[Clinical application of biofragmentable anastomosis ring for intestinal anastomosis].
To compare the efficacy of the biofragmentable anastomotic ring (BAR) with conventional hand-sutured and stapling techniques,and to evaluate the safety and applicability of the BAR in intestinal anastomosis. The totol of 498 patients performed intestinal anastomosis from January 2000 to November 2005 were allocated to BAR group (n=186), hand-sutured group (n=177) and linear cutter group (n=135). The operative time, postoperative convalescence and corresponding complication were recorded. Postoperative anastomotic inflammation and anastomotic stenosis were observed during half or one year follow-up of 436 patients. The operative time was (102 +/- 16) min in the BAR group, (121 +/- 15) min in the hand-sutured group, and (105 +/- 18 ) min in the linear cutter group. The difference was significant statistically (P <0.05). The operative time in BAR group and linear cutter group was shorter than hand-sutured group. One case of anastomotic leakage was noted in the BAR group, one case in the hand-sutured group, and none in the linear cutter group. They were cured by conservative methods. One case of anastomotic obstruction happened in the BAR group, one case in the hand-sutured group. Two of them were cured by conservative methods. Two cases of anastomotic obstruction happened in the hand-sutured group. However, one of them required reoperation to remove the obstruction. In the BAR, hand-sutured and the linear cutter group, the postoperative first flatus time was (67.2+/- 4.6) h, (70.2 +/- 5.8) h and (69.2 +/- 6.2)h, respectively. No significant differences were observed among three groups(P > 0.05). The rate of postoperative anastomotic inflammation was 3.0 % (5/164) in the BAR group, 47.8 % (76/159) in hand-sutured group and 7.1 % (8/113) in the linear cutter group. The difference was significant statistically (P <0.05). The rate of postoperative anastomotic inflammation in the BAR group and in the linear cutter group was less than that in hand-sutured group. BAR is one of rapid,safe and effective methods in intestinal anastomosis. It has less anastomotic inflammatory reaction than hand-sutured technique. It should be considered equal to manual and stapler methods.


Does preconditioning affect recovery in stunned myocardium?
In this study, to determine whether preconditioning enhances the process of recovery from post-ischemic dysfunction, ultrasonic crystals were placed in 8 open-chest dogs to measure regional myocardial wall thickening in the ischemic area. A carotid-circumflex coronary artery bypass was created with an electromagnetic flow probe and a fixed stenosis was produced. Ventricular pacing was performed for 15 minutes at a rate of 190-220 bpm. After a 15 minutes rest period, a second pacing was performed in a similar manner. After cessation of the first pacing, circumflex wall thickening remained reduced significantly. Three minutes after cessation of the second pacing, circumflex thickening decreased further. After 15 minutes, wall thickening improved to the value recorded before the second pacing. The degree of improvement from 3 minutes to 15 minutes after the second pacing was greater than that after the first pacing. Thus, preceding demand ischemia modifies the rate of functional recovery from the next post-ischemic dysfunction, indicating that preconditioning of the ischemic myocardium enhances recovery from stunning.


A Rare Report of Two Cases: Ancient Schwannoma of Infratemporal Fossa and Verocay Schwannoma of Buccal Mucosa.
Schwannoma is a benign tumor that originates from Schwann cells of the peripheral nerve. Occurring as a common tumor in the head and neck region, its intraoral presentation is rare which accounts for only 1%. They are solitary, slow-growing, smooth-surfaced, usually asymptomatic, and encapsulated tumor. This paper comprises two case reports, both of which presented with an intraoral soft tissue swelling which turned out to be schwannoma of buccal mucosa and infratemporal fossa with extension into the oral cavity, respectively. The treatment was done with complete surgical excision. Soft tissue tumors of the oral cavity can present with similar clinical feature, which can make it difficult to distinguish one lesion from the other. Thus, final diagnosis for such lesions can only be rendered based on complete analysis of clinical, radiological, surgical, and histopathological findings.


Automated classification of tailed bacteriophages according to their neck organization.
The genetic diversity observed among bacteriophages remains a major obstacle for the identification of homologs and the comparison of their functional modules. In the structural module, although several classes of homologous proteins contributing to the head and tail structure can be detected, proteins of the head-to-tail connection (or neck) are generally more divergent. Yet, molecular analyses of a few tailed phages belonging to different morphological classes suggested that only a limited number of structural solutions are used in order to produce a functional virion. To challenge this hypothesis and analyze proteins diversity at the virion neck, we developed a specific computational strategy to cope with sequence divergence in phage proteins. We searched for homologs of a set of proteins encoded in the structural module using a phage learning database. We show that using a combination of iterative profile-profile comparison and gene context analyses, we can identify a set of head, neck and tail proteins in most tailed bacteriophages of our database. Classification of phages based on neck protein sequences delineates 4 Types corresponding to known morphological subfamilies. Further analysis of the most abundant Type 1 yields 10 Clusters characterized by consistent sets of head, neck and tail proteins. We developed Virfam, a webserver that automatically identifies proteins of the phage head-neck-tail module and assign phages to the most closely related cluster of phages. This server was tested against 624 new phages from the NCBI database. 93% of the tailed and unclassified phages could be assigned to our head-neck-tail based categories, thus highlighting the large representativeness of the identified virion architectures. Types and Clusters delineate consistent subgroups of Caudovirales, which correlate with several virion properties. Our method and webserver have the capacity to automatically classify most tailed phages, detect their structural module, assign a function to a set of their head, neck and tail genes, provide their morphologic subtype and localize these phages within a "head-neck-tail" based classification. It should enable analysis of large sets of phage genomes. In particular, it should contribute to the classification of the abundant unknown viruses found on assembled contigs of metagenomic samples.


On the histogenesis of Ewing's sarcoma. An ultrastructural, immunohistochemical, and cytochemical study.
Forty-two cases of Ewing's sarcoma (ES) have been studied with light microscopy during the 9-year period 1974 to 1982. Thirty-three patients had ES of bone, and in 9 patients the tumor was located in the extraskeletal soft tissues. Cases which fulfilled all the morphologic criteria were accepted as typical ES (31 cases), and those with some architectural or cytologic peculiarities were considered atypical forms of ES (11 cases). An immunohistochemical study (PAP method) to evaluate the presence in the tumor cells of the following markers: myoglobin, F-VIII-related antigen, lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and immunoglobulins (IgG, IgA, IgM, kappa and lambda light chains), was performed with negative results in all cases (paraffin blocks were available in 38 cases). The cytochemical study on fresh tissue imprints from five patients (PAS, Sudan Black, alpha-naphthyl acetate esterase, acid phosphatase, beta glucuronidase, myeloperoxidases, naphthol-AS-D chloroacetate esterase and alkaline phosphatase) gave no pattern of histogenetic significance, PAS being the best morphologic marker in tissue sections and touch preparations. A detailed ultrastructural study was performed on 34 cases; the main findings may be summarized as follows: medium sized cells, polygonal shape, oval nuclei, smooth nuclear envelope, abundant euchromatin, well-developed nucleolonema, scant membranous organelles, abundant hyaloplasmic glycogen, occasional lipid vacuoles, straight cell membranes, and primitive intercellular junctions. No differences were found between bone and extraskeletal ES; moreover, typical and atypical forms showed moderate quantitative differences with no qualitative change. The histogenesis is discussed; no functional or morphologic markers have been found to suggest the cell of origin; however, some cell lines may be excluded. It is the impression of the authors that they are dealing with a primitive noncommitted mesenchymal cell.


[Cloning and expression of human single-chain Fv antibody against A beta(1-42) peptide involved in Alzheimer disease].
Screening of antibody clones specific for beta amyloid peptide 1-42 from human phage-display single-chain Fv (scFv) antibody library, and to clone the antibody gene and to express it in a bacterial system, with an ultimate intention to obtain human anti-A beta(1-42) antibody for Alzheimer disease (AD) therapy. beta amyloid peptide 142 was bound on the solid surface of 96 wells plate as the antigen for the binding antibody clones from a human phage-display scFv antibody library. After four rounds of biopanning, random, well-separated colonies were identified by ELISA test. The specific positive phage clones were transfected into the host E. coli HB2151 to express soluble scFv antibodies. These antibodies were identified by SDS-PAGE and Western blot and their antigen-binding activities were determined by ELISA. Genes of the positive scFv antibodies were then sequenced. ELISA test showed that 7 clones could bind A beta(1-42). The soluble scFv antibody from clone A10 was expressed successfully to produce a 33000 protein present mainly in the whole cell extract which was five folds in amount to that of the control as determined by A490 nm. DNA sequencing demonstrated that the gene of the positive antibody was the scFv gene and the deduced amino acids sequence confirmed its typical antibody V domain structure. The specific antibody against A beta(1-42) was successfully identified from human phage-display scFv antibody library. The soluble scFv antibody specific to A beta(1-42) was expressed by E. coli HB2151 in a significant quantity. This cloned antibody promises to provide a solid basis for future studies of the pathogenesis and development of therapeutic agents for Alzheimer's disease.


Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations.
The polyspecific organic cation transporters 1 and 2 (Oct1 and -2) transport a broad range of substrates, including drugs, toxins, and endogenous compounds. Their strategic localization in the basolateral membrane of epithelial cells in the liver, intestine (Oct1), and kidney (Oct1 and Oct2) suggests that they play an essential role in removing noxious compounds from the body. We previously showed that in Oct1(-/-) mice, the hepatic uptake and intestinal excretion of organic cations are greatly reduced. Since Oct1 and Oct2 have extensively overlapping substrate specificities, they might be functionally redundant. To investigate the pharmacologic and physiologic roles of these proteins, we generated Oct2 single-knockout and Oct1/2 double-knockout mice. Oct2(-/-) and Oct1/2(-/-) mice are viable and fertile and display no obvious phenotypic abnormalities. Absence of Oct2 in itself had little effect on the pharmacokinetics of tetraethylammonium (TEA), but in Oct1/2(-/-) mice, renal secretion of this compound was completely abolished, leaving only glomerular filtration as a TEA clearance mechanism. As a consequence, levels of TEA were substantially increased in the plasma of Oct1/2(-/-) mice. This study shows that Oct1 and Oct2 together are essential for renal secretion of (small) organic cations. A deficiency in these proteins may thus result in increased drug sensitivity and toxicity.


Electroacupuncture improves synaptic plasticity by regulating the 5-HT1A receptor in hippocampus of rats with chronic unpredictable mild stress.
To investigate the antidepressant effects of electroacupuncture (EA) on chronic unpredictable mild stress (CUMS) in rats, as well as the effects of EA on hippocampal neurons, synaptic morphology, and 5-hydroxytryptamine (HT) receptor expression. Forty adult male Wistar rats were randomly divided into normal control, CUMS, EA, and paroxetine groups. CUMS modeling was performed for 21 days, followed by 14 days of intervention: rats in the EA group underwent stimulation of GV20 and GV29 acupuncture points for 30 minutes daily; rats in the paroxetine group were administered paroxetine daily. Behavioral tests, transmission electron microscopy, western blotting, and real-time quantitative polymerase chain reaction were used to evaluate the effects of the intervention. EA treatment reversed the behavioral changes observed in rats due to CUMS modeling; it also improved the pathological changes in organelles and synaptic structures of hippocampal neurons, and upregulated the protein and mRNA expression levels of 5-HT1A receptor. There were no significant differences in 5-HT1B receptor protein and mRNA expression levels among the groups. EA treatment can alleviate depression-like symptoms in CUMS rats. The underlying mechanism may include promoting the expression of 5-HT1A receptor mRNA and protein, thereby improving synaptic plasticity in the hippocampus.


Experimental and theoretical elucidation of SPAAC kinetics for strained alkyne-containing cycloparaphenylenes.
Tuning strained alkyne reactivity via organic synthesis has evolved into a burgeoning field of study largely focused on cyclooctyne, wherein physical organic chemistry helps guide rational molecular design to produce molecules with intriguing properties. Concurrent research in the field of carbon nanomaterials has produced new types of strained alkyne macrocycles, such as cycloparaphenyleneacetylenes, that possess uniquely curved aromatic π systems but hover on the edge of stability. In 2018, we introduced a strained alkyne scaffold that marries the synthetic accessibility and stability of cyclooctyne with the curved π system of carbon nanomaterials. These molecules are strained alkyne-containing cycloparaphenylenes (or [n+1]CPPs), which have been shown to possess size-dependent reactivity as well as the classic characteristics of the unfunctionalized parent CPP, such as a tunable HOMO-LUMO gap and bright fluorescence for large sizes. Herein, we elaborate further on this scaffold, introducing two modifications to the original design and fully characterizing the kinetics of the strain-promoted azide-alkyne cycloaddition (SPAAC) for each [n+1]CPP with a model azide. Additionally, we explain how electronic (the incorporation of fluorine atoms) and strain (a meta linkage which heightens local strain at the alkyne) modulations affect SPAAC reactivity via the distortion-interaction computational model. Altogether, these results indicate that through a modular synthesis and rational chemical design, we have developed a new family of tunable and inherently fluorescent strained alkyne carbon nanomaterials.


When is a mental health professional competent to assess a person's decision to hasten death?
As the country continues to debate the legality of aid-in-dying, it appears inevitable that at some point there will be a need for mental health professionals to be involved in assessments of individuals asking for a hastened death. I designed this article to provide a set of guidelines that will allow both mental health professionals and potential consultees to determine if a professional has the training and expertise necessary to be a competent consultant.


Relationships among plasma cortisol, adrenocorticotrophin, and severity of injury in recently injured patients.
When samples were taken within 2 hr of accidental injury, plasma cortisol levels increased with injury severity score (ISS) in patients with minor and moderate injuries (ISS, 1-12) but decreased at higher ISS. Radioimmunoassay of adrenocorticotrophin (ACTH) showed very variable plasma concentrations at all ISS ranges. Like cortisol, ACTH increased with ISS up to a score of about 13, but it thereafter plateaued, and in patients with severe injuries plasma cortisol fell in relation to ACTH as well as in absolute terms. This suggested that although ACTH secretion was generally far from maximal the relatively low cortisol concentrations in the most severely injured were at least partly due to a poor response of the adrenal cortex to ACTH. In patients who presented late (more than 2 hr after injury) plasma cortisol levels were more variable and more strongly related to ACTH than at shorter times after injury. The variability of cortisol also increased with age. Patients with severe head injuries had cortisol and ACTH concentrations similar to those without head injuries but with a similar ISS from injuries in other parts of the body.


pH-Switchability and Second-Order Nonlinear Optical Properties of Monocyclopentadienylruthenium(II)/iron(II) Tetrazoles/Tetrazolates: Synthesis, Characterization, and Time-Dependent Density Functional Theory Calculations.
Tetrazole/tetrazolate monocyclopentadienyliron(II) and ruthenium(II) compounds of general formulas [(η5-C5H5)M(dppe)(N4(H)CC6H4NO2)][PF6]/[(η5-C5H5)M(dppe)(N4CC6H4NO2)] were investigated for their pH-switching second-order nonlinear optical (SONLO) properties. Compounds [(η5-C5H5)M(dppe)(N4CC6H4NO2)] (M = Fe, Ru) and compound [(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)][PF6] were fully characterized by (1H-, 13C-, 31P-) NMR, cyclic voltammetry, and elemental analysis, and compounds [(η5-C5H5)Fe(dppe)(N4CC6H4NO2)] and [(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)][PF6] were further characterized by single-crystal X-ray diffraction; the synthesis of [(η5-C5H5)Fe(dppe)(N4(H)CC6H4NO2)][PF6] was unsuccessful. Time-dependent density functional theory calculations were performed using PBE0 and CAM-B3LYP functionals to evaluate the first hyperpolarizability (βtot) of the tetrazole/tetrazolate complexes and for a detailed analysis of the experimental data. Both functionals predict (i) high first hyperpolarizabilities for the tetrazolate complexes [(η5-C5H5)M(dppe)(N4CC6H4NO2)], with βtot[Ru] ≈ 1.2βtot[Fe], and (ii) a 3-fold reduction in βtot[Ru] upon protonation, in complex [(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)]+, forecasting [(η5-C5H5)Ru(dppe)(N4CC6H4NO2)]/[(η5-C5H5)Ru(dppe)(N4(H)CC6H4NO2)]+ complexes as on/off, pH-switchable SONLO forms.


The influence of sample size on preferences from experience.
People often learn from experience about the distribution of outcomes of risky options. Typically, people draw small samples, when they can actively sample information from risky gambles to make decisions. We examine how the size of the sample that people experience in decision from experience affects their preferences between risky options. In two studies (N = 40 each), we manipulated the size of samples that people could experience from risky gambles and measured subjective selling prices and the confidence in selling price judgements after sampling. The results show that, on average, sample size influenced neither the selling prices nor confidence. However, cognitive modelling of individual-level learning showed that around half of the participants could be classified as Bayesian learners, whereas the other half adhered to a frequentist learning strategy and that if learning was cognitively simpler more participants adhered to the latter. The observed selling prices of Bayesian learners changed with sample size as predicted by Bayesian principles, whereas sample size affected the judgements of frequentist learners much less. These results illustrate the variability in how people learn from sampled information and provide an explanation for why sample size often does not affect judgements.


Nucleation in a liquid droplet.
The droplet-based microreactors in microfluidic systems have been used to synthesize nanocrystals of a variety of metals and semiconductors, which involves the nucleation and growth processes. Considering the limited numbers of solvent atoms and solute atoms/particles in a stationary droplet, we derive analytical expressions of the changes of the Gibbs free energy and the Helmholtz free energy for the concurrent formation of multiple microclusters of the same size in the liquid droplet. Both the changes of the Gibbs free energy and the Helmholtz free energy are dependent on the ratio of the number of microclusters to the solvent atoms and the interface energy between the solution and the microclusters. Using the change of the free energy, which is an approximation of the Gibbs free energy and the Helmholtz free energy, we obtain the critical nucleation number of the solute atoms/particles in the microclusters for the concurrent nucleation of multiple nuclei of the same size. The critical nucleation number of the solute atoms/particles is dependent on the ratio of the number of nuclei in the droplet to the solvent atoms, and the maximum change of the free energy for the concurrent nucleation of multiple nuclei of the same size increases with the increase of the ratio of the number of the nuclei in the droplet to the number of the solvent atoms.


Penicillamine and other remittive agents in rheumatoid arthritis: comparisons and interaction.
Penicillamine treatment of rheumatoid arthritis was compared with gold and other remittive agents by reviewing the literature and studying the patients in our penicillamine clinic with respect to their previous responses to chrysotherapy. Penicillamine compares well with other remittive agents with respect to efficacy and toxicity. Prior chrysotherapy does not determine or predict the subsequent efficacy of penicillamine . Patients who reacted adversely to gold tended to react adversely to penicillamine; proteinuria and rash tended to recur.


Near field communications technology and the potential to reduce medication errors through multidisciplinary application.
Patient safety requires optimal management of medications. Electronic systems are encouraged to reduce medication errors. Near field communications (NFC) is an emerging technology that may be used to develop novel medication management systems. An NFC-based system was designed to facilitate prescribing, administration and review of medications commonly used on surgical wards. Final year medical, nursing, and pharmacy students were recruited to test the electronic system in a cross-over observational setting on a simulated ward. Medication errors were compared against errors recorded using a paper-based system. A significant difference in the commission of medication errors was seen when NFC and paper-based medication systems were compared. Paper use resulted in a mean of 4.09 errors per prescribing round while NFC prescribing resulted in a mean of 0.22 errors per simulated prescribing round (P=0.000). Likewise, medication administration errors were reduced from a mean of 2.30 per drug round with a Paper system to a mean of 0.80 errors per round using NFC (P<0.015). A mean satisfaction score of 2.30 was reported by users, (rated on seven-point scale with 1 denoting total satisfaction with system use and 7 denoting total dissatisfaction). An NFC based medication system may be used to effectively reduce medication errors in a simulated ward environment.


Health support program for family members with hospitalized child.
In 2001, we began conducting Health Support Programs on the pediatric ward of Miyazaki Medical College Hospital. The program is designed to help family members who accompany and care for their children who are ill and hospitalized to practice some physical movements for their own benefit. An interview survey was undertaken to clarify the effects and the purpose of the program by evaluating subjective data from program participants, as well as by evaluating changes in participants' blood pressure rates. Findings indicate that the program's effects include "reduction of stress and/or lack of exercise," "refreshing effect," "comfort and/or exhilaration," "relaxation," and "alleviation of physical symptoms." We also have noted that mothers become more aware of their own health issues and that the program offers an opportunity to reexamine their health conditions. Furtherrnore, we have learned that for parents and children who participate together, the program offers a fun environment, and that, on occasion, mothers are the ones who are cared for in the program.


Identification of the N gene protein of bacteriophage lambda.
The N gene protein, pN, of bacteriophage lambda stimulates early gene transcription by allowing mRNA chain elongation to proceed into genes distal to transcription termination sites normally recognized by the Escherichia coli transcription termination protein rho. pN has previously eluded detection on sodium dodecyl sulfate/polyacrylamide gels because of its small size, its instability, and the difficulty of distinguishing pN itself both from host proteins and from other early lambda proteins whose synthesis depends on pN action. These problems have now been overcome and we find that the major form of pN present in crude cell extracts of infected cells has an apparent molecular weight of 13,500. lambdabio256, a deletion-substitution mutant terminating in N, codes for a shorter pN of molecular weight 12,500. A nonsense fragment of 10,500 molecular weight coded by lambdaN(am7) has also been identified. These conclusions are based on examination of the electrophoretic profiles of the proteins synthesized after infection of UV-irradiated E. coli by various lambdaN(-) temperature-sensitive, nonsense, and deletion-substitution mutants. It has also been possible to distinguish pN itself from other early lambda polypeptides by infecting ron(-) cells with either lambdaN(mar) phage allowing pN synthesis but not pN action or lambdaN(am) phage defective in pN synthesis and pN action. Our results together with previous data are discussed with respect to the possible existence of multiple molecular weight forms of pN and the location of the coding sequences in the N gene region.


Liquid chromatography/negative ion atmospheric pressure photoionization mass spectrometry: a highly sensitive method for the analysis of organic explosives.
Gas chromatography/mass spectrometry (GC/MS) is applied to the analysis of volatile and thermally stable compounds, while liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) and liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) are preferred for the analysis of compounds with solution acid-base chemistry. Because organic explosives are compounds with low polarity and some of them are thermally labile, they have not been very well analyzed by GC/MS, LC/APCI-MS and LC/ESI-MS. Herein, we demonstrate liquid chromatography/negative ion atmospheric pressure photoionization mass spectrometry (LC/NI-APPI-MS) as a novel and highly sensitive method for their analysis. Using LC/NI-APPI-MS, limits of quantification (LOQs) of nitroaromatics and nitramines down to the middle pg range have been achieved in full MS scan mode, which are approximately one order to two orders magnitude lower than those previously reported using GC/MS or LC/APCI-MS. The calibration dynamic ranges achieved by LC/NI-APPI-MS are also wider than those using GC/MS and LC/APCI-MS. The reproducibility of LC/NI-APPI-MS is also very reliable, with the intraday and interday variabilities by coefficient of variation (CV) of 0.2-3.4% and 0.6-1.9% for 2,4,6-trinitrotoluene (2,4,6-TNT).


MALDI-TOF mass spectrometry on intact bacteria combined with a refined analysis framework allows accurate classification of MSSA and MRSA.
Fast and reliable detection coupled with accurate data-processing and analysis of antibiotic-resistant bacteria is essential in clinical settings. In this study, we use MALDI-TOF on intact cells combined with a refined analysis framework to demonstrate discrimination between methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus. By combining supervised and unsupervised machine learning methods, we firstly show that the mass spectroscopy data contains strong signal for the clustering of MSSA and MRSA. Then we concentrate on applying supervised learning to extract and verify the important features. A new workflow is proposed that allows for extracting a fixed set of reference peaks so that any new data can be aligned to it and hence consistent feature matrices can be obtained. Also note that by doing so we are able to examine the robustness of the important features that have been found. We also show that appropriate size of the benchmark data, appropriate alignment of the testing data and use of an optimal set of features via feature selection results in prediction accuracy over 90%. In summary, as proof-of-principle, our integrated experimental and bioinformatics study suggests a novel intact cell MALDI-TOF to be of great promise for fast and reliable detection of MRSA strains.


Circulating miRNA29 family expression levels in patients with essential hypertension as potential markers for left ventricular hypertrophy.
The role of microRNAs (miRs,miRNAs) in the pathogenesis of cardiovascular diseases such as hypertension, as well as their diagnostic potential, has recently attracted much attention. However, target-organ damage (TOD) of hypertension remains a substantial challenge due to the lack of specific biomarkers. The present study was undertaken to identify and validate the potential of circulating miRs as novel biomarkers for TOD. We assessed the expression levels of miR-29a, miR-29b, and miR-29c in 54 patients with untreated essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography, office, and ambulatory blood pressure monitoring. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of selected miRs. The expression level of miR-29a, miR-29b, and miR-29c correlations between blood pressure and echocardiography parameters were assessed using the Spearman correlation coefficient. We observed higher expression levels of miR-29a (31.50 ± 3.90 vs 26.55 ± 1.74; p < 0.001), miR-29b (32.31 ± 2.85vs 27.21 ± 1.59; p < 0.001), and miR-29c (31.13 ± 3.42 vs 25.96 ± 1.88; p < 0.001) in hypertensive patients compared with healthy control individuals. In hypertension patients, 25 patients were left ventricular hypertrophy (LVH), miR-29a (32.82 ± 4.06 vs 30.07 ± 3.68; p = 0.012), miR-29b (33.27 ± 2.84 vs 30.71 ± 3.04; p = 0.02), and miR-29c (32.33 ± 3.52 vs 29.55 ± 3.46; p = 0.005) in LVH patients compared with nLVH patients. We found miR-29a, miR-29b, and miR-29c expression levels showed significant positive correlations with office SBP (p = 0.579, p < 0.001; r = 0.576, p < 0.001; r = 0.598, p < 0.001), office DBP (p = 0.243, p = 0.026; r = 0.304, p = 0.005; r = 0.287, p = 0.008), office PP(r = 0.49, p < 0.001; r = 0.442, p < 0.001; r = 0.479, p < 0.001), 24 h mean SBP(p = 0.511, p < 0.001; r = 0.6, p < 0.001; r = 0.533, p < 0.001), 24 h mean DBP (p = 0. 304, p = 0.005; r = 0.283, p = 0.009; r = 0.340, p = 0.002), and 24 h mean PP (p = 0.385, p < 0.001; r = 0. 506, p < 0.001; r = 0.386, p < 0.001), respectively. The expression levels of miR-29a, miR-29b, and miR-29c were positively related to LVMI (r = 0.65, p < 0.001; r = 0.715, p < 0.001; r = 0.654, p < 0.001), respectively. Circulating the miR-29 family may possibly represent potential non-invasive markers of hypertension and TOD in essential hypertensive patients.


Light-actuated high pressure-resisting microvalve for on-chip flow control based on thermo-responsive nanostructured polymer.
A simple light-actuated microvalve using a quartz halogen illuminator with tungsten filament was introduced to manipulate flow path effectively in micro-total analysis systems, which reduces system complexity and the need for on-chip integration. The microvalve device in cyclic olefin copolymer (COC) microchip functions very well based on the thermo-responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), whose pressure-tolerance can be tuned by changing the mechanical strength of polymer monolith inside the microchannel with the choice of suitable amount of monomer and crosslinker. The response time and pressure resistance of the valve can be optimized by the tetrahydrofuran composition in the polymerization mixture as well. Very importantly, the microvalve can withstand the leakage pressure up to around 1350 psi, and its opening and closing response time is only 4.0 and 6.2 s respectively. Microchips with such valves will be very useful in drug delivery, chemical analysis and proteomic analysis.


Efficacy of Botulinum Toxin for Treating Sialorrhea in Neuromuscular Conditions.
Background: Drooling related to bulbar weakness and dysfunction is a common concern in patients with neuromuscular disease. While there are numerous medications to manage sialorrhea, they are often limited by side effects and lack of efficacy. Botulinum toxin has shown to benefit ALS patients in a few studies, but there is scant data on the benefit in other neuromuscular conditions. Objective: To assess the effectiveness of Botulinum toxin in reducing sialorrhea in patients with various neuromuscular disease. Design/Methods: 25 patients (19M, 6F; 54.36 ± 17.09 yr) with documented neuromuscular illness and concern for drooling was followed for 6 weeks after Botulinum toxin injection. These patients had one of the following diagnoses: Duchenne muscular dystrophy (3), myotonic dystrophy (3), oculopharyngeal muscular dystrophy (1), inclusion body myositis (2), primary lateral sclerosis (1), amyotrophic lateral sclerosis (9), spinal muscular atrophy type 2 and 3 (2), spinal-bulbar muscular atrophy (2), and Becker's muscular dystrophy (2). A subjective drooling scale (1: markedly worse, 5: markedly better) and drooling thickness score (0=normal, 100=thick) was calculated on these patients prior to the injection and 4 and 6 weeks after the injection. Botulinum toxin 20-30 units were injected into bilateral parotid gland (70% of the dose) and submandibular gland (30% of the dose). Results: The drooling thickness score at before the injection was 75.2 ± 10.46. At 4 and 6 weeks, average scores reduced to 47.2 ± 6.14 and 18.8 ± 5.26, respectively (p < 0.05). The average pre injection perception about drooling was 3.0 (p < 0.05). The average change in perception was +0.84 and +1.28 at 4 and 6 weeks, respectively, (p < 0.05) implying significant improvement. There were no reported adverse effects. Conclusion: This study provides preliminary evidence for the use of botulinum toxin for refractory sialorrhea for a variety of neuromuscular conditions.


Incubated or superfused rat lung parenchymal strip: a valid preparation for direct measurement of beta-responses.
Responses to the beta-adrenoceptor agonists isoprenaline (Iso) (non selective), salbutamol (Sal) (beta 2-selective) and noradrenaline (NA) (beta 1-selective) were studied on incubated and superfused rat lung strip. In both conditions, Iso and Sal elicited dose-related relaxations of lung strip and these responses were unaffected by the presence of phentolamine (Phen) 10(-5) M. Contractile responses to NA were obtained when it was used alone whereas in the presence of Phen 10(-5) M, NA elicited relaxant responses. The relative potencies of Iso : Sal : NA (plus Phen) were 100 : 20 : 0.69. This demonstrates that beta 2-adrenoceptor is the predominant beta-subtype involved in responses. Propranolol (10(-4) M) completely abolished the relaxant responses to Iso. However, after the addition of Iso tissue responded normally to drugs acting by other mechanisms. Thus, relaxations were obtained with caffeine and contractions with acetylcholine (AcH) or NA. This shows that responses to Iso are mediated only by beta-adrenoceptors. Propranolol and the selective beta-blocking agents butoxamine (beta 2) and atenolol (beta 1) competitively antagonized the effects of Iso. The Schild plots obtained had slopes which did not differ significantly from -1 and mean pA2 values were: 7.82 for propranolol; 6.32 for butoxamine and 5.22 for atenolol. These experiments were carried out in the absence of catecholamine uptake inhibitors, since in a preliminary set of experiments no significant changes of lung strip responses to Iso were observed in the presence of cocaine (10(-5) M) or corticosterone (10(-5) M). In conclusion, it appears that incubated rat lung strip possesses intrinsic tone and, although it cannot be considered a representative preparation of peripheral airways, it provides a valid model for investigating the direct-effects of drugs which act at beta-adrenoceptors.


Intramural injection of biodegradable microspheres as a local drug-delivery system to inhibit neointimal thickening in a rabbit model of balloon angioplasty.
Restenosis remains the major limitation of coronary angioplasty. The objective of this study was to develop microspheres able to be delivered at the angioplasty site for long-term drug release and to test their effects in a model of balloon angioplasty. Polylactic-co-glycolide acid microspheres (5-10 microm in diameter) were prepared by using an oil-in-water emulsion-solvent evaporation method. In vitro experiments with hydrocortisone-loaded microspheres revealed a hydrocortisone release for 4 weeks. We studied the in vivo effect of injection of microspheres into the arterial wall of New Zealand White rabbits by using a perforated balloon. Deep penetration of microspheres in the arterial wall was documented immediately after angioplasty. Intimal hyperplasia was assessed in iliac arteries 4 weeks after angioplasty. The morphometric analysis was performed in four groups of animals; the first group was subjected only to conventional angioplasty (control, n = 10), whereas the other three groups after conventional angioplasty were received perforated balloon angioplasty with saline (n = 10), microspheres (n = 10), or hydrocortisone-loaded microspheres (n = 7). Intramural injection of saline did not induce greater intimal hyperplasia compared with control (0.17 +/- 0.03 vs. 0.18 +/- 0.03 mm2, respectively). Microspheres injection was associated with a trend toward a greater degree of intimal hyperplasia that did not reach statistical significance. Hydrocortisone-loaded microspheres were associated with a significant reduction in intimal hyperplasia compared with unloaded microspheres (0.16 +/- 0.02 vs. 0.26 +/- 0.03 mm2, respectively). The polylactic-co-glycolide acid microspheres are well tolerated, easily injected into the arterial wall, and the increase of intimal hyperplasia is easily inhibited by release of hydrocortisone for 4 weeks after initial injury.


The role of muscle in the development and differentiation of spinal motoneurons: in vitro studies.
Results of in vivo experiments suggest that muscle cells, and probably other cell types, produce factors upon which motoneurons depend for survival and normal development. Most attempts to characterize such factors have used cultures of enriched or identified motoneurons, and have studied effects of muscle-derived substances on survival, neurite outgrowth and acetylcholine synthesis. Results from different laboratories vary widely, both in terms of the estimated abundance of motoneurons as a fraction of total dissociated spinal cord and in terms of the molecular weight estimates for factors tentatively proposed as candidate motoneuron growth factors. Nevertheless, there are several independent reports of 40-55 kDa species affecting each of the three parameters of spinal neuron development. We have begun to characterize one of these, partially purified from extracts of denervated muscle on the basis of its neurite-promoting activity for a subpopulation of 4.5-day embryonic chicken spinal neurons. Comparison between the factors under study in different systems, and confirmation of their importance in vivo, await the preparation of specific blocking antibodies.


[Early diagnosis of painful diabetic neuropathy by corneal confocal microscopy].
To explore the early diagnosis of painful diabetic neuropathy by observing the alterations in corneal innervation with corneal confocal microscopy. Fifty aged-matched control subjects, 45 diabetic neuropathy including 20 subjects with type 2 diabetes and painful neuropathy (PDN) and 25 subjects with type 2 diabetes and painless neuropathy (PLN) underwent detailed evaluations of their neuropathic symptoms. The examinations of visual analogue scale (VAS), contact heat evoked potential (CHEP) and corneal confocal microscopy (CCM) were employed to quantify small nerve fiber pathology and their degree of pain. We evaluated the use of a novel in vivo technique CCM in assessing painful neuropathy compared to CHEP. The results of CHEP and CCM were significantly different in the diabetic groups compared to controls. T test indicated patients with PDN had significant reductions in corneal nerve fiber length (NFL), nerve branch density (NBD), nerve fiber density (NFD) and increased corneal nerve fiber tortuosity (NFT) (13 ± 4 vs 11 ± 3, 62 ± 24 vs 47 ± 19, 32 ± 13 vs 22 ± 8, 2.8 ± 0.9 vs 3.2 ± 0. 8; t = 40.43, 27.27, 42.21, 194.39, P = 0.039, 0.011, 0.017, 0.006), (t = 40.43, 27.27, 42.21, 194.39, P = 0.039, 0.011, 0.017, 0.006). Pearson's correlation analysis showed pain severity correlated significantly with cornea nerves damage. VAS correlated significantly with NFL, NBD, NFD and NFT (r = 0.782, -0.376, -0.504, all P < 0.001). CCM provides a sensitive and noninvasive modality of detecting small nerve fiber damage in patients with PFN. And these abnormalities may be a sensitive predictor for the presence of pain in diabetic neuropathy patients.


Aptamers as analytical reagents.
Many important analytical methods are based on molecular recognition. Aptamers are oligonucleotides that exhibit molecular recognition; they are capable of specifically binding a target molecule, and have exhibited affinity for several classes of molecules. The use of aptamers as tools in analytical chemistry is on the rise due to the development of the "systematic evolution of ligands by exponential enrichment" (SELEX) procedure. This technique allows high-affinity aptamers to be isolated and amplified when starting from a large pool of oligonucleotide sequences. These molecules have been used in flow cytometry, biosensors, affinity probe electrophoresis, capillary electrochromatography, and affinity chromatography. In this paper, we will discuss applications of aptamers which have led to the development of aptamers as chromatographic stationary phases and applications of these stationary phases; and look towards future work which may benefit from the use of aptamers as stationary phases.


Systems biology for battling rheumatoid arthritis: application of the Entelos PhysioLab platform.
A large-scale mathematical model, the Entelos Rheumatoid Arthritis (RA) PhysioLab platform, has been developed to describe the inflammatory and erosive processes in afflicted joints of people suffering from RA. The platform represents the life cycle of inflammatory cells, endothelium, synovial fibroblasts, and chondrocytes, as well as their products and interactions. The interplay between these processes culminates in clinically relevant measures for inflammation and erosion. The simulation model is deterministic, which allows tracing back the mechanism of action for a particular simulation result. Different patient phenotypes are represented by different virtual patients. The RA PhysioLab platform has been used to systematically and quantitatively study the predicted therapeutic effect of modulating several molecular targets, which resulted in a ranking of putative drug targets and a workflow to confirm the simulations experimentally. In addition, critical pathways were identified that drive the predicted disease outcome. Within these pathways, targets were identified from public literature that were not previously associated with arthritis. The model provides insights into the biology of RA and can be used as a platform for hypothesis-driven research. Case studies of therapies directed against IL-12 and IL-15 illustrate the approach, with emphasis on the analysis of system dynamics.


An Investigation on Ground Electrodes of Capacitive Coupling Human Body Communication.
Utilizing the body surface as the signal transmission medium, capacitive coupling human body communication (CC-HBC) can achieve a much higher energy efficiency than conventional wireless communications in future wireless body area network (WBAN) applications. Under the CC-HBC scheme, the body surface serves as the forward signal path, whereas the backward path is formed by the capacitive coupling between the ground electrodes (GEs) of transmitter (TX) and receiver (RX). So the type of communication benefits from a low forward loss, while the backward loss depending on the GE coupling strength dominates the total transmission loss. However, none of the previous works have shown a complete research on the effects of GEs. In this paper, all kinds of GE effects on CC-HBC are investigated by both finite element method (FEM) analysis and human body measurement. We set the TX GE and RX GE at different heights, separation distances, and dimensions to study the corresponding influence on the overall signal transmission path loss. In addition, we also investigate the effects of GEs with different shapes and different TX-to-RX relative angles. Based on all the investigations, an analytical model is derived to evaluate the GE related variations of channel loss in CC-HBC.


Analytical solutions of drying in porous media for gravity-stabilized fronts.
We develop a mathematical model for the drying of porous media in the presence of gravity. The model incorporates effects of corner flow through macroscopic liquid films that form in the cavities of pore walls, mass transfer by diffusion in the dry regions of the medium, external mass transfer over the surface, and the effect of gravity. We consider two different cases: when gravity opposes liquid flow in the corner films and leads to a stable percolation drying front, and when it acts in the opposite direction. In this part, we develop analytical results when the problem can be cast as an equivalent continuum and described as a one-dimensional (1D) problem. This is always the case when gravity acts against drying by opposing corner flow, or when it enhances drying by increasing corner film flow but it is sufficiently small. We obtain results for all relevant variables, including drying rates, extent of the macroscopic film region, and the demarkation of the two different regimes of constant rate period and falling rate period, respectively. The effects of dimensionless variables, such as the bond number, the capillary number, and the Sherwood number for external mass transfer are investigated. When gravity acts to enhance drying, a 1D solution is still possible if an appropriately defined Rayleigh number is above a critical threshold. We derive a linear stability analysis of a model problem under this condition that verifies front stability. Further analysis of this problem, when the Rayleigh number is below critical, requires a pore-network simulator which will be the focus of future work.


Favorable changes in lipid metabolism and cardiovascular parameters after icodextrin use in peritoneal dialysis patients.
Better control of cardiovascular function in patients on peritoneal dialysis (PD) is critical because PD patients have a tendency to overhydration, which has been proved to be associated with cardiovascular and patient outcome. In the general population, lipid metabolism is also considered to be an important indicator of future cardiovascular events. Icodextrin has been used to improve ultrafiltration volume without increasing dextrose load. We therefore expected that parameters of lipid metabolism and cardiovascular function could both be improved, or at least maintained, after icodextrin use in PD patients. We therefore analyzed those parameters in 14 prevalent PD patients who required a switch from dextrose to icodextrin solution for the long dwell at 1 year before the switch, at the time of the switch, and at 1 and 2 years after the switch. In the study patients, cardiovascular remodeling evaluated by ultrasonographic left ventricular mass index was diminished, but the intima media area of the cervical artery was elevated after icodextrin use. Intima media thickness did not change over time. Biochemical indices such as brain natriuretic peptide, atrial natriuretic peptide, lipoprotein A, total cholesterol, and triglycerides were all lower after icodextrin use. These results indicate that icodextrin has the potential to improve lipid metabolism, volemic status, and cardiac hypertrophy in prevalent PD patients. However, atherosclerotic vascular change is refractory to improvement.


Review of published studies of orally administered asbestos.
There has been great public concern about the adverse health effects resulting from the presence of asbestos fibers in municipal drinking water supplies. This article reviews and summarizes the experimental findings of 11 published papers that have evaluated the carcinogenic potential of asbestos following its ingestion. The long-term, high-level ingestion of various types of asbestos fibers in more than one animal species failed to produce any definite, reproducible, organ-specific carcinogenic effect.


Total contact casting: its effect on contralateral plantar foot pressure.
Total contact casts (TCC) are commonly used in the treatment of neuropathic ulcers of the foot related to diabetes. However, casts may alter the gait pattern and increase loading parameters of the contralateral foot. We determined the effects of total contact casting on plantar pressure parameters for the contralateral extremity. Ten healthy subjects consented to walk, for four consecutive trials, along a 25-meter corridor while wearing a running shoe (RS), fiberglass TCC and a traditional TCC. Parameters of peak pressure, contact time and pressure-time integrals for the contralateral forefoot, metatarsal V area and heel were recorded using the novel Pedar system of plantar pressure measurement. Repeated measures analyses of variance (footwear x region) were used to analyze the recorded parameters with post-hoc Tukeys selected for follow-up analysis. Each of the measured parameters for the forefoot, lateral foot over metatarsal V and heel regions on the contralateral foot were similar regardless of footwear worn. Use of a TCC does not appear to affect contralateral foot contact pressure parameters and likely does not increase the risk of contralateral ulceration.


Functional dissociations in top-down control dependent neural repetition priming.
Little is known about the neural mechanisms underlying top-down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task. In the study phase subjects were required to respond to either pictures or words that were presented superimposed on each other. In the repetition phase only words were presented that were new, previously attended or ignored, or picture names that were derived from previously attended or ignored pictures. Relative to new words we found repetition priming for previously attended words. Previously ignored words showed a reduced priming effect, and there was no significant priming for pictures repeated as picture names. Brain imaging data showed that neural priming of words in the left prefrontal cortex (LIPFC) and left fusiform gyrus (LOTC) was affected by attention, semantic compatibility of superimposed stimuli during study and cross-modal priming. Neural priming reduced for words in the LIPFC and for words and pictures in the LOTC if stimuli were previously ignored. Previously ignored words that were semantically incompatible with a superimposed picture during study induce increased neural priming compared to semantically compatible ignored words (LIPFC) and decreased neural priming of previously attended pictures (LOTC). In summary, top-down control induces dissociable effects on neural priming by attention, cross-modal priming and semantic compatibility in a way that was not evident from behavioral results.


Perceptual grouping in shape from shading.
We report on the reversal of asymmetry in visual-search tasks with shaded items. Previous studies have suggested that the target of a bottom-lit disk among distractors of top-lit disks is detected in a rapid and parallel manner, but not vice versa. However, in this study, we have shown that the compound items of top-lit disks were searched more quickly than those composed of bottom-lit disks where the items had to be segregated from their background. By modulating the inter-element distances, we confirmed that the reversal of search asymmetry cannot be due to the grouping of items. Further, we showed that the regions of the top-lit disks were perceived as figure more consistently than those of bottom-lit disks. The results indicate that the boundary assignment to the compound items of the top-lit disks enhances the segregation of search items from the background, and that the search mechanism may access the relatively higher representation that includes figure-ground relations.


Effect of gestational diabetes on blood sugar, liver and renal function tests.
Type 2 diabetes adversely affects the liver and kidney function tests. This study was conducted to determine that either the liver and kidney functions are disturbed in the patients having gestational diabetes mellitus (GDM). One hundred and three women with GDM, and 97 healthy pregnant women (HPW) in their third trimester were registered in the Obs/Gyn Unit of Khyber Teaching Hospital, Peshawar in the time period Apr-Sep 2012. Blood sugar level, glycosylated haemoglobin status HbAlc, haemoglobin concentration, platelet count, liver function tests including alanine amino transferase (ALT), alkaline phosphatase (ALP) and bilirubin, renal function tests including urea and creatinine were determined. Blood glucose level and HbAlc of GDM was significantly higher (p < 0.001) than HPW. Fasting and random blood glucose and HbA1c of GDM and HPW were 110.90 +/- 9.10 vs 84.68 +/- 7.01 mg/dl, 148.53 +/- 7.21 vs 124.42 +/- 9.46 mg/dl and 6.49 +/- 1.20 vs 4.99 +/- 0.55 respectively. Haemoglobin percentage, platelet count, ALT, ALP, serum bilirubin and urea were not significantly different among the two groups. However, mean serum creatinine (0.82 +/- 0.32 mg/dl) in GDM was significantly higher (p < 0.05) than in HPW (0.74 +/- 0.15 mg/dl). In gestational diabetes the LFTs may not be disturbed, however serum creatinine value is increased.


Synthesis, characterisation and thermo-physical properties of highly stable graphene oxide-based aqueous nanofluids for potential low-temperature direct absorption solar applications.
Two types of highly stable 0.1% graphene oxide-based aqueous nanofluids were synthesised and investigated. The first nanofluid (GO) was prepared under the influence of ultrasonic irradiation without surfactant. The second nanofluid was treated with tetra ethyl ammonium hydroxide to reduce the graphene oxide to form reduced graphene oxide (RGO) during ultrasonic irradiation. The GO and RGO powders were characterised by various techniques such as field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction and Raman. Also UV-visible absorption spectroscopy was carried out and band gap energies were determined. Optical band gap energies for indirect transitions ranged from 3.4 to 4.4 eV and for direct transitions they ranged between 2.2 and 3.7 eV. Thermal conductivity measurements of the GO-based aqueous nanofluid revealed an enhancement of 9.5% at 40 °C compared to pure water, while the RGO-based aqueous nanofluid at 40 °C had a value 9.23% lower than pure water. Furthermore, the photothermal response of the RGO-based aqueous nanofluid had a temperature increase of 13.5 °C, (enhancement of 60.2%) compared to pure water, the GO-based aqueous nanofluid only displayed a temperature rise of 10.9 °C, (enhancement of 46.6%) after 20 min exposure to a solar irradiance of 1000 W m-2. Both nanofluid types displayed good long-term stability, with the GO-based aqueous nanofluid having a zeta potential of 30.3 mV and the RGO-based aqueous nanofluid having a value of 47.6 mV after 6 months. The good dispersion stability and photothermal performance makes both nanofluid types very promising working fluids for low-temperature direct absorption solar collectors.


Review of Hyperkalemia in End Stage Renal Disease.
Potassium balance is maintained in the body by balancing the intake with the excretion and the transcellular shifts of potassium. Excretion of potassium is mainly renal as the contribution of the colon to the net potassium secretion of the colon to the net potassium secretion is trivial in patients with normal renal function. As the majority of potassium excretion is renal, it is not surprising to note that patients with end stage renal disease (ESRD) are at an increased risk of developing hyperkalemia in ESRD patients has been estimated to be 3-5%. Maintenance of a stable serum potassium level in patients with ESRD is crucial. We will review the various measures for the management and prevention of hyperkalemia in ESRD patients such as dietary restrictions, dialysis and drugs enhancing extra renal elimination of potassium.


Serum testosterone measurements.
Serum testosterone and especially free testosterone is one of the parameters commonly used to evaluate androgen excess or deficiency. The authors equilibrated serum samples with 14C-labeled testosterone followed by an ammonium sulfate precipitation to compare the "apparent free testosterone concentration" with "total" serum testosterone concentration in the following populations: normal males and females; females presenting with gynecologic problems, particularly hirsutism and/or virilization; and males and females on maintenance hemodialysis. Total serum testosterone for each specimen was assayed with five different commercially available RIA kits encompassing a variety of technics: direct assay technics, assays utilizing extraction procedures prior to RIA; tritium-labeled tracer as well as iodine-labeled tracers. Clinical correlations improve strikingly when apparent free testosterone concentrations rather than total serum testosterone concentrations are used.


Noncanonical autophagy in dendritic cells triggers CNS autoimmunity.
Reactivation and expansion of myelin-reactive CD4+ T cells within the central nervous system (CNS) are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We demonstrated that accumulation of myelin-specific CD4+ T cells within the CNS and subsequent clinical disease development require autophagy related (ATG) protein-dependent phagocytosis in dendritic cells (DCs). Genetic ablation of this pathway impairs presentation of myelin-associated antigen following phagocytosis of injured, phosphatidylserine-exposing oligodendroglial cells. Thus, DCs use ATG-dependent phagocytosis for enhanced presentation of myelin antigen, thereby linking oligodendrocyte injury with antigen processing and T cell-pathogenicity during autoimmune CNS inflammation.


Smaller building blocks form larger assemblies: aggregation behavior of biaryl-based dendritic facial amphiphiles.
Synthesis and micellar behavior of biaryl-based benzyl ether dendritic molecules prepared from a new biaryl building block are described. The key objective of the study is to tune the size of individual dendritic molecules and investigate its effect on aggregation behavior of the resulting micelle-like assemblies. We show that the functional group placement in the building block influences flexibility of the dendritic backbone and interior volume available for packing the hydrophobic groups, which is reflected in different aggregation behavior and aggregate size of the two types of micellar assemblies.


Internal multiplicity in emotion-focused psychotherapy.
Emotion-focused therapy regards the client's problems as indications that the inner dialogue among voices of the self has become fractious, often because one or more voices have developed emotion schemes that are based on maladaptive emotions. The goal of therapy is to transform such maladaptive emotions into more adaptive ones. The therapist's interventions focus on facilitating the client's process of dialogue among the voices of the self and guiding the client toward experiencing of adaptive emotions. These new experiences contribute to a dynamic shift in the relation among the voices. A case study illustrates how a male client's rage and hopelessness transformed into assertiveness and tenderness as the various voices learned to respect and help each other within the self.


Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantation.
The prevalence and prognostic relevance of recurrent gains of CKS1B (cyclin kinase subunit 1B) gene at chromosome 1q21 region was investigated by interphase fluorescence in situ hybridisation in a cohort of 99 multiple myeloma (MM) patients treated with intensive chemotherapy followed by autologous stem cell transplantation. CKS1B amplification (3-8 CKS1B signals) was detected in 31of 99 (31%) patients and was associated with deletions of p53 (P = 0.003) and 13q (P = 0.039) but not with translocation t(11;14) or t(4;14). CKS1B amplification was associated with bone marrow plasmacytosis (P = 0.02), but there was no correlation with patient age, gender, disease stage, lytic bone lesions, albumin, creatinine, C-reactive protein or beta-2 microglobulin levels. Patients with CKS1B amplification had a significantly shorter progression-free survival than those without such amplification (18.5 vs. 25.7 months, P = 0.035). Likewise, a shorter overall survival (44.8 months vs. not reached) was observed; however, the difference did not reach statistical significance (P = 0.20). Seven patients had paired bone marrows obtained at diagnosis and at relapse, the percentage of cells with CKS1B amplification and the level of amplification were significantly increased in the relapse marrows. In this cohort of patients, CKS1B was frequently amplified in MM and may represent genetic instability associated with disease progression.


Erosive effects of common beverages on extracted premolar teeth.
Dental erosion is highly prevalent today, and acidic drinks are thought to be an important cause. The aim of the present investigation was to determine the erosive potential of a range of common beverages on extracted human teeth. The beverages were tested for their individual pHs using a pH meter. The clinical effects of the most erosive beverages were determined by the degree of etching and Vickers microhardness of enamel. The results showed that many common beverages have pHs sufficiently low to cause enamel erosion. Lime juice concentrate (pH 2.1) had the lowest pH, followed by Coca-cola and Pepsi (both with pH 2.3) and Lucozade (pH 2.5). The erosive potential of these beverages was demonstrated by the deep etching of the enamel after five minutes. The Vickers Hardness of enamel was reduced by about 50 per cent in the case of lime juice (p < 0.001) and 24 per cent in the case of Coca-cola (p < 0.004). Addition of saliva to 50 per cent (v/v) of Coca-cola completely reversed the erosive effects on the enamel. Although only a few of the beverages with the lowest pHs were tested, the present study showed that the most acidic drinks had the greatest erosive effects on enamel. While saliva was protective against erosion, relatively large volumes were required to neutralize the acidity.


Phosphorylation of estrogen receptor-alpha at Ser167 is indicative of longer disease-free and overall survival in breast cancer patients.
Ser(167) was first identified as a major phosphorylation site of the estrogen receptor -alpha (ER) positive in the MCF7 breast cancer cell line. Subsequent studies have shown that Ser(167) phosphorylation is important in the regulation of ER activity and have identified p90RSK and AKT as protein kinases that phosphorylate Ser(167). The purpose of this study was to determine the importance of Ser(167) phosphorylation in breast cancer progression. Immunohistochemical staining of primary breast cancer biopsies (n = 290) was carried out using antibodies specific for ER phosphorylated at Ser(167) and for phosphorylated p44/p42 mitogen-activated protein kinase (MAPK), phosphorylated p90RSK, and phosphorylated AKT. In ER-positive breast cancer patients, Ser(167) phosphorylation was associated with low tumor grade (P = 0.011), lymph node negativity (P = 0.034), and relapse-free (P = 0.006) and overall (P = 0.023) survival. Further, Ser(167) phosphorylation was strongly associated with phosphorylated p90RSK (P < 0.001), previously shown to phosphorylate Ser(167) in vitro, as well as being associated with phosphorylated MAPK (P < 0.0005). The activities of both kinases also seemed to be indicative of better prognosis. There was, however, no association between HER2 positivity and Ser(167) phosphorylation nor were the activities of MAPK or p90RSK associated with HER2 status, suggesting that other cell surface receptors may be important in regulating these activities in breast cancer. These findings show that phosphorylation at Ser(167) of ER predicts for likelihood of response of ER-positive breast cancer patients to endocrine therapies.


The proliferation of mature oligodendrocytes in vitro is stimulated by basic fibroblast growth factor and inhibited by oligodendrocyte-type 2 astrocyte precursors.
Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) are mitogens for bipotential oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells. We investigated the mitogenic effect of these growth factors on quiescent mature oligodendrocytes (OL) expressing myelin basic protein (MBP) in OL cultures that were treated for 3 days with cytosine arabinoside (ARA-C) in order to kill O-2A precursors which divide in chemically defined medium. After treatment with ARA-C proliferation decreased and O-2A precursors identified with A2B5 monoclonal antibody were nearly undetectable. After exposure of mature OL to bFGF, cell proliferation increased markedly within 24 hr. PDGF had a much weaker effect. Cultures treated with ARA-C for 3 days and then with bFGF for the next 24 hr and incubated with BrdU for the last 2 hr before the end of the experiment were immunolabeled with anti-MBP or A2B5 and anti-bromodeoxyuridine (BrdU) antibodies. Eighty-seven percent of the cells were MBP+, 10% were both MBP+ and BrdU+, and none was A2B5+ BrdU+, showing that at least a part of the population of mature MBP+ OL retains the ability to reenter the cell cycle in vitro. Since mature OL did not proliferate in response to bFGF in the cultures not treated with ARA-C, i.e., in the presence of O-2A progenitors, we assumed that these precursors were responsible for the lack of mitogenic effect of bFGF on MBP+ OL in such conditions. Conditioned medium from O-2A precursors almost halved the bFGF-induced OL proliferation after treatment with ARA-C, suggesting that O-2A progenitors control the proliferation of a subpopulation of mature OL (possibly young mature OL) via the secretion of active molecule(s).


Charge-Displacement Analysis via Natural Orbitals for Chemical Valence in the Four-Component Relativistic Framework.
We have recently introduced a simple yet powerful tool for analyzing quantitatively the coordination bond in terms of the donation and back-donation constituents of the Dewar-Chatt-Duncanson model. Our approach is based on the decomposition, via natural orbitals for chemical valence (NOCV), of the so-called charge-displacement (CD) function into additive chemically meaningful components (Bistoni et al. J. Chem. Phys. 2015, 142, 084112 ). The method, referred to as NOCV/CD, provides clear-cut measures of donation and back-donation charge flows following bond formation, and its robustness has been demonstrated by a tight correlation of the related charge-transfer estimates with experimental observables. In this paper we extend the NOCV/CD analysis scheme to the four-component relativistic framework, which includes spin-orbit coupling variationally. This formalism is incorporated into a recently developed, highly efficient parallel version of the relativistic Dirac-Kohn-Sham (DKS) program BERTHA (Rampino et al. J. Chem. Theory Comput. 2014, 10, 3766-3776 ). We test the accuracy and numerical stability of this new implementation through the analysis of the convergence properties of the basis sets employed to expand the DKS spinor solution and those used to linearize the electronic density in the density-fitting algorithm speeding up the evaluation of the DKS matrix. An illustration of NOCV/CD analysis in the relativistic framework is also given through a study of the metal-carbonyl coordination bond in a series of [M-CO]+ (M = Cu, Ag, Au) complexes of group 11 metals, where relativistic effects, including spin-orbit coupling, are found to play an important role.


[A three-year follow-up observation of a pedigree of maturity onset diabetes of the young caused by a novel mutation of glucokinase and literature review].
Objective: To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK). Methods: The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD. Results: Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband's father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline. Conclusions: Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.


MicroRNAs: an epigenetic tool to study celiac disease.
This article summarizes recent findings on the role of microRNAs (miRNAs) in biological processes associated with the regulation of chronic inflammation and autoimmunity. miRNAs are small non-coding RNA molecules that have been recently emerged as a new class of modulators of gene expression at the post-transcriptional level. MiRNAs bind to complementary sequences of specific targets of messengers RNA, which can interfere with protein synthesis. We reviewed studies that evaluated the expression patterns of miRNAs in different autoimmune diseases, especially in celiac disease (CD). CD is a chronic enteropathy triggered by gluten proteins, characterized by altered immune responses in genetically susceptible individuals that results in damage to the bowel mucosa. CD has a high prevalence and an effective treatment by a specific diet ("gluten free diet"). Genetic factors confer susceptibility but do not explain the whole disease, suggesting that environmental factors do play a relevant role in the development of the condition.The evaluation of the potential role of miRNA is of particular interest in CD given that these epigenetic mechanisms in the pathogenesis of autoimmune and inflammatory diseases have been recently described. Improving our understanding of miRNAs in CD will contribute to clarify the role of altered epigenetic regulation in the development and course of this disease.


Serum paraoxonase levels in gastric cancer.
Serum paraoxonase (PON) is a calcium-dependent esterase that is known to contribute to the antioxidant protection conferred by high-density lipoprotein (HDL) on low-density lipoprotein (LDL) oxidation. Serum PON activity was shown to be reduced in patients with diseases such as myocardial infarction, diabetes mellitus, etc in comparison to healthy subjects. However, the relation of serum PON levels to cancer is still not known. So, we intended to measure serum PON, HDL, LDL and very low-density lipoprotein (VLDL) levels and to investigate the relation of serum PON to plasma lipoproteins in the patients with gastric cancer. We measured serum PON, HDL, LDL and VLDL levels in 20 patients with gastric cancer and in 20 age-and gender-matched healthy controls. We investigated the relationship between PON and HDL, PON and LDL, and PON and VLDL. Serum HDL levels were lower in the patients than in controls (33.10 +/- 7.75 mg/dL, and 47.30 +/- 6.65 mg/dL, respectively) (p<0.0001). Serum VLDL levels were lower in the patients than in controls (21.65 +/- 6.92 mg/dL, and 33.10 +/- 6.09 mg/dL, respectively) (p<0.0001). Serum LDL levels measured in the patients were not significantly different from those of the controls. Serum PON levels were lower in the patients than in controls (67.10 +/- 17.92 U/L, and 87.50 +/- 23.39 U/L, respectively) and there was a positive correlation between serum PON and HDL levels (r: 0.52, p<0.05). We concluded that the patients with gastric cancer had low serum PON, HDL, and VLDL levels compared to healthy controls. The importance of PON as a predictive risk factor for cancer should be assessed in future studies.


Food waste and the food-energy-water nexus: A review of food waste management alternatives.
Throughout the world, much food produced is wasted. The resource impact of producing wasted food is substantial; however, little is known about the energy and water consumed in managing food waste after it has been disposed. Herein, we characterize food waste within the Food-Energy-Water (FEW) nexus and parse the differential FEW effects of producing uneaten food and managing food loss and waste. We find that various food waste management options, such as waste prevention, landfilling, composting, anaerobic digestion, and incineration, present variable pathways for FEW impacts and opportunities. Furthermore, comprehensive sustainable management of food waste will involve varied mechanisms and actors at multiple levels of governance and at the level of individual consumers. To address the complex food waste problem, we therefore propose a "food-waste-systems" approach to optimize resources within the FEW nexus. Such a framework may be applied to devise strategies that, for instance, minimize the amount of edible food that is wasted, foster efficient use of energy and water in the food production process, and simultaneously reduce pollution externalities and create opportunities from recycled energy and nutrients. Characterization of FEW nexus impacts of wasted food, including descriptions of dynamic feedback behaviors, presents a significant research gap and a priority for future work. Large-scale decision making requires more complete understanding of food waste and its management within the FEW nexus, particularly regarding post-disposal impacts related to water.


Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematosus and other autoimmune diseases.
Expression of the highly conserved 90 kDa heat shock protein (Hsp90) is elevated in the peripheral blood mononuclear cells of approximately 25% of patients with SLE. Conflicting data have been published about the frequency of antibodies to Hsp90 with the previous methodology using a complex Western blot system. We now describe an ELISA to measure autoantibodies to Hsp90 and Hsp70 in SLE patients, healthy controls and patients with a variety of autoimmune rheumatic diseases. IgG and IgM antibodies were elevated in 26 and 35% of SLE patients, respectively. These results show autoantibodies to Hsp90 (but not Hsp70) are elevated in a significant proportion of patients with SLE (P < 0.025) compared to healthy controls; and that those with raised antibody levels were more likely to have renal disease and a low C3 level (P < 0.02).


Future warmer seas: increased stress and susceptibility to grazing in seedlings of a marine habitat-forming species.
Increases in seawater temperature are expected to have negative consequences for marine organisms. Beyond individual effects, species-specific differences in thermal tolerance are predicted to modify species interactions and increase the strength of top-down effects, particularly in plant-herbivore interactions. Shifts in trophic interactions will be especially important when affecting habitat-forming species such as seagrasses, as the consequences on their abundance will cascade throughout the food web. Seagrasses are a major component of coastal ecosystems offering important ecosystem services, but are threatened by multiple anthropogenic stressors, including warming. The mechanistic understanding of seagrass responses to warming at multiple scales of organization remains largely unexplored, especially in early-life stages such as seedlings. Yet, these early-life stages are critical for seagrass expansion processes and adaptation to climate change. In this study, we determined the effects of a 3 month experimental exposure to present and predicted mean summer SST of the Mediterranean Sea (25°C, 27°C, and 29°C) on the photophysiology, size, and ecology (i.e., plant-herbivore interactions) of seedlings of the seagrass Posidonia oceanica. Warming resulted in increased mortality, leaf necrosis, and respiration as well as lower carbohydrate reserves in the seed, the main storage organ in seedlings. Aboveground biomass and root growth were also limited with warming, which could hamper seedling establishment success. Furthermore, warming increased the susceptibility to consumption by grazers, likely due to lower leaf fiber content and thickness. Our results indicate that warming will negatively affect seagrass seedlings through multiple direct and indirect pathways: increased stress, reduced establishment potential, lower storage of carbohydrate reserves, and increased susceptibly to consumption. This work provides a significant step forward in understanding the major mechanisms that will drive the capacity of seagrass seedlings to adapt and survive to warming, highlighting the potential additive effects that herbivory will have on ultimately determining seedling success.


Toxic effects of sodium dodecyl sulfate on planarian Dugesia japonica.
Sodium dodecyl sulfate (SDS) is an anionic surfactant, which is widely used in various fields in human life. However, SDS discharged into the water environment has a certain impact on aquatic organisms. In this study, planarian Dugesia japonica (D. japonica) was used to identify the toxic effects of SDS. A series of SDS solutions with different concentrations were used to treat planarians for the acute toxicity test , and the results showed that the semi-lethal concentration (LC50) of SDS to D. japonica at 24 h, 48 h, 72 h, and 96 h were 4.29 mg/L, 3.76 mg/L, 3.45 mg/L, and 3.20 mg/L respectively. After the planarians were exposed to 0.5 mg/L and 1.0 mg/L SDS solutions for 1, 3, and 5 days, the activities of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) content were measured to detect the oxidative stress and lipid peroxidation in planarians. Random amplified polymorphic DNA (RAPD) analysis was performed to detect the genotoxicity caused by SDS to planarians. The results showed that the activities of SOD, CAT, and MDA content increased after the treatment, indicating that SDS induced oxidative stress in planarians. RAPD analysis showed that the genomic template stability (GTS) values of planarians treated by 0.5 mg/L and 1.0 mg/L SDS for 1, 3, and 5 days were 67.86%, 64.29%, 58.93%, and 64.29%, 60.71%, 48.21%, respectively. GTS values decreased with the increasing of SDS concentration and exposure time, indicating that SDS had genotoxicity to planarians in a time and dose-related manner. Fluorescent quantitative PCR (qPCR) was used to investigate the effects of SDS on gene expression of planarians. After the planarians were exposed to 1.0 mg/L SDS solution for 1, 3, and 5 days, the expression of caspase3 was upregulated, and that of piwiA, piwiB, PCNA, cyclinB, and RAD51 were downregulated. These results suggested that SDS might induce apoptosis, affect cell proliferation, differentiation, and DNA repair ability of planarian cells and cause toxic effects on planarian D. japonica.


Atopic dermatitis as an actual problem of modern allergology.
The etiology of atopic dermatitis is multifactorial and therefore therapy design of this disease should be complex and should cover all sites of pathologic process that underlies this disease. The therapy of atopic dermatitis is presented according to actual state. The importance of topical therapy is held considering patient's age, stage of the disease, dispersion and severity of the clinical manifestation, effect and tolerance of the previous treatments.


Lectin Sequence Distribution in QTLs from Rice (Oryza sativa) Suggest A Role in Morphological Traits and Stress Responses.
Rice (Oryza sativa) is one of the main staple crops worldwide but suffers from important yield losses due to different abiotic and biotic stresses. Analysis of quantitative trait loci (QTL) is a classical genetic method which enables the creation of more resistant cultivars but does not yield information on the genes directly involved or responsible for the desired traits. Lectins are known as proteins with diverse functions in plants. Some of them are abundant proteins in seeds and are considered as storage/defense proteins while other lectins are known as stress-inducible proteins, implicated in stress perception and signal transduction as part of plant innate immunity. We investigated the distribution of lectin sequences in different QTL related to stress tolerance/resistance, morphology, and physiology through mapping of the lectin sequences and QTL regions on the chromosomes and subsequent statistical analysis. Furthermore, the domain structure and evolutionary relationships of the lectins in O. sativa spp. indica and japonica were investigated. Our results revealed that lectin sequences are statistically overrepresented in QTLs for (a)biotic resistance/tolerance as well as in QTLs related to economically important traits such as eating quality and sterility. These findings contribute to the characterization of the QTL sequences and can provide valuable information to the breeders.


Comparison of microbial communities in swine manure at various temperatures and storage times.
This study was designed to investigate the effects of temperature and storage time on the evolution of bacterial communities in swine manure. Manure was stored at -20°C, 4°C, 20°C, or 37°C and sampled at 7-day intervals over 28 days of storage, for a total of 5 time points. To assess the bacterial species present, 16S ribosomal RNA gene sequences were analyzed using pyrosequencing. After normalization, 113,934 sequence reads were obtained, with an average length of 466.6±4.4 bp. The diversity indices of the communities reduced as temperature and storage time increased, and the slopes of rarefaction curves decreased from the second week in samples stored at -20°C and 4°C. These results indicate that the richness of the bacterial community in the manure reduced as temperature and storage time increased. Firmicutes were the dominant phylum in all samples examined, ranging from 89.3% to 98.8% of total reads, followed by Actinobacteria, which accounted for 0.6% to 7.9%. A change in community composition was observed in samples stored at 37°C during the first 7 days, indicating that temperature plays an important role in determining the microbiota of swine manure. Clostridium, Turicibacter, Streptococcus, and Lactobacillus within Firmicutes, and Corynebacterium within Actinobacteria were the most dominant genera in fresh manure and all stored samples. Based on our findings, we propose Clostridium as an indicator genus of swine manure decomposition in an anaerobic environment. The proportions of dominant genera changed in samples stored at 20°C and 37°C during the fourth week. Based on these results, it was concluded that the microbial communities of swine manure change rapidly as storage time and temperature increase.


Necrotizing Enterocolitis in the Full-Term Infant.
Necrotizing enterocolitis in full-term infants is relatively rare. When seen, it is usually associated with perinatal asphyxia, sepsis, or specific forms of congenital heart disease. It can also be associated with endocrinopathies. In this review, a full-term infant was found to have necrotizing enterocolitis and persistent hypoglycemia. Evaluation for hypoglycemia revealed pan-hypopituitarism, and magnetic resonance imaging confirmed this diagnosis. Timely evaluation and early initiation of hormone replacement therapy is essential to minimize long-term morbidities and mortality associated with pan-hypopituitarism.


Analysis of adult disease characteristics and mortality on MIMIC-III.
To deeply analyze the basic information and disease information of adult patients in the MIMIC-III (Medical Information Mart for Intensive Care III) database, and provide data reference for clinicians and researchers. Tableau2019.1.0 and Navicat12.0.29 were used for data analysis and extraction of disease distribution of adult patients in the MIMIC-III database. A total of 38,163 adult patients were included in the MIMIC-III database. Only 38,156 patients with the first diagnosis were selected. Among them, 21,598 were males accounting for 56.6% the median age was 66 years (Q1-Q3: 53-78), the median length of a hospital stay was 7 days (Q1-Q3: 4-12), and the median length of an ICU stay was 2.1 days (Q1-Q3: 1.2-4.1). Septicemia was the disease with the highest mortality rate among patients and the total mortality rate was 48.9%. The disease with the largest number of patients at the last time was other forms of chronic ischemic heart disease. By analyzing the patients' basic information, the admission spectrum and the disease morbidity and mortality can help more researchers understand the MIMIC-III database and facilitate further research.


Building a Database of Data Sets for Health Services Research.
The Database of Data Sets (DB/DS) for Health Services Research will be an online searchable directory of data sets which are available, often with restrictions and confidentiality safeguards, for use by health care researchers. The DB/DS project is aimed at a wide audience, and intends to include a very broad range of health care data sets, ranging from state hospital discharge data bases, to national registries and health survey data sets, to institutional clinical databases. The intended users are the same community of researchers, policy-makers, administrators and practitioners who are served by the National Library of Medicine's current bibliographic databases. This paper describes a pilot phase of the DB/DS project in which the issues involved in creating such a database were explored with an initial set of 20 representative data sets.


Adrenal causes of hypertension: pheochromocytoma and primary aldosteronism.
The clinical presentations of the patient with pheochromocytoma -- a rare endocrine neoplasm -- include adrenal incidentaloma, hypertensive paroxysms, sustained apparent polygenic hypertension, hypertension in pregnancy, and hypertensive crisis induced by anesthesia. Although when undiagnosed a pheochromocytoma can be lethal, it can usually be cured with surgery. Biochemical documentation with measurements of fractionated metanephrines and catecholamines should precede imaging studies. Abdomen and pelvis computed imaging is usually the first imaging test. Careful preoperative pharmacologic preparation is important for a successful surgical outcome. Adrenal pheochromocytomas can usually be removed laparoscopically, whereas, catecholamine-secreting paragangliomas typically require an open approach. All first degree relatives of pheochromocytoma patients should have biochemical testing. In addition, molecular genetic testing for germline mutations should be considered in most patients with adrenal pheochromocytoma and in all patients with paraganglioma. Primary aldosteronism is a relatively common form of secondary hypertension -- affecting 5 to 10% of all patients with hypertension. A plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio should be obtained in patients with hypertension and hypokalemia, resistant hypertension, adrenal incidentaloma and hypertension, onset of hypertension at a young age (e.g., < 20 years of age), severe hypertension (e.g., > or =160 mm Hg systolic or > or =100 mm Hg diastolic), or whenever the clinician is considering other forms of secondary hypertension. The PAC/PRA ratio is a case finding test and a positive result should be confirmed with aldosterone suppression testing with either oral or intravenous sodium loading. The treatment goals for patients with primary aldosteronism are to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage. Both the subtype of primary aldosteronism and patient preference should dictate the treatment approach.


Lysogenic Streptococcus suis isolate SS2-4 containing prophage SMP showed increased mortality in zebra fish compared to the wild-type isolate.
Streptococcus suis (S. suis) infection is considered to be a major problem in the swine industry worldwide. Based on the capsular type, 33 serotypes of S. suis have been described, with serotype 2 (SS2) being the most frequently isolated from diseased piglets. Little is known, however, about the pathogenesis and virulence factors of S. suis. Research on bacteriophages highlights a new area in S. suis research. A S. suis serotype 2 bacteriophage, designated SMP, has been previously isolated in our laboratory. Here, we selected a lysogenic isolate in which the SMP phage was integrated into the chromosome of strain SS2-4. Compared to the wild-type isolate, the lysogenic strain showed increased mortality in zebra fish. Moreover the sensitivity of the lysogenic strain to lysozyme was seven times higher than that of the wild-type.


Advancing Age and the Odds of Upgrading and Upstaging at Radical Prostatectomy in Men with Gleason Score 6 Prostate Cancer.
To identify a subset of men with Gleason score (GS) 6 prostate cancer who are at high risk for upgrading/upstaging who should be recommended for multiparametric magnetic resonance imaging. Between 1992 and 2017, a total of 3571 men with GS6 prostate cancer were consecutively treated at a single institution with radical prostatectomy. Logistic regression multivariable analyses to determine the odds of upgrading and upstaging were performed, adjusting for age and year of diagnosis, clinical T category, prostate-specific antigen level, number of biopsy cores, and percentage of positive biopsy cores. Of 3571 men, the disease of 115 (3.22%), 245 (6.86%), and 254 (7.11%) was upgraded, was upstaged, or had positive surgical margins (R1), respectively. Older age at diagnosis was associated with an increased risk of upgrading disease to GS7 or higher, prostatectomy T3/T4, and R1 with adjusted odds ratios (95% confidence intervals) of 1.05 (1.01-1.08; P = .005), 1.02 (1.00-1.05; P = .048), and 1.02 (1.002-1.05; P = .03), respectively. Older age was associated with an increasing proportion of men with disease upgraded to GS7 or higher (T1c: P = .002; T2 or higher: P = .04) or upstaged to pT3/4 or pT2R1 (T1c: P = .02; T2 or higher: P = .02) among men with ≥ 33% but not < 33% positive biopsy cores. Before initiating active surveillance, performing multiparametric magnetic resonance imaging in otherwise healthy older men with GS6 prostate cancer and ≥ 33% positive biopsy cores should be considered.


A benign serous ovarian cystadenoma studied by chromosome and quantitative DNA analysis.
In a benign serous ovarian cystadenoma studied by chromosome and quantitative DNA analysis, a diploid mode was found in cells from the cystic wall. The cells from the cystic fluid, however, showed both a diploid and a triploid population. The latter may represent a fist step into malignant transformation.


Integrin αVβ3 silencing sensitizes malignant glioma cells to temozolomide by suppression of homologous recombination repair.
Integrins have been suggested as possible targets in anticancer therapy. Here we show that knockdown of integrins αVβ3, αVβ5, α3β1 and α4β1 and pharmacological inhibition using a cyclo-RGD integrin αVβ3/αVβ5 antagonist sensitized multiple high-grade glioma cell lines to temozolomide (TMZ)-induced cytotoxicity. The greatest effect was observed in LN229 cells upon integrin β3 silencing, which led to inhibition of the FAK/Src/Akt/NFκB signaling pathway and increased formation of γH2AX foci. The integrin β3 knockdown led to the proteasomal degradation of Rad51, reduction of Rad51 foci and reduced repair of TMZ-induced DNA double-strand breaks by impairing homologous recombination efficiency. The down-regulation of β3 in Rad51 knockdown (LN229-Rad51kd) cells neither further sensitized them to TMZ nor increased the number of γH2AX foci, confirming causality between β3 silencing and Rad51 reduction. RIP1 was found cleaved and IκBα significantly less degraded in β3-silenced/TMZ-exposed cells, indicating inactivation of NFκB signaling. The anti-apoptotic proteins Bcl-xL, survivin and XIAP were proteasomally degraded and caspase-3/-2 cleaved. Increased H2AX phosphorylation, caspase-3 cleavage, reduced Rad51 and RIP1 expression, as well as sustained IκBα expression were also observed in mouse glioma xenografts treated with the cyclo-RGD inhibitor and TMZ, confirming the molecular mechanism in vivo. Our data indicates that β3 silencing in glioma cells represents a promising strategy to sensitize high-grade gliomas to TMZ therapy.


Correlation of Xiphopubic Distance, Body Weight, Height and Body Mass Index with Intravesical and Abdominal Initial Resting Pressures in Urodynamic Testing in the Sitting Position.
To compare the initial resting intravesical pressure (pves ) and abdominal pressure (pabd ) in the sitting position with the typical range of values, to assess the correlation between such pressures and patient xipho-pubic distance, body weight, height and body mass index (BMI), and to estimate if xipho-pubic distance can be a guide to interpret initial resting pressures in urodynamic testing. Women with lower urinary tract symptomatology referred for urodynamic testing were consecutively enrolled in a prospective study. Conventional cystometry was done following "good urodynamic practices". The correlation between initial resting pves and pabd and xipho-pubic distance, body weight, height and BMI were studied using simple and multiple linear regression analysis. Statistical significance was defined as P < 0.05. One hundred women aged (mean ± SD) 59.2 ± 13.3 were studied. There was a significant correlation between both pves and pabd , and xipho-pubic distance, body weight and BMI and no correlation with height. Over the multiple analysis, xipho-pubic distance and body weight correlated independently with pves ; body weight correlated independently with pabd . Three patients had pves and/or pabd out of typical range, with BMIs values of 18.48, 18.72 and 35.81 kg/m2 . There was a wide range of difference between xipho-pubic distance and initial resting pressures. Out of range initial resting pressures occur in underweight (or close to) or severely obese patients. Xipho-pubic distance and body weight correlated independently with pves . Body weight correlated independently with pabd . Xipho-pubic distance cannot be a guide to interpret the initial resting pressures.


TRI-PLEDs: a case report.
This case report shows an example of TRI-PLEDs, periodic discharges occurring independently on 3 different areas. The phenomenon of the PLED is briefly discussed.


Subcutaneous endometriosis: a rare cause of deep dyspareunia.
Endometriosis is a growth of endometrial tissue outside the uterine cavity which is responsive to hormonal stimulation. Extrapelvic endometriosis is less common of which skin is the most common site. The patient presents with mass, pain and cyclic symptoms. Subcutaneous endometriosis is very rare and has been reported only thrice in the literature. We report a case where the patient with lower abdominal pain and dyspareunia. Dyspareunia due to subcutaneous endometriosis has not been reported before when there is no evidence of intrapelvic endometriosis on laparoscopy.