A non-toxic lectin for antigen delivery of plant-based mucosal vaccines

RicinB, the non-toxic galactose/N-acetylgalactosamine-binding subunit of ricin, was fused to a model antigen, green fluorescent protein (GFP), and expressed in tobacco plants and hairy root cultures to test for utility in mucosal vaccine delivery/adjuvancy. The fusion protein retained both GFP fluorescence and galactose/galactosamine-binding activity. Intranasal immunization of mice with galactosamine-affinity purified ricinB:GFP recovered from tobacco root cultures triggered significant increases in GFP-specific serum IgGs. This strong humoral response was comparable to that observed following GFP immunization with cholera toxin adjuvant. GFP at the same concentrations but without an adjuvant was non-immunogenic. Induction of higher levels of IgG(1) than IgG(2a) following ricinB:GFP immunization suggested the presence of a Th2 response. Serum and fecal anti-GFP IgA were also induced by immunization with ricinB:GFP. Our data suggest that ricinB can be used as an adjuvant and antigen carrier to the mucosa and is efficient in eliciting systemic and mucosal immune responses.     

Consequences of In Utero Zika Virus Exposure and Adverse Pregnancy and Early Childhood Outcomes: A Prospective Cohort Study

We aimed to describe adverse pregnancy outcomes among women who had symptomatic, RT-PCR-confirmed ZIKV infection and early childhood outcomes among their infants. We enrolled pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection in a prospective cohort study, and their infants in a prospective pediatric cohort study. We defined adverse pregnancy and early childhood outcomes based on selected neurologic, ophthalmologic, auditory, musculoskeletal, and anthropometric abnormalities. We used RT-PCR and serologic tests to determine the ZIKV infection status of the child. Between 10 March and 24 November 2016, we enrolled 546 pregnant women with RT-PCR-confirmed ZIKV infection. The overall risk of adverse pregnancy and early childhood outcomes possibly related to in utero ZIKV exposure was 15.7% (95% CI: 12.8–19.0), distributed as follows: 3.6% (95% CI: 2.3–5.6) severe sequelae or fatality; 2.7% (95% CI: 1.6–4.5) major abnormalities; 9.4% (95% CI:7.1–12.2) mild abnormalities. The risk of severe sequelae or fatality was higher when ZIKV infection occurred during the first trimester (7.0%), compared to the second (2.7%) or third trimester (1.4%) (p = 0.02). Among the infants for whom ZIKV infection status could be determined, the vertical transmission rate was 3.0% (5/167) (95% CI: 1.1–7.2). Among pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection, severe or major pregnancy or early childhood outcomes were present in 6.3% of fetuses and infants. Severe outcomes occurred more frequently in fetuses and infants whose mothers had been infected in the first trimester.     

Laparoscopic incisional and ventral hernia repair in a district general hospital

IntroductionThe laparoscopic approach to repairing ventral and incisional hernias has gained increasing popularity worldwide. We reviewed the experience of laparoscopic ventral hernia repair at a district general hospital in the UK with particular reference to patients with massive defects (diameter ≥15cm) and the morbidly obese.MethodsA total of 144 patients underwent laparoscopic ventral (incisional or umbilical/paraumbilical) hernia repair between April 2007 and September 2012.ResultsThe prevalence of conversion to open surgery was 2.8%. The prevalence of postoperative complications was 3.5%. Median postoperative follow-up was 30.2 months. A total of 5.6% cases suffered late complications and 2.8% developed recurrence. Thirty-four patients underwent repair of defects ≥10cm in diameter with a prevalence of recurrence of 5.6%. Sixteen patients underwent repair of ‘massive’ incisional hernia (diameter ≥15cm) with a prevalence of recurrence of 12.5%. Sixteen patients with a body mass index (BMI) ≥40kg/m² (range, 40–61kg/m²) underwent laparoscopic repair with a prevalence of recurrence of 6.3% (p>0.05 vs BMI <40kg/m²).ConclusionsLaparoscopic ventral hernia repair can be carried out safely with a low prevalence of recurrence. It may have advantages in morbidly obese patients in whom open repair would represent a significant undertaking. Laparoscopic ventral hernia repair may be used in cases of large and massive hernias, in which the risk of recurrence increases but is comparable with open repair and associated with low morbidity.     

Altered tissue repair in hevin-null mice: Inhibition of fibroblast migration by a matricellular SPARC homolog

Matricellular proteins such as hevin, secreted protein acidic and rich in cysteine, and thrombospondin‐2 play an important role during tissue repair through their influence on fundamental cellular activities such as adhesion, migration, proliferation, and extracellular matrix synthesis/reorganization. We have investigated the role played by hevin during excisional and incisional cutaneous wound repair in hevin‐null mice. Hevin‐null animals both close and heal their skin wounds faster than wild‐type animals, as evidenced by enhanced macrophage infiltration of wound beds at early time points, the earlier appearance of mature extracellular matrix, and the overall higher maturity score. In addition, fibrovascular invasion of polyvinyl alcohol sponges was more robust in hevin‐null mice, a result indicating that differences in cell migration might underlie the observed alterations in wound repair. Experiments in vitro showed that hevin induced the deadhesion and inhibited the migration of primary dermal fibroblasts in a Rac‐1–dependent manner. These findings indicate that the differences in wound repair between hevin‐null and wild‐type animals can be attributed in part to the deadhesive function of hevin and reduced cell migration within dermal wound beds in which this protein is expressed.     

Combination of short CAG and GGN repeats in the androgen receptor gene is associated with acne risk in North East China

Background Acne vulgaris is one of the most common skin disorders, and androgen is known to play a key role in the development of acne. However, the exact genetic mechanism by which androgen receptor (AR) gene affects acne development is still unclear. Objective Our study aimed to investigate whether CAG and GGN polymorphism of the AR gene are associated with acne risk. Patients and methods Two hundred thirty‐eight patients and 207 controls were included in the study. The repeat lengths of the AR gene were determined by GeneScan analysis. Results Men with CAG < 23 and women with CAG < 24 had significant risk compared to those men with CAG ≥ 23 [odds ratio (OR), 2.07; 95% confidence interval (95% CI), 1.21–3.54] and women with CAG ≥ 24 (OR, 2.05; 95% CI, 1.18–3.56). In males, GGN repeats, considered independently of the CAG repeat, have no significant effect on the acne risk; however, when combined with CAG repeats, the acne patients exhibited significantly higher frequency of the haplotypes CAG < 23/GGN ≤ 23 (OR, 3.33; 95% CI, 1.10–10.07; P < 0.05) compared with the controls. Conclusion Our results of this study strongly indicated that a shorter CAG repeat length and specific haplotypes of AR attributed to the risk of acne development and thus could serve as a susceptibility marker.     

Ecologically dependent postmating isolation between sympatric host forms of Neochlamisus bebbianae leaf beetles

Ecological speciation is the promotion of reproductive isolation via the divergent adaptation of populations to alternative environments. A prediction peculiar to ecological speciation is that hybrids between such populations should be adapted poorly to parental environments, yielding reduced fitness and postmating isolation. However, F₁ analyses alone cannot demonstrate that ecological (“extrinsic”) factors contribute to such isolation. Rather, this requires documenting a “switch” in the relative fitnesses of reciprocal backcrosses between environments. Specifically, each backcross should exhibit higher fitness in the environment of its pure parent, with which it shares the most genes, including environment-specific ones. In contrast, because genetic proportions are expected to be similar for all backcrosses (≈¾ from one parental type and ≈¼ from the other), the more general genetic incompatibilities responsible for “intrinsic” isolation predict no such environment-specific fitness switches. Thus, although intrinsic isolation may contribute to the fitness reduction and variation underlying such patterns, it offers an insufficient explanation for them. Here, we present a quantitative genetic “backcross” analysis of sympatric Neochlamisus bebbianae leaf beetle populations adapted to maple versus willow host plants. Results statistically supported ecological speciation predictions, notably the switch in relative fitness for backcross types, the expected rank order of cross type fitnesses, and appreciable extrinsic isolation. We additionally documented genetic variation in host-associated fitness, ruled out nongenetic maternal effects, and discuss the maintenance of ecological differentiation in sympatry. In summary, our study provides a rare and strongly supported demonstration of genetically based, ecologically dependent postmating isolation during ecological speciation.     

Recurrent herpetic keratitis during topical acyclovir application.

Dendritic herpetic keratitis developed in a 49-year-old patient during topical acyclovir treatment. A positive herpes simplex culture was obtained. After acyclovir was replaced by trifluorothymidine and interferon, the dendritic lesion disappeared and herpes simplex culture became negative. Six months later a carcinoma of the larynx was diagnosed. The acyclovir-resistant herpetic keratitis may be associated with the carcinoma because resistant herpes simplex virus strains are predominantly described in patients suffering from immune deficiency.     

Management of complicated fractures involving the orbits and nasoethmoid complex in young children

This article presents some ideas and techniques for surgical reduction of complicated orbit and nasoethmoid complex fractures in young children. Operative techniques for surgical exposure and fracture reduction and fixation have evolved from standard facial incisions and wire fixation to complete exposure of the cranium and orbits via a bicoronal scalp flap, application of rigid plating techniques, and use of cranial bone grafts when necessary. This evolution of surgical techniques has been accompanied by an overall improvement in cosmetic and functional results.     

Development of a colorimetric dosimeter for quality control of blood units and irradiators

The development is reported of a reproducible colorimetric irradiation dosimeter that is easy to prepare as well as to interpret. Optimal chloroform, dithizone, and paraffin concentrations to produce a distinctive color change at > 1500 cGy (optimized for 3000 cGy) were determined by combining various concentrations of each component at 65 degrees C. The melted dosimetric material was poured into molds, allowed to solidify, and irradiated with doses ranging from 0 to 3000 cGy. Color change was evaluated visually and spectrophotometrically to determine reproducibility. Twenty-percent chloroform (wt/wt) and a dithizone concentration of 5.0 × 10(-5) M combined in paraffin (TP-2) produced optimal color change from pink to green after > 1500 cGy. The change was reproducible, and 50 individuals were able to distinguish between irradiated and nonirradiated dosimeters. Additionally, five of five of these individuals correctly ranked five dosimeters in order of increasing irradiation from 0 to 3000 cGy, in increments of 750 cGy. This dosimeter is easy to make and easy to read and may allow blood banks to show unit-by-unit quality assurance for irradiated blood components and quality control of the irradiator itself.