Bicistronic expression plasmid encoding allergen and anti-IgE single chain variable fragment antibody as a novel DNA vaccine for allergy therapy and prevention

Several approaches have been applied in order to alleviate the difficulties allergic patients are suffering from. Among them DNA vaccination and anti-IgE antibody have shown promising results. Herewith, a combination of both strategies is proposed to minimize IgE production while inducing high levels of blocking IgG and strong Th1 immune responses. A bicistronic expression plasmid including an internal ribosomal entry site (IRES) can express both, allergen and a single chain variable fragment (scFv) antibody against human IgE within antigen presenting cells (APCs) including B cells. Presentation of allergen derived peptides via MHC I and MHC II stimulates specific Th1 responses resulting in high levels of IFN-gamma and IgG. Anti-IgE scFv antibody binds to newly synthesized IgE molecules within B cell cytoplasm and also to free serum IgE, thereby inhibiting attachment of IgE to its receptors on basophils and mast cells. Also, IgE-anti-IgE complex functions as blocking antibody and neutralizes allergens entering the body. Additionally, anti-IgE scFv antibody binds to membrane bound IgE (mIgE) on B cells and interferes with IgE expression. Using assays, such as enzyme linked immunosorbent assay (ELISA), IgG and IgE production in response to this expression system can be evaluated. Also, rat basophil leukemia cell assay (using RBL-2H3 cells) can show the amount of functional IgE in sera as basophil mediator release is regarded as an indicator of the allergic hypersensitive reactions. The proposed approach may result in high levels of blocking IgG and low levels of IgE secretion from B cells. Additionally, it can inhibit activity of IgE in degranulation of basophils and mast cells.     

Emergent image-guided treatment of a large CSF leak to reverse "in-extremis" signs of intracranial hypotension

We report the use of an emergent, targeted fibrin spinal epidural blood patch with subarachnoid saline infusion to rapidly reverse "in-extremis" clinical and imaging signs of posterior-fossa coning brought about by acute-on-chronic intracranial hypotension, itself consequent to a cervicothoracic CSF leak. Treatment resulted in a dramatic recovery and eventual discharge with return to normal lifestyle and occupation. The clinical and imaging danger signs are reviewed; fibrin patch technique and potential pitfalls in postprocedure management are analyzed.     

Adams-Oliver syndrome and isolated aplasia cutis congenita in two siblings

Adams-Oliver syndrome is a rare congenital anomaly complex characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects. We present a 9-year-old girl with a large, congenital scalp defect on her vertex, without underlying bone defect. Brachydactyly and syndactylia of her toes were also evident. Her 13-year-older brother had an 8 x 5 cm scalp defect without any limb defects (isolated ACC).     

Sex bias in response to hepatitis B vaccination in end-stage renal disease patients: Meta-analysis

AIM: To systematically review the literature for studies investigating the potential effect of gender of dialysis patients on the immunogenicity of hepatitis B virus vaccines.METHODS: Literature searches were conducted by the MEDLINE and Google Scholar. The key words used included “hepatitis B (HB)”, “vaccine”, “dialysis”, “hemodialysis”, “sex”, “male” and “female”. Data of seroresponse to HB vaccine in clinical trials regarding sex of the recipients have been achieved and analyzed. Finally data from 19 clinical trials have been pooled and analyzed.RESULTS: Analysis of response to HB vaccination in our dialysis population showed males significantly respond less to hepatitis B vaccination (P = 0.002, Z = 3.08) with no significant heterogeneity detected [P = 0.766; heterogeneity χ² = 14.30 (df = 19); I² = 0%]. A reanalysis of the pooled data was conducted regarding the dialysis mode to evaluate potential differential impact of sex on HB vaccine response. Hemodialysis was the only subgroup that showed a significant difference regarding dialysis mode in response to HB vaccination regarding sex (P = 0.042, Z = 2.03).CONCLUSION: This Meta-analysis showed significant effect for the sex of chronic kidney disease and dialysis patients on the immunogenicity of HB vaccine. This sex discrimination was most prominent among hemodialysis patients.     

Methods for identification of Candida auris,the yeast of global public health concern: A review

Candida auris has recently emerged as a fungus able to cause severe infections, especially bloodstream infections with high mortality rates. This multi-drug-resistant yeast has the capacity of persistence on environmental surfaces, and has been reported to cause hospital-acquired infections. The development of faster and inexpensive tools for identification is critical to controlling, preventing and establishing early diagnosis of this emerging pathogen. Identification of C. auris by use of conventional laboratory methods is challenging, and it is commonly misidentified as other Candida species. Less expensive, reliable DNA-based tests have been used for identifying C. auris in environmental and clinical samples. Matrix-assisted laser desorption ionization–time of flight mass spectrometry is also a useful tool for identification of cultured isolates. This review provides a succinct overview of the available methods for identification of C. auris with particular emphasis on their relative advantages and drawbacks.     

Association between polymorphisms in DNA repair genes (XRCC1 and XRCC7) and risk of preeclampsia

Purpose

Although the exact genes involved in preeclampsia (PE) are still not fully discovered, an important role for oxidative stress in its pathogenesis is accepted. XRCC1 (MIM: 194360) and XRCC7 (MIM: 600899) play a crucial role in the DNA repair pathways. Functional polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC7 (G6721T) may be risk factors for PE. In the present study, the association between the genetic polymorphisms of XRCC1 and XRCC7 and risk of PE is investigated.

Methods

The present case–control study was performed on 151 preeclapmtic patients, and a total of 344 normal pregnant women, as a control group. Control women had no history of pregnancies with PE.

Results

Neither polymorphism of Arg194Trp XRCC1 nor polymorphism of G6721T XRCC7 associated with the risk of PE. The Gln/Gln genotype of Arg399Gln XRCC1 polymorphism increased the risk of PE (OR?=?2.39, 95?% CI: 1.38–4.14, P?=?0.002). Statistical analysis revealed that the haplotype “194Arg-399Gln” showed higher frequency among PE patients compared to the controls (OR?=?1.65, 95?% CI: 1.23–2.19, P?=?0.001).

Conclusions

The present results suggest that the 399Gln allele of the XRCC1 is significant risk factor for PE development.     

Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women

Background

In spite of several studies, the impact of homocysteine level and folic acid supplementation on bone metabolism is yet to be recognized. In this registered clinical trial (IRCT2014042217385N1), we aimed to find out the power of 6-month folic acid supplementation on homocysteine level and bone metabolism.

Methods

Forty postmenopausal osteoporotic women (50 to 87 years) were enrolled in the study. All participants were randomized to receive folic acid 1 mg (n = 17) or placebo (n = 14). At baseline, 3 months, and finally 6 months post intervention, the level of homocysteine, vitamin B12, and bone biomarkers were measured.

Results

Both groups were similar at baseline. The homocysteine decreased in both groups but statistically non-significant (P > 0.05). The changes of the serum level of vitamin B12, osteocalcin, and β cross laps were significant between groups after 6 months (P ≤ 0.05).

Conclusion

The trend of changes of bone biomarkers after 6 months folic acid supplementation shows that homocysteine concentration and/or folic acid supplementation have impact on the rate of bone metabolism. However, further investigations by larger sample size and differentiating age and gender are still needed to clarify the exact role of folate, homocysteine and vitamin B12.