Artificial-infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease

Vaccination with recombinant outer surface protein A (OspA) from Borrelia burgdorferi provides excellent antibody-mediated protection against challenge with the pathogen in animal models and in humans. However, the bactericidal antibodies are ineffective in the reservoir host, since OspA is expressed by spirochetes only in the vector, but rarely, if at all, in mammals. Using an artificially generated immune serum (anti-10(8) spirochetes) with high protective potential for prophylactic and therapeutic treatment, we have now isolated from an expression library of B. burgdorferi (strain ZS7) three novel genes, zs7.a36, zs7.a66 and zs7.a68. All three genes are located, together with ospA/B, on the linear plasmid lp54, and are expressed in vitro and in ticks. At least temporarily two of them, ZS7.A36 and ZS7.A66, are also expressed during infection. The respective natural antigens are poorly immunogenic ininfected normal mice but elicited antibodies in Lyme disease patients. We show that recombinant preparations of ZS7.A36, ZS7.A66 and ZS7.A68 induce functional antibodies in rabbits capable of protecting immunodeficient mice against subsequent experimental infection. These findings suggest that all three recombinant antigens represent potential candidates for a "second generation" vaccine to prevent and/or cure Lyme disease.     

Familial occurrence of the Wiedemann-Beckwith syndrome and persistent fontanel

We describe a family in which 3 sisters gave birth to 8 infants with the Wiedemann-Beckwith syndrome. The clinical manifestations in all the affected individuals included macroglossia, macrosomia and omphalocele, while their mothers all were entirely normal. Pedigree analysis suggests that familial occurrence of the Wiedemann-Beckwith syndrome may be due to delayed mutation.     

A set of specific miRNAs is connected with murine and human gastric cancer

MircoRNAs as a new class of regulatory molecules have been investigated in many specific cells and organs in healthy and diseased conditions. Although miRNA signatures can be directly assessed in patients' affected tissues such as tumor sections, recent studies revealed that miRNA profiles can also be obtained indirectly, that is, from the patients' peripheral blood. For better understanding of miRNA's contribution to gastric carcinoma (one of the leading causes of cancer‐related mortality worldwide), we screened for deregulated miRNAs in blood collected from human cancer patients and compared the expression patterns with a gastric carcinoma mouse model (Tff1 knock‐out). The profiles were assessed using species‐specific miRNA microarrays. Among many dozens of deregulated miRNAs (219 in H. sapiens; 75 in M. musculus), a subset of eight miRNAs comparable in sequence from both species was noted. By in silico analysis, their involvement in targeting neoplastic and MAPkinase pathways was demonstrated. We found a high probability of linkage of all noted miRNAs to pathways in cancer with P‐values of 0.013 and 0.018 in mice and humans, respectively. Linkage to the MAPK‐signaling pathway in mice was observed with a P‐value of 0.01. Moreover, when comparing the 219 deregulated miRNAs obtained from blood with deregulated miRNAs derived from gastric cancer (GC) tissues, as published previously, 24 miRNAs were identical. If confirmed in a larger patient pool, these miRNAs could constitute appropriate blood‐born biomarkers for GC. © 2012 Wiley Periodicals, Inc.     

Carbohydrate-Deficient Transferrin in Healthy Women: Relation to Estrogens and Iron Status

The determination of carbohydrate-deficient transferrin (CDT) in serum has been found useful as a marker of increased alcohol consumption of >60 g/day. It is not clear why the reference range is different for women (0 to 26 units/liter) and men (0 to 20 units/liter). We evaluated serum COT in 286 healthy subjects (209 women, 77 men) using a commercially available radioimmunoassay. Premenopausal women had higher CDT levels than postmenopausal women, whereas no age-related difference of CDT levels was found in men. In postmenopausal women, higher CDT levels were associated with estrogen replacement therapy. In premenopausal women, however, neither the phase of the menstrual cycle nor contraceptive steroid use showed a significant association with the increase in CDT levels. No significant correlations were found between CDT and either serum estradiol or serum iron. In conclusion, both premenopausal state and postmenopausal estrogen replacement therapy seem to increase serum levels of CDT. Therefore, menopausal status and exogenous estrogens should be considered when interpreting CDT values in women.     

Vaccine-Relevant Human Papillomavirus (HPV) Infections and Future Acquisition of High-Risk HPV Types in Men

Background.Little is known about type-specific associations between prevalent human papillomavirus (HPV) infections and risk of acquiring other HPV types in men. Data on natural clustering of HPV types are needed as a prevaccine distribution to which postvaccine data can be compared. Methods.Using data from a randomized controlled trial of male circumcision in Kisumu, Kenya, adjusted mean survival ratios were estimated for acquisition of any-HPV, high-risk (HR) HPV, and individual HR-HPV types among men uninfected as compared to those infected with vaccine-relevant HPV types 16, 18, 31, 45, 6, or 11 at baseline. Results.Among 1097 human immunodeficiency virus-negative, uncircumcised men, 2303 incident HPV infections were detected over 2534 person-years of follow-up. Although acquisition of individual HR-HPV types varied by baseline HPV type, there was no clear evidence of shorter times to acquisition among men without vaccine-relevant HPV-16, -18, -31, -45, -6, or -11 infections at baseline, as compared to men who did have these infections at baseline. Conclusions.These prospective data on combinations of HPV infections over time do not suggest the potential for postvaccination HPV type replacement. Future surveillance studies are needed to definitely determine whether elimination of HPV types by vaccination will alter the HPV type distribution in the population.     

Wound infections following open reduction and internal fixation of calcaneal fractures with an extended lateral approach

Purpose

Post-operative wound infections (PWI) following calcaneal fracture surgery can lead to prolonged hospital stay and additional treatment with antibiotics, surgical debridement or implant removal. Our aim was to determine the incidence of superficial and deep PWI and to identify risk factors (RF).

Methods

This study is a retrospective case series. All consecutive patients from 2000 to 2010 with a closed unilateral calcaneal fracture treated with open reduction and internal fixation (ORIF) by an extended lateral approach were included. Patient, fracture, trauma and peri-operative characteristics were collected, including RF such as smoking, diabetes mellitus, time to operation, pre-operative in- or outpatient management and wound closure technique. The primary end point was a PWI as defined by the US Centers for Disease Control and Prevention.

Results

A total of 191 patients were included of which 47 patients (24.6 %) had a PWI; 21 (11.0 %) and 26 (13.6 %) patients had a superficial and deep wound infection, respectively. American Society of Anesthesiologists (ASA) classification higher than ASA 1 was associated with an increased risk. Placement of a closed suction drain at the end of surgery was associated with less PWI (35 % vs 15 %, p = 0.002). In this study, none of the previously reported RF were associated with an increased risk for PWI.

Conclusions

ORIF of displaced calcaneal fractures is associated with a high rate of PWI of 25 %. Factors that were associated with an increased risk were ASA classification other than 1 and absence of a closed suction drain placement. A closed suction drain may be a protective measure to avoid wound complications.