from community hospitals and 48 (14%) from independent medical centers. 117 (34%) were residents in postgraduate year 4 or 5 (PGY4/PGY5). 275 (81%) respondents were planning to pursue fellowship training after finishing residency. Three quarters of all respondents did not feel comfortable about performing liver, biliary and pancreatic procedures. Fellowships accredited by the Americas Hepato-Pancreatico-Biliary Association (AHPBA) are the most common pathway considered by residents for HPB training. CONCLUSIONS: GS residents are not comfortable in considering performing complex HPB cases on completion of residency training. GS residents consider AHPBA accredited fellowships to be more suitable for advanced training in HPB surgery.

Profound hypothermia decreases cardiac apoptosis through Akt survival pathway.

BACKGROUND: Hypothermia increases the tolerable ischemia time for myocardium in hemorrhagic shock, but precise mechanisms are not clearly established. Here we studied activation of Akt cell survival pathway in a rodent model of emergency preservation and delayed resuscitation. STUDY DESIGN: Wistar-Kyoto rats underwent 40% blood volume arterial hemorrhage during 10 minutes and were randomized into 2 groups based on core body temperatures (n = 7/group): hypothermia (15 degrees C) and normothermia (37 degrees C). Hypothermia was induced by infusing cold isotonic solution using cardiopulmonary bypass (CPB) setup. After reaching target body temperature, low-flow state (CPB flow rate of 20 mL/kg/min) was maintained for 60 minutes. Hypothermic rats were rewarmed to baseline temperature; all rats were resuscitated on CPB and monitored for 3 hours. The normothermia group underwent identical CPB management. Sham rats (no hemorrhage, no instrumentation) were used as controls (n = 7). Tissues were harvested at the end of experiment. RESULTS: Induction of hypothermia increased survival rates (100% versus 0% in normothermia group). Western blot analysis of cardiac tissue revealed increased levels of phospho-Akt (active) in hypothermia and sham groups compared with the normothermia group (p < 0.05). Among downstream targets of Akt, phospho-GSK-3beta (inactive), phospho-Bad (inactive), beta-catenin, and Bcl-2 were considerably elevated in the hypothermia group compared with the normothermia group. Hypothermia also showed decreased activity of caspase-3 protein compared with normothermia (p < 0.05), suggesting decreased apoptosis. CONCLUSIONS: Profound hypothermia increases survival in a rodent model of hemorrhagic shock and prolonged low-flow state. Hypothermia preserves Akt signaling pathway in cardiomyocytes with a concurrent decrease in cardiac apoptosis.

Colovesical fistula repair: is early Foley catheter removal safe?

BACKGROUND: Colovesical fistula (CVF) are the most common occurring fistulae secondary to diverticulitis. Review of the literature reveals great variability in postoperative Foley catheter management, as well as the role of a cystogram. The purpose of this study was to review our experience in early vs. late removal of the Foley catheter after CVF repair secondary to diverticulitis. Our hypothesis was that early Foley catheter removal is not associated with increased complications, and postoperative cystogram is of low value. METHODS: This is a retrospective study (January 2002-March 2008) of all patients with a diagnosis of CVF secondary to diverticulitis, who were treated with a sigmoidectomy and takedown of the fistula. Hospital records were reviewed and demographics, days to Foley removal, performance of cystogram, type of repair, complications, and comorbidities were recorded. Patients were separated into two groups according to early or late Foley catheter removal. Removal of the Foley catheter in < or = 7 d was considered early, and removal in >7 d was considered late. RESULTS: Thirty-two patients were identified, with a mean age of 65.2 y (42-91). Mean duration of Foley catheter stay was 15.6 d (3-42). Six patients had early postoperative Foley catheter removal and 26 patients had late Foley catheter removal. Four patients had complex bladder repair, and they all had late Foley catheter removal. From the 28 patients with simple bladder repair, six had early removal and 22 had late removal. Patients with early Foley catheter removal did not have significant complications compared with patients with late Foley catheter removal. Eleven patients got a cystogram postoperatively to detect possible bladder leaks. All cystograms performed were negative. CONCLUSIONS: Patients with a diagnosis of CVF secondary to diverticulitis may have their Foley catheter removed in 7 d without any increased complications. The role of the cystogram is unclear; however, no value was added in simple bladder repairs.

Surviving blood loss without fluid resuscitation.

BACKGROUND: Patients with massive blood loss often die before delivery of definitive care, especially in austere environments. Strategies that can maintain life during evacuation and transport to higher levels of care may be lifesaving. We have previously shown that administration of histone deacetylase inhibitors (HDACI) enhance gene transcription through specific modifications of DNA-associated histone proteins. Furthermore, it protects against organ damage when given before hemorrhage. The current experiment was done to test whether administration of HDACI after lethal hemorrhage, without fluid resuscitation, would improve outcome by creating a pro-survival phenotype. METHODS: Seventy-two male Wistar-Kyoto rats (n = 12 per group) were subjected to 60% blood volume loss for 1 hour (40% arterial bleed for 10 minutes and 20% venous bleed for 50 minutes). After hemorrhage, animals were randomized to receive one of two HDACI: (1) valproic acid (VPA, 300 mg/kg in 0.25 mL saline), or (2) suberoyanilide hydroxamic acid (SAHA, 7.5 mg/kg in 0.25 mL saline). Control groups included (3) no hemorrhage (Sham), (4) no resuscitation (NR), (5) 0.9% saline resuscitation, 3 times the volume of shed blood (NS), and (6) vehicle control, 0.25 mL 0.9% saline (VEH). Hemodynamic data were recorded continuously, and physiologic parameters were measured serially. Survival for 3 hours was the primary endpoint for this experiment. RESULTS: Nonresuscitated shock (NR group) was highly lethal and only 25% of the animals survived for 3 hours. Administration of HDACI after hemorrhage (without fluid resuscitation) significantly improved survival (75% and 83% in VPA and SAHA groups, respectively, p < 0.05 vs. NR). Survival was 40%, 100%, and 100% in the VEH, Sham, and NS resuscitation groups, respectively. CONCLUSIONS: This study demonstrates that post-shock administration of HDACI can significantly improve early survival in a highly lethal model of hemorrhagic shock, even in the absence of conventional fluid resuscitation. This approach may be especially relevant for austere environments where fluids are in limited supply, such as a battlefield.