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.

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.

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.

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.

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.

Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer.

The microenvironment plays an important role in tumorigenesis. Fibroblast activation protein alpha (FAP) is overexpressed by fibroblasts present in the microenvironment of many tumors. High FAP expression is a negative prognostic factor in several malignancies, but this has not been investigated in epithelial ovarian cancer (EOC). The aim of this study is to define the value of FAP in EOC. Immunohistochemical staining using an anti-FAP antibody was performed on 338 EOC tissues. mRNA levels in cancer cell lines and FAP silencing using siRNA was also done. FAP immunoexpression by tumor stroma was a significant predictive factor for platinum resistance (p = 0.0154). In survival analysis of days to recurrence, FAP stoma (+) was associated with shorter recurrence than those with FAP (-) stroma (p = 0.0247). In 21.8 % of tumors, FAP protein was expressed by the tumor epithelium, and FAP mRNA was more highly expressed in tumors (n = 489) than in normal tissues (n = 8) (p = 3.88 × 10(-4)). In vitro, addition of FAP to EOC cells induced a 10-12 % increase in cell viability both in the presence and absence of cisplatin. Conversely, siRNA silencing of FAP resulted in ~10 % reduction in EOC cell proliferation. We have shown that FAP expression in EOC is associated with poorer clinical outcomes. FAP may have novel cell-autonomous effects suggesting that targeting FAP could have pleiotropic anti-tumor effects, and anti-FAP therapy could be a highly effective novel treatment for EOC, especially in cisplatinum-resistant cases.

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.

Association between Angiotensinogen M235T Polymorphism and Preeclampsia in Iranian Pregnant Women.

OBJECTIVE: To determine the possible association between the M235T variant of angiotensinogen gene and preeclampsia in Iranian preeclamtic women with hypertension during pregnancy. MATERIALS AND METHODS: During a case control study, we used polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis to investigate the association between M235T polymorphism in preeclamtic women compared to normotensive controls. RESULTS: The M235T polymorphism was significantly associated with increased preeclampsia risk in the studied population as supported by a p value of 0.017 and chi-square value of 8.12. The frequency of mutated allele and genotype distribution showed a significant difference between preeclamtic women and control groups. CONCLUSION: The result indicates that the AGT M235T polymorphism plays a significant role in preeclampsia observed in selected Iranian preeclamtic women, and it can be considered as a major risk factor for preeclampsia.

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.

Prevalence of Addiction to the Internet, Computer Games, DVD, and Video and Its Relationship to Anxiety and Depression in a Sample of Iranian High School Students.

OBJECTIVE: The objective of this study was to assess the prevalence of addiction to the Internet, computer games, DVD, and video and its relationship to anxiety and depression in a sample of Iranian high school students. METHODS: In this cross-sectional study 1020 high school students (males and females) were selected randomly from different areas of Shiraz city in southern Iran. They were interviewed according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) ed (DSM-IV) criteria. RESULTS: About 50% of the students were females, 277 students (27.2%) were studying in the first year of high school, 242 (23.7%) were in the second year, and others in the third year. The prevalence of anxiety was significantly higher in females than in males (p < 0.05). The prevalence of anxiety was lower among students of the third year (p < 0.05). The prevalence of depression was significantly higher in students with lower economic status defined as family monthly income. Internet dependence was seen only in 5 students. The prevalence of anxiety was significantly higher in the students who used internet for chatting, amusement, and reading news (p < 0.05). The prevalence of anxiety was significantly higher in students who were DVD or video CD dependents (p < 0.05). The students who used especial drugs or had especial diseases had higher rates of depression and anxiety (p < 0.05). CONCLUSION: Internet addiction may cause depression and anxiety in high school students. It seems necessary to develop an Internet addiction prevention program for adolescents taking into account the psychological factors such as depression and Internet use habits.

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.

Is there any relation between cervical cord plaques and discopathy in patients with multiple sclerosis?

INTRODUCTION: Multiple sclerosis (MS) is the most common chronic autoimmune demyelinating disease of the central nervous system. The purpose of this study is to determine the relationship between the site of the cervical discopathy and cervical spinal cord plaque in MS patients. METHODS: This retrospective study included all patients with a definite diagnosis of MS who were treated at an outpatient clinic between September 2004 and September 2011. All patients underwent cervical magnetic resonance imaging (MRI) for primary investigation of the disease. Cervical MRI scans were evaluated for detection of any evidence of cervical discopathy and cervical MS plaques. Any correlation between the site of the MS lesions and discopathy was recorded. RESULTS: From 536 patients who were involved in the study, 214 patients had both cervical discopathy and cervical cord plaques. In this group 148 (69.1% of patients) had cervical plaque at the same site of cervical discopathy. The number of patients with cervical cord plaque and discopathy at same site was significantly higher than those with plaque and discopathy at different sites (P<0.05). CONCLUSION: The study data suggests a possible correlation between cervical discopathy and cervical MS plaque.

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.

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.

Surgical excision followed by low dose rate radiotherapy in the management of resistant keloids.

BACKGROUND: Depending on the cause, 40-90% of every deep dermis insult ends up in scar formation. Several modalities have been suggested as a treatment but a high rate of recurrence is reported in most of those interventions. High dose radiotherapy has been shown to be effective in reducing the recurrence rate. This study tried to determine the effectiveness of low dose rate radiotherapy following surgical excision in treating resistant keloids. METHODS: Between January 2008 and April 2011, seventeen patients (mostly burn patients) with 26 keloids went through surgical resection followed by radiotherapy. A total dose of 15 Gy in 5 fractions was administered to the areas of scar formation. RESULTS: All patients were followed for at least 11 months (mostly for 20 months). No recurrence occurred. There was no complication or adverse effect. CONCLUSION: Surgical excision followed by low dose postoperative radiotherapy was an efficient treatment for keloids that were resistant to many other modalities.

Explosive attack: Lessons learned in Seyed Al Shohada mosque attack, April 2008, Shiraz, Iran.

INTRODUCTION: The threat of explosive attacks has become a worldwide problem. Bombing is the preferred method of attacks. These attacks result in specific physical and psychiatric trauma. In this paper, we present an epidemiologic description of the physical injuries of patients who survived the explosive attack in Seyed Al Shohada mosque April 2008 Shiraz, Iran. MATERIALS AND METHODS: All medical records of the patients admitted at Shiraz Hospitals on April 2008 due to Seyed Al Shohada mosque bombing attacks, Shiraz, Iran, were reviewed. RESULTS: A total of 202 patients were referred to the hospitals over 24 h following the terrorist attack. One hundred sixty-four patients were admitted for short periods of observation (<24 h). Thirty-eight patients needed more than 1 day of hospitalization. The mean age of the patients was 26.2 (range 2 to 51) years. One hundred thirty-five (66.8%) patients were males. Twenty-six (12.8%) were children. Burn was the most prevalent cause of admission. Five (13.5%) patients needed chest tube insertion and eight (21%) needed skin grafts due to burn. Overall, 12 patients expired (5%). Three (25%) of them were children (2 and 6, and 11 years old). Mortality rate was significantly higher among the children than adults (P value <0.05). The most important cause of death was head trauma which was seen in five (41.6%) of the expired patients followed by burn (including air way burn) in four (33%), and internal bleeding in three (25%). Patients with head trauma had significantly a higher rate of mortality than other patients (P value <0.05). DISCUSSION: Following a bombing attack, numerous victims were brought to the emergency unit suffering from a combination of multi-organ injuries caused by the blast, penetrating injuries caused by shrapnel and other debris, and burns. It is important for a physician to be familiar with the clinical features and treatments of explosive attacks victims. Early management of patients at the scene and hospital may save their life.

The use of micro pulse oximetery as a new detector of tissue perfusion in solid organ transplantation.

Vascular complications are a frequent cause of transplant failure; angiography, duplex sonography, computerized tomography (CT) scan, CT-angiography and microdialysis are the methods that were suggested for the detection of arterial obstruction after transplantation. In this study, we suggest a new method. Eight healthy adult dogs were included in the trial. All cases were operated by the same surgeon and the liver, pancreas, spleen, kidney and bowel tissue were exposed. The probes of the device, which were designed for this study, were inserted on the organ parenchyma. The device, a neonatal pulse oximeter, has two probes that were fixed by a holder in front of each other; the distance between the probes was changeable via a spring. The pulse and the oxygen saturation of the tissue were measured initially. Following this, by inducing ischemia with vessel clamping, the pulse and the oxygen saturation were measured again. The collected data were analyzed under the supervision of a statistician. In the liver and spleen, we could not detect a clear pulse wave and oxygenation. On the other hand, in the pancreas, kidney and bowel, we detected a clear curve of oxygenation and pulse in all cases. Obstruction caused significant changes: the pulse was not detected and the oxygenation decreased significantly. Our study suggests that with early diagnosis, the surgeons can detect arterial occlusion immediately and early intervention may decrease parenchymal damage. This study is the first experience in this field, and these findings need to be validated with further studies.