NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

Usage of stem cells in oral and maxillofacial region.

Malformations of the maxillofacial region has disturbing psychosocial effects and causes enormous socioeconomic concerns. The management of maxillofacial defects caused by congenital anomalies, trauma, osteoporotic fractures, periodontitis, or cancer treatment is challenging for oral and maxillofacial surgeons. Numerous approaches have been recommended for the managing of these deficiencies. The traditional treatment for maxillofacial defects or their repair is an intricate process by autologous bone grafts from the scapula, ribs, fibula, or iliac crest origins. Regenerative medicine is well thought-out as a perfect substitute approach for autologous bone grafts to renovate bone deficiencies. The use of stem cells has improved results and offered a technique to reconstruct craniofacial bone defects. The field of tissue engineering for the regeneration of maxillofacial needs integration of biochemical and biomaterial engineering aspects with cell transplantation to generate better-quality biomimetic scaffolds, prevascularize three-dimensional (3D) tissue structures, and engineer the composite interface of diverse facial tissues. In this review, we have discussed the application of different adult stem cells to repair oral and maxillofacial defects in animal models and clinical trials.

Sildenafil efficacy in erectile dysfunction secondary to spinal cord injury depends on the level of cord injuries.

To evaluate the efficacy of sildenafil in the treatment of neurogenic erectile dysfunction (ED) secondary to upper motor neuron (UMN) and lower motor neuron (LMN) spinal cord injury (SCI). After taking consents 105 patients suffering from ED were enrolled in this prospective study. Seventy-two patients had signs and symptoms of UMN and 33 patients had signs and symptoms of LMN or mixed (UMN and LMN) spinal cord injuries. The patients took 50-100 mg sildenafil or placebo tablet at least 45 min before sexual intercourse. Based on a IIEF questionnaire, success in achieving erection adequate for sexual intercourse was compared between sildenafil and placebo groups in UMN and non-UMN spinal cord injuries. In patients with UMN disease, sildenafil was effective in 82% of patients and its efficacy was statistically higher than placebo (82 vs. 25%, p < 0.05). Twenty-eight per cent of patients with non-UMN disease had a favourable response to sildenafil that was not statistically different from placebo. Sildenafil seems more effective in the treatment of neurogenic ED secondary to UMN spinal cord injury compared with that secondary to LMN injury. Actually, its efficacy on LMN injuries does not seem different from placebo and administration of this treatment may not be effective in spinal cord injury which has caused LMN symptoms.

Oxidation and electrical properties of chromium-iron alloys in a corrosive molten electrolyte environment.

Chromium-iron (CrFe) binary alloys have recently been proposed to serve as the "inert" anode for molten oxide electrolysis (MOE). Herein, the effects of anodic polarization on physical and functional properties of CrFe anodes in the corrosive environment of MOE are studied via empirical observations and theoretical calculations. The findings indicate that the alloys form an inner chromia-alumina solid-solution covered by an MgCr2O4 spinel layer. A survey into the electrical properties of the detected oxides suggests that the layered oxide scale function as an efficient conductor of electricity at elevated temperature. The formation mechanism of the oxides is also investigated.

Preliminary results of endovascular abdominal aortic aneurysm exclusion with the AneuRx stent-graft.

OBJECTIVES: This study evaluated the clinical effectiveness of the Medtronic AneuRx stent-graft in patients with infrarenal abdominal aortic aneurysms (AAAs) who were treated in an endovascular suite. BACKGROUND: The use of endovascular stent-graft prosthesis for the treatment of AAAs is receiving increasing attention as an alternative to standard surgical repair. Endovascular treatment of AAAs offers the potential to avoid the significant morbidity and mortality associated with surgical repair. METHODS: In this series, 215 patients have undergone AAA exclusion with the AneuRx stent-graft. Six-month follow-up is available in 132 patients; one-year follow-up is available in 84 and two-year follow-up in 22. RESULTS: Of the patients, one hundred ninety-two (89%) were male; 87% had hypertension, and 58.6% were American Society of Anesthesiologists grade IV or higher. The procedural success was 99.5%; we were unable to place the device in one patient. There was no procedural or one-month mortality. There were no acute conversions to surgical repair. One patient had a non-Q-wave myocardial infarction 24 h after the procedure. Endoleaks were present in 82 patients (42%) at discharge, 15 patients (11.3%) at six months and 10 patients (11.9%) at one year. Twenty-two patients had a secondary procedure for endoleak repair of which three were conversions to surgical repair. Twelve late deaths have occurred, none due to device failure or AAA rupture. Mean hospital stay was 1.9 days. CONCLUSIONS: These results reveal that infrarenal AAAs can be safely and successfully treated in an endovascular suite with the AneuRx stent-graft. Further follow-up is needed to determine the long-term efficacy of endoluminal treatment to prevent rupture and death due to AAAs.

HLA-DR antigen-negative acute myeloid leukemia.

Human leukocyte antigen (HLA) Class II antigens are variably expressed on acute myeloid leukemia (AML) blasts. The biological and clinical significance of HLA Class II antigen expression by AML cells is not known. Therefore, we sought to characterize cases of AML without detectable HLA-DR expression. Samples from 248 consecutive adult AML patients were immunophenotyped by multiparameter flow cytometry at diagnosis. HLA-DR antigens were not detected on AML cells from 43 patients, including 20 with acute promyelocytic leukemia (APL), and 23 with other subtypes of AML. All APL cases had t(15;17), but there were no characteristic chromosome abnormalities in non-APL cases. No direct expression of other antigens was identified in HLA-DR-negative APL and non-APL cases. Interestingly, cells from three HLA-DR-negative non-APL patients had similar morphology to that of the hypogranular variant of APL. This morphology, however, was not present in any HLA-DR-positive AML cases. Treatment response was similar in the 23 HLA-DR-negative non-APL and the 205 HLA-DR-positive patients. Finally, relapse was infrequently associated with changes in HLA-DR antigen expression, as the HLA-DR antigen was lost at relapse in only 4% of HLA-DR-positive cases, and was gained at relapse in only 17% of HLA-DR-negative cases. We conclude that HLA-DR-negative AML includes approximately equal numbers of APL and non-APL cases, and that the morphology of HLA-DR-negative non-APL cases can mimic the hypogranular variant of APL. The diagnosis of APL cannot be based on morphology and lack of HLA-DR antigen expression; rather, it requires cytogenetic or molecular confirmation.

Phenytoin mouthwash to treat cancer therapy-induced oral mucositis: A pilot studyPrimary neuroendocrine carcinoma of breast: A rare tumor.

BACKGROUND: Oral mucositis is one of the most common side effects of cancer therapy with no definite treatment. Phenytoin has positive effects on healing of mucosal and dermal wounds. In this study efficacy of 1% phenytoin mouthwash on severity of mucositis (on the basis of WHO scale), pain relief (based on Visual Analogue Scale), and improvement of patients' quality of life (on the basis of EORTC-QLQ-H and N35 questionnaire) was evaluated. MATERIALS AND METHODS: In a pilot -double-blind randomized clinical trial, eight patients in study group were given 1% phenytoin mouthwash while eight patients in control group used normal saline. Data analysis was performed by Mann-Whitney and Repeated Measured ANOVA tests. RESULTS: Reduction of mucositis severity was observed, but the difference was not significant. On the other hand, patients on phenytoin therapy had better pain relief (VAS# 6.75 ± 1.58 at the beginning of the study reached to # 3.75 ± 1.16 after 3 weeks in phenytoin group) and improvement in quality of life (score of QOL was 70.63 ± 5.5 that reached to 63.61 ± 6.39 in phenytoin group) than normal saline group significantly (P < 0.05). CONCLUSION: One percent phenytoin mouthwash caused pain relief and improvement of life quality significantly in patients with mucositis due to cancer therapy, but it did not reduce the severity of mucositis in a statistically significant scale.

Unusual etiology of cough in a woman with asthma.

A case of multiple symmetric lipomatosis (Madelung's disease) acquired through chronic use of corticosteroids is reported. Presumed symptoms of asthma, which consisted of a barking cough, were treated with escalating doses of steroids. We postulate that excessive use of steroids led to extensive mediastinal fatty infiltration with narrowing of the trachea and mainstem bronchi as noted both radiographically and bronchoscopically. When the steroids were tapered, there was marked improvement of the patient's symptoms and resolution of the upper airway intrathoracic obstruction. When patients with asthma are receiving optimal therapy and fail to improve, other causes for their symptoms should be considered.

Congenital subclavian steal syndrome in an adult with a left aortic arch.

To our knowledge, all of the cases of congenital subclavian steal syndrome encountered to date in adults have involved a right aortic arch. We present an angiographically proven case of congenital subclavian steal syndrome involving a left aortic arch in an adult.

Re-evaluation of the first phenytoin paste healing effects on oral biopsy ulcers.

BACKGROUND: Until now, several formulations of topical phenytoin have been used to promote wound healing. AIM: This study was aimed at re-evaluating the effects of a newly formulated phenytoin mucoadhesive paste on wound healing after oral biopsy. SUBJECTS AND METHODS: In a double-blind clinical trial, 35 consecutive patients with oral lichenoid or lichen planus lesions were randomized into two groups. After incisional biopsy, patients applied simple, or 1% phenytoin paste at least three times a day (after each meal), for 4 days. They were evaluated every other day for size of wound closure, severity of pain, and diameter of the inflammatory halo. This study was approved by Medical Ethics committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran. Statistical analysis was performed using Mann-Whitney U test and Ordinal Logistic Regression. RESULTS: Of 35 patients, 17 (10 [10/17, 59%]) men, 7 (7/17, 41%) women, mean age: 40 (4.11) were in phenytoin group, and 18 (9 [9/9, 50%]) men, 9 (9/9, 50%) women, mean age: 43.1 (5.15) were in placebo group. There were no significant differences between both study groups in terms of age and sex (male/female ratio) (P = 0.76, P = 0.88). As all biopsies were done by means of punch number 8, the incisions were of 10 mm length. After second and third appointments, it was observed that patients in the treatment group showed quicker wound closure and less pain compared to control group significantly (P < 0.05). Although not significant, patients treated with phenytoin paste had smaller inflammatory halo than controls. CONCLUSION: Applying 1% phenytoin mucoadhesive paste on oral biopsy incisions resulted in accelerated wound healing and decrease in pain.

Non-linear adaptive phenomena which decrease the risk of infection after pre-exposure to radiofrequency radiation.

Substantial evidence indicates that adaptive response induced by low doses of ionizing radiation can result in resistance to the damage caused by a subsequently high-dose radiation or cause cross-resistance to other non-radiation stressors. Adaptive response contradicts the linear-non-threshold (LNT) dose-response model for ionizing radiation. We have previously reported that exposure of laboratory animals to radiofrequency radiation can induce a survival adaptive response. Furthermore, we have indicated that pre-exposure of mice to radiofrequency radiation emitted by a GSM mobile phone increased their resistance to a subsequent Escherichia coli infection. In this study, the survival rates in animals receiving both adapting (radiofrequency) and challenge dose (bacteria) and the animals receiving only the challenge dose (bacteria) were 56% and 20%, respectively. In this light, our findings contribute to the assumption that radiofrequency-induced adaptive response can be used as an efficient method for decreasing the risk of infection in immunosuppressed irradiated individuals. The implication of this phenomenon in human's long term stay in the space is also discussed.

Impact of milk components on recovery of viral RNA from MS2 bacteriophage.

Noroviruses are responsible for approximately 44 % of outbreaks involving dairy products for which causative agents are reported. Recovery of viruses from milk and dairy products is a difficult task. The role of different components of milk in the recovery of viral RNA was evaluated in this study. Four model milk formulations (A-D) were prepared by mixing different combinations of lactose, whey protein, casein, and fat in water. Each model formulation was spiked with five concentrations of bacteriophage MS2. The phenol-guanidine thiocyanate-chloroform protocol was used for extracting viral RNA from the model milk formulations and then extracted RNA was measured by a nanodrop spectrophotometer in ng/µl. The results showed that casein and whey protein had the highest negative impact on RNA yield, especially when the number of MS2 was less than 1.3 pfu/ml. The highest RNA recovery was obtained from the model milk formulation containing all four components; lactose, whey protein, casein, and fat. The amount of extracted RNA was closely correlated with the dry matter content of each formulation and the spiked concentration of coliphage using response surface modeling (R²:0.93). It was determined that milk fat is the most effective component in facilitating RNA extraction and the highest RNA yield can be achieved via elimination of whey protein and casein from milk by centrifugation at 40,000×g for 60 min. To achieve the highest viral RNA recovery efficiency by the proposed method, milk fat must be recombined with the supernatant of the centrifuged sample and then homogenized before performing the extraction protocol.

Single-center experience of percutaneous abdominal aortic aneurysm repair with local anesthesia and conscious sedation: technique and results.

AIM: Totally percutaneous endovascular abdominal aortic aneurysm repair (PEVAR) by using the "Preclose" technique has been previously described. We retrospectively analyzed data, collected prospectively at our institution, regarding PEVAR via femoral artery access with local anesthesia and conscious sedation. METHODS: Between January 2001 and May 2009, 1150 patients underwent PEVAR in the endovascular suite of the cardiac catheterization laboratory at our institution. Of those procedures, 915 (79%) were performed with local anesthesia and conscious sedation. RESULTS: The majority of patients were male (87%). Their mean age was 72±10 years, and 98% had a risk status of American Society of Anesthesiologists class III or IV. The PEVAR involved bilateral percutaneous femoral access with 12F to 24F sheaths (depending on the stent-graft system). The mean total procedure time was 149 minutes. Percutaneous closure of the arterial access sites with the Prostar XL was successful in 1727 (94.3%) of the 1830 femoral arteries in which PEVAR was attempted, whereas 103 femoral arteries (5.6%) required surgical repair because adequate hemostasis was not attained at the access site. There were no procedural deaths, but 6 patients (0.6%) died within 30 days of the procedure: 3 died of intestinal ischemia, 1 of stroke, 1 of refractory ventricular arrhythmia, and 1 of worsening renal failure. Mean length of hospital stay was 1.3±2 days. CONCLUSION: PEVAR with local anesthesia and intravenous sedation is safe and feasible and should be considered for patients for whom general anesthesia poses a high risk.

Impact of milk components in recovery of the MS2 bacteriophage as an indicator of enteric viruses.

The objective of this study was to characterize the role of milk components in the recovery of viral particles from raw milk. For such characterization, four model milk formulations (A-D) were constituted by mixing different combinations of lactose, whey protein, casein, and fat into water. Each model formulation was spiked with six concentrations of bacteriophage MS2. The soluble and insoluble components of each model milk formulation were separated by centrifugation at 40,000 x g and viruses were enumerated in each supernatant fluid and pellet by the double agar layer (DAL) method. When samples were spiked with MS2 at concentrations lower than 4.8 x 10(5) pfu/ml, milk components did not significantly impact the overall recovery. However, the impact of milk components was measurable at higher concentrations. In general, higher numbers of MS2 were recovered from supernatant fluids of model milk formulations containing no fat. The highest number of viral particles were recovered from the pellet of model C (lactose+whey protein+casein). The recovery efficiency of MS2 was correlated with the dry matter contents of each model milk formulation and the initial spiking concentration of coliphage using response surface modeling.

Should preoperative, post-chemoradiotherapy endoscopy be routine for esophageal cancer patients?

Chemoradiation therapy is used widely for locoregional esophageal cancer. Patients with persistent disease may benefit from surgery. Preoperative esophagoscopy can identify persistent tumor but its accuracy is uncertain. The primary objective of this study is to assess the extent of agreement between esophagoscopy and surgical pathology in patients treated with neoadjuvant chemoradiation. A retrospective chart review of patients who underwent chemoradiation, preoperative endoscopy and surgery from January 1996 to December 2002 was performed. Cohen's kappa statistic was used to measure the degree of agreement between findings at endoscopic biopsy and surgical pathology. Thirty cases were identified. All patients received chemoradiation followed by surgical resection. There was insufficient agreement between tumor size (kappa 0.25, standard error 0.17, P = 0.07) and appearance (kappa 0.19, standard error 0.18, P = 0.14). Preoperative endoscopy revealed atypia/inflammation in 15 cases and dysplasia in eight. Of these 23 cases, 11 were adenocarcinomas at surgery. Only nine patients had concurrence between surgical pathology and endoscopy. The positive and negative predictive values of esophagoscopy for identifying residual tumor were 100% and 11%, respectively. Our data suggests that after chemoradiation, esophagoscopy is unreliable for excluding residual disease. The roles of other modalities need to be explored.

Vasculitis with eosinophilia and digital gangrene in a patient with acquired immunodeficiency syndrome.

Fewer than 40 cases of vasculitis have been described in the setting of human immunodeficiency virus infection. We describe a patient with the acquired immunodeficiency syndrome (AIDS), a heavy smoker, who developed a syndrome of constitutional symptoms, eosinophilia and digital gangrene. Vasculitis of the digital arteries was documented by angiography. He responded to high dose corticosteroid therapy with arrest of the ischemic process. After steroids were discontinued, he suffered a relapse of the vasculitis documented by skin biopsy. In patients with AIDS with this serious, potentially steroid responsive condition, steroid therapy should be considered in spite of the preexisting immunodeficiency state.