[Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis].

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

Effects of a recovery management intervention on Chinese heroin users' community recovery through the mediation effect of enhanced service utilization.

BACKGROUND: This study investigates whether a recovery management intervention (RMI) can improve the utilization of community drug treatment and wraparound services among heroin users in China and subsequently lead to positive recovery outcomes. METHODS: Secondary analysis was conducted drawing data from a randomized controlled trial; 100 heroin users with no severe mental health problems were recruited in two Shanghai districts (Hongkou and Yangpu) upon their release from compulsory rehabilitation facilities. A latent variable modeling approach was utilized to test whether the RMI influences heroin users' perceived motivation and readiness for treatment, enhances treatment and wraparound service participation, and, in turn, predicts better recovery outcomes. RESULTS: Enrollment in drug treatment and other social service utilization increased significantly as a result of RMI rather than an individual drug user's motivation and readiness for treatment. Increased service utilization thus led to more positive individual recovery outcomes. In addition to this mediation effect through service utilization, the RMI also improved participants' community recovery directly. CONCLUSIONS: Findings suggest that better drug treatment enrollment, community service utilization and recovery outcomes can be potentially achieved among heroin users in China with carefully designed case management interventions.

Is Mycobacterium tuberculosis a closer relative to Gram-positive or Gram-negative bacterial pathogens?

The phylogenetic position of Mycobacterium tuberculosis relative to other bacteria is controversial. Its cell wall has characteristics of both Gram-positive and Gram-negative bacteria. In the standard reference of bacterial phylogeny based on 16S ribosomal RNA sequence comparison, M. tuberculosis belongs to the high G+C Gram-positive bacteria that form a monophyletic group with the low G+C Gram-positive bacteria such as Bacillus subtilis. Some analyses indicate no particular relationship between these two groups. The availability of the complete genome sequence of M. tuberculosis allows us to reexamine this issue from genomic perspectives, as genome-based phylogenies may be more representative of the evolutionary history of whole organisms than molecular trees. In the genome tree constructed based on conserved gene content, M. tuberculosis is more related to Gram-negative than to Gram-positive bacteria as reflected by the evolutionary distance between nearest ancestral units. This conclusion may be supported by another analysis showing that M. tuberculosis shares relatively more orthologous genes for energy production and conversion with Gram-negative bacteria, in particular, Escherichia coli and Pseudomonas aeruginosa, than with Gram-positive bacteria.

The potential of human neutrophil peptides in tuberculosis therapy.

The problems of drug resistance and bacterial persistence in tuberculosis have prompted scientists to search for clues from the latest advances in microbiology and immunology. Recent research on human neutrophil peptides (HNPs) has highlighted their bactericidal action against Mycobacterium tuberculosis and suggested that neutrophils may play a more important defensive role in tuberculosis than previously thought. Human neutrophil peptides belong to a family of antimicrobial and cytotoxic peptides known as 'defensins'. Neutrophils use both oxidative and non-oxidative microbicidal mechanisms to provide the host with innate immunity against microbial infections. Defensins are most abundant among an array of oxygen-independent antimicrobial proteins and peptides in neutrophil granules. Defensins are effective against a wide spectrum of microbes including bacteria, viruses, fungi, spirochetes and mycobacteria. In addition to direct antimicrobial activity, HNPs can potentially influence the inflammatory or immune responses by modulating cytokine production or acting like opsonins or chemotactic factors. HNPs are active against M. tuberculosis grown in vitro or within macrophages. HNPs released by neutrophils recruited in the early lesion could attract monocytes to the site and macrophages may in vivo uptake the extracellular HNPs and kill the intracellular pathogens. As such, HNPs are potential therapeutic agents against tuberculosis. HNPs are also cytotoxic against a wide range of normal mammalian cells; however, there is evidence that defensins may not cause significant cytotoxicity at the therapeutic level. Finally, the clinical application of HNPs must be evaluated in the context of possible drug resistance, as some resistance-associated genes have been identified.

Thalidomide and tuberculosis.

The anti-inflammatory and immunomodulatory effects of thalidomide have led scientists to explore its clinical therapeutic values. Thalidomide is now being considered as an adjuvant treatment for tuberculosis. This literature review examines the drug's mechanism of action and clinical applications. Thalidomide affects cytokine production and T lymphocyte proliferation. It appears that thalidomide suppresses TNF-alpha production by macrophages and thereby reduces inflammatory response. Thalidomide elevates the IFN-gamma level and modulates several other cytokines as well, noteworthily IL-2 and IL-12. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells. This finding is important, since CD8+ T cells have been shown to be contributory to the protective immune response to Mycobacterium tuberculosis infection. The clinical application of thalidomide as part of standard tuberculosis therapy is inconclusive amid variability among reports. However, thalidomide has been shown to be an effective adjuvant for tuberculosis patients complicated with severe inflammatory reaction or wasting conditions.

Analysis of electroosmotic flow with step change in zeta potential.

The term electroosmotic flow refers to the bulk flow of an aqueous solution induced by the application of the electric field to the zeta potential. The characteristics of EOF in a microchannel depend upon the nature of the zeta potential, i.e., whether it is uniform or nonuniform. In this study, the full Navier-Stokes equation and the Nernst-Planck equation are used to model the change in EOF characteristics that occur when a step change in zeta potential is applied. It is found that the thickness of the electrical double layer gradually increases downstream from the location at which the zeta potential is increased. The results indicate that a step change in zeta potential causes a significant variation in the velocity profile and in the pressure distribution.

Discrete probability estimation for classification using certainty-factor-based neural networks.

Traditional probability estimation often demands a large amount of data for a problem of industrial scale. Neural networks have been used as an effective alternative for estimating input-output probabilities. In this paper, the certainty-factor-based neural network (CFNet) is explored for probability estimation in discrete domains. A new analysis presented here shows that the basis functions learned by the CFNet can bear precise semantics for dependencies. In the simulation study, the CFNet outperforms both the backpropagation network and the system based on the Rademacher-Walsh expansion. In the real-data experiments on splice junction and breast cancer data sets, the CFNet outperforms other neural networks and symbolic systems.

The application of certainty factors to neural computing for rule discovery.

Discovery of domain principles has been a major long-term goal for scientists. This paper presents a new system named DOMRUL for learning such principles in the form of rules. A distinctive feature of the system is the integration of the certainty factor (CF) model and a neural network. These two elements complement each other. The CF model offers the neural network better semantics and generalization advantage, and the neural network overcomes possible limitations such as inaccuracies and overcounting of evidence associated with certainty factors. It is a major contribution of this paper to show mathematically the quantizability nature of the CFNet since previously the quantizability of the CF model was demonstrated only empirically. The rule discovery system can be applied to any domain without restriction on both the rule number and rule size. In a hypothetical domain, DOMRUL discovered complex domain rules at a considerably higher accuracy than a commonly used rule-learning program C4.5 in both normal and noisy conditions. The scalability in a large domain is also shown. On a real data set concerning promoters prediction in molecular biology, DOMRUL learned rules with more complete semantics than C4.5.

The certainty factor-based neural network in continuous classification domains.

The integration of certainty factors (CFs) into the neural computing framework has resulted in a special artificial neural network known as the CFNet. This paper presents the cont-CFNet, which is devoted to classification domains where instances are described by continuous attributes. A new mathematical analysis on learning behavior, specifically linear versus nonlinear learning, is provided that can serve to explain how the cont-CFNet discovers patterns and estimates output probabilities. Its advantages in performance and speed have been demonstrated in empirical studies.

Electroosmotic Flow in Microchannels.

The electroosmotic flow induced by an applied electrostatic potential field through microchannels between two parallel plates and a 90 degrees bend is analyzed in this work. A nonlinear, two-dimensional Poisson-Boltzmann equation governing the electrical double-layer field and the Laplace equation governing the electrostatic field distribution in microchannels are numerically solved using a finite-difference method. A body force caused by the interaction between the electrical double-layer field and the applied electrostatic field is included in the full Navier-Stokes equations. The effects of the electrical double-layer field and the applied electrostatic field on the fluid velocity distribution, pressure drop, and skin friction are discussed. A small pressure drop along the parallel plates is detected, although it is always neglected in the literature. Pressure is not a constant across the channel height. The axial velocity profile is no longer flat across the channel height when the Reynolds number is large. A separation bubble is detected near the 90 degrees junction when the Reynolds number is large. Copyright 2001 Academic Press.

Inhibitors of adenosine catabolism improve recovery of dog myocardium after ischemia.

The effects of inhibitors of adenosine catabolism on contractile function and metabolites were assessed during 15 minutes of ischemia followed by 30 minutes of reperfusion in the open-chest dog heart. As compared to sham treatment, pretreatment with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and dipyridamole (DP) protected contractile function during ischemia, and improved recovery of high energy phosphate content and contractile function during reperfusion following ischemia. Testing EHNA and DP in a free-radical generating system indicated both compounds have some scavenging ability, suggesting the effect of EHNA + DP may not be on adenosine nucleotide metabolism alone. Comparison of end diastolic segment lengths to contractile function indicated the results were not affected by changes in preload resulting from peripheral vasodilation.

Contractility, ATP, and creatine phosphate during myocardial ischaemia and reperfusion: the effects of adenosine and inhibition of adenosine catabolism in the dog heart.

Provision of AMP or adenosine to heart cells during recovery from episodes of myocardial ischaemia accelerates physiological, biochemical, and structural recovery. Inhibition of adenosine loss from the tissue during ischaemia should have a similar effect. This hypothesis was tested in dog heart by infusion of adenosine and inhibitors of adenosine catabolism prior to, during, and following ischaemia. Post-ischaemic recovery of ATP and contractile function was accelerated significantly by adenosine and by inhibitors of adenosine catabolism both singly and in combination. Contractility and ATP levels during ischaemia were also increased by these inhibitors.

Electrokinetic injection techniques in microfluidic chips.

The separation efficiency of a microfluidic chip is influenced to a significant degree by the flow field conditions within the injection microchannel. Therefore, an understanding of the physics of the flow within this channel is beneficial in the design and operation of such a system. The configuration of an injection system is determined by the volume of the sample plug that is to be delivered to the separation process. Accordingly, this paper addresses the design and testing of injection systems with a variety of configurations, including a simple cross, a double-T, and a triple-T configuration. This paper also presents the design of a unique multi-T injection configuration. Each injection system cycles through a predetermined series of steps, in which the electric field magnitude and distribution within the various channels is strictly manipulated, to effectuate a virtual valve. The uniquemulti-T configuration injection system presented within this paper has the ability to simulate the functions of the cross, double-T, and triple-T systems through appropriate manipulations of the electric field within its various channels. In other words, the proposed design successfully combines several conventional injection systems within a single microfluidic chip.