Advancing gastrointestinal cancer diagnostics: a systematic review and meta-analysis of circulating microRNA-1246 as a non-invasive biomarker.

BACKGROUND: Despite numerous reports on the alterations of microRNA-1246 (miR-1246) expression level in digestive system cancers, its role in gastrointestinal cancers (GICs) remains unclear. This meta-analysis aimed to assess the diagnostic potential of circulating miR-1246 in GICs. METHODS: Meta-disc version 1.4 and Comprehensive Meta-Analysis (CMA) version 3.7 software were used to calculate pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), area under the curve (AUC), Q*index and summary receiver-operating characteristic (SROC). Subgroup analyses were conducted for cancer type, sample type and geographical region. Publication bias was assessed using Begg's and Egger's tests. RESULTS: A total of 14 articles involving 18 studies and 1526 participants (972 cases and 554 controls) were included. The diagnostic accuracy of miRNA-1246 in GICs was as follows: pooled sensitivity: 0.81 (95% CI: 0.79 - 0.83), specificity: 0.74 (95% CI: 0.71 - 0.77), PLR: 3.315 (95% CI: 2.33 - 4.72), NLR: 0.221 (95% CI: 0.153 - 0.319), DOR: 16.87 (95% CI: 9.45 - 30.09), AUC: 0.891, and Q*-index: 0.807. No publication bias was found based on Begg's (p = 0.172) and Egger's (p = 0.113) tests. CONCLUSION: Circulating miR-1246 shows promise as a non-invasive biomarker for early detection of GICs.

Alterations in hypothalamic-pituitary axis (HPA) hormones 6 months after cranial radiotherapy in adult patients with primary brain tumors outside the HPA region.

BACKGROUND: Cranial radiotherapy is a common treatment for brain tumors, but it can affect the hypothalamic-pituitary (H-P) axis and lead to hormonal disorders. This study aimed to compare serum levels of HPA hormones before and after cranial radiation. MATERIALS AND METHODS: This study involved 27 adult patients who underwent brain tumor resection before the initiation of radiotherapy, and none had metastatic brain tumors. All participants had the HPA within the radiation field, and their tumors were located in brain areas outside from the HPA. Serum levels of HPA hormones were recorded both before and 6 months after cranial radiotherapy. RESULTS: A total of 27 adult patients, comprising 16 (59.3%) males and 11 (40.7%) females, with a mean age of 56.37 ± 11.38 years, were subjected to evaluation. Six months post-radiotherapy, serum levels of GH and TSH exhibited a significant decrease. Prior to radiotherapy, a substantial and direct correlation was observed between TSH and FSH (p = 0.005) as well as LH (p = 0.014). Additionally, a significant and direct relationship was noted between serum FSH and LH (p < 0.001) before radiotherapy. After radiotherapy, a significant and direct correlation persisted between TSH and FSH (p = 0.003) as well as LH (p = 0.005), along with a significant and direct relationship between serum FSH and LH (p < 0.001). Furthermore, a significant and direct association was identified between changes in serum GH levels and FSH (p = 0.04), as well as between serum LH and FSH (p < 0.001). CONCLUSION: Reduced serum levels of HPA hormones are a significant complication of cranial radiotherapy and should be evaluated in follow-up assessments.

Diagnostic accuracy of tumor M2-pyruvate kinase (tM2-PK) as a non-invasive biomarker in colorectal cancer: A systematic review and meta-analysis.

INTRODUCTION: The tumor pyruvate kinase M2 isoform (tM2-PK) is a glycolytic enzyme isoform that is present on the surface of rapidly proliferating cancer cells. The objective of this investigation was to assess the efficacy of the tM2-PK measurement assay in detecting colorectal cancer (CRC) through the analysis of serum/plasma and stool samples obtained from patients. METHODS: The pooled diagnostic performance measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the area under the curve (AUC), Q*index, and summary receiver-operating characteristic curve (SROC), were computed using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software. The statistical methods of I2 and chi-square were employed to assess the presence of heterogeneity. The estimation of publication bias was conducted through the implementation of Begg's rank correlation and Egger's regression asymmetry tests. RESULTS: A total of 28 studies were found, involving 2900 participants (1560 cases and 1340 controls). The diagnostic accuracy of tM2-PK was calculated in CRC based on the pooled sensitivity of 83.70% (95% CI: 82.0% - 85.30%), specificity of 74.0% (95% CI: 72.0% - 76.0%), PLR of 4.432 (95% CI: 3.33 - 5.60), NLR of 0.187 (95% CI: 0.144 - 0.243), DOR of 30.182 (95% CI: 19.761 - 46.10) as well as AUC at 91.6%, and Q*-index at 85.0%. Publication bias was seen based on Begg's (p = 0.0006) and Egger's (p = 0.00015) tests. CONCLUSION: The results demonstrate that tM2-PK exhibits promise as a fair marker for CTRC, with the potential to serve as a non-invasive biomarker.

A free fatty acid receptor agonist inducing autophagy in HT-29 cells by downregulating the AKT/mTOR signaling pathway.

AIMS: GW9508, a free fatty acid receptor agonist acts in a G-coupled protein receptor 40 (GPR40)-dependent pathway. Here, we investigated the induction of stress oxidative and autophagy by GW9508 in the human colorectal cancer cell line (HT-29) and the crosstalk between autophagy and apoptotic in HT-29 cells. METHODS: HT-29 was treated with GW9508 at a concentrations range of 50-500 µM in fibrin gel. Cell viability was investigated using an MTT assay. Induction of autophagy and apoptosis was assessed through Western blotting for associated proteins, acridine orange staining, MDC staining, qRT-PCR, and electron microscopy. Also, we estimated the molecular interactions between GW9805 and some markers through molecular docking. RESULTS: GW9508 inhibited HT-29 cell proliferation, induced apoptosis, and resulted in autophagy. The induced autophagy in cells was confirmed by the observation of autophagosomes, the presence of autophagy markers, including beclin-1, LC3, AMPK, and lack expression of mTOR and AKT. Moreover, GW9508 treatment significantly increased the expression of catalase and superoxide dismutase in cells. DISCUSSION: Our results indicated that GW9508 could induce autophagy by inhibiting the Akt/mTOR in HT-29. Hence, GW9508 is suggested as a novel anticancer reagent.

Conditions for Insertion of the Laryngeal Mask Airway in an Innovative Method vs the Classic Method.

Background: A laryngeal mask airway (LMA) is a simple and non-invasive device used to establish the airway and maintain ventilation and oxygenation during short-duration medical procedures. Objectives: This study aimed to compare the placement of an LMA using an innovative technique vs the classic method. Methods: This clinical trial was conducted at Faiz Hospital in Isfahan. Out of 110 candidates for elective eye surgery, 10 patients were excluded from the study as they did not meet the inclusion criteria. Ultimately, 100 patients were randomly allocated to 2 groups of 50 each. One group underwent LMA insertion using the classic method, while the other group underwent insertion using the face-to-face triple maneuver technique (FFTMT). Data, including laryngeal mask insertion conditions, hemodynamic responses, and clinical complications, were collected, entered into SPSS version 26, and analyzed. Results: There were no significant differences between the 2 groups in terms of laryngeal mask placement time (P = 0.061), number of attempts to place the LMA (P = 0.059), oropharyngeal leak pressure (OLP; P = 0.942), frequency of hoarseness (P > 0.99), or laryngospasm (P > 0.99). However, it is noteworthy that FFTMT appeared to provide easier placement of the LMA (P < 0.0001), required fewer attempts, and offered better quality of ventilation with a lower presence of blood on the cuff (P = 0.038). Conversely, the FFTMT group had a higher frequency of sore throat (P < 0.0001). Conclusions: The performance of LMA using FFTMT is comparable to the classic method. In procedures under general anesthesia where the surgeon has access to the patient's head and neck (such as cataract surgery), airway management with LMA using FFTMT (while maintaining the patient's sterile covering) appears to be effective in case of an emergency.

Maternal supplementation of nano-selenium in a plant-based diet improves antioxidant competence of female Arabian yellowfin sea bream (Acanthopagrus arabicus) breeders and their progeny.

Antioxidants such as selenium (Se) play vital roles in reproduction success and larval development in fish. A three-month feeding experiment was conducted to examine the impact of enriching a plant-based diet (60% of fishmeal was substituted with a blend of plant ingredients) with nano-selenium (nano-Se) on antioxidant metabolism in female brooders and the progeny of Arabian yellowfin sea bream (Acanthopagrus arabicus). At this point, the plant-based diet was supplemented with graded levels of nano-Se at 0, 0.5, 1, 2, and 4 mg/Kg diet. Moreover, a fishmeal-based diet served as a positive control (FMD-Control). Broodfish were randomly distributed into eighteen 10 m3 rectangular concrete tanks (8 males and 8 females in each tank). Each experimental diet was subjected to three replications. Selenium retention increased in the serum, liver, ovary, eggs, and three-day larvae with increasing dietary nano-Se levels (P < 0.05). Supplementing the plant-based diet with 2-4 mg nano-Se/Kg significantly enhanced normal embryogenesis, fertilization, hatching, and larval survival rates. Generally, fish fed on plant-based diets with lower nano-Se supplementation (0-0.5 mg/Kg) had higher catalase and superoxide dismutase activities in the liver, ovaries, eggs, and larvae compared to the other groups. Glutathione peroxidase activity and total antioxidant capacity markedly increased, whereas lipid peroxidation decreased in the liver, ovary, serum, eggs, and progeny of broodfish fed with nano-Se supplemented diets (P < 0.05). In conclusion, supplementation of 2-4 mg nano-Se /Kg in a plan-based feed is recommended for the improvement of antioxidant defense in female A. arabicus brooders and their progeny.

Outcomes of dura-splitting technique compared to conventional duraplasty technique in the treatment of adult Chiari I malformation: a systematic review and meta-analysis.

Chiari malformation type I is a developmental abnormality with an array of surgical techniques introduced for the management of it. The most common technique is foramen magnum decompression with duraplasty. Dura-splitting technique as one of the non-dura-opening techniques is a less known procedure that spares the internal layer of the dura and can theoretically result in fewer complications compared to duraplasty. So, we performed a review of literature and meta-analysis on different clinical and radiological aspects of this technique and compared its outcomes to duraplasty. MOOSE guidelines were followed. A systematic search of three databases based on predefined search strategy and inclusion/exclusion criteria was performed. After quality assessment and data extraction by two authors, summarized data were presented in form of tables, and meta-analysis results were illustrated in forest plots. A review of 10 included studies consisting of 370 patients revealed significantly shorter operation duration and less intraoperative blood loss in the dura-splitting technique compared to duraplasty. Interestingly, there was no significant difference between these two techniques in terms of clinical and radiological outcomes. Overall complication rate and incidence of CSF-related complications or infections were significantly in favor of the dura-splitting technique. Dura-splitting technique can be considered as a safe and effective surgical procedure for Chiari I malformation with comparable outcomes and fewer complications compared to duraplasty, although this interpretation is derived from retrospective observational studies and lack of a prospective clinical trial is evident.

Effects of zinc chelating nutrients on Aflatoxin production in Aspergillus flavus.

Aflatoxins are carcinogenic metabolites produced by Aspergillus and Penicillium spp. Aflatoxin contamination of food is a serious health hazard. Some metal ions (such as Zn2+) affect Aspergillus growth and aflatoxin biosynthesis. Presence of zinc in the growth medium incites aflatoxin production. This study investigates the effect of zinc binding amino acids and peptides on aflatoxin synthesis in indigenous toxigenic Aspergillus species isolated from agro-ecological zones in Northern Iran. Zinc (II) chelating nutrients (such as Histidine (His), Cysteine (Cys), Histidine-Cysteine (His-Cys), and triple peptide (Asn-Cys-Ser) were added to the growth medium of toxigenic Aspergillus isolates and incubated at temperature range of 25-40 °C. Aflatoxin production on different culture media was tested using ELISA. Addition of cysteine to Sabouraud dextrose broth (SDB) medium significantly reduced aflatoxin production, which could be related to its zinc chelating property. Aflatoxin production was drastically restrained at high concentration of His, especially in combination with Cys, at high pH values and incubation temperature (pH = 7.5, temperature = 40 °C). Aflatoxin production was low in presence of triple peptide (Asn-Cys-Ser) at concentration of 500 mg/L. From the application perspective, natural zinc chelators can be used as harmless aflatoxin-production inhibitors.

Single-Stage Management of Dynamic Malperfusion Using a Novel Arch Remodeling Hybrid Graft.

BACKGROUND: Organ malperfusion remains challenging, causing complications associated with acute DeBakey I dissections. We describe the results of malperfusion management after implantation of the Ascyrus Medical Dissection Stent (AMDS; Ascyrus Medical, Boca Raton, FL), an adjunct to current surgical aortic dissection repair. METHODS: From March 2017 to January 2019, 47 consecutive patients (median age, 65 years; interquartile range, 15.8 years; 61.9% male) presented with acute DeBakey I aortic dissections and underwent emergent surgical aortic repair with AMDS implantation. Malperfusion was detected preoperatively in 55.3% (n = 26) of patients. Two patients were excluded from efficacy analysis due to lack of follow-up. Overall, 66 vessel malperfusions were identified, consisting of 1.5% (n = 1) coronary, 33.3% (n = 22) supraaortic, 21.2% (n = 14) visceral, 24.2% (n = 16) renal, and 15.1% (n = 10) extremities. Three patients (11.5%) had clinical evidence of paralysis at presentation. RESULTS: All 26 device implants were successful. In the malperfusion cohort, 30-day mortality was 7.7% (n = 2). A new neurologic deficit identified postoperatively in patients without neurologic symptoms preoperatively occurred in 7.7% (n = 2). During the follow-up period, 95.5% (n = 63) of vessel malperfusions had resolved without an additional procedure, including 95.5% (n = 21) supraaortic, 92.9% (n = 13) visceral, 93.8% (n = 15) renal, and 100% (n = 10) extremity. All patients with paralysis at presentation had complete resolution. CONCLUSIONS: The AMDS provides an effective single-stage malperfusion management strategy. In this study, dynamic malperfusion involving supraaortic, visceral, spinal cord, and lower extremities were treated concurrently with the index standard-of-care operation without delay in life-saving care.

Dissected Aorta Repair Through Stent Implantation trial: Canadian results.

OBJECTIVES: We describe the Canadian results of the Ascyrus Medical Dissection Stent (AMDS), a novel partially uncovered aortic arch hybrid graft implanted antegrade during hypothermic circulatory arrest to promote true lumen expansion and enhance aortic remodeling. METHODS: From March 2017 to February 2018, 16 consecutive patients (66 ± 12 years; 38% female) presented with acute type A aortic dissections and underwent emergent surgical aortic repair with AMDS implantation. All patients presented with DeBakey I aortic dissection, with evidence of malperfusion in 50% (n = 8) of patients. All cases were performed under hypothermic circulatory arrest with an additional average duration for AMDS implantation time of 2.1 minutes. RESULTS: All 16 device implantations were successful. Overall 30-day mortality was 6.3% (n = 1) and stroke occurred in 6.3% (n = 1) of cases. There was no incidence of device-related aortic injury or aortic arch branch vessel occlusion. During the follow-up period, 12 patients had completed at least 1 postoperative computed tomography scan. At initial follow-up computed tomography scan, complete or partial thrombosis, and remodeling of the aortic arch occurred in 91.7% of cases (n = 11/12) and in the proximal descending thoracic aorta, complete or partial thrombosis, and remodeling occurred in 91.7% (n = 11/12). CONCLUSIONS: Preliminary results suggest that the AMDS is a safe, feasible and reproducible adjunct to current surgical approaches for acute DeBakey I aortic dissection repair. Further, the AMDS manages malperfusion and promotes early positive remodeling in the aortic arch and distal dissected segments, with favorable FL closure rates at follow-up. Ongoing follow-up will provide additional insight into the long-term effects of the AMDS.

Cognitive and hippocampus biochemical changes following sleep deprivation in the adult male rat.

Sleep deprivation (SD) influences physiological processes such as cognitive function. The balance of oxidant and antioxidant markers, neurotrophic factors and magnesium are affected by sleep deprivation but there is no difference between pre and post training sleep deprivation. This study was designed to investigate memory retrieval and biochemical factors such as oxidant and antioxidant enzyme, brain-derived neurotrophic factor (BDNF) and magnesium levels in the hippocampus following pre and post-training sleep deprivation. Male Wistar rats (weighing 200 ±â€¯20 g) in below groups were used: control 1, 24, 48 and 72 h SD before training groups, control2, 24 h SD1 after training (being evaluated 24 h after training) and SD2 24 after training (being evaluated 48 h after training). Memory was evaluated 90 min, 24 h or 48 h after training by step-through passive avoidance apparatus. Multiple platforms method was used to induce SD. Oxidant and antioxidant markers including glutathione (GSH), glutathione reductase (GPx), malonedialdehyde (MDA), Total antioxidant concentration, catalase, superoxide dismutase (SOD), magnesium and BDNF were assessed in the hippocampus or/and brain. 72 h pre-training SD impaired short and long-term memory significantly. There was no significant difference in hippocampus oxidant and antioxidant markers compared to control. Hippocampal BDNF and magnesium did not show any changes in all SD groups. Lack of correlation between memory impairment and levels of BDNF, magnesium and/or oxidant and antioxidant balance in the hippocampus is likely to be related to animal locomotor activity in the multiple platforms method. More research is needed to clarify the role of neurochemical systems.

Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors.

High aerobic glycolysis, as one of the hallmarks of cancer cells, requires nicotinamide adenine dinucleotide (NAD+) as a vital co-factor, to guarantee the flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer metabolism, is a source of NAD+ additional to lactate dehydrogenase (LDH). The current study aimed to elucidate the kinetic parameters of MDH in human breast cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis-Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the crude extracts of human breast tumors and healthy tissue samples, which were obtained directly from the operating theatre. To assess the potential role of MDH in supporting glycolysis, the MDH activity was measured when the LDH activity was inhibited by different concentrations of oxamate, an inhibitor of LDH in breast cancer cell lines. The Km of cancerous MDH (C-MDH) was the same as the healthy MDH, although the Vmax of C-MDH was higher relative to the healthy MDH. Notably, the MDH activity was increased in the MDA-MB-231 cell line, which was treated with the LDH inhibitor (oxamate), but not in the MCF-7 cell line (P<0.05). The higher tendency of C-MDH for NAD+ and malate generation in cancer cells is an effective approach for supporting glycolysis. Increasing MDH activity in the absence of LDH demonstrates the supportive role of MDH in glycolysis. Therefore, decreasing MDH activity and expression in a forward reaction may present as a valid molecular target to abolish its potential effect on tumor metabolism.

In vitro antileishmanial activity of fisetin flavonoid via inhibition of glutathione biosynthesis and arginase activity in Leishmania infantum.

With the increasing emergence of drug resistant Leishmania sp. in recent years, combination therapy has been considered as a useful way to treat and control of Leishmaniasis. The present study was designed to evaluate the antileishmanial effects of the fisetin alone and combination of fisetin plus Meglumine antimoniate (Fi-MA) against Leishmania infantum. The IC50 values for fisetin were obtained 0.283 and 0.102 µM against promastigotes and amastigote forms, respectively. Meglumine antimoniate (MA, Glucantime) as control drug also revealed IC50 values of 0.247 and 0.105 µM for promastigotes and amastigotes of L. infantum, respectively. In order to determine the mode of action of fisetin and Meglumine antimoniate (MA, Glucantime), the activities of arginase (ARG), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. Moreover, intracellular glutathione (GSH) and nitric oxide (NO) levels in L. infantum-infected macrophages and L. infantum promastigotes which were treated with IC50 concentrations of fisetin, MA and Fi-MA were investigated. Our results showed that MA decreased CAT and SOD activity and increased NO levels in L. infantum-infected macrophages. In promastigotes, MA inhibited parasite SOD activity and reduced parasite NO production. The decreased levels of most of the antioxidant enzymes, accompanying by the raised level of NO in treated macrophages with MA, were observed to regain their normal profiles due to Fi-MA treatment. Furthermore, fisetin could prevent the growth of promastigotes by inhibition of ARG activity and reduction of GSH levels and NO production. In conclusion, these findings showed that fisetin improves MA side effects.

Pulsed Electromagnetic Fields for Postsurgical Pain Management in Women Undergoing Cesarean Section: A Randomized, Double-Blind, Placebo-controlled Trial.

OBJECTIVES: To evaluate the efficacy of pulsed electromagnetic field (PEMF) in relation to reducing postoperative pain, analgesic use, and wound healing in patients undergoing Cesarean section (C-section). METHODS: This randomized, double-blind, placebo-controlled trial evaluated 72 women who underwent elective C-section. Thirty-six patients were assigned to the active-PEMF and 36 to the sham-PEMF groups. The participants were asked to report their pain intensity on a Visual Analog Scale (VAS) at 2, 4, 6, 12, and 24 hours and 2, 4, and 7 days after surgery. The amount of analgesics used was recorded. The surgical site was evaluated to assess the wound-healing process on the seventh postoperative day. RESULTS: Postoperative pain VAS scores were significantly lower in the active-PEMF group in all the measured periods within the early and the late postoperative periods. Fewer women in the active-PEMF group experienced severe postoperative pain within 24 hours postoperatively (36% vs. 72%, P=0.002). Analgesic use during the first 24 hours after C-section was 1.9-times lower in the active-PEMF group (1.6±0.7 vs. 3.1±1.2, P<0.001). The total analgesic use during the seventh postoperative days was 2.1-times lower in the active-PEMF group than in the sham group (1.7±0.7 vs. 3.7±1.1, P<0.001). Seven days postoperatively, patients in the active-PEMF group had better wound healing with no exudate, erythema, or edema (P=0.02). CONCLUSIONS: PEMF treatment after C-section decreases postsurgical pain, analgesic use, and surgical wound exudate and edema significantly, and is associated with a high level of patient satisfaction.

Blood Levels of Oxidant/Antioxidant Parameters in Rats Infected with Toxoplasma gondii.

Toxoplasmosis is a common parasitic infection in the world. Since increased free radicals and oxidative stress are reported in many parasitic diseases the purpose of the present study was to evaluate the oxidative stress in acute and chronic toxoplasmosis. RH strains of Toxoplasma tachyzoites were used in the present study. Twenty-five female rats were infected with the parasite while 25 other rats were as the control group that received normal saline. Zero-, 5-, 7-, 10-, and 45-day postinfection (DPI) blood samples were taken. Some parameters related to oxidant and antioxidants such as antioxidant enzymes, malondialdehyde, and total antioxidant capacity were measured. On day 7 after infection, GPX activity and GSH level were significantly increased and in the mentioned day the amount of total antioxidant capacity was significantly reduced. In other cases, there were no significant differences between the groups in different days. Overall, based on the results it seems that, on day 7 after infection, in infected rats responses to oxidative stress were triggered and led to decrease of total antioxidant capacity. Furthermore, glutathione was increased to cope with stress. It seems that probably antioxidant defense system entered the infection to the chronic phase and changed the parasites stage.

One-year outcomes from the international multicenter study of the Zenith Alpha Thoracic Endovascular Graft for thoracic endovascular repair.

OBJECTIVE: This study evaluated the safety and effectiveness of the Zenith Alpha Thoracic Endovascular Graft (Cook Medical, Bloomington, Ind) for the treatment of descending thoracic aortic aneurysms and large ulcers. METHODS: The Zenith Alpha Thoracic Endovascular Graft, with a 16F to 20F delivery system, was developed to address vascular access issues associated with larger-profile devices and to increase conformability in tortuous anatomy. This prospective, nonrandomized, multicenter study was conducted in Europe, Japan, and the United States. The main anatomical inclusion criteria included proximal neck seal zone of ≥20 mm, aortic arch radius of ≥20 mm, and a neck diameter of 15 to 42 mm. Patients were evaluated preprocedure, predischarge, and postdischarge 1, 6, and 12 months and yearly thereafter through 5 years. RESULTS: Between March 2010 and January 2013, 110 patients (64 men and 46 women; mean age, 72 ± 10 years) were enrolled in the study for the treatment of descending thoracic aortic aneurysms (n = 90) or ulcers (n = 20). Access was percutaneous in 36% (40 of 110) of patients. The study device was successfully implanted in all but two patients (both due to inability to gain access or advance to the target treatment site). There was no 30-day mortality. Five deaths occurred ≤1 year (only one was aneurysm-related by independent adjudication), resulting in a 95% freedom from all-cause mortality and a 99% freedom from thoracic aortic aneurysm-related mortality. At one or more time points ≤1 year, type I endoleak (all distal) was observed in 4 patients, type III endoleak in 2, and aneurysm growth in 4. Five patients experienced stroke ≤1 year (2 procedure-related). No aortic rupture, paraplegia, paralysis, or permanent spinal cord injury was observed ≤1 year. CONCLUSIONS: Early outcomes after Zenith Alpha implantation appear promising and suggest expanded thoracic endovascular aortic repair applicability in patients with smaller access vessels. Longer-term follow-up is ongoing.

Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues.

BACKGROUND: Aerobic glycolysis rate is higher in breast cancer tissues than adjacent normal tissues which providethe ATP, lactate and anabolic precursors required for tumourgenesis and metastasis. Lactate dehydrogenase (LDH) is a critical enzyme during aerobic glycolysis as it is typically responsible for the production of lactate and regeneration of NAD(+), which allows for the continued functioning of glycolysis even in the absence of oxygen. LDH has been found to be highly expressed in breast tumors. Enzyme kinetic characteristics is related to environmentinvolving the enzyme, and tumor microenvironment has distinct features relative to adjacent normal tissues, thus we hypothesized that LDH should have different kinetic characteristics in breast tumors compared to normal breast tissues. METHODS: LDH was partially purifiedfrom human breast tumors and normal tissues, which were obtained directly from operating room. TheMichaelis-Menten constant (Km), maximum velocity (Vmax), activation energy (Ea) and enzyme efficiency in breast tumors and normal tissueswere determined. RESULTS: It was found that tumor LDH affinity in forward reaction was the same as normal LDH but Vmax of cancerous LDH was higher relative to normal LDH. In reverse reaction, affinity of tumor LDH for lactate and NAD(+) was lower than normal LDH, also enzyme efficiency for lactate and NAD(+) was higher in normal samples. The Ea of reverse reaction was higher in cancerous tissues. CONCLUSIONS: It was concluded that thelow LDH affinity for lactate and NAD(+) is a valuable tool for preserving lactate by cancer cells. We also conclude that increasing of LDH affinity may be a valid molecular target to abolish lactate dependent tumor growth and kinetic characteristics of LDH could be a novel diagnostic parameter for human breast cancer.

Effects of Echinacea purpurea on Hepatic and Renal Toxicity Induced by Diethylnitrosamine in Rats.

BACKGROUND: Nitrites are mainly used in food preservation. These materials could change to nitrosamine due to the effect of heat and gastric acid. Nitrosamine is absorbed in intestine and enters the liver and hepatocytes by portal venous system, and hampers the detoxification system of liver by interfering in cytochrome P450 enzymes, so, the liver gently proceeds to cirrhosis and cancer. OBJECTIVES: The current study aimed to investigate the hepatic and renal protective effects of aerial parts of Echinacea purpurea extract (EPE) on injury induced by diethylnitrosamine (DEN). MATERIALS AND METHODS: Twenty Wistar rats were divided into 4 groups. Groups were as follow: Control group (normal saline), DEN (200 mg/kg, IP, a single dose), EPE (100 mg/kg, orally, daily) and DEN + EPE which received as group DEN and EPE. After 30 days, Blood samples, and liver and kidney tissues were taken for further examination. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), BUN, Creatinine and total and direct bilirubin were estimated in serum. RESULTS: DEN induced hepatotoxicity and nephrotoxicity in all the treated animals by elevated serum ALT, AST, ALP and BUN, creatinin and total and direct bilirubin levels. AST, BUN and total and direct bilirubin significantly decreased in DEN + EPE compared to DEN group. After 30 days of DEN administration, histopathological investigation revealed proliferation of hepatic stellate cells and early fibrosis which were partly improved by EPE administration. CONCLUSIONS: The current study findings indicated that Echinacea purpurea extract played an important role in the protection against DEN toxicity in rats.

The effect of butter oil on avoidance memory in normal and diabetic rats.

OBJECTIVES: Since diabetes mellitus is accompanied by cognitive impairment in diabetic patient and animal models and since lipids play important roles in neuronal membrane composition, structure and function; we intended to evaluate the effect of dietary butter oil on passive avoidance memory of streptoztosin (STZ)-induced diabetic rats in this study. MATERIALS AND METHODS: THIRTY SIX ADULT MALE RATS WERE RANDOMLY ALLOCATED TO FOUR EQUAL GROUPS: normal (N) and diabetic control (D) groups with free access to regular rat diet; but the diet of normal butter oil (NB) and diabetic butter oil (DB) groups was supplemented with 10% butter oil. Diabetes in D and DB groups was induced by intravenous (i.v.) injection of 50 mg/kg.bw of STZ. Passive avoidance memory and cholesterol of brain and hippocampal tissues has been measured six weeks after diabetes confirmation. RESULTS: Diabetes, especially in diabetic butter oil group decreased the abilities of learning and memory. The level of cholesterol in hippocampus was higher in NB (P< 0.05) and DB (P< 0.01) groups. CONCLUSION: We suggest consumption of butter oil may worsen cognitive impairment of diabetic animal. This may be related to the higher elevation of cholesterol in the hippocampus of diabetic animals.

The Ross full root replacement in adults with bicuspid aortic valve disease.

BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve disease (BAVD) is the most common congenital cardiac lesion causing aortic stenosis in adults. This lesion can be associated with a histological abnormality of the aortic wall and dilated or aneurysmal ascending aorta. In younger patients, the Ross operation offers several advantages over conventional aortic valve replacement (AVR); however, the rationale of performing this procedure on adults in the face of BAVD have been questioned. METHODS: Between 1994 and 2009, a total of 101 adult patients (mean age 36 years; range: 18-61 years) with BAVD underwent the Ross full root replacement at the authors' institution. Of these patients, 23 (23%) had an aneurysmal ascending aorta (4.0-5.2 cm) associated with BAVD which was resected at the time of, or subsequent to, a Ross AVR. The end point of the study was freedom from Ross autograft dilatation > 4.0 cm, dysfunction, or valve repair or replacement. RESULTS: The mean follow up was 6.0 +/- 3.9 years. At the latest follow up, 19 patients (19%) had a dilated ascending aorta with a mean size 45.1 mm (range: 40-64 mm). Eight patients (8%) required a redo operation on the autograft. Three of seven patients undergoing reoperation had their autograft valve preserved; the remaining four underwent a modified Bentall root replacement. One patient had a repair of a left ventricular pseudoaneurysm below the Ross valve. Only three patients with preoperative ascending aorta dilation developed late autograft dilation. Freedom from autograft dilatation > 4.0 cm, dysfunction, repair or replacement was 80% at 10 years. CONCLUSION: Mid-term results indicate that Ross AVR in adults with BAVD had good outcomes, with a low incidence of autograft-related complications. In almost half of the patients undergoing reoperation, the autograft valve was preserved. The incidence of autograft valve insufficiency and dilatation might be further reduced by: (i) aggressively treating any postoperative systemic hypertension; (ii) externally fortifying the annulus and sinotubular junction of the autograft with Dacron strips; and/or (iii) replacing a dilated ascending aorta with a Dacron interposition graft. The preoperative diagnosis of BAVD and/or aneurysmal ascending aorta is not predictive of late autograft dilatation or failure.