Disease severity in respiratory syncytial virus infection: Role of host genetic variation

Respiratory syncytial virus (RSV) infection is the most common cause of bronchiolitis and pneumonia in the pediatric population worldwide. The immunopathology of RSV infection varies considerably and severe disease occurs only in a minority of the population. There are many factors (host, viral, and environmental) that contribute to the complicated disease phenotype. In this regard, host factors are decisive for pulmonary susceptibility to RSV infection. Host genetic diversity certainly affects the balance between control of viral replication and tissue damage during RSV infection, consequently impacting on diseases outcome. In this review, we discuss the role of host genetic variation in disease caused by RSV aiming to highlight genetic risk factors for one of the most common diseases in early childhood. Our findings clearly indicate that the response of each individual to infection is influenced by genetic diversity mainly linked to the regulation of host immune responses. Future genetic association and functional studies using more powerful and consistently reproducible approaches will likely be able to confirm, refine, and expand our developing concept of RSV disease pathogenesis.     

Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome

OBJECTIVES: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). METHODS: Twenty two patients (10 males, 12 females, mean age 39 years, range 10-65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. RESULTS: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). CONCLUSIONS: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.     

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.

     

Development of rapid PCR method for simultaneous identification of species, specific capsular type, and toxigenicity of Pasteurella sp. isolates

Toxigenicity, species, and type species of Pasteurella multocida isolates cannot be differentiated by morphology or standard biochemical reactions. A more rapid method is needed for P. multocida detection from clinical cases. These findings provide rapid insights into the characteristics of P. multocida isolates and suggest that this method can identify toxigenic and specific capsular type P. multocida. A PCR assay has been developed for rapid detection of P. multocida and differentiation of capsular types A and D. In this rapid method, kmt1, capA and capD, and toxA genes were amplified and a reliable multiplex PCR method for the detection of P. multocida in sheep and goats in the south of Iran was designed. Twenty isolates were obtained, which evinced characteristic morphological and cultural properties. Ten samples were identified simultaneously through the presence of the kmt1 gene as P. multocida species, the hydD–hydC gene as type A capsule, and the toxA gene as dermonecrotic toxin by mPCR, but none of them belonged to type D.     

Monoclonal antibodies targeting CD38 in hematological malignancies and beyond

CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti-tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38-targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody-mediated autoimmune diseases.     

Seroprevalence of Neospora spp. in Horses in North East of Iran

Background

Neospora caninum, an obligate intracellular protozoan parasite, is recognized as a major cause of abortion in cattle, while limited information is presently available on the seroprevalence of Neospora antibodies in horses’ worldwide. The aim of the present study was to determine serologic prevalence of Neospora infection in horses in Iran.

Methods

Sera from 150 horses from Mashhad suburb in Razavi Khorasan Province, northeast Iran were examined for antibodies to Neospora spp. using Neospora modified direct agglutination test (N-MAT).

Results

Antibodies to this parasite were detected in 45 (30%) of the examined serum samples. Thirty four percent of the samples had titer of 1:40 while then reduced to 30% when 1:80 serum dilution was applied as significant cut off titer.

Conclusion

This study is the first investigation carried out on the Neospora in horses in Iran and indicates that horses in Iran are exposed to this parasite.