Carcinoma involving the gallbladder: a retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma

<p>Abstract</p> <p>Background</p> <p>Carcinoma of the gallbladder (GBC) clinically mimics benign gallbladder diseases and often escapes detection until advanced stage. Despite the frequency of cholecystectomy, diagnosis of GBC remains problematic in many situations. We sought to identify pathologic features that contribute to the difficulty in recognition of GBC.</p> <p>Methods</p> <p>We identified 23 patients (ranged from 45 to 86 years, male to female ratio 1:4.5) with carcinoma involving the gallbladder referred to an academic medical center over a period of 10 years for study. This includes 10 cases of primary GBC, 6 cases of metastatic tumor to gallbladder, 6 cases of directly invasive adenocarcinoma arising elsewhere in the biliary tree, and one case of unidentified origin adenocarcinoma. Primary tumors include adenocarcinoma not otherwise specified (NOS) in 6 cases, papillary adenocarcinoma in 2 cases, and single cases of undifferentiated carcinoma and combined adenocarcinoma and neuroendocrine carcinoma (NEC). Metastatic tumors to gallbladder were from a wide range of primary sites, predominantly the gastrointestinal tract.</p> <p>Results</p> <p>These cases illustrate seven potential pitfalls which can be encountered. These include: 1) mistakenly making a diagnosis of adenocarcinoma of gallbladder when only benign lesions such as deeply penetrating Rokitansky-Aschoff sinuses are present (overdiagnosis), 2) misdiagnosing well-differentiated invasive carcinoma with minimal disease as benign disease (underdiagnosis), 3) differentiating between primary NEC of gallbladder and metastasis, 4) confusing primary mucinous adenocarcinoma of gallbladder with pseudomyxoma peritonei from a low grade appendiceal neoplasm disseminated to gallbladder, 5) confusing gangrenous necrosis related to cholecystitis with geographic tumoral necrosis, 6) undersampling early, grossly occult disease, and 7) misinterpreting extracellular mucin pools.</p> <p>Conclusions</p> <p>Clinical history and a high index of suspicion are prerequisite to detecting GBC. Detection of GBC at an early stage is difficult because the symptoms mimic benign gallbladder diseases. Misinterpretation of subtle microscopic abnormalities contributes diagnostic failures in early cases. Careful attention to any evidence of mural thickening, thorough sampling, particularly in older patients, and close examination of any deeply situated glandular structures are critical. Correlations with radiographic and clinical findings are important helps to avoid misdiagnosis in this commonly resected organ.</p

The antimicrobial resistance patterns and associated determinants in Streptococcus suis isolated from humans in southern Vietnam, 1997-2008

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus suis </it>is an emerging zoonotic pathogen and is the leading cause of bacterial meningitis in adults in Vietnam. Systematic data on the antimicrobial susceptibility profiles of <it>S. suis </it>strains isolated from human cases are lacking. We studied antimicrobial resistance and associated resistance determinants in <it>S. suis </it>isolated from patients with meningitis in southern Vietnam.</p> <p>Methods</p> <p><it>S. suis </it>strains isolated between 1997 and 2008 were investigated for their susceptibility to six antimicrobial agents. Strains were screened for the presence and expression of tetracycline and erythromycin resistance determinants and the association of <it>tet</it>(M) genes with <it>Tn</it>916- like transposons. The localization of tetracycline resistance gene <it>tet</it>(L) was determined by pulse field gel electrophoresis and Southern blotting.</p> <p>Results</p> <p>We observed a significant increase in resistance to tetracycline and chloramphenicol, which was concurrent with an increase in multi-drug resistance. In tetracycline resistance strains, we identified <it>tet</it>(M), <it>tet</it>(O), <it>tet</it>(W) and <it>tet</it>(L) and confirmed their expression. All <it>tet</it>(M) genes were associated with a <it>Tn</it>916-like transposon. The co-expression of <it>tet</it>(L) and other tetracycline resistance gene(s) encoding for ribosomal protection protein(s) was only detected in strains with a minimum inhibitory concentration (MIC) of tetracycline of ≥ 64 mg/L</p> <p>Conclusions</p> <p>We demonstrated that multi-drug resistance in <it>S. suis </it>causing disease in humans in southern Vietnam has increased over the 11-year period studied. We report the presence and expression of <it>tet</it>(L) in <it>S. suis </it>strains and our data suggest that co-expression of multiple genes encoding distinct mechanism is required for an MIC ≥ 64 mg/L to tetracycline.</p

Single photon emission from plasma treated 2D hexagonal boron nitride

© 2018 The Royal Society of Chemistry. Artificial atomic systems in solids are becoming increasingly important building blocks in quantum information processing and scalable quantum nanophotonic networks. Amongst numerous candidates, 2D hexagonal boron nitride has recently emerged as a promising platform hosting single photon emitters. Here, we report a number of robust plasma and thermal annealing methods for fabrication of emitters in tape-exfoliated hexagonal boron nitride (hBN) crystals. A two-step process comprising Ar plasma etching and subsequent annealing in Ar is highly robust, and yields an eight-fold increase in the concentration of emitters in hBN. The initial plasma-etching step generates emitters that suffer from blinking and bleaching, whereas the two-step process yields emitters that are photostable at room temperature with emission wavelengths greater than ∼700 nm. Density functional theory modeling suggests that the emitters might be associated with defect complexes that contain oxygen. This is further confirmed by generating the emitters via annealing hBN in air. Our findings advance the present understanding of the structure of quantum emitters in hBN and enhance the nanofabrication toolkit needed to realize integrated quantum nanophotonic circuits

The importance of waist circumference and body mass index in cross-sectional relationships with risk of cardiovascular disease in Vietnam

BackgroundWaist circumference (WC) is an indicator of intra-abdominal adipose tissue, high levels of which confer an increased risk of cardiometabolic disease. Population data on WC should be more informative than data on body mass index (BMI), which is a general indicator of body size. This study aimed to evaluate the importance of WC relative to BMI in cross-sectional relationships with blood pressure (BP), glucose, and total cholesterol (TC) in the adult population of Vietnam.MethodsThe data were collected in a population-based survey conducted during 2009-10 using the "WHO STEPwise approach to surveillance of risk factors for non-communicable disease" (STEPS) methodology. The survey participants (n = 14 706 aged 25 to 64 years) were selected by multi-stage stratified cluster sampling from eight provinces representative of the eight geographical regions of Vietnam. All measurements were performed in accordance with the STEPS protocols. All analyses were performed using complex survey methods.ResultsThe measurements of WC and BMI were highly correlated (men r = 0.80, women r = 0.77). For men, the strongest and predominant associations with BP, glucose, and TC were for WC or an index based on WC. For women, this was true for glucose but BMI was more important for BP and TC. WC or an index based on WC provided better discrimination than BMI of hypertension and elevated glucose, and of raised TC for men. Information on four new anthropometric indices did not improve model fit or subject discrimination.ConclusionFor BP/hypertension, glucose/elevated glucose, and TC/raised TC, WC was more informative than BMI for Vietnamese men, but both WC and BMI were important for Vietnamese women. Both WC and BMI need to be assessed for estimation of CVD risk in Vietnam

Efficient Construction of an Inverted Minimal H1 Promoter Driven siRNA Expression Cassette: Facilitation of Promoter and siRNA Sequence Exchange

RNA interference (RNAi), mediated by small interfering RNA (siRNA), is an effective method used to silence gene expression at the post-transcriptional level. Upon introduction into target cells, siRNAs incorporate into the RNA-induced silencing complex (RISC). The antisense strand of the siRNA duplex then "guides" the RISC to the homologous mRNA, leading to target degradation and gene silencing. In recent years, various vector-based siRNA expression systems have been developed which utilize opposing polymerase III promoters to independently drive expression of the sense and antisense strands of the siRNA duplex from the same template.We show here the use of a ligase chain reaction (LCR) to develop a new vector system called pInv-H1 in which a DNA sequence encoding a specific siRNA is placed between two inverted minimal human H1 promoters (approximately 100 bp each). Expression of functional siRNAs from this construct has led to efficient silencing of both reporter and endogenous genes. Furthermore, the inverted H1 promoter-siRNA expression cassette was used to generate a retrovirus vector capable of transducing and silencing expression of the targeted protein by>80% in target cells.The unique design of this construct allows for the efficient exchange of siRNA sequences by the directional cloning of short oligonucleotides via asymmetric restriction sites. This provides a convenient way to test the functionality of different siRNA sequences. Delivery of the siRNA cassette by retroviral transduction suggests that a single copy of the siRNA expression cassette efficiently knocks down gene expression at the protein level. We note that this vector system can potentially be used to generate a random siRNA library. The flexibility of the ligase chain reaction suggests that additional control elements can easily be introduced into this siRNA expression cassette

Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A4 hydrolase (encoded by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. METHODS: We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. RESULTS: LTA4H genotype predicted survival of human immunodeficiency virus (HIV)-uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM. HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. CONCLUSIONS: LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals

Guidelines for developing and reporting machine learning predictive models in biomedical research : a multidisciplinary view

BACKGROUND: As more and more researchers are turning to big data for new opportunities of biomedical discoveries, machine learning models, as the backbone of big data analysis, are mentioned more often in biomedical journals. However, owing to the inherent complexity of machine learning methods, they are prone to misuse. Because of the flexibility in specifying machine learning models, the results are often insufficiently reported in research articles, hindering reliable assessment of model validity and consistent interpretation of model outputs. OBJECTIVE: To attain a set of guidelines on the use of machine learning predictive models within clinical settings to make sure the models are correctly applied and sufficiently reported so that true discoveries can be distinguished from random coincidence. METHODS: A multidisciplinary panel of machine learning experts, clinicians, and traditional statisticians were interviewed, using an iterative process in accordance with the Delphi method. RESULTS: The process produced a set of guidelines that consists of (1) a list of reporting items to be included in a research article and (2) a set of practical sequential steps for developing predictive models. CONCLUSIONS: A set of guidelines was generated to enable correct application of machine learning models and consistent reporting of model specifications and results in biomedical research. We believe that such guidelines will accelerate the adoption of big data analysis, particularly with machine learning methods, in the biomedical research community

Novel Evidence of HBV Recombination in Family Cluster Infections in Western China

Two hepatitis B virus (HBV) C/D recombinants were isolated from western China. No direct evidence indicates that these new viruses arose as a result of recombination between genotype C and D or a result of convergence. In this study, we search for evidence of intra-individual recombination in the family cluster cases with co-circulation of genotype C, D and C/D recombinants. We studied 68 individuals from 15 families with HBV infections in 2006, identified individuals with mixed HBV genotype co-infections by restriction fragment length polymorphism and proceeded with cloning and DNA sequencing. Recombination signals were detected by RDP3 software and confirmed by split phylogenetic trees. Families with mixed HBV genotype co-infections were resampled in 2007. Three of 15 families had individuals with different HBV genotype co-infections in 2006. One individual (Y2) had a triple infection of HBV genotype C, D and C/D recombinant in 2006, but only genotype D in 2007. Further clonal analysis of this patient indicated that the C/D recombinant was not identical to previously isolated CD1 or CD2, but many novel recombinants with C2, D1 and CD1 were simultaneously found. All parental strains could recombine with each other to form new recombinant in this patient. This indicates that the detectable mixed infection and recombination have a limited time window. Also, as the recombinant nature of HBV precludes the possibility of a simple phylogenetic taxonomy, a new standard may be required for classifying HBV sequences

Dried blood spots as a source of anti-malarial antibodies for epidemiological studies

BACKGROUND: Blood spots collected onto filter paper are an established and convenient source of antibodies for serological diagnosis and epidemiological surveys. Although recommendations for the storage and analysis of small molecule analytes in blood spots exist, there are no published systematic studies of the stability of antibodies under different storage conditions. METHODS: Blood spots, on filter paper or glass fibre mats and containing malaria-endemic plasma, were desiccated and stored at various temperatures for different times. Eluates of these spots were assayed for antibodies against two Plasmodium falciparum antigens, MSP-119 and MSP2, and calculated titres used to fit an exponential (first order kinetic) decay model. The first order rate constants (k) for each spot storage temperature were used to fit an Arrhenius equation, in order to estimate the thermal and temporal stability of antibodies in dried blood spots. The utility of blood spots for serological assays was confirmed by comparing antibodies eluted from blood spots with the equivalent plasma values in a series of samples from North Eastern Tanzania and by using blood spot-derived antibodies to estimate malaria transmission intensity in this site and for two localities in Uganda. RESULTS: Antibodies in spots on filter paper and glass fibre paper had similar stabilities but blood was more easily absorbed onto filter papers than glass fibre, spots were more regular and spot size was more closely correlated with blood volume for filter paper spots. Desiccated spots could be stored at or below 4 degrees C for extended periods, but were stable for only very limited periods at ambient temperature. When desiccated, recoveries of antibodies that are predominantly of IgG1 or IgG3 subclasses were similar. Recoveries of antibodies from paired samples of serum and of blood spots from Tanzania which had been suitably stored showed similar recoveries of antibodies, but spots which had been stored for extended periods at ambient humidity and temperature showed severe loss of recoveries. Estimates of malaria transmission intensity obtained from serum and from blood spots were similar, and values obtained using blood spots agreed well with entomologically determined values. CONCLUSION: This study has demonstrated the suitability of filter paper blood spots paper for collection of serum antibodies, and provided clear guidelines for the treatment and storage of filter papers which emphasize the importance of desiccation and minimisation of time spent at ambient temperatures. A recommended protocol for collecting, storing and assaying blood spots is provided

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

&lt;b&gt;Background&lt;/b&gt; Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods and findings&lt;/b&gt; The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems