Immune Responses to O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 Ogawa in Adult Bangladeshi Recipients of an Oral Killed Cholera Vaccine and Comparison to Responses in Patients with Cholera

Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae O1 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection.     

Usefulness of left atrial volume index to predict heart failure hospitalization and mortality in ambulatory patients with coronary heart disease and comparison to left ventricular ejection fraction (from the Heart and Soul Study)

The predictive value of left atrial (LA) dilatation in ambulatory adults with coronary artery disease is not known. It was hypothesized that echocardiographic LA volume index (LAVI) predicts heart failure (HF) hospitalization and mortality with similar statistical power as left ventricular ejection fraction (LVEF) in ambulatory adults with coronary artery disease. We measured LAVI in 935 adults without atrial fibrillation, atrial flutter, or significant mitral valve disease in the Heart and Soul Study. LAVI was calculated using the biplane method of disks. Outcomes included HF hospitalization and mortality. Logistic regression odds ratios (ORs) were calculated and adjusted for age, demographics, medical history, left ventricular mass, diastolic function, and LVEF. Mean LAVI was 32 +/- 11 ml/m2, and mean LVEF was 62 +/- 10%. Sixty-six patients (7%) had LAVI >50 ml/m2. There were 108 HF hospitalizations and 180 deaths at 4.3 years of follow-up. C statistics calculated as the area under the receiver-operator characteristic curve were the same (0.60) for LAVI and LVEF in predicting mortality. The unadjusted OR for HF hospitalization was 4.4 for LAVI >50 ml/m2 and 5.3 for LVEF <45% (p <0.001). In those with normal LVEF, the ORs for LAVI >50 ml/m2 were 5.2 for HF hospitalization (p <0.0001) and 2.5 for mortality (p = 0.006). After multivariate adjustment, LAVI >50 ml/m2 was predictive of HF hospitalization (OR 2.4, p = 0.02), and LAVI >40 ml/m2 was predictive of mortality (OR 1.9, p = 0.005). In conclusion, LAVI had similar predictability as LVEF for HF hospitalization and mortality in ambulatory adults with coronary artery disease.     

From the Cover: Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes

Adaptive features of innate immunity, recently described as “trained immunity,” have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. The enhanced function of circulating monocytes persisted for at least 3 mo after vaccination and was accompanied by increased expression of activation markers such as CD11b and Toll-like receptor 4. These training effects were induced through the NOD2 receptor and mediated by increased histone 3 lysine 4 trimethylation. In experimental studies, BCG vaccination induced T- and B-lymphocyte–independent protection of severe combined immunodeficiency SCID mice from disseminated candidiasis (100% survival in BCG-vaccinated mice vs. 30% in control mice). In conclusion, BCG induces trained immunity and nonspecific protection from infections through epigenetic reprogramming of innate immune cells.     

Infiltrated leishmaniasis recidivans cutis on the face: a rare clinical presentation

Cutaneous leishmaniasis is a protozoan disease caused by Leishmania and transmitted by the bite of some species of sand flies. Usually it presents with variety of clinical manifestations depending on both the infecting species of Leishmania and the immune response of the host. Leishmaniasis recidivans cutis (LRC) is a unique form of cutaneous leishmaniasis characterized by unusual clinical features and its chronic relapsing nature. It is an evolving form of cutaneous leishmaniasis which clinically presents as a spreading of the initial nodule, leading to a plaque formation simulating discoid lupus erythematosus. A clinical course of leishmania recidivans is probably related to changes in cell-mediated immunity leading to localized or diffuse lesions. We report a case that presented with infiltrated, atrophic plaque on a patient's face. Clinically, the lesion resembled the lesion of discoid lupus erythematosus and lupus vulgaris but the cutaneous biopsy proved the diagnosis to be LRC.     

An assessment of the efficacy of blue light phototherapy in the treatment of acne vulgaris

Background Acne vulgaris is a common skin condition that affects 8 out of 10 people. It varies from mild to severe, and different treatments target various aspects of the disease. Propionibacterium acnes, one of the culprits involved in the pathogenesis of acne vulgaris, is the main target of all major medical treatments used. Studies conducted in recent years have shown favorable effects within the visible light spectrum for the treatment of acne vulgaris. Objective In this study, we have evaluated the use of intense blue light within the spectral range of 415–425 nm (peak 420 nm) in the treatment of acne vulgaris. Methods Twenty‐one patients with mild to moderate facial acne were treated with blue light phototherapy. All patients were given 14‐min treatment sessions twice a week for 4 weeks. Acne severity was assessed using the Leeds Technique for grading and lesion counts. Disability was assessed using the Dermatology Life Quality Index (DLQI). In addition, standard digital and cross‐polarized light photographs were taken and graded by a blinded evaluator. Visual analog scale (VAS) scores and cultures for P. acnes were carried out before starting the treatment and upon completion of the treatment. Results Significant improvement was achieved in the Leeds Acne Grade (P = 0.001). The inflammatory (P = 0.001) and noninflammatory (P = 0.06) lesion counts also improved significantly. A similar change was noted in the DLQI (P = 0.001); a degree of significance was also achieved in the patients’ and the investigators’ VAS scores (P = 0.01 and P = 0.001, respectively). P. acnes colony counts failed to show a significant decrease at the end of the treatment and remained almost constant (P = 0.660). Conclusions We believe that blue light does appear to have some role in the management of acne and may be beneficial for the treatment of a select group of mild to moderate acne patients.     

Nanosensors for diagnosis with optical,electric and mechanical transducers

Nanosensors with high sensitivity utilize electrical, optical, and acoustic properties to improve the detection limits of analytes. The unique and exceptional properties of nanomaterials (large surface area to volume ratio, composition, charge, reactive sites, physical structure and potential) are exploited for sensing purposes. High-sensitivity in analyte recognition is achieved by preprocessing of samples, signal amplification and by applying different transduction approaches. In this review, types of signals produced and amplified by nanosensors (based on transducers) are presented, to sense exceptionally small concentrations of analytes present in a sample. The use of such nanosensors, sensitivity and selectivity can offer different advantages in biomedical applications like earlier detection of disease, toxins or biological threats and create significant improvements in clinical as well as environmental and industrial outcomes. The emerging discipline of nanotechnology at the boundary of life sciences and chemistry offers a wide range of prospects within a number of fields like fabrication and characterization of nanomaterials, supramolecular chemistry, targeted drug supply and early detection of disease related biomarkers.

Nanosensors with high sensitivity utilize electrical, optical, and acoustic properties to improve the detection limits of analytes.     

A miniaturized electronic sensor for instant monitoring of ethanol in gasohol fuel blends

Gasoline–ethanol (gasohol) fuel blends have gained considerable attention in the petroleum and energy sectors as relatively cheaper and greener high-octane alternative fuels with gasoline-comparable efficiency in modern transportation vehicles. However, due to different combustion rates the relative concentration of ethanol in gasohol fuel blends may vary over time. Furthermore, there is a need to monitor ethanol concentration in fuel blends for quality control applications. This article reports a miniaturized electronic sensor based on an interdigital capacitor (IDC) as the transducer and a dual-imprinted titania–polyaniline composite film as the receptor. The device has an active surface area of 0.9 cm² and is easy to fabricate. The receptor material is synthesized by imprinting ethanol in both titania sol (EITS, the matrix) and polyaniline nanoparticles (EIPani, the filler), and subsequently mixing them to obtain a dual-imprinted EITS–EIPani composite. The structural and morphological characteristics of the receptor layers are determined with Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM), respectively. The IDC devices are fabricated with pristine EITS and dual-imprinted EITS–EIPani composite to test their metrological sensor characteristics in standard ethanol solutions and real-time gasohol fuel blends. The instant shift in capacitance is measured upon exposure to different concentrations of ethanol. These devices show excellent sensitivity and selectivity patterns and demonstrate reliable sensor response toward ethanol in different gasohol fuel blends with 1–10 vol% ethanol. The results of this study reveal that these miniaturized ethanol sensors are potentially useful for rapid analysis of ethanol in gasohol and may be optimized for onboard fuel quality control applications.

A schematic representation of the developed setup for ethanol sensing measurements in gasohol blends.     

Propionibacterium acnes and Staphylococcus epidermidis Isolated from Refractory Endodontic Lesions Are Opportunistic Pathogens

The predominant cultivable microbiota from 20 refractory endodontic lesions (9 with abscesses and 11 without abscesses) were determined, and Propionibacterium acnes and Staphylococcus epidermidis were among the most predominant organisms. The number of species identified from lesions with abscesses (14.1 ± 2.6) was significantly greater (P < 0.001) than the number from lesions without abscesses (7.4 ± 5.9). Comparison of perioral isolates using repetitive extragenic palindromic PCR of the same species from the same subjects demonstrated that the endodontic and skin populations were significantly different. The P. acnes isolates were typed on the basis of recA gene sequence comparison, and only three types (types I, II, and III) were identified among 125 isolates examined. However, we found that type I (type IA and IB) isolates were primarily isolated from the skin, while types II and III were significantly more likely to be isolated from the endodontic lesions (P < 10⁻¹⁰). We found that the robustness of the recA phylotypes was not strong by comparing the partial gene sequences of six putative virulence determinants, PAmce, PAp60, PA-25957, PA-5541, PA-21293, and PA-4687. The resulting neighbor-joining trees were incongruent, and significant (phi test; P = 2.2 × 10⁻⁷) evidence of recombination was demonstrated, with significant phylogenetic heterogeneity being apparent within the clusters. P. acnes and S. epidermidis isolated from refractory endodontic infections, with or without periapical abscesses, are likely to be nosocomial infections.Propionibacterium acnes and coagulase-negative staphylococci, including Staphylococcus epidermidis, have been identified among the microflora of endodontic infections (8, 12, 40, 50, 52, 55, 56, 63, 64), but their importance as endodontic pathogens has largely been ignored due to their nearly universal presence on the skin and the consequent likelihood of sample contamination. However, there is now considerable evidence that these organisms are increasingly isolated from human infections, and so their association with endodontic infections requires clarification. P. acnes, a non-spore-forming, Gram-positive anaerobic or aerotolerant rod, is a member of the resident microflora of the large intestine, conjunctiva, and external ear canal (10, 15) and accounts for approximately half of the total skin microbiota (59), predominating over other pilosebaceous flora (16, 39). Although traditionally considered to be relatively nonpathogenic, an increasing number of studies have implicated P. acnes as an opportunistic pathogen responsible for a wide range of infections and inflammatory conditions. In addition to its well-established role in the pathogenesis of acnes vulgaris (16, 34), it has also been linked to synovitis-acnes-pustulosis-hyperostosis-osteitis syndrome (44, 54), sarcoidosis (17), and prostate cancer (14). Recent studies have revealed trauma and surgery as the predisposing factors associated with numerous P. acnes infections, which include brain abscesses (36), osteomyelitis after lumbar puncture (1), discitis after surgery (23), spodylodiscitis following epidural catheterization (22, 25), postoperative mediastinitis (19, 58), endophthalmitis (7), and endocarditis (21). Furthermore, it is also emerging as an important pathogen in infections related to medical foreign-body implants, such as intraocular lenses (65), ventroperitoneal shunts, orthopedic implants (9, 28, 51), silicone implants (2), prosthetic heart valves (33, 42), and prosthetic joints (38, 61).S. epidermidis is part of the human skin microflora, where, as a commensal organism, it usually exists in a benign relationship with the host. Although it is ranked first in nosocomial and implant-based infections, perhaps due to its ubiquity on the skin, it is more likely to contaminate devices at the time of insertion. As a recognized opportunistic pathogen, it is responsible for nosocomial infections of indwelling medical devices (43), such as peripheral or central intravenous catheters (CVCs), prosthetic joints, vascular grafts, and central nervous system shunts (46), and cardiac device infections, such as prosthetic valve endocarditis (PVE) (13), as well as ventricular assist device driveline-related infections (4). Clearly, a characteristic shared by both of these organisms is an association with the infection of prosthetic devices.The treatment of endodontic infections involves the insertion of gutta-percha into the debrided and disinfected root canal and the restoration of the tooth. This treatment may fail, with the root canal becoming infected. A range of bacteria have been isolated from such infected sites, including P. acnes and S. epidermidis, but these have generally been considered contaminants. The objective of the present study was to confirm the endodontic origin of P. acnes and S. epidermidis isolates recovered from refractory endodontic infections. We have used DNA fingerprinting of the P. acnes and S. epidermidis isolates from endodontic lesions and samples from the perioral skin of the same individual using repetitive extragenic palindromic PCRs (REP-PCRs) (3). The recA phylotypes of the P. acnes isolates were determined, as we expected to find that the predominant phylotypes from the endodontic lesions would be types II and III, which are almost exclusively associated with infections of implanted prostheses, while types IA and IB are usually isolated from skin (26, 30, 31, 62). We also investigated the phylogenetic status and robustness of the recA phylotypes by comparing the intrastrain relationships of partial gene sequences of six putative virulence determinants, PAmce (mammalian cell entry gene), PAp60, PA-25957, PA-5541, PA-21293, and PA-4687 (20, 35). Here we have set out to determine if P. acnes and S. epidermidis isolated from refractory endodontic lesions are contaminants arising during the sample collection process or if they represent nosocomial infections.