Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection

To further understand the role of NS1-specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody subclass profiles and NS1-specific memory B-cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess NS1-specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1-specific NS1-Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross-reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.     

Recycled Untreated Rubber Waste for Controlling the Alkali–Silica Reaction in Concrete

Recycled rubber waste (RW) is produced at an alarming rate due to the deposition of 1.5 billion scrap tires annually around the globe, which causes serious threats to the environment due to its open land filling issues. This study investigates the potential application of RW in concrete structures for mitigating the alkali–silica reaction (ASR). Various proportions of RW (5%, 10%, 15%, 20%, and 25%) partially replaced the used aggregates. RW was procured from a local rubber recycling unit. Cubes, prisms, and mortar bar specimens were prepared using a mixture design recommended by ASTM C1260 and tested for evaluating the compressive and flexural strengths and expansion in an ASR conducive environment for specimens incorporating RW. It was observed that the compressive and flexural strength decreased for specimens incorporating RW compared to that of the control specimens without RW. For example, an 18% and an 8% decrease in compressive and flexural strengths, respectively, were observed for specimens with 5% of RW by aggregates volume at 28 days. Mortar bar specimens without RW showed an expansion of 0.23% and 0.28% at 14 and 28 days, respectively, indicating the potential ASR reactivity in accordance with ASTM C1260. A decrease in expansion was observed for mixtures incorporating RW. Specimens incorporating 20% of RW by aggregate volume showed expansions of 0.17% at 28 days, within the limit specified by ASTM C1260. Moreover, specimens incorporating RW showed a lower reduction in compressive and flexural strengths under an ASR conducive environment compared to that of the control specimen without RW. Micro-structural analysis also showed significant micro-cracking for specimens without RW due to ASR. However, no surface cracks were observed for specimens incorporating RW. It can be argued that the use of RW in the construction industry assists in reducing the landfill depositing issues with the additional benefit of limiting the ASR expansion.     

Potential of Waste Marble Sludge for Repressing Alkali-Silica Reaction in Concrete with Reactive Aggregates

The continuous development of the marble industry has led to an increase in the accumulation of waste marble sludge causing landfilling and health-associated issues. The intention of the current study is to explore the potential of waste marble sludge powder (MS) utilization as a means of controlling alkali-silica reaction (ASR) in concrete. Specimen (cubes, prisms, and mortar bars) were prepared to incorporate reactive aggregates and various proportions of MS ranging from 5% to 40% as a replacement for aggregates. Expansion and mechanical strength characteristics were determined to investigate the effectiveness of MS to control ASRfor up to 150 days. Results revealed that on replacing aggregates in the control specimen with 25% MS, the ASR expansion at 14 days reduced from 0.23% to 0.17%, and the expansion at 28 days reduced from 0.28% to 0.17% which is within limits as per American Standard for Testing of Materials (ASTM) C1260. Furthermore, specimens incorporating MS exhibited improved compressive and flexural strength as compared to the identical specimen without MS. Microstructural analysis using Scanning electron microscopy (SEM) revealed micro-cracks in the control specimen while the specimen incorporating MS was found intact. Thus, it can be foreseen that the use of MS as a partial replacement of aggregates can control ASR in concrete as well as reduce the dumping and harmful emissions issue.     

Management of thoracic esophageal perforations

Objective: To assess our results of a prospective algorithm applied to patients with thoracic esophageal perforation. Methods: A retrospective review of a prospective algorithm. Patients with esophageal perforation underwent an esophagram. If there was a contained esophageal perforation they were admitted, kept nothing by mouth, and restudied in 3–5 days. If the leak was not contained, they underwent operative repair. Results: From 1/1998 to 6/2009 there were 81 patients. The gastrograffin swallow showed 56 patients had contained perforations and 25 did not. Twenty-two of the 25 patients with noncontained perforation underwent immediate operative repair (one patient refused surgery, two were not stable enough for the operating room); their morbidity was 68% and there were six (24%) operative mortalities. Median hospital length of stay (LOS) was 11 days (range, 2–120). Of the 56 patients with contained perforations, 26 were managed successfully without surgery. However, 30 of the patients initially treated nonoperatively eventually required operations due to new pleural effusion, mediastinal abscess, or conversion to noncontained perforation. Their morbidity was 41% and there were three operative mortalities (5%). On univariate analysis, these patients were more likely to have undergone previous esophageal procedures (surgical or dilation) (p = 0.03), had new or increased pleural effusion (p = 0.04), and had greater than 24 h between diagnosis and treatment (p = 0.02). Only greater than 24 h between diagnosis and treatment remained a significant predictor on multivariate analysis. Their median hospital LOS was 21 days (range, 7–77). Conclusion: Contained thoracic esophageal perforations can usually be safely managed nonoperatively without significant morbidity or mortality. However, careful in-hospital monitoring is needed if surgery is not chosen.     

A rare cause of abdominal pain

Pacemaker migration is a rare, but important, complication of pacemaker insertion mainly documented in children. We report the case of a 60-year-old woman who was admitted with right iliac fossa pain thought to be caused by appendicitis. She was noted to have both an epicardial and endocardial pacemaker in situ. Imaging and laparoscopy revealed migration of the epicardial pacemaker to the right iliac fossa. We describe the possible mechanisms of pacemaker migration.     

Non-secretory myeloma: a rare variant of multiple myeloma

The spectrum of plasma cell neoplasm represents indolent conditions like Monoclonal Gammopathy of Undetermined Significance (MGUS) to more aggressive multiple myeloma and plasma cell leukemia. Non-secretory myeloma comprises less than 01% of this spectrum where serum protein electrophoresis and quantitative immunoglobulins remain essentially normal. We are presenting a case report of this rare variant involving the sternum of an adult male.     

Rectal fistulae after salvage high‐intensity focused ultrasound for recurrent prostate cancer after combined brachytherapy and external beam radiotherapy

OBJECTIVE

To report on the high rectal fistula rate associated with salvage high‐intensity focused ultrasound (HIFU) after the failure of combined brachytherapy and external beam radiotherapy (EBRT) for prostate cancer; salvage ablative therapy for prostate cancer is indicated when there is local recurrence after RT, brachytherapy or their combination.

PATIENTS AND METHODS

We retrospectively reviewed all men with prostate cancer treated with HIFU between 1 March 2005 and 31 May 2007, and identified five men treated after the failure of both brachytherapy and EBRT for localized prostate cancer.

RESULTS

Three of the five men had iodine‐seed implantation brachytherapy combined with EBRT as primary treatment, one had high‐dose rate brachytherapy combined with EBRT and one had salvage iodine‐seed brachytherapy for failed EBRT. Three of the five patients developed a recto‐urethral fistula after HIFU.

CONCLUSIONS

The high rate of recto‐urethral fistula formation in this group might reflect an impaired blood supply or HIFU‐associated near‐field heating of the rectal wall. Tissue viability and healing might affect this group regardless of the salvage method. Careful patient selection and avoidance of rectal diagnostic biopsies might minimize the risk. Emerging ablative therapies regarded as less invasive than traditional therapies must be used with caution.     

Mechanisms of antimicrobial resistance among hospital-associated pathogens

Introduction: The introduction of antibiotics revolutionized medicine in the 20th-century permitting the treatment of once incurable infections. Widespread use of antibiotics, however, has led to the development of resistant organisms, particularly in the healthcare setting. Today, the clinician is often faced with pathogens carrying a cadre of resistance determinants that severely limit therapeutic options. The genetic plasticity of microbes allows them to adapt to stressors via genetic mutations, acquisition or sharing of genetic material and modulation of genetic expression leading to resistance to virtually any antimicrobial used in clinical practice.

Areas covered: This is a comprehensive review that outlines major mechanisms of resistance in the most common hospital-associated pathogens including bacteria and fungi.

Expert commentary: Understanding the genetic and biochemical mechanisms of such antimicrobial adaptation is crucial to tackling the rapid spread of resistance, can expose unconventional therapeutic targets to combat multidrug resistant pathogens and lead to more accurate prediction of antimicrobial susceptibility using rapid molecular diagnostics. Clinicians making treatment decisions based on the molecular basis of resistance may design therapeutic strategies that include de-escalation of broad spectrum antimicrobial usage, more focused therapies or combination therapies. These strategies are likely to improve patient outcomes and decrease the risk of resistance in hospital settings.