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.     

Vasoactive effects of stable aqueous suspensions of single walled carbon nanotubes in hamsters and mice

Single-walled carbon nanotubes synthesized with iron (Fe-SWCNT) or gadolinium (Gd-SWCNT) show promise as high performance multimodal contrast and drug-delivery agents. Our purpose was to evaluate potential vasoactive effects of SWCNT. Stable aqueous solutions of Fe-SWCNTs or Gd-SWCNTs were made using the biocompatible amphiphilic polymer N-(carbonyl-methoxypolyethyleneglycol 2000)-1,2-distearoylsn-glycero-3- phosphoethanolamine (PEG-DSPE). Both aggregated and non-aggregated (sonicated) formulations were tested. The initial vasoactivity of the formulations and their potential for inducing pro-inflammatory endothelial dysfunction were investigated in the hamster cheek pouch and murine cremaster muscle intravital microscopy models. These models provide an assay to test several formulations/dosages in a paired fashion. Abluminal exposure to small arterioles exposes both endothelial and vascular smooth muscle cells. Using abluminal exposures of dosages that would approximate the first pass of an i.v. bolus injection, both Fe-SWCNTs and Gd-SWCNTs were immediately vasoactive. Aggregated formulations induced dilation and non-aggregated formulations induced constriction in both hamsters and mice. Endothelial dysfunction was evident after exposure to either aggregated or non-aggregated forms. General loss of dilator capability was seen after exposure to non-aggregated but not aggregated forms. Thus concentrations mimicking bolus dosing of PEG-DSPE coated SWCNT induce both acute and chronic vascular responses.     

Cystic Optic Chiasm Lesion: Atypical Magnetic Resonance Imaging Findings

Intrinsic cystic lesions in the optic chiasm are an uncommon cause of bitemporal hemianopia compared with compressive lesions extrinsic to the chiasm. A 40-year-old man presented with difficulty driving. Clinical assessment revealed a bitemporal hemianopia. Magnetic resonance imaging showed an unusual cystic appearance of the chiasm. The appearance was felt to be most likely secondary to previous infective or inflammatory disease, but biopsy was not undertaken given the very significant risk of further visual loss.     

Left ventricular pseudoaneurysm after mitral valve replacement

Development of left ventricular pseudoaneurysm is a rare complication of mitral valve surgery and requires urgent surgical intervention. We describe a case of pseudoaneurysm of membranous septum following repeat mitral valve replacement with the use of multimodality imaging.     

Gangrene in Takayasu’s arteritis: a report of two cases and review of literature

Takayasu’s arteritis (TA) is a granulomatous large vessel vasculitis more commonly seen in India. The vascular inflammation in TA results in stenoses of affected vessels. Usually this is a slow process with good collateral circulation; only rarely does critical limb ischemia result. We present two patients of TA who presented with gangrene of extremities, and review eight prior such patients reported in the literature. With appropriate diagnosis and treatment with oral corticosteroids and low-dose aspirin, none of our patients had recurrence at a mean follow-up of 3.8 ± 2.8 years. Although rare, TA can present with gangrene and rheumatologists need to be aware of this unusual but limb-threatening manifestation of TA to institute appropriate therapy in a timely manner.     

Severe wasting among Indian infants <6 months: Findings from the National Family Health Survey 4

Burden and risk factors for wasting in the first 6 months of life among Indian children are not well documented. We used data from India's National Family Health Survey 4 to estimate the prevalence of severe wasting (weight for length < ‐3 SD) among 18,898 infants under 6 months of age. We also examined the association of severe wasting with household, maternal, and child‐related factors using multivariable logistic regression analysis. Prevalence of severe wasting among infants less than 6 months of age was 14.8%, ranging from 3.5 to 21% across states. Low birth weight (<2,500 g; adjusted odds ratio [AOR] 1.40, 95% CI [1.19, 1.65]), nonutilization of supplementary nutrition by mother during lactation (AOR 1.23, 95% CI [1.05, 1.43]), and anthropometric assessment during summer (AOR 1.37, 95% CI [1.13, 1.65]) and monsoon months (AOR 1.53, 95% CI [1.20, 1.95]) were associated with higher odds of severe wasting. Infants aged 2 to 3 months (AOR 0.78, 95% CI [0.66, 0.93]) and 4 to 5 months (AOR 0.65, 95% CI [0.55, 0.73]) had lower odds of severe wasting as compared with the 0‐ to 1‐month category. This analysis reveals a high burden of severe wasting in infants less than 6 months in India. Preventive interventions must be targeted at reducing low birth weight due to fatal growth restriction and prematurity. Appropriate care practices at facilities and postdischarge with extra attention to those born small and sick can prevent further deterioration in nutritional status.     

Efficacy of phytol-derived diterpenoid immunoadjuvants over alum in shaping the murine host's immune response to Staphylococcus aureus

The ubiquitous gram-positive bacterium Staphylococcus aureus occupies a unique niche in humans for its ability to survive both as a commensal and a life-threatening pathogen. Its complex relationship with the host and its ability to engender a throng of virulence factors, have hindered the development of a successful vaccine against it. The use of immunoadjuvants to enhance host immunity and prevent the shift from commensalism to pathogenicity is a rational approach for containing infection. The objective of this study was to understand the mechanisms by which alum and two phytol-derived immunoadjuvants, phytanol (PHIS-01) ¹ and phytanyl chloride (PCl) ² shape the interaction between S. aureus and its murine host. We studied the effects of the phytol derivatives, relative to alum, on the induction of inflammatory cytokines and chemokines, recruitment of CD11b⁺ cells, generation of specific anti-S. aureus antibodies and in vitro clearance of S. aureus. Our results showed that both PHIS-01 and PCl were stronger inducers of protective cytokines IL-17 and IL-1β than alum, and far exceeded alum in enhancing anti-S. aureus antibody response. However, both alum and the phytol derivatives (particularly PCl) promoted efficient recruitment of CD11b⁺ cells. Furthermore, PHIS-01, alum and to a lesser extent, PCl were able to up-regulate the expression of key inflammation-related genes that were highly down-regulated by S. aureus alone. In vitro killing assays showed that both PHIS-01 and PCl were far more potent than alum in promoting S. aureus clearance; this indicated their efficiency in shaping an effective anti-S. aureus immune microenvironment. In summary, our study provides evidence for the better effectiveness of phytol-derived immunoadjuvants over alum in enhancing anti-S. aureus immunity.