Oral vaccination with novel Lactococcus lactis mucosal live vector-secreting Brucella lumazine synthase (BLS) protein induces humoral and cellular immune protection against Brucella abortus.

This work aimed to provide recombinant Lactococcus lactis as a potential live vector for the manufacture of recombinant Brucella abortus (rBLS-Usp45). The sequences of the genes were collected from the GenBank database. Using Vaxijen and ccSOL, the proteins' immunogenicity and solubility were evaluated. Mice were given oral vaccinations with recombinant L. lactis. Anti-BLS-specific IgG antibodies were measured by ELISA assay. Cytokine reactions were examined using real-time PCR and the ELISA technique. The BLS protein was chosen for immunogenicity based on the vaccinology screening findings since it had maximum solubility and antigenic values ​​of 99% and 0.75, respectively. The BLS gene, digested at 477 bp, was electrophoretically isolated to demonstrate that the recombinant plasmid was successfully produced. Protein-level antigen expression showed that the target group produced the 18 kDa-sized BLS protein, whereas the control group did not express any proteins. In the sera of mice given the L. lactis-pNZ8148-BLS-Usp45 vaccine 14 days after priming, there was a significant level of BLS-specific IgG1, IgG2a (P < 0.001) compared to the PBS control group. Vaccinated mice showed higher levels of IFN-γ, TNFα, IL-4, and IL-10 in samples obtained on days 14 and 28, after receiving the L. lactis-pNZ8148-BLS-Usp45 and IRBA vaccines (P < 0.001). The inflammatory reaction caused less severe spleen injuries, alveolar edema, lymphocyte infiltration, and morphological damage in the target group's spleen sections. Based on our findings, an oral or subunit-based vaccine against brucellosis might be developed using L. lactis-pNZ8148-BLS-Usp45 as a novel, promising, and safe alternative to the live attenuated vaccines now available.

Associations of BCL2 CA-Repeat Polymorphism and Breast Cancer Susceptibility in Isfahan Province of Iran.

BCL2 apoptosis regulator (BCL2) is a cause of tumorigenesis whose CA-repeat promoter polymorphisms has inconsistent association with various types of cancers. The association of BCL2 polymorphism with breast cancer was investigated in the Isfahan province of Iran. PCRamplification of the CA-repeat was followed by polyacrylamide gel electrophoresis and direct sequencing for 120 breast cancer women and an equal number of corresponding healthy control individuals. Seven different alleles, ranging from 11 to 17 CA-repeats were observed. Short alleles with 11 to 14 repeats were protective (OR 0.363, P = 0.001), but large alleles with 15 to 17 repeats were threatening against breast cancer development (OR 2.780, P = 0.001). Accordingly, genotypes with large alleles showed a higher risk of breast cancer development (OR 3.400, P = 0.004). ERS1\ERBB2 positive breast cancer patients, but not PGRpositive ones, showed protection against breast cancer (OR 0.405, OR 0.346 respectively). In conclusion, women with at least one large allele of BCL2 were 3.4 times at higher risk of breast cancer development in the Isfahan province of Iran.

The COronavirus Pandemic Epidemiology (COPE) Consortium: A Call to Action.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

Rheumatology Care Using Telemedicine.

Introduction: People living in many parts of the world have limited access to diagnostic studies and therapies for rheumatologic, musculoskeletal, and connective tissue diseases. The challenge has been particularly poignant for rural areas of low- and middle-income countries. Objectives: We report on the implementation of a telemedicine program in Iran for the evaluation and treatment of patients with rheumatologic and musculoskeletal diseases. More than 4,800 patients were seen remotely over a span of 5 years by a rheumatologist in the United States. The remote rheumatologist was aided by a general physician and a nurse at a local charity hospital in northeastern Iran that has a catchment area that includes rural regions extending to the border of Afghanistan. Seventy to 90 patients were evaluated online by the remote rheumatologist 3 days a week. A subset of patients was evaluated by the rheumatologist in person every 4 months. Materials and Methods: The population of rheumatology patients was evaluated using descriptive statistics. Information collected included demographic information consisting of age, gender, and primary rheumatologic diagnosis. Results: The average age of patients who were seen was 52 years and 89% of patients were women. Approximately 50% of patients were Afghan refugees. The most common disorders included osteoarthritis (1,149, 23.6%), rheumatoid arthritis (653, 13.4%), axial spondyloarthropathies (647, 13.3%), lumbar spinal stenosis (427, 8.8%), meniscal tear of the knee (326, 6.7%), and psoriatic arthritis (217, 4.5%). Certain conditions were lower than expected such as lupus (19, 0.4%) and fibromyalgia (169, 3.5%). Diagnostic tests included serologic tests (1,328, 27.3%), plain radiographs (946, 19.5%), magnetic resonance imaging (899, 18.5%), bone densitometry (147, 3.0%), and electromyography and nerve conduction study (132, 2.7%). The most common medications prescribed were non-steroidal anti-inflammatory drugs (791, 16.3%), methotrexate (764, 15.7%), pregabalin (234, 4.8%), duloxetine (230, 4.7%), sulfasalazine (177, 3.6%), etanercept (97, 2.0%), tofacitinib (64, 1.3%), adalimumab (18, 0.4%), and infliximab (9, 0.2%). Conclusions: Telemedicine is becoming more prevalent. We report the successful use of this service in evaluation and management of rheumatic diseases in a region with limited access to rheumatologic care. We have shown that patients can be seen, evaluated, and successfully treated with a variety of medications, including biologic agents.

Validity and reliability of Persian version of Listening Styles Profile-Revised (LSP- R) in Iranian students.

Background: Individuals' listening styles differs based on their characters, professions and situations. This study aimed to assess the validity and reliability of Listening Styles Profile- Revised (LSP- R) in Iranian students. Methods: After translating into Persian, LSP-R was employed in a sample of 240 medical and nursing Persian speaking students in Iran. Statistical analysis was performed to test the reliability and validity of the LSP-R. Results: The study revealed high internal consistency and good test-retest reliability for the Persian version of the questionnaire. The Cronbach's alpha coefficient was 0.72 and intra-class correlation coefficient 0.87. The means for the content validity index and the content validity ratio (CVR) were 0.90 and 0.83, respectively. Exploratory factor analysis (EFA) yielded a four-factor solution accounted for 60.8% of the observed variance. Majority of medical students (73%) as well as majority of nursing students (70%) stated that their listening styles were task-oriented. Conclusion: In general, the study finding suggests that the Persian version of LSP-R is a valid and reliable instrument for assessing listening styles profile in the studied sample.

Interferon-beta in pediatric multiple sclerosis patients: safety in short-term prescription.

None of the approved immunomodulatory drugs in adults Multiple Sclerosis (MS) patients have been officially approved for the pediatric patients and are currently used off-label in this population. In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a (Avonex(®)) and subcutaneously injected interferon beta1-b (Betaferon(®)) in children with definite relapsing-remitting MS (RRMS). Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonald's criteria, were enrolled in this study. Six patients were treated with Avonex(®) 30 µg, intramuscularly every week, and seven patients were treated with Betaferon(®) 250 µg, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Eleven girls and two boys, mean (SD) age of 14.7 (1.9) years, were studied. Following nine months of using interferon-beta, nine patients (69.2%) had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children.

The role of nitric oxide and protein kinase C in lipopolysaccharidemediated vascular hyporeactivity.

PURPOSE: Overactivation of nitric oxide and protein kinase C (PKC) pathway has been reported to play a role in the pathogenesis of vascular hyporesponsiveness of endotoxic shock. In this study we investigated the role of nitric oxide and PKC in lipopolysaccharide (LPS) mediated vascular hyporeactivity. METHODS: Contraction to phenylephrine and endothelium-dependent and independent vasodilation in the presence and absence of a nonspecific NO inhibitor (L-NAME) and potent PKC inhibitor (chelerythrine) were examined. RESULTS: In LPS treated rats, contractile response of aortic rings to phenylephrine and relaxation in response to acetylcholine were reduced, but relaxation induced by sodium nitroprusside remained unchanged. The attenuation of contractile response to phenylephrine in the presence of L-NAME and chelerythrine was more pronounced in aortic ring isolated from LPS treated rats than control. L-NAME decreased acetylcholine -dependent vasodilation in both group but it was more pronounced in LPS treated rats. Chelerythrine pretreatment improved maximal relaxation to acetylcholine in aortic ring isolated from LPS treated rats. CONCLUSION: These data indicate that the vascular hyporesponsiveness to phenylephrine and acetylcholine after treatment with LPS may be related to an enhanced NO production in the smooth muscle cells and PKC plays a role as an intracellular mediator of LPS-induce NOS activity and vascular suppression.