The neural structures of theory of mind are valence-sensitive: evidence from three tDCS studies.

Several cortical structures are involved in theory of mind (ToM), including the dorsolateral prefrontal cortex (dlPFC), the ventromedial prefrontal cortex (vmPFC), and the right temporo- parietal junction (rTPJ). We investigated the role of these regions in mind reading with respect to the valence of mental states. Sixty-five healthy adult participants were recruited and received transcranial direct current stimulation (tDCS) (1.5 mA, 20 min) with one week interval in three separate studies. The stimulation conditions were anodal tDCS over the dlPFC coupled with cathodal tDCS over the vmPFC, reversed stimulation conditions, and sham in the first study, and anodal tDCS over the vmPFC, or dlPFC, and sham stimulation, with an extracranial return electrode in the second and third study. During stimulation, participants underwent the reading mind from eyes/voice tests (RMET or RMVT) in each stimulation condition. Anodal left dlPFC/cathodal right vmPFC stimulation increased the accuracy of negative mental state attributions, anodal rTPJ decreased the accuracy of negative and neutral mental state attributions, and decreased the reaction time of positive mental state attributions. Our results imply that the neural correlates of ToM are valence-sensitive.

Identification of novel candidate biomarkers of epithelial ovarian cancer by profiling the secretomes of three-dimensional genetic models of ovarian carcinogenesis.

Epithelial ovarian cancer (EOC) is still considered the most lethal gynecological malignancy and improved early detection of ovarian cancer is crucial to improving patient prognoses. To address this need, we tested whether candidate EOC biomarkers can be identified using three-dimensional (3D) in vitro models. We quantified changes in the abundance of secreted proteins in a 3D genetic model of early-stage EOC, generated by expressing CMYC and KRAS(G) (12) (V) in TERT-immortalized normal ovarian epithelial cells. Cellular proteins were labeled in live cells using stable isotopic amino acid analogues, and secreted proteins identified and quantified using liquid chromatography-tandem mass spectrometry. Thirty-seven and 55 proteins were differentially expressed by CMYC and CMYC+KRAS(G) (12) (V) expressing cells respectively (p < 0.05; >2-fold). We evaluated expression of the top candidate biomarkers in ∼210 primary EOCs: CHI3L1 and FKBP4 are both expressed by >96% of primary EOCs, and FASN and API5 are expressed by 86 and 75% of cases. High expression of CHI3L1 and FKBP4 was associated with worse patient survival (p = 0.042 and p = 0.002, respectively). Expression of LGALS3BP was positively associated with recurrence (p = 0.0001) and suboptimal debulking (p = 0.018) suggesting that these proteins may be novel prognostic biomarkers. Furthermore, within early stage tumours (I/II), high expression of API5, CHI3L1 and FASN was associated with high tumour grade (p = 3 × 10(-4) , p = 0.016, p = 0.010, respectively). We show in vitro cell biology models of early-stage cancer development can be used to identify novel candidate biomarkers for disease, and report the identification of proteins that represent novel potential candidate diagnostic and prognostic biomarkers for this highly lethal disease.

Modulation of innate immune response, mucosal parameters and disease resistance in rainbow trout (Oncorhynchus mykiss) upon synbiotic feeding.

The present study investigates the effects of dietary supplements of galactooligosaccharides (GOS), Pediococcus acidilactici and P. acidilactici + GOS on innate immune response, skin mucus as well as disease resistance of rainbow trout (Oncorhynchus mykiss) fingerlings (15.04 ± 0.52 g). After 8 weeks of feeding, several innate immune (lysozyme, alternative complement and respiratory burst activities) and skin mucus parameters (bactericidal activity against Streptococcus faecium, Streptococcus iniae, Serratia marcescens, Staphylococcus aureus and Escherichia coli and mucus protein content) were studied. The results indicated that the three supplemented diet significantly increased innate immune response and skin mucus parameters in rainbow trout. The highest innate immune response, skin mucus activity as well as protein level was observed in synbiotic fed fish. Furthermore, at the end of the feeding experiment, some fish were intraperitoneally injected with Streptococcus iniae to determine the disease resistance. The mortality of fingerlings fed supplemented diet was significantly lower than fish from control group being the lowest mortality recorded in synbiotic fed fish group.

Expression of DNA repair proteins in endometrial cancer predicts disease outcome.

OBJECTIVE: The consequences of defective homologous recombination and other DNA repair pathways are important in disease outcomes of numerous tumor types. The objective of this study was to explore BRCA1, PARP, FANCD2, PTEN, H2AX, and ATM protein expression in endometrial cancer (EC). METHODS: PARP1, γH2AX, ATM, FANCD2, PTEN, BRCA1, and p53 proteins were evaluated in EC tissue microarray (TMA) and their expressions were correlated with clinical and pathological parameters in 357 patients. RESULTS: In type I EC, PARP1(+), ATM(+), and FANCD2(+) were associated with high tumor grade (p 0.031, p 0.0045, p 0.0062 respectively); γH2AX(+) and FANCD2(+) with advanced tumor stage (p 0.0004, p 0.0085 respectively); γH2AX(+), FANCD2(+) and p53(+) with the presence of lympho-vascular invasion (p 0.0004, p 0.0042, p 0.0098 respectively); and γH2AX(+) and ATM(+) with tumor recurrence (p 0.0203, p 0.0465) respectively. In type II EC, only PARP1(+) was associated with tumor stage (p 0.0499). EC patients with p53(+) or FANCD2(+) were more likely to recur with 5year recurrence free survival (RFS) probability of 71.4% in comparison to 85.5% for the other patients and they were more likely to have shorter 5year overall survival (OS) of 66.46% in comparison to 78.5% of those other patients Finally, patients with ATM(+) and p53(+) or FANCD2(+) were more likely to recur with 5year RFS probability of 68% versus 80.3% for the other patients. CONCLUSION: DNA repair proteins seemed to play an important role in EC, and their expressions can forecast for poor outcomes.

The effects of dietary xylooligosaccharide on mucosal parameters, intestinal microbiota and morphology and growth performance of Caspian white fish (Rutilus frisii kutum) fry.

The present study investigates the effects of different levels of dietary xylooligosaccharide (XOS) on skin mucus bactericidal activity and protein content, intestinal microbiota and morphology as well as growth performance of Caspian white fish (Rutilus frisii kutum) fry. The specimens (1.54 ± 0.03 g) were fed experimental diets supplemented with different levels of XOS [0% (control), 1%, 2% and 3%] for 8 weeks. The results revealed that feeding on XOS significantly increased skin mucus antibacterial activity and protein levels (P < 0.05) and the highest levels were observed in 3% XOS treatment. The total autochthonous intestinal heterotrophic bacteria significantly increased following XOS administration in diet (P < 0.05). Administration of 2 or 3% XOS in fry diet significantly elevated the autochthonous lactic acid bacteria (P < 0.05). However, dietary XOS had no significant effect on intestinal morphology, growth performance and diet utilisation of Caspian white fish fry (P > 0.05). These results demonstrate beneficial effects of dietary XOS on different parameters of mucosal immunity (both skin mucus and intestinal microbiota) and encourage further studies regards various aspect of XOS administration in early life stages of fish.

Estimated prevalence and incidence of multiple sclerosis in Iran.

BACKGROUND: Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system and its epidemiology has changed in recent years. Previously, Iran was considered to have a low MS prevalence. In this study, we aimed to update the prevalence and incidence of MS in Iran. PATIENTS AND METHODS: This study was conducted based on the data derived from the new report of Iran's Ministry Of Health and Medical Education (MOHME) regarding the patients who have registered to obtain support for treatment in Iran till the end of 2013. RESULTS: Among the 42,200 registered patients, 32,477 were female and 9,723 were male (sex ratio: 3.34: 1), and 4,545 were diagnosed in 2013. This resulted in a prevalence of 54.51 and an incidence of 5.87 per 100,000. CONCLUSION: According to our study results, Iran has a medium-to-high prevalence rate of MS. According to the previous epidemiologic studies from Iran, it seems that the prevalence of MS significantly has increased during recent years. This rate is similar to what is seen in many western countries.

Hospital mortality associated with stroke in southern iran.

BACKGROUND: Unlike the western hemisphere, information about stroke epidemiology in southern Iran is scarce. The aim of this study was to determine the main epidemiological characteristics of patients with stroke and its mortality rate in southern Iran. METHODS: A retrospective, single-center, hospital-based longitudinal study was performed at Nemazee Hospital in Shiraz, Southern Iran. Patients with a diagnosis of hemorrhagic and ischemic strokes were identified based on the International Classification of Diseases, 9th and 10th editions, for the period between 2001 and 2010. Demographics including age, sex, area of residence, socioeconomic status, length of hospital stay, and discharge destinations were analyzed in association with mortality. RESULTS: 16351 patients with a mean age of 63.4 years (95% CI: 63.1, 63.6) were included in this analysis. Men were slightly predominant (53.6% vs. 46.4%). Forty-seven percent of the total sample was older than 65,17% were younger than 45, and 2.6% were children younger than 18. The mean hospital stay was 6.3 days (95% CI: 6.2, 6.4). Among all types of strokes, the overall hospital mortality was 20.5%. Multiple logistic regression revealed significantly higher in-hospital mortality in women and children (P<0.001) but not in patients with low socioeconomic status or from rural areas. During the study period, the mortality proportions increased from 17.8% to 22.2%. CONCLUSION: In comparison to western countries, a larger proportion of our patients were young adults and the mortality rate was higher.

The role of routine chest radiography in initial evaluation of stable blunt trauma patients.

BACKGROUND: Radiology plays an important role in evaluation of a trauma patient. Although chest radiography is recommended for initial evaluation of the trauma patient by the Advanced Trauma Life Support course, we hypothesized that precise physical examinations and history taking accurately identify those blunt trauma patients at low risk for chest injury, making routine radiographs unnecessary. Thus, this study was performed to investigate the role of chest radiography in initial evaluation of those trauma patients with normal physical examination. METHODS: In this prospective cross-sectional study, all the hemodynamically stable blunt trauma patients with negative physical examination result referred to our trauma center during a 4-month period (March-June 2009) were included. Chest radiographies were performed and reviewed for abnormalities. RESULTS: During the study period, 5091 blunt trauma patients referred to our center, out of which, 1008 were hemodynamically stable and had negative physical examination result. Only 1 (0.1%) patient had abnormal chest radiography that showed perihilar lymphadenopathy, unrelated to trauma. CONCLUSION: Performing routine chest radiography in stable blunt trauma patients is of low clinical value. Thus, decision making for performing chest radiography in blunt trauma patients based on clinical findings would be efficacious and resource saving.

Cross-Neutralization of Vanguard C4 Vaccine Against Australian Isolates of Canine Parvovirus Variants CPV-2a, CPV-2b, and CPV-2c.

Canine parvovirus type 2 (CPV-2) remains one of the most significant viral pathogens in dogs in Australia and worldwide despite the availability of safe and effective CPV vaccines. At least three different variants of CPV-2 have emerged and spread all around the world, namely CPV-2a, CPV-2b, and CPV-2c. The ability of the current vaccines containing either original CPV-2 type or CPV-2b variant to cross protect the heterologous variants has been well demonstrated in laboratory studies, despite some concerns regarding the vaccine efficacy against the emerging variants. Vanguard®, a series of multivalent vaccines, has been in the market for a considerable period of time and demonstrated to provide efficacy against all three types of CPV variants CPV-2a, CPV-2b, and CPV-2c. The purpose of this study was to evaluate the ability of the recently registered Vanguard C4 vaccine to induce cross-neutralizing antibodies against the Australian isolates of CPV-2a, CPV-2b, and CPV-2c variants. Blood samples collected from dogs vaccinated with Vanguard C4 were analyzed by virus neutralizing assays developed for each of three CPV variants. The results of the study demonstrated that Vanguard vaccine induced cross-neutralizing antibodies against the Australian isolates of CPV-2a, CPV-2b, and CPV-2c, thus offering cross protection against all three Australian CPV variants.

Association of zinc deficiency and depression in the patients with end-stage renal disease on hemodialysis.

INTRODUCTION: Depression is a common psychological symptom in patients undergoing chronic hemodialysis. In the general population, low serum zinc level is associated with major depression. The current study surveys the possible relationship between the prevalence of depression and plasma level of zinc in patients on hemodialysis (HD). PATIENTS AND METHODS: A total of 135 patients with end-stage renal disease (ESRD) on HD were enrolled in the study. The severity of depression was assessed using Beck Depression Inventory (BDI). Plasma zinc level was measured from fasting samples. RESULTS: Mean age of the patients was 52.45 (standard deviation: 15.33) years. In all, 76% of the patients had some degree of depression according to BDI scoring system (BDI >14). The mean level of plasma zinc in the depressed patients was significantly lower than the rest of the patients (67.46 ± 29.7 vs. 85.26 + 40.05). DISCUSSION: Zinc deficiency may be a reversible cause which might contribute to the increased rate of depression in HD patients. This is the first study reporting the association of zinc deficiency with the presence of depression in HD patients; therefore, these findings need further investigations.

Impact of oral zinc therapy on the level of sex hormones in male patients on hemodialysis.

BACKGROUND: Sexual dysfunction in chronic renal failure patients undergoing hemodialysis is common. It is demonstrated that the zinc level is significantly lower in the hemodialysis patients. OBJECTIVE: In this clinical trial, we investigate the effect of zinc supplement therapy on the serum levels of sexual hormones in hemodialysis male patients. PATIENTS AND METHODS: We carried out a clinical trial study including 100 of our male patients with end-stage renal disease on hemodialysis. Testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and zinc plasma level were measured in all of the patients. The patients received zinc supplement (zinc sulfate, 250 mg/day) for 6 weeks, and sex hormones and zinc plasma level were checked again. RESULTS: Serum level of FSH and prolactin did not have any significant changes before and after intervention, but serum level of testosterone, LH, and zinc increased significantly. DISCUSSION: These results suggest that although zinc administration did not have a definite effect on hemodialysis patients with sexual dysfunction, it can cause increase in the serum level of sex hormones which may improve the sexual function of the patients in some aspects.

Diagnostic Challenges in Canine Parvovirus 2c in Vaccine Failure Cases.

In this study, three different diagnostic tests for parvovirus were compared with vaccination status and parvovirus genotype in suspected canine parvovirus cases. Faecal samples from vaccinated (N17) and unvaccinated or unknown vaccination status (N41) dogs that had clinical signs of parvovirus infection were tested using three different assays of antigen tests, conventional and quantitative PCR tests. The genotype of each sample was determined by sequencing. In addition to the suspected parvovirus samples, 21 faecal samples from apparently healthy dogs were tested in three diagnostic tests to evaluate the sensitivity and specificity of the tests. The antigen test was positive in 41.2% of vaccinated dogs and 73.2% of unvaccinated diseased dogs. Conventional PCR and qPCR were positive for canine parvovirus (CPV) in 82.4% of vaccinated dogs and 92.7% of unvaccinated dogs. CPV type-2c (CPV-2c) was detected in 82.75% of dogs (12 vaccinated and 36 unvaccinated dogs), CPV-2b was detected in 5.17% dogs (one vaccinated and two unvaccinated) and CPV-2a in 1.72% vaccinated dog. Mean Ct values in qPCR for vaccinated dogs were higher than the unvaccinated dogs (p = 0.049), suggesting that vaccinated dogs shed less virus, even in clinical forms of CPV. CPV-2c was the dominant subtype infecting dogs in both vaccinated and unvaccinated cases. Faecal antigen testing failed to identify a substantial proportion of CPV-2c infected dogs, likely due to low sensitivity. The faecal samples from apparently healthy dogs (n = 21) showed negative results in all three tests. Negative CPV faecal antigen results should be viewed with caution until they are confirmed by molecular methods.

Effect of zinc supplementation on triglyceride, cholesterol, LDL, and HDL levels in zinc-deficient hemodialysis patients.

INTRODUCTION: Zinc deficiency is known to occur in widely diverse areas of world. It has now been recognized in many disease states, such as ESRD patients on maintenance hemodialysis (HD). The purpose of this research was to study the effects of zinc supplementation on the concentration of serum zinc, total cholesterol, triglyceride, and cholesterol fractions (HDL, LDL) in HD patients. PATIENTS AND METHODS: In a double blind trial, the effects of oral zinc supplementation on the serum concentration of zinc, total cholesterol, HDL and LDL cholesterol, and triglyceride in HD patients were evaluated. RESULTS: After 42 days, the mean serum zinc concentration among participants in the zinc-supplemented group increased. There was a significant elevation in the serum total cholesterol and also in mean the serum LDL and HDL cholesterol and serum triglyceride for the subjects in the zinc-supplemented group. DISCUSSION: A suboptimal level of the serum total cholesterol concentration is a factor associated with malnutrition and morbidity in the HD patients. Maintenance HD patients with both low serum zinc and low serum total cholesterol concentrations may benefit from zinc supplementation. Therefore, it is advisable to obtain baseline measurement of the serum zinc and total cholesterol concentrations in maintenance HD patients.

Effect of fluid therapy on prevention of acute renal failure in Bam earthquake crush victims.

BACKGROUND: At 5:28 a.m. (local time) on December 26, 2003, an earthquake measuring 6.51 on the Richter scale struck the city of Bam in the Kerman Province in southeastern Iran. Among the most important morbid events in survivors were acute renal problems. Clinical findings, laboratory data, and management of the renal victims, all of whom were transferred to Shiraz Hospitals, have been the subject of this analysis. METHOD: Medical records of twenty patients with acute renal failure admitted to three university hospitals and one community hospital were reviewed. RESULTS: Overall, 801 patients were transferred to Shiraz hospitals, of whom 20 (mean age 36.2 +/- 14.8 years, 15 males) developed acute renal failure with mean duration of 14.5 +/- 9.6 days. Total mortality was 21 (2.6%) and acute renal failure mortality was 3 (15%). Seven patients received standard fluid therapy and 13 patients received variable volume treatment. In total, 79 dialysis sessions were performed in 15 patients (mean 5.2, 3.3 +/- 1 sessions per patients). There was a positive correlation between time spent under rubble and peak serum CK (creatine phosphokinase) level (p = 0.035), acute renal failure duration (p = 0.047), and admission potassium levels (p = 0.033). Serum CK level was positively correlated with acute renal failure duration (p = 0.008). Patients who had received standard treatment had significantly shorter duration of acute renal failure (7.1 versus 9.4 days, p = 0.008) and less need for dialysis (1 versus 6, p = 0.007) than patients who were treated variably. CONCLUSION: In victims of earthquake, time spent under rubble and peak serum CK level can serve to estimate morbidity, and early standard treatment may decrease renal morbidity.

Behavioral Neurology of Multiple Sclerosis and Autoimmune Encephalopathies.

Multiple sclerosis (MS) is the most common nontraumatic cause of physical disability in young adults. Cognitive and neuropsychiatric problems are common in this disease independent of motor disability. Such problems especially in mild cases are ignored by physicians, although they may have a major impact on quality of life. Neurobehavioral changes may affect the adherence to treatment and worsen the ultimate prognosis. Although many studies have been performed in this regard, it seems that combining cognitive evaluations with other outcome measures in MS will enhance the understanding of neurobehavioral changes in MS.

A novel three-way rearrangement involving ETV6 (12p13) and ABL1 (9q34) with an unknown partner on 3p25 resulting in a possible ETV6-ABL1 fusion in a patient with acute myeloid leukemia: a case report and a review of the literature.

BACKGROUND: Acute myeloid leukemia (AML) is commonly characterized by several chromosomal abnormalities resulting in the formation of chimeric genes that play various roles in leukemogenesis. Translocations resulting in the ETV6-ABL1 fusion gene are rare in AML and other hematologic malignancies with only thirty-two previously reported cases in the literature, five of which were AML. FINDINGS: Herein, we report the case of a 73-year-old male with acute myeloid leukemia arising from MDS, negative for PDGFRA and PDGFRB, positive for bone marrow eosinophilia, rash, and marked fluid retention, which improved dramatically with imatinib therapy. Conventional cytogenetics revealed a t(3;9)(p25;q34), t(5;18)(q13;p11.2), and additional material of unknown origin at 12p11.2 in 2 out of 10 metaphases analyzed. Interphase FISH studies showed evidence of ETV6 (12p13) and ABL1 (9q34) rearrangements in 41.3 % and 5.7 % of the cells respectively. FISH studies on previously G-banded metaphases showed colocalization of ABL1 and ETV6 signals to the short arm of chromosome 3 at 3p25 suggesting a possible ETV6-ABL1 fusion. Subtelomeric metaphase FISH studies also showed the presence of a subtelomere 3p signal on the long arm of the derivative 9, and no subtelomere 3p signal on the derivative chromosome 12. CONCLUSIONS: These findings suggest a complex rearrangement involving an insertion of ETV6 into 3p25 followed by a reciprocal translocation involving 3p25 and 9q34, resulting in a possible ETV6-ABL1 fusion. This case highlights the importance of FISH to characterize complex rearrangements in myeloid malignancies, particularly those resulting in clinically significant chimeric genes.

Strategies in evaluation and management of Bam earthquake victims.

BACKGROUND: On 26 December 2003, an earthquake measuring 6.5 on the Richter scale occurred in the city of Bam in southeastern Iran. Bam was destroyed completely, > 43,000 people were killed, and 30,000 were injured. The national and international responses were quick and considerable. Many field hospitals were created and large numbers of patients were evacuated from their homes and transported to hospitals throughout Iran. Nearly 700 patients were transferred to Chamran hospital in Shiraz within the first 48 hours after the earthquake. METHODS: This is a retrospective study based on the medical records of earthquake casualties dispatched to Chamran Hospital. A screening tunnel composed of multiple stations was prepared before patients entered to facilitate the large influx of patients. Each of the victims was passed through this screening tunnel and assigned into one of three groups: (1) those needing emergency surgical intervention; (2) those needing less urgent surgery; and (3) those needing elective operations, supportive care, observation, and/or rehabilitation. RESULTS: Among the 708 patients, 392 were male (male/female ratio: 1.24) with a mean value of their ages of 30.5 years. (range: 1.5 months-70 years). Extremity fractures (136, 19%) were more common than were axial skeleton fractures (28, 4%). Out of the total 708 patients, 152 (21.5%) patients needed emergency operations, 26 (4%) needed less urgent surgery, and 530 (74.5%) required wound care or antibiotic therapy and other forms of supportive care. Some complications occurred, such as two patients with compartment syndromes of the leg, three required below-the-knee amputation, eight suffered acute renal failure, two developed fat emboli syndrome, and one had a brain injury that resulted in death. CONCLUSION: A comprehensive disaster plan is required to ensure a prompt disaster response and coordinated management of a multi-casualty incident. This can influence the outcomes of patients directly. A patient screening tunnel has advantages in rapid and effective evaluation and management of victims in any multi-casualty incident.