Antibody-Secreting Cell Responses after Vibrio cholerae O1 Infection and Oral Cholera Vaccination in Adults in Bangladesh

Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. cholerae infection using a flow cytometrically defined population and compared V. cholerae-specific responses in adult patients with V. cholerae O1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either cholera toxin B subunit (CtxB) or V. cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. cholerae infection is endemic and those where it is not.     

Hip surgery and its evidence base: progress over a decade?

Background

The burden of traumatic and elective hip surgery is set to grow. With an increasing number of techniques and implants against the background of an aging population, the emphasis on evidence-based treatment has never been greater. The purpose of this study was to assess changes in the levels of evidence in the hip literature over a decade.

Materials and methods

Articles pertaining to hip surgery from the years 2000 and 2010 in Hip International, Journal of Arthroplasty, Journal of Bone and Joint Surgery and The Bone and Joint Journal were analysed. Articles were ranked by a five-point level of evidence scale and by type of study, according to guidelines from the Centre for Evidence-based Medicine.

Results

531 articles were analysed from 48 countries. The kappa value for the inter-observer reliability showed excellent agreement between the reviewers for study type (κ = 0.956, P < 0.01) and for levels of evidence (κ = 0.772, P < 0.01). Between 2000 and 2010, the overall percentage of high-level evidence (levels I and II) studies more than doubled (12 to 31 %, P < 0.001). The most frequent study type was therapeutic; the USA and UK were the largest producers of published work in these journals, with contributions from other countries increasing markedly over the decade.

Conclusions

There has been a significant increase in high levels of evidence in hip surgery over a decade (P < 0.001). We recommend that all orthopaedic journals consider implementing compulsory declaration by authors of the level of evidence to help enhance quality of evidence.

Level of evidence

Level 2: economic and decision analysis.

     

Direct mean strain estimation for elastography using nearest-neighbor weighted least-squares approach in the frequency domain

Ultrasound elastography is emerging with enormous potential as a medical imaging modality for effective discrimination of pathological changes in soft tissue. It maps the tissue elasticity or strain due to a mechanical deformation applied to it. The strain image most often calculated from the derivative of the local displacement field is highly noisy because of the de-correlation effect mainly due to unstable free-hand scanning and/or irregular tissue motion; consequently, improving the SNR of the strain image is still a challenging problem in this area. In this paper, a novel approach using the nearest-neighbor weighted least-squares is presented for direct estimation of the ‘mean’ axial strain for high quality strain imaging. Like other time/frequency domain reported schemes, the proposed method exploits the fact that the post-compression rf echo signal is a time-scaled and shifted replica of the pre-compression rf echo signal. However, the elegance of our technique is that it directly computes the mean strain without explicitly using any post filter and/or previous local displacement/strain estimates as is usually done in the conventional approaches. It is implemented in the short-time Fourier transform domain through a nearest-neighbor weighted least-squares-based Fourier spectrum equalization technique. As the local tissue strain is expected to maintain continuity with its neighbors, we show here that the mean strain at the interrogative window can be directly computed from the common stretching factor that minimizes a cost function derived from the exponentially weighted windowed pre- and post-compression rf echo segments in both the lateral and axial directions. The performance of our algorithm is verified for up to 8% applied strain using simulation and experimental phantom data and the results reveal that the SNR of the strain image can be significantly improved compared to other reported algorithms in the literature. The efficacy of the algorithm is also tested with in vivo breast data known to have malignant or benign masses from histology.     

Enumeration of Gut-Homing β7-Positive,Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients,Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique

Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are noninvasive mucosal pathogens that cause acute watery diarrhea in people in developing countries. Direct assessment of the mucosal immune responses to these pathogens is problematic. Surrogate markers of local mucosal responses in blood are increasingly being studied to determine the mucosal immune responses after infection. However, the volume of blood available in children and infants has limited this approach. We assessed whether an approach that first isolates β7-positive cells from a small volume of blood would allow measurement of the antigen-specific immune responses in patients with cholera and ETEC infection. β7 is a cell surface marker associated with mucosal homing. We isolated β7-expressing cells from blood on days 2, 7, and 30 and used an enzyme-linked immunosorbent spot (ELISPOT) assay to assess the gut-homing antibody-secreting cells (ASCs) specific to pathogen antigens. Patients with ETEC diarrhea showed a significant increase in toxin-specific gut-homing ASCs at day 7 compared to the levels at days 2 and 30 after onset of illness and to the levels in healthy controls. Similar elevations of responses to the ETEC colonization factors (CFs) CS6 and CFA/I were observed in patients infected with CS6- and CFA/I-positive ETEC strains. Antigen-specific gut-homing ASCs to the B subunit of cholera toxin and cholera-specific lipopolysaccharides (LPS) were also observed on day 7 after the onset of cholera using this approach. This study demonstrates that a simple ELISPOT assay can be used to study the mucosal immunity to specific antigens using a cell-sorting protocol to isolate mucosal homing cells, facilitating measurement of mucosal responses in children following infection or vaccination.     

Death audit in the neonatal ICU of a tertiary care hospital in Bangladesh: a retrospective chart review

Background: Expectant reduction of neonatal mortality and formulation of preventive strategies can only be achieved by analysis of risk factors in a particular setting. This study aimed to document incidence of neonatal death and to analyze the risk factors associated with neonatal death.

Methods: This retrospective study was carried out in department of Neonatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) over a 12-month period from January to December 2015. The newborns that died within 28 d of life were defined as “Cases” and “Control” were the surviving newborn discharged to home as healthy. Two birth weight and gestational age matched controls were taken for each case. Maternal, obstetric, and newborn characteristics were analyzed between both the groups. Data analysis was performed using SPSS version 20.0 (SPSS Inc., Chicago, IL). A probability of Results: During the study period, the proportion of death was 9.6% (64/612). Both in Chi-square analysis and in logistic regression analysis, less than four antenatal visits (odds ratio (OR) 2.78; 95% CI: 1.23–6.28, p?=?.014) and sepsis (OR 2.37; 95% CI: 1.07–5.26, p?=?.034) were found to be independent risk factors for deaths, whereas LUCS found to be protective for deaths (OR 0.40; 95% CI: 0.19–0.83, p?=?.015).

Conclusion: In conclusion, less than four antenatal visits and presence of sepsis were found to be independent risk factors whereas LUCS protective of newborn death.     

Iron supplementation decreases plasma zinc but has no effect on plasma fatty acids in non-anemic women

Limited information is available on the role of iron in fatty acid metabolism in humans. We hypothesized that iron supplementation will increase desaturase activity, and so, the aim of this study was to determine the effect of iron supplementation on fatty acid desaturase activity in young women. Participants were randomly assigned to a control group (CG) or supplementation group (SG) who were provided with 37.4 mg of elemental iron daily for 12 weeks. Forty women completed the trial, n = 19 in CG and n = 21 in SG. The mean ages were 25.2 and 24.6 years, and body mass indices were 21.8 and 21.2 (kg/m²) in CG and SG, respectively. Serum ferritin concentrations increased significantly (P < .01) in subjects assigned to SG but were unchanged in CG. Serum iron concentrations were not significantly changed. Plasma zinc concentrations at the end of the intervention were similar to baseline values for individuals in CG but were decreased significantly (P = .004) in SG. Plasma fatty acids, phospholipid fatty acids, and desaturase activities, expressed as precursor-to-product ratios, were not significantly affected by the intervention, although in SG the concentration of serum ferritin was correlated positively (P < .05) with Δ6-desaturase activity. Supplementing non-anemic women with low dose iron improves iron status but has no significant effect on desaturase activity. The lack of a clear effect on an indirect indicator of desaturase activity may be related to the antagonism between iron and zinc, as illustrated by the decrease in plasma zinc concentrations in women who were supplemented with iron.