Search

Diagnosis of any infectious disease is vital for opportune treatment and to prevent dissemination. RT-qPCR tests for detection of SARS-CoV-2, the causative agent for COVID-19, are ideal in a hospital environment. However, mass testing requires cheaper and simpler tests, especially in settings that lack sophisticated machinery. The most common current diagnostic method is based on nasopharyngeal sample collection, RNA extraction, and RT-qPCR for amplification and detection of viral nucleic acids. Here, we show that samples obtained from nasopharyngeal swabs in VTM and in saliva can be used with or without RNA purification in an isothermal loop-mediated amplification (LAMP)-based assay, with 60–93% sensitivity for SARS-CoV-2 detection as compared to standard RT-qPCR tests. A series of simple modifications to standard RT-LAMP published methods to stabilize pH fluctuations due to salivary acidity resulted in a significant improvement in reliability, opening new avenues for efficient, low-cost testing of COVID-19 infection.

A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find that 4MU treatment reduces pericellular hyaluronan, destabilizes interactions between DC and T-cells, and prevents T-cell proliferation in vitro and in vivo. These effects were observed only when 4MU was added prior to initial antigen presentation but not later, consistent with 4MU-mediated inhibition of de novo antigenic responses. Building on these findings, we find that 4MU delays rejection of allogeneic pancreatic islet transplant and allogeneic cardiac transplants in mice and suppresses allogeneic T-cell activation in human mixed lymphocyte reactions. We conclude that 4MU, an approved drug, may have benefit as an adjunctive agent to delay transplantation rejection.

SummaryWe have identified a novel role for filamentous bacteriophage in the delayed healing associated with chronic Pseudomonas aeruginosa (Pa) wound infections. Pf phage delays wound re-epithelialization in the absence of live Pa, indicative that Pf effects on wound healing are independent of Pa pathogenesis. Pf phage directly inhibits autocrine signaling of CXCL1 (KC) to impede keratinocyte migration and wound re-epithelization. In agreement with these studies, a prospective cohort study of 36 human patients with chronic Pa wound infections revealed that wounds infected with Pf positive strains of Pa took longer to heal and were more likely to increase in size compared to wounds infected with Pf negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian target cells. We propose that Pf phage may have potential as a biomarker and therapeutic target in delayed wound healing.

Dry ports are intermodal transport hubs in the inland, which operate as centres for the transshipment of sea cargo to inland destinations. They could make the import and export easier and increase trade. This paper considers conditions to construct them in the Indochina area including three countries Vietnam, Lao People's Democratic Republic (Laos) and Cambodia. Accordingly, the general characteristics of dry ports and the conditions to develop them are reviewed. Transportation systems in the Indochina area are then analysed. Consequently, a suggested dry port system is presented, which promises to bring many benefits for the Indochina region. Finally, some conclusions and suggestions are presented.

Evaluation for malignancy of the adrenal cortex, adrenal cortical carcinoma (ACC), is a challenge in surgical pathology due to its relative rarity and histologic overlap with its benign counterpart, adrenocortical adenoma (ACA). We characterized a cohort of human ACC and ACA, including a molecular screen, with a goal of identifying potential diagnostic adjuncts. Thirty-six cases of ACC underwent histologic and clinical review. In the 31 ACC cases with available material and a cohort of 10 ACA cases, a multiplex nucleotide amplification molecular screen from formalin-fixed, paraffin-embedded tissue was peformed. ACCs demonstrated a wide variety of clinical and histologic characteristics with overall poor but unpredictable survival for subjects with ACC. By mutational screen, 12/31 (38.7%) carcinomas harbored CTNNB1 mutations, 1 with an additional TP53 mutation; 1 case each had isolated APC and TP53 mutations; 16 were wild-type for all tested loci; and 1 case demonstrated repeated assay failures. Two of the 10 ACA (20%) demonstrated CTNNB1 mutations by mutational screen, with no additional mutations. Immunohistochemistry for beta-catenin was performed and compared with the results of the molecular screen. Strong nuclear beta-catenin immunopositivity corresponded to the presence of CTNNB1 mutation by genotyping in 10 of 12 cases (83% sensitivity); the mismatched case(s) demonstrated strong membranous staining by immunohistochemistry. Seventeen of the 18 cases without CTNNB1 mutation showed membranous staining or did not stain (94% specificity); the mismatched case demonstrated scattered (

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine tumor, often metastatic at presentation, with a median survival time of 6.8 months for stage IV disease. Current chemotherapeutic regimens are largely ineffective. It is still unknown whether established oncogenes or tumor suppressors are major players in the pathogenesis of MCC. Recently, a new polyomavirus has been identified in 50 to 80% of MCC, but a mechanistic role for this virus in the pathogenesis of MCC has not yet been demonstrated. We hypothesized that deregulation of signaling pathways that are commonly activated in cancer may contribute to MCC tumorigenesis and may provide insights into targeted therapy approaches for this malignancy. Design: We retrospectively profiled 60 primary MCC samples diagnosed at the MGH from 1995 to 2010 using a recently developed SNaPshot genotyping assay to screen for the presence of common mutations in 13 cancer genes, many of which are targeted by FDA approved drugs or by targeted agents undergoing clinical trials. In addition, all MCC samples were tested for the presence of Merkel cell polyomavirus (MCPyV) using PCR. Results: The SnaPshot assay identified mutations in 15% (9/60) of MCC primary tumors. The TP53 tumor suppressor gene was mutated in 3 of 60 cases and activating mutations in the p110 alpha subunit of the phosphatidylinositol 3-kinase (PIK3CA) gene were found in 6 of 60 cases. Sanger sequencing of the primary MCC tumors identified one additional PIK3CA mutation (R19K) that has not been previously described in cancer. In primary MCC cell lines, we observed that the presence of a PI3KCA activating mutation was associated with sensitivity to treatment with NVP-BEZ-235, a dual PI3K-mTOR inhibitor currently under active clinical development. Clinical correlations with PIK3CA mutational status and the presence of MCPyV are ongoing. Conclusions: We discovered that a subset of patients with MCC (10%) carry activating mutations in PIK3CA. Furthermore, we found that a MCC cell line harboring a PIK3CA mutation is selectively sensitive to a PI3K inhibitor under clinical development. Our results suggest the relevance of screening patients with MCC for activation of the PI3K pathway, as these cancers may be particularly sensitive to PI3K pathway inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2210. doi:10.1158/1538-7445.AM2011-2210

Simulation models have been used successfully to model traffic systems, test various traffic control algorithms and solve traffic problems in many developed countries. However, they are unlikely to produce reliable results if applied to Vietnam's mixed traffic conditions, where motorbikes are the principle means of transportation. This paper models and simulates the mixed traffic system. Accordingly, the traffic system is characterised and the logic of the simulation model is introduced briefly. In order to validate and demonstrate the usefulness of the simulation model, a case study is presented. Finally, some conclusions and suggestions are proposed.