Suppressor of cytokine signaling in allergic inflammation

The immunopathological hallmark of allergic diseases is elevated total and allergen specific serum IgE levels along with inflammation. This inflammation results from the activation of a cadre of hematopoietic and nonhematopoetic cells. This coordinated activation is the result of the increased production of a variety of soluble factors including chemokines and cytokines. The magnitude and the duration of cytokine action will determine the response to an allergen, either mounting a low-grade immunologic response or resulting in exaggerated reaction such as asthma or atopic dermatitis. Thus, the action of cytokines is tightly regulated both developmentally and within the cell. The suppressor of cytokine signaling (SOCS) protein family represents a novel group of cytoplasmic negative feedback regulators of type I and II cytokines. Several of the signaling pathways regulated by SOCS proteins are important in allergic immune responses. Thus, SOCS proteins may be important regulators of atopy.     

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.     

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.     

Let us talk about eggs! Professional resistance to elective egg vitrification and gendered medical paternalism

In this paper, by applying a feminist bioethical perspective, we identify a new form of medical paternalism that still shapes contemporary legal policies on human egg cryopreservation performed without medical reasons. The fear of negligent, careless women who opt to delay their pregnancy for mere convenience is a widely known gender biased stereotype. Nevertheless, the opinions and judgments of medical professionals on this issue have not yet been sufficiently explored by in-depth research. In this essay, therefore, first we look at the broader bioethical, legal, and social aspects of human egg cryopreservation. In the second part of the paper we discuss a unique qualitative study conducted with professionals working at Hungarian IVF clinics. We argue, based on a bioethical analysis of the collected data, that when new reproduction technologies provide opportunities for women to widen their range of reproductive choices, the traditional forms of medical paternalism can be reinforced by gendered paternalism, as well. We identify several elements of gendered paternalism that characterized the attitudes of the IVF staff and discuss the professionals’ resistance to elective egg freezing and vitrification of eggs for the future. We conclude by suggesting directions for future policy. Although we focus on the Hungarian case in this paper, we are aware that similar attitudes can be observed in some other countries where this technology has become available and requested by women, but where they also face difficulties in their access to it.     

Anterior segment parameters associated with extramuscular manifestations in polymyositis and dermatomyositis

AIM: To evaluate the efficacy and safety of high-dose ultrasound cyclo-plasty (UCP) for the treatment of refractory glaucoma in Chinese patients. METHODS: In this 6-month retrospective study, 37 eyes of 37 patients suffering from severe glaucoma with uncontrolled intraocular pressure (IOP) of ≥21 mm Hg underwent 8-s ultrasonic cyclocoagulation with ten active piezoelectric elements. A complete ophthalmic examination was performed before and at 1d, 1, 3, 6mo after UCP. Therapeutic success was defined as IOP reduction from baseline ≥20% and IOP > 5 mm Hg without adding new glaucoma medication compare to baseline at the 6-month follow-up visit. In addition to mean IOP at each follow-up visit, medications used and complications were also detected and compared to baseline. RESULTS: After UCP procedure, the mean IOP was significantly reduced (P<0.01) from the preoperative 44.1±11.9 mm Hg to postoperative 26.7±11.8 mm Hg at 3mo, and 30.4±14.5 mm Hg at 6mo. The overall mean IOP reductions achieved at 3 and 6mo were 39% and 31%. Sixty-one percent of patients responded well to UCP treatment with a mean IOP reduction of 48% at 3mo and 42% at 6mo. Ocular pain in most of patients were alleviated. No serious intraoperative or postoperative complications occurred. CONCLUSION: High-dose UCP treatment is an effective and safe procedure to reduce IOP in Chinese patients with severe glaucoma.     

Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients

Purpose

The role of tonsillectomy in the treatment of IgA nephropathy in Caucasian patients is controversial.

Methods

A retrospective cohort study was conducted in 264 patients with biopsy-proven primary IgA nephropathy to examine the association between tonsillectomy and long-term renal survival, defined as the incidence of estimated glomerular filtration rates (eGFRs) of ≤30 ml/min/1.73 m² or end-stage renal disease (the composite of initiation of dialysis treatment or renal transplantation). The association of tonsillectomy with renal end-points was examined using the Kaplan–Meier method and Cox models.

Results

One-hundred and sixty-six patients did not undergo tonsillectomy (Group I, follow-up 130 ± 101 months) and 98 patients underwent tonsillectomy (Group II, follow-up 170 ± 124 months). The mean renal survival time was significantly longer for both end-points between those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points.

Conclusion

Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed.     

Serosurvey of pathogenic hantaviruses among forestry workers in Hungary

Objectives

The aim of the study was to survey the prevalence of human hantavirus infections among forestry workers, who are considered a risk population for contracting the disease. Sera collected from volunteers were tested for antibodies against Dobrava-Belgrade (DOBV) and Puumala (PUUV) viruses.

Material and Methods

For serological analyses, full capsid proteins of DOBV and PUUV viruses were produced in a bacterial expression system, while Ni-resin was used for protein purification. Samples were screened for anti-hantavirus antibodies by ELISA, results were confirmed by Western blot analysis.

Results

A total of 835 samples collected from 750 males and 85 females were tested by indirect ELISA and positive test results were confirmed by Western blot assay. Out of the 45 ELISA-reactive samples, 38 were confirmed by Western blot analysis. The regional distribution of seropositive individuals was as follows: 1.9% (2/107) in the Danube-Tisza Plateau (Great Plains), 3.1% (10/321) in the Southern Transdanubian region, 5.2% (13/248) in the Northern Transdanubian, and 8.2% (13/159) in the North Hungarian Mountains.

Conclusions

Our data show marked geographic differences in seroprevalence of pathogenic hantaviruses within Hungary, indicating elevated exposure to hantavirus infections in some areas.     

Limitations of non-echo planar diffusion weighted magnetic resonance imaging (non-EPI MRI) in cholesteatoma surveillance after ossicular chain reconstruction. A prospective study

ObjectiveNon-echo planar diffusion weighted magnetic resonance imaging is a reliable surveillance tool of residual cholesteatoma nowadays. It is not known whether the material of the ossicular chain prosthesis modifies the sensitivity and specificity of MRI in these cases. The aim of the study was to compare the sensitivity, specificity and a localization-specific accuracy of non-EPI DW MRI sequences for residual cholesteatoma in the following 3 subgroups: patients with titanium ossicular prosthesis (group T), with autologous cortical bone columella (group A) or without any reconstruction (group WR) of hearing bones.MethodsThis prospective study covered 28 cases with cholesteatoma of the middle ear undergone second-look surgery, who had preoperative PROPELLER DW-MRI. Surgical findings were compared to the results of the DWI-MRI.ResultsThe overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were: 0.76-0.8-0.76-0.8. Group T, group A and group WR sensitivity was 0.83-0.6-1, specificity: 0.75-0.75-0.85, PPV: 0.83-0.75-0.66, NPV: 0.75-0.6-1. Overall accuracy was 0.78. Size of missed cholesteatoma was 2-4 mm (mean: 2.66±1.15).ConclusionsVarious materials are suitable for ossicular chain reconstruction. The poor detectability of residual or recurrent cholesteatoma in the middle ears reconstructed with autologous bony prosthesis may still claim second-look surgery instead of the usage of non- EPI DWI sequences independently in these patients.     

Effects of yoga on cardiovascular disease risk factors: A systematic review and meta-analysis

Background

The aim of this review was to systematically assess and meta-analyze the effects of yoga on modifiable biological cardiovascular disease risk factors in the general population and in high-risk disease groups.

Methods

MEDLINE/PubMed, Scopus, the Cochrane Library, and IndMED were screened through August 2013 for randomized controlled trials (RCTs) on yoga for predefined cardiovascular risk factors in healthy participants, non-diabetic participants with high risk for cardiovascular disease, or participants with type 2 diabetes mellitus. Risk of bias was assessed using the Cochrane risk of bias tool.

Results

Forty-four RCTs with a total of 3168 participants were included. Risk of bias was high or unclear for most RCTs. Relative to usual care or no intervention, yoga improved systolic (mean difference (MD) = − 5.85 mm Hg; 95% confidence interval (CI) = − 8.81, − 2.89) and diastolic blood pressure (MD = − 4.12 mm Hg; 95%CI = − 6.55, − 1.69), heart rate (MD = − 6.59 bpm; 95%CI = − 12.89, − 0.28), respiratory rate (MD = − 0.93 breaths/min; 95%CI = − 1.70, − 0.15), waist circumference (MD = − 1.95 cm; 95%CI = − 3.01, − 0.89), waist/hip ratio (MD = − 0.02; 95%CI = − 0.03, − 0.00), total cholesterol (MD = − 13.09 mg/dl; 95%CI = − 19.60, − 6.59), HDL (MD = 2.94 mg/dl; 95%CI = 0.57, 5.31), VLDL (MD = − 5.70 mg/dl; 95%CI = − 7.36, − 4.03), triglycerides (MD = − 20.97 mg/dl; 95%CI = − 28.61, − 13.32), HbA1c (MD = − 0.45%; 95%CI = − 0.87, − 0.02), and insulin resistance (MD = − 0.19; 95%CI = − 0.30, − 0.08). Relative to exercise, yoga improved HDL (MD = 3.70 mg/dl; 95%CI = 1.14, 6.26).

Conclusions

This meta-analysis revealed evidence for clinically important effects of yoga on most biological cardiovascular disease risk factors. Despite methodological drawbacks of the included studies, yoga can be considered as an ancillary intervention for the general population and for patients with increased risk of cardiovascular disease.