Mechanical and electronic properties of pristine and Ni-doped Si, Ge, and Sn sheets.
Silicene, a graphene analogue of silicon, has been generating immense interest due to its potential for applications in miniaturized devices. Unlike planar graphene, silicene prefers a buckled structure. Here we explore the possibility of stabilizing the planar form of silicene by Ni doping using first principles density functional theory based calculations. It is found that planar as well as buckled structure is stable for Ni-doped silicene, but the buckled sheet has slightly lower total energy. The planar silicene sheet has unstable phonon modes. A comparative study of the mechanical properties reveals that the in-plane stiffness of both the pristine and the doped planar silicene is higher compared to that of the buckled silicene. This suggests that planar silicene is mechanically more robust. Electronic structure calculations of the planar and buckled Ni-doped silicene show that the energy bands at the Dirac point transform from linear behavior to parabolic dispersion. Furthermore, we extend our study to Ge and Sn sheets that are also stable and the trends of comparable mechanical stability of the planar and buckled phases remain the same.


An observer tool to enhance learning of incoming anesthesia residents' skills during simulation training of central venous catheter insertion: a randomized controlled trial.
Central venous catheter (CVC) insertion using simulation is an essential skill for anesthesiologists. Simulation training is an effective mean to master this skill. Given the large number of residents and the limited duration of training sessions, the active practice time is limited and residents remain observers of their colleagues for much of the session. To improve learning during observation periods, the use of an observer tool (OT) has been advocated but its educational effectiveness is not well defined. Incoming anesthesia residents were randomized to use an OT (i.e. procedural skill-based checklist) (OT+) or not (OT-) when observing other residents during a simulation bootcamp. The primary outcome was a composite score (total 60 points) evaluating CVC procedural skills rated immediately after the training. This score covers theoretical knowledge explored by multiple choice questions (MCQs) (/20), perceived improvement in knowledge and skills (/20), perceived impact on future professional life (/10) and satisfaction (/10). Measurements were repeated 1 month later. Residents in each group recorded the number of CVCs placed and their clinical outcomes (attempts, complications) during the first month of their clinical rotation using a logbook. Immediately after training, the composite score was similar between the two groups: 45.3 ± 4.2 (OT+, n = 49) and 44.4 ± 4.8 (OT-, n = 42) (p = 0.323). Analysis of sub-items also showed no difference. Results at 1 month were not different between groups. Analysis of the logbook showed no difference between groups. No serious complications were reported. The use of a procedural task-based OT by incoming anesthesia residents and used during CVC insertion simulation training was not associated with better learning outcomes, neither immediately after the session nor when re-evaluated 1 month later. The training at least once on simulator of all residents could limit the impact of OT. Further studies are necessary to define the place of OT in simulation training.


[Production and application of polyclonal antibody against mouse frataxin].
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. FXN is a mitochondrial protein which plays an important role in the regulation of intracellular iron trafficking, biogenesis of iron-sulfur cluster and heme, and removal of reactive oxygen species. Our previous work showed that tissue-specific expression of FXN in cerebellum and heart generates two novel isoforms. In order to find the isoforms in mouse tissues, we tried to obtain a polyclonal antibody against mouse Fxn with high specificity and sensitivity. Thus, the recombinant plasmid pET24(+)-mFxn was constructed to express his-tagged Fxn in BL21 (DE3) cells. The expressed protein is a mature form with 130 amino acids (aa, 14.38 kDa) without the N-terminal signal peptide (77 aa), purified on Ni-NTA column and further dialyzed with Centrifugal Filtration Device. The polyclonal antibody against Fxn was produced by immunizing rabbits with highly purified protein. The collected antiserums were preliminarily purified by precipitation with (NH4)2SO4. Western blotting analysis and cell immunofluorescence showed that the obtained antibody was able to detect both purified and endogenous Fxn. It also worked well in immunoprecipitation with mouse tissues. This is the first time, to our knowledge, to report that mouse Fxn was used as immunogen to generate antibody with high specificity and sensitivity. This work provides a powerful tool for our further research on mouse Fxn isoforms.


Comparison of the Protective Effects of Melatonin and Silymarin Against Gentamicin-Induced Nephrotoxicity in Rats.
This study compared the possible protective effects of silymarin and melatonin against gentamicin (GEN)-induced nephrotoxicity in rats. Rats were allocated to 6 groups: Group I, control group; Groups II and III, administered with silymarin or melatonin; Group IV, injected with GEN; and Groups V and VI, administered with silymarin or melatonin, and then injected with GEN. Compared with the rats in the control group, all rats injected with GEN significantly presented elevated levels of serum creatinine and urea that was accompanied by an increase in relative kidney weight, increase in renal reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and reduction in renal glutathione (GSH) level and superoxide dismutase (SOD) activity. Silymarin and melatonin pretreatment significantly lowered the elevated serum urea and creatinine concentration, kidney weight, and renal ROS and MDA levels. In addition, silymarin and melatonin significantly enhanced renal GSH level and SOD activity. This study indicates that silymarin and melatonin can attenuate renal injury in rats treated with GEN possibly by reducing the ROS level.


Salmonella enterica serotype Cerro among dairy cattle in New York: an emerging pathogen?
The focus of this study was Salmonella enterica serotype Cerro, a potentially emerging pathogen of cattle. Our objectives were to document the within-herd prevalence of Salmonella Cerro among a sample of New York dairy herds, to describe the antimicrobial resistance patterns and pulsed-field gel electrophoresis types of the isolates, and to elucidate the status of this serotype as a bovine pathogen. Data were collected prospectively from dairy herds throughout New York that had at least 150 lactating cows and that received clinical service from participating veterinarians. Following enrollment, Salmonella surveillance consisted of both environmental screening and disease monitoring within the herd. Herds positive by either environmental or fecal culture were sampled during three visits to estimate the within-herd prevalence of Salmonella. Among 57 enrolled herds, 44 (77%) yielded Salmonella-positive samples during the study period. Of these, 20 herds (46%) were positive for Salmonella Cerro. Upon follow-up sampling for estimation of prevalence, Cerro was identified in 10 of the 20 herds; the median within-herd Cerro prevalence was 17%, with a maximum of 53%. Antimicrobial resistance ranged from zero to nine drugs, and eight (40%) of the Cerro-positive farms generated drug-resistant isolates. Eight XbaI pulsed-field gel electrophoresis types were represented among 116 isolates tested, although 89% of these isolates shared the predominant type. Among herds with clinical cases, cattle that had signs consistent with salmonellosis were more likely to test positive for Cerro than apparently healthy cattle, as estimated by a logistic regression model that controlled for herd as a random effect (odds ratio: 3.9). There is little in the literature concerning Salmonella Cerro, and published reports suggest an absence of disease association in cattle. However, in our region there has been an apparent increase in the prevalence of this serotype among cattle with salmonellosis. Other Salmonella serotypes important to bovine health have emerged to become leading causes of human foodborne disease, and close monitoring of Cerro is warranted.


Older but Not Wiser: the Age-Driven Changes in Neutrophil Responses during Pulmonary Infections.
Elderly individuals are at increased risk of life-threatening pulmonary infections. Neutrophils are a key determinant of the disease course of pathogen-induced pneumonia. Optimal host defense balances initial robust pulmonary neutrophil responses to control pathogen numbers, ultimately followed by the resolution of inflammation to prevent pulmonary damage. Recent evidence suggests that phenotypic and functional heterogeneity in neutrophils impacts host resistance to pulmonary pathogens. Apart from their apparent role in innate immunity, neutrophils also orchestrate subsequent adaptive immune responses during infection. Thus, the outcome of pulmonary infections can be shaped by neutrophils. This review summarizes the age-driven impairment of neutrophil responses and the contribution of these cells to the susceptibility of the elderly to pneumonia. We describe how aging is accompanied by changes in neutrophil recruitment, resolution, and function. We discuss how systemic and local changes alter the neutrophil phenotype in aged hosts. We highlight the gap in knowledge of whether these changes in neutrophils also contribute to the decline in adaptive immunity seen with age. We further detail the factors that drive dysregulated neutrophil responses in the elderly and the pathways that may be targeted to rebalance neutrophil activity and boost host resistance to pulmonary infections.


Derivation of multiple cranial tissues and isolation of lens epithelium-like cells from human embryonic stem cells.
Human embryonic stem cells (hESCs) provide a powerful tool to investigate early events occurring during human embryonic development. In the present study, we induced differentiation of hESCs in conditions that allowed formation of neural and non-neural ectoderm and to a lesser extent mesoderm. These tissues are required for correct specification of the neural plate border, an early embryonic transient structure from which neural crest cells (NCs) and cranial placodes (CPs) originate. Although isolation of CP derivatives from hESCs has not been previously reported, isolation of hESC-derived NC-like cells has been already described. We performed a more detailed analysis of fluorescence-activated cell sorting (FACS)-purified cell populations using the surface antigens previously used to select hESC-derived NC-like cells, p75 and HNK-1, and uncovered their heterogeneous nature. In addition to the NC component, we identified a neural component within these populations using known surface markers, such as CD15 and FORSE1. We have further exploited this information to facilitate the isolation and purification by FACS of a CP derivative, the lens, from differentiating hESCs. Two surface markers expressed on lens cells, c-Met/HGFR and CD44, were used for positive selection of multiple populations with a simultaneous subtraction of the neural/NC component mediated by p75, HNK-1, and CD15. In particular, the c-Met/HGFR allowed early isolation of proliferative lens epithelium-like cells capable of forming lentoid bodies. Isolation of hESC-derived lens cells represents an important step toward the understanding of human lens development and regeneration and the devising of future therapeutic applications.


scATAC-seq preprocessing and imputation evaluation system for visualization, clustering and digital footprinting.
Single-cell ATAC-seq (scATAC-seq) is a recently developed approach that provides means to investigate open chromatin at single cell level, to assess epigenetic regulation and transcription factors binding landscapes. The sparsity of the scATAC-seq data calls for imputation. Similarly, preprocessing (filtering) may be required to reduce computational load due to the large number of open regions. However, optimal strategies for both imputation and preprocessing have not been yet evaluated together. We present SAPIEnS (scATAC-seq Preprocessing and Imputation Evaluation System), a benchmark for scATAC-seq imputation frameworks, a combination of state-of-the-art imputation methods with commonly used preprocessing techniques. We assess different types of scATAC-seq analysis, i.e. clustering, visualization and digital genomic footprinting, and attain optimal preprocessing-imputation strategies. We discuss the benefits of the imputation framework depending on the task and the number of the dataset features (peaks). We conclude that the preprocessing with the Boruta method is beneficial for the majority of tasks, while imputation is helpful mostly for small datasets. We also implement a SAPIEnS database with pre-computed transcription factor footprints based on imputed data with their activity scores in a specific cell type. SAPIEnS is published at: https://github.com/lab-medvedeva/SAPIEnS. SAPIEnS database is available at: https://sapiensdb.com.


Optimal sludge retention time for a bench scale MBR treating municipal sewage.
Membrane bioreactors allow for higher sludge concentrations and improved degradation efficiencies with respect to conventional activated sludge. However, in the current practice these systems are often operated under sub-optimal conditions, since so far no precise indications have yet been issued on the optimal operating conditions of MBR for municipal wastewater treatment. This paper reports some results of four years of operation of a bench scale membrane bioreactor where steady state conditions were investigated under different sludge retention times. The whole experimental campaign was oriented towards the investigation of optimal process conditions in terms of COD removal and nitrification, biomass activity and growth, and sludge characteristics. The membrane bioreactor treated real municipal sewage, and four different sludge ages were tested (20, 40, 60, and 80 days) and compared with previous data on complete sludge retention. The results showed that the the biology of the system, as assessed by the oxygen uptake rate, is less affected than the sludge physical parameters. In particular, although the growth yield was observed to dramatically drop for SRT higher than 80 days, the biological activity was maintained under all the tested conditions. These considerations suggest that high SRT are convenient in terms of limited excess sludge production without losses of the treatment capacity. Physical characteristics such as the viscosity and the filterability appear to be negatively affected by prolonged sludge retention times, but their values remain within the ranges normally reported for conventional activated sludge.


Purification and amino-terminal sequence of an insulin-like growth factor-binding protein secreted by rat liver BRL-3A cells.
A protein preparation that specifically binds insulin-like growth factors (IGFs) I and II was purified from medium conditioned by rat liver BRL-3A cells using molecular sieve chromatography in 1 M acetic acid followed by affinity chromatography on IGF-II-agarose. The affinity-purified IGF-binding protein exhibits a single major band with apparent Mr = 36,300 under reducing conditions on sodium dodecyl sulfate-polyacrylamide gels. The IGF-binding protein is efficiently and specifically cross-linked to either 125I-IGF-I (human) or 125I-IGF-II (rat) using disuccinimidyl suberate. An IGF-binding protein of similar apparent molecular weight was also affinity purified from rat hepatoma H-35 cell conditioned medium and found to differ from the BRL-3A protein such that potent polyclonal antisera prepared in rabbits against the purified BRL-3A IGF-binding protein exhibited a much lower titer for the H-35 protein in an enzyme-linked immunosorbent assay and upon immunoblotting. In order to determine whether a single BRL-3A IGF-binding protein is present in the affinity-purified preparation, the protein was prepared for sequencing on a Sephacryl S-300 column in 6 M guanidine HCl after reduction and alkylation. The amino acid composition (expressed in percentages) of this IGF-binding protein was determined to be: Cys = 5.5, Lys = 4.8, His = 2.8, Arg = 7.8, Asx = 10.2, Thr = 5.1, Ser = 3.9, Glx = 15.7, Gly = 17.4, Ala = 7.3, Val = 4.6, Met = 1.4, Ile = 2.4, Leu = 8.3, Tyr = 1.0, Phe = 1.9. Sequencing of the NH2-terminal portion of this protein led to the identification of 31 amino acids in the following order: Phe-Arg-Cys-Pro-Pro-Cys-Thr-Pro-Glu-Arg-Leu-Ala-Ala-Cys-Gly-Pro-Pro-Pro- Asp-Ala-Pro-Cys-Ala-Glu-Leu-Val-Arg-Glu-Pro-Gly-Cys. We conclude that rat liver BRL-3A cells secrete a single major IGF-binding protein capable of binding both IGF-I and IGF-II.


Protective effect of gastrodin on peripheral neuropathy induced by anti-tumor treatment with vincristine in rat models.
Cancer is a common disease threatening human health, chemotherapy is widely used in clinical treatment of cancer, but chemotherapy-induced peripheral neuropathy (CIPN) has a relevant impact on life quality of cancer patients. Administration of gastrodin can relieve chronic pain to cancer patients with CIPN and attenuated the inflammatory response by reducing the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). However, its exact molecular mechanisms remain unclear. In this study, we established an animal model of CIPN using Walker-256 breast cancer cell and vincristine. We found that the mechanical and thermal pain threshold of rats was decreased with treatment of vincristine. Using gastrodin could restore the mechanical and thermal threshold without interfering anti-tumor effect of vincristine. Gastrodin relieved CIPN by inhibiting activation of spinal microglia through Fractalkine (CX3CL1) and its receptor CX3CR1, then inhibited P38/mitogen-activated protein kinase (MAPK) signaling pathway and reduced the expression of inflammatory factor TNF-α and interleukin-1β (IL-1β). Taking together, our study demonstrated that gastrodin is a potential drug for the treatment of CIPN and likely to improve cancer patient's life quality.


Rapid shallow breathing caused by pulmonary vascular congestion in cats.
The vasculature of one lung of unanesthetized spontaneously breathing decerebrate cats was isolated and congested with blood. Such pulmonary vascular congestion (PVC) consistently resulted in a shallow tachypnea associated with expiratory activation of the diaphragm and thyroarytenoid muscles, signifying augmented expiratory braking. With progressive increases in pulmonary vascular pressure, tachypnea and expiratory braking increased progressively and ultimately obscured phasic activity in the diaphragm and thyroarytenoid. Thus the apnea caused by PVC constitutes not an arrest of neural respiratory activity but rather a continuous activation of thoracic inspiratory and laryngeal adductor muscles. When capsaicin, a neurotoxin that activates nonmyelinated afferents, was injected into the pulmonary artery of the isolated lung, it produced changes in timing and distribution of respiratory motor output that resembled those with PVC but were more abrupt in onset. Capsaicin, applied perineurally to the cervical vagi, preferentially blocked the conduction of nonmyelinated afferent fibers. This procedure, which produced little degradation in Hering-Breuer reflexes, eliminated tachypnea and expiratory braking caused by PVC or capsaicin injection. The results indicate that activation of pulmonary vagal afferent fibers of C or A-delta category in unanesthetized cats reflexly modifies the respiratory motor output in a way that resembles the human response to PVC or pulmonary embolism. This is a brain stem reflex.


The antagonistic effect of antipsychotic drugs on a HEK293 cell line stably expressing human alpha1A1-adrenoceptors.
Antipsychotic drugs often cause orthostatic hypotension, probably through antagonist action on resistance vessel alpha(1A)-adrenoceptors. Here we have tested this possibility directly using cells transfected with a relevant human alpha(1A)-adrenoceptor splice variant. To determine a splice variant which was relevant, we used quantitative real-time polymerase chain reaction (qPCR) to determine the prevalence in human subcutaneous small arteries of three of the five splice variants ADRA1A_v1-5, which encode functional protein: alpha(1A1)-, alpha(1A3)-, alpha(1A4)-adrenoceptors. Our statistical analysis showed higher transcription levels of alpha(1A1)- than of alpha(1A3)- and alpha(1A4)-adrenoceptors (1.6 and 5.8 times, respectively). We therefore chose to study the alpha(1A1)-adrenoceptor, and the cDNA encoding it was transfected into the Flp-In-293 (modified from HEK-293) cell line to produce a cell line stably expressing a functional form of this splice variant. The expression of recombinant alpha(1A1)-adrenoceptor subtype was confirmed by Western immunoblot analysis, and its functionality demonstrated using a Fura-2 assay by a rise in intracellular calcium concentration ([Ca(2+)](i)) when challenged with phenylephrine (EC(50)=1.61x10(-8) M). From Schild analysis, prazosin, sertindole, risperidone, and haloperidol caused a concentration-dependent, rightward shift of the cumulative concentration-response curves for phenylephrine in cells expressing human recombinant alpha(1A1)-adrenoceptors to yield pK(B) values of 8.40, 8.05, 8.26 and 7.38, respectively. In [7-methoxy-(3)H]-prazosin binding experiments, high expression was seen (B(max)=48.5+/-16.7 pmol/mg protein, +/-S.E.M.) along with high affinity binding to a single site (K(d)=0.210+/-0.034 nM). The pharmacological profiles of recombinant human alpha(1A1)-adrenoceptors in competition binding studies confirmed much higher antagonist affinity of sertindole and risperidone than haloperidol for these receptors. In summary, it can be concluded that there is an approximately 10-fold higher adrenoceptor affinity of risperidone and sertindole for human alpha(1A1)-adrenoceptors compared to haloperidol. These findings are consistent with the observation that risperidone and sertindole have a higher incidence of orthostatic hypotension than haloperidol.


[Characteristics of ladasten effect in neurasthenia patients with various EEG parameters].
Clinical and electroencephalographic (EEG) analysis ofladasten action in anxiety-asthenic patients with respect to their EEG-defined individual typological characteristics was carried out. Primary psychopathologic disorders and ladasten effects were assessed by objective classification methods (factor and cluster analyses), and individual EEG types characterized by marked or reduced alpha rhythm were determined. No significant correlations between baseline EEG results and the initial mental condition indices were found. Significant differences ofladasten action in patients with different EEG types were found. It was established that, in patients with marked alpha rhythm corresponding to asthenic personal traits, ladasten exhibits predominantly a psychostimulant action assessed by clinical rating scales, which is accompanied by high frequencies of alpha rhythm increase and beta 1 and beta 2 rhythms decrease. In patients with reduced alpha rhythm and the EEG type corresponding to asthenic personal traits, ladasten action was characterized by an increase of alpha-rhythm low frequencies and the opposite reaction of beta 1 and beta 2 rhythms, whose are typical for the EEG pattern of anxiolytic effect. These results may indicate that the effect of ladasten depends on the initial brain activity level, which varies in patients with different individual typological traits.


Top 10 Research Priorities for U.S. Military En Route Combat Casualty Care.
Within the Military Health System, the process of transporting patients from an initial point of injury and throughout the entire continuum of care is called "en route care." A Committee on En Route Combat Casualty Care was established in 2016 as part of the DoD Joint Trauma System to create practice guidelines, recommend training standards, and identify research priorities within the military en route care system. Following an analysis of currently funded research, future capabilities, and findings from a comprehensive scoping study, members of a sub-working group for research identified the top research priorities that were needed to better guide evidence-based decisions for practice and policy, as well as the future state of en route care. Based on the input from the entire committee, 10 en route care research topics were rank-ordered in the following manner: (1) medical documentation, (2) clinical decision support, (3) patient monitoring, (4) transport physiology, (5) transfer of care, (6) maintaining normothermia, (7) transport timing following damage control resuscitation or surgery, (8) intelligent tasking, (9) commander's risk assessment, and (10) unmanned transport. Specific research questions and technological development needs were further developed by committee members in an effort to guide future research and development initiatives that can directly support operational en route care needs. The research priorities reflect three common themes, which include efforts to enhance or increase care provider capability and capacity; understand the impact of transportation on patient physiology; and increase the ability to coordinate, communicate, and facilitate patient movement. Technology needs for en route care must support interoperability of medical information, equipment, and supplies across the global military health system in addition to adjusting to a dynamic transport environment with the smallest possible weight, space, and power requirements. To ensure an evidence-based approach to future military conflicts and other medical challenges, focused research and technological development to address these 10 en route care research gaps are urgently needed.


Quantification and source identification of polycyclic aromatic hydrocarbons in sediment, soil, and water spinach from Hanoi, Vietnam.
Polycyclic aromatic hydrocarbons (PAHs) were quantified in sediment, soil, and plant material from Hanoi, Vietnam, and an aquatic production system in peri-urban Hanoi. The sum of the concentration of 16 US-EPA priority PAHs ( summation PAH16) ranged between 0.44 and 6.21 mg kg(-1) dw in sediment and between 0.26 and 1.35 mg kg(-1) dw in soil, with decreasing concentrations from the urban area to the peri-urban area, indicating contributions from urban and industrial sources. Double plots of diagnostic source ratios indicate that PAHs originate from mixed petrogenic and pyrogenic sources, the latter being predominant. The predominance of low molecular weight (LMW) PAHs in the sediment samples suggests that petrogenic sources are more prevalent in the water environment than in the soil. In contrast, high molecular weight (HMW) PAHs dominated in water spinach which probably reflects the plant's uptake of particle-bound PAHs that originate from pyrogenic sources.


[Use of capnography in the emergency department].
In Denmark, capnography is routinely used in monitoring patients with artificial airways. Non-invasive capnography is occasionally used by prehospital providers, but not applied inside hospital walls. Multiple studies illustrate benefits from capnography in non-intubated patients. Non-invasive capnography may reveal altered ventilation in conditions such as opioid-induced respiratory depression and acute dyspnoea, during metabolic acidosis and among patients with seizures and cerebral damage. Implementation requires education, guidelines for inhospital use and financial investment.


Label-free intraoperative parathyroid localization with near-infrared autofluorescence imaging.
The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification. The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid. The study was conducted at the Vanderbilt University endocrine surgery center. Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings. The detection rate of parathyroid glands was measured. The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state. NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.


Diagnostic Utility of Carbohydrate Breath Tests for SIBO, Fructose, and Lactose Intolerance.
Unexplained bloating, gas, and pain are common symptoms. If routine tests are negative, such patients are often labeled as irritable bowel syndrome. To determine the diagnostic utility of breath tests that assess for small intestinal bacterial overgrowth (SIBO), fructose or lactose intolerance, and the predictive value of symptoms. Patients with gas, bloating, diarrhea, abdominal pain (≥ 6 months), and negative endoscopy and radiology tests were assessed with symptom questionnaires, glucose (75 g), fructose (25 g), or lactose (25 g) breath tests. Breath tests were categorized as positive when H2 (≥ 20 ppm) or CH4 (≥ 15 ppm) increased above baseline values or as hypersensitive when symptoms changed significantly without rise in H2/CH4 or as negative. 1230 patients (females = 878) underwent 2236 breath tests. The prevalence of SIBO was 33% (294/883), fructose intolerance was 34% (262/763), and lactose intolerance was 44% (260/590). Hypersensitivity was found in 16% and 9%, respectively, during fructose and lactose breath tests. Although gas (89%), abdominal pain (82%), and bloating (82%) were highly prevalent, pretest symptoms or their severity did not predict an abnormal breath test, but symptoms during the breath test facilitated diagnosis of SIBO, fructose, and lactose intolerance and hypersensitivity. Approximately 45% of patients with unexplained gas and bloating had SIBO, fructose, or lactose intolerance; another 9-16% had visceral hypersensitivity. Pretest symptoms were poor predictors, but symptoms during the breath tests were useful. Breath tests are safe, provide significant diagnostic yield, and could be useful in routine gastroenterology practice.


[Specific glucocorticoid receptor in human liver cytosol].
Specific cytoplasmic glucocorticoid receptors were isolated from biopsy material of liver tissue, obtained after operation of the patients with chronic impairment of bili ferous tract or from the patients with ulcerous disease of stomach within the stage of remission. The receptors isolated were saturated with dexamethasone; the dissociation constant value (Kdiss) of the complex was 1.37 10(-8) M and the amount of binding sites (n) was 1.96 10(-14) mol/mg of protein as calculated from a Scatchards' plot. Dexamethasone, corticosterol, hydrocortisone and deoxycorticosterol exhibited the highest competition for the binding sites of the receptor. The receptor of human liver studied was similar in its main properties to the dexamethasone-binding receptor from liver tissue of experimental animals.


Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan.
Two new influenza virus neuraminidase inhibitors (NAIs), peramivir and laninamivir, were approved in 2010 which resulted to four NAIs that were used during the 2010-2011 influenza season in Japan. This study aims to monitor the susceptibility of influenza virus isolates in 2009-2010 and 2010-2011 influenza seasons in Japan to the four NAIs using the fluorescence-based 50% inhibitory concentration (IC₅₀) method. Outliers were identified using box-and-whisker plot analysis and full NA gene sequencing was performed to determine the mutations that are associated with reduction of susceptibility to NAIs. A total of 117 influenza A(H1N1)pdm09, 59 A(H3N2), and 18 type B viruses were tested before NAI treatment and eight A(H1N1)pdm09 and 1 type B viruses were examined from patients after NAI treatment in the two seasons. NA inhibition assay showed type A influenza viruses were more susceptible to NAIs than type B viruses. The peramivir and laninamivir IC₅₀ values of both type A and B viruses were significantly lower than the oseltamivir and zanamivir IC₅₀ values. Among influenza A(H1N1)pdm09 viruses, the prevalence of H274Y viruses increased from 0% in the 2009-2010 season to 3% in the 2010-2011 season. These H274Y viruses were resistant to oseltamivir and peramivir with 200-300 fold increase in IC₅₀ values but remained sensitive to zanamivir and laninamivir. Other mutations in NA, such as I222T and M241I were identified among the outliers. Among influenza A(H3N2) viruses, two outliers were identified with D151G and T148I mutations, which exhibited a reduction in susceptibility to oseltamivir and zanamivir, respectively. Among type B viruses, no outliers were identified to the four NAIs. For paired samples that were collected before and after drug treatment, three (3/11; 27.3%) H274Y viruses were identified among A(H1N1)pdm09 viruses after oseltamivir treatment but no outliers were found in the laninamivir-treatment group (n=3). Despite widespread use of NAIs in Japan, the prevalence of NAI-resistant influenza viruses is still low.


Transition of care: health care professionals' view.
There is much anxiety regarding the transfer of adolescents with chronic illness to adult services. Transfer of patients can be haphazard if the transition has not been planned. Problems and obstacles to transition have been identified and discussed by various authors. The purpose of this small study was to explore the views and needs of health care professionals from one National Health Service trust regarding the transition of care for adolescents with a chronic condition from children's to adult services and to identify possible ways to improve the current services for this particular group of young adults. The sample comprised 40 health care professionals, nurses from the children's department and adult ward, doctors, psychologists, physiotherapists and pharmacists currently working in the same hospital trust. A postal survey was conducted. The data were analysed using descriptive statistics and content analysis. The main findings suggest that there is a need for a planned transition programme, supported by a clinical protocols and a specialist unit for adolescents. Health care professionals' views of patients and family/carers' needs and how such needs may be met were identified.


ANCA-negative ANCA-associated vasculitis: pitfalls of the 'vasculitis screen'.
Despite its recognition as an 'ANCA-associated vasculitis' (AAV), eosinophilic granulomatosis with polyangiitis (EGPA) is ANCA negative in up to 60% of cases. Herein, we report the case of a young man with a clinical syndrome highly suggestive of EGPA but with repeated negative ANCA serology, ultimately presenting with cardiac arrest before recognition of the primary systemic vasculitis, whereupon he received successful induction therapy with high dose glucocorticoids and cyclophosphamide. The case illustrates the importance of awareness of ANCA negative AAV among general physicians in order to minimise morbidity and mortality.


[Renal neuroendocrine tumor (carcinoid) : a case report].
A 32-year-old man was referred to our hospital for treatment of left renal cystic tumor, which was detected by computed tomographic (CT) scan 3 years ago. CT scan showed a multilocular cyst (5 cm in diameter) with a solid tumor in the left kidney which was enhanced with contrast. There was no evidence of extrarenal invasion or distant metastasis. We performed retroperitoneal laparoscopic radical nephrectomy. Pathological examinations revealed a cellular arrangement specific to carcinoid tumor and positive for CD56 (NCAM) and neuron-specific enolase. The cell proliferation rate was estimated to be under 2% with Ki67 staining. The pathological diagnosis was renal neuroendocrine tumor (carcinoid). At the 9-month follow up, he had no evidence of local recurrence or metastasis.


Bridging coarse-grained models by jump-in-sample simulations.
We present an efficient method to construct coarse-grained (CG) models from models of finer resolution. The method estimates the free energies in a generated sample of the CG conformational space and then fits the entire effective potential surface in the high-dimensional CG conformational space. A jump-in-sample algorithm that uses a random jumping walk in the CG sample is used to iteratively estimate the free energies. We test the method in a tetrahedral molecular fluid where we construct the intermolecular effective potential and evaluate the CG molecular model. Our algorithm for calculating the free energy involves an improved Wang-Landau (WL) algorithm, which not only works more efficiently than the standard WL algorithm, but also can work in high-dimensional spaces.


[RNAase activity in pig embryo kidney culture during interferon formation].
In production by pig embryo kidney cell (PEK) culture of interferon induced by UV-irradiated Newcastle disease virus, T strain, an increase in the activity of intracellular RNA-ase is observed at the optimal pH 8.5. RNA-ases of experimental cell extract have exonuclease activity in contrast to control cell enzymes which show endo- and exonuclease activity. A thermolable inhibitor absent in control cells was detected in experimental PEK cells.


Hot electron and thermal effects in plasmonic catalysis of nanocrystal transformation.
Plasmonic metal nanoparticles have the ability to harvest visible light and cause effective energy conversion, and they are considered as promising catalysts to drive chemical reactions. Although plasmonic catalysis has been widely used to mediate the reaction of organic molecules, the mechanism of contribution of thermal and hot carriers remains unclear. The catalysis of hot carriers is normally proposed as the dominant role of plasmonic catalysis, while the contribution of plasmonic thermal effects is often ignored, since the molecules on the metal surface are unstable at high temperatures. Here, plasmon catalytic nanocrystal transformation including oxidation reaction and optimization of the crystal structure is employed to investigate the plasmonic contributions of hot electron and thermal effects in plasmonic catalysis. It is found that the transformation rate and the corresponding product are very different with and without the assistance of hot electron catalysis. The thermal effect plays a dominant role in plasmon-catalyzed material transformation, and hot electrons can promote the oxidation reaction by facilitating the generation of active oxygen. The investigation provides insight into the specific role of hot electron and thermal effects in plasmonic catalysis, which is critically important for exploiting the highly localized fast plasmonic thermal effect and for designing energy-efficient plasmonic catalysts.


Epidermal growth factor in urine from patients with bladder cancer.
Epidermal growth factor (EGF), a mitogenic polypeptide with a molecular weight of 6000, is excreted in human urine in nanomolar quantities. Recently, some reports showed that urothelial neoplasm was related to the concentration of EGF in urine. In this study, EGF concentration in urine was measured by enzyme-linked immunosorbent assay (ELISA) in 207 samples from 112 male patients (30-90 years old, median 66.2) who had previously been treated for bladder cancer. Then, we tried to clarify the significance of urinary EGF as a marker for recurrence of bladder cancer in comparison with urine cytology. The samples were collected on occasional follow up cystoscopy. Urine from nine age-adjusted males without urological disease was also measured to obtain normal control values. In 123 samples from patients without tumors, EGF concentrations in urine decreased with age. In 84 samples obtained from patients with recurrent tumor, EGF concentrations were significantly lower than those in 123 samples from patients without tumors (P < 0.001) Furthermore, EGF concentrations in longitudinal samples collected the same patients during tumor recurrence and at the times when no tumor was detected were measured in 56 patients. EGF concentrations in the samples collected during tumor recurrence was significantly lower than that in specimens collected when there was no tumor (P < 0.01). There were no significant differences between the same samples collected during tumor recurrence with regard to tumor grade, stage shape and number of tumors. However, EGF concentration in urine from patients with carcinoma in situ (CIS) was lower than that in specimens from patients without CIS. These results indicate the usefulness of determining the EGF concentration as a marker for detecting bladder cancer recurrence. Urine cytology was also examined in the same series and findings were compared with those of urinary EGF. On cytology, class IV and V were considered positive, and on urinary EGF, less than 10 ng/mgCr were considered positive. Sensitivity was 25% for cytology and 57% for urinary EGF, while specificity was 98% and 66%, respectively. The predictive positive value was 0.88 and 0.53, respectively. With the combined use of urinary EGF and cytology, the sensitivity, specificity and predictive positive value were 68%, 64% and 0.92, respectively. In conclusion, urinary EGF seems to be a useful marker for detecting bladder cancer recurrence if performed in addition to cytology. cancer recurrence if performed in addition to cytology.


Inferring the role of transcription factors in regulatory networks.
Expression profiles obtained from multiple perturbation experiments are increasingly used to reconstruct transcriptional regulatory networks, from well studied, simple organisms up to higher eukaryotes. Admittedly, a key ingredient in developing a reconstruction method is its ability to integrate heterogeneous sources of information, as well as to comply with practical observability issues: measurements can be scarce or noisy. In this work, we show how to combine a network of genetic regulations with a set of expression profiles, in order to infer the functional effect of the regulations, as inducer or repressor. Our approach is based on a consistency rule between a network and the signs of variation given by expression arrays. We evaluate our approach in several settings of increasing complexity. First, we generate artificial expression data on a transcriptional network of E. coli extracted from the literature (1529 nodes and 3802 edges), and we estimate that 30% of the regulations can be annotated with about 30 profiles. We additionally prove that at most 40.8% of the network can be inferred using our approach. Second, we use this network in order to validate the predictions obtained with a compendium of real expression profiles. We describe a filtering algorithm that generates particularly reliable predictions. Finally, we apply our inference approach to S. cerevisiae transcriptional network (2419 nodes and 4344 interactions), by combining ChIP-chip data and 15 expression profiles. We are able to detect and isolate inconsistencies between the expression profiles and a significant portion of the model (15% of all the interactions). In addition, we report predictions for 14.5% of all interactions. Our approach does not require accurate expression levels nor times series. Nevertheless, we show on both data, real and artificial, that a relatively small number of perturbation experiments are enough to determine a significant portion of regulatory effects. This is a key practical asset compared to statistical methods for network reconstruction. We demonstrate that our approach is able to provide accurate predictions, even when the network is incomplete and the data is noisy.


Clinical comparison of the effectiveness of single-file reciprocating systems and rotary systems for removal of endotoxins and cultivable bacteria from primarily infected root canals.
This clinical study was conducted to compare the effectiveness of single-file reciprocating systems and rotary systems in removing endotoxins and cultivable bacteria from primarily infected root canals. Forty-eight primarily infected root canals were selected and randomly divided into 4 groups: WaveOne (Dentsply Maillefer, Ballaigues, Switzerland) (n = 12); Reciproc (VDW, Munich, Germany) (n = 12), ProTaper (Dentsply Maillefer) (n = 12), and Mtwo (VDW) (n = 12). Samples were collected before and after chemomechanical preparation. The irrigation was performed by using 2.5% sodium hypochlorite. A chromogenic limulus amebocyte lysate assay test was used to quantify endotoxins. Culture techniques were used to determine bacterial colony-forming unit counts. In the baseline samples (ie, samples collected before chemomechanical preparation), endotoxins and cultivable bacteria were recovered from 100% of the root canal samples. No differences were found in the median percentage values of endotoxin reduction achieved with reciprocating systems (ie, WaveOne [95.15%] and Reciproc [96.21%]) and with rotary systems (ie, ProTaper [97.98%] and Mtwo [96.34%]) (P < .05). Both single-file reciprocating systems (ie, WaveOne [99.45%] and Reciproc [99.93%]) and rotary systems (ProTaper [99.85%] and Mtwo [99.41%]) were effective in reducing the cultivable bacteria (all P < .05). Moreover, the culture analysis revealed no differences in bacterial load reduction (P > .05). Both single-file reciprocating systems (ie, WaveOne and Reciproc instruments) and rotary systems (ie, ProTaper and Mtwo instruments) showed similar effectiveness in reducing endotoxins and cultivable bacteria from primarily infected root canals, but they were not able to eliminate them from all root canals analyzed.


Hallux rigidus. Excisional arthroplasty.
The authors feel that capsular interposition arthroplasty can give predictable pain relief in carefully selected individuals with severe (grade III) hallux rigidus. Attention to the relative lengths of the first and second metatarsals, minimal shortening of the proximal phalanx, and use of the dorsal capsule and EHB tendon as an interposition all contribute to good to excellent objective and subjective results. Approximately 30% of patients undergoing this procedure experience some degree of transfer metatarsalgia postoperatively and probably require orthoses for sports. The authors feel that this operation presents a reasonable alternative to many patients who are candidates for an arthrodesis of the first MTP joint for advanced degenerative disease.


In vitro and in vivo antibacterial activities of DK-507k, a novel fluoroquinolone.
The antibacterial activities of DK-507k, a novel quinolone, were compared with those of other quinolones: ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sitafloxacin, and garenoxacin (BMS284756). DK-507k was as active as sitafloxacin and was as active as or up to eightfold more active than gatifloxacin, moxifloxacin, and garenoxacin against Streptococcus pneumoniae, methicillin-susceptible and methicillin-resistant Staphylococcus aureus, and coagulase-negative staphylococci. DK-507k was as active as or 4-fold more active than garenoxacin and 2- to 16-fold more active than gatifloxacin and moxifloxacin against ciprofloxacin-resistant strains of S. pneumoniae, including clinical isolates and in vitro-selected mutants with known mutations. DK-507k inhibited all ciprofloxacin-resistant strains of S. pneumoniae at 1 microg/ml. A time-kill assay with S. pneumoniae showed that DK-507k was more bactericidal than gatifloxacin and moxifloxacin. The activities of DK-507k against most members of the family Enterobacteriaceae were comparable to those of ciprofloxacin and equal to or up to 32-fold higher than those of gatifloxacin, levofloxacin, moxifloxacin, and garenoxacin. DK-507k was fourfold less active than sitafloxacin and ciprofloxacin against Pseudomonas aeruginosa, while it was two to four times more potent than levofloxacin, gatifloxacin, moxifloxacin, and garenoxacin against P. aeruginosa. In vivo, intravenous treatment with DK-507k was more effective than that with gatifloxacin and moxifloxacin against systemic infections caused by S. aureus, S. pneumoniae, and P. aeruginosa in mice. In a mouse model of pneumonia due to penicillin-resistant S. pneumoniae, DK-507k administered subcutaneously showed dose-dependent efficacy and eliminated the bacteria from the lungs, whereas gatifloxacin and moxifloxacin had no significant efficacy. Oral treatment with DK-507k was slightly more effective than that with ciprofloxacin in a rat model of foreign body-associated urinary tract infection caused by a P. aeruginosa isolate for which the MIC of DK-507k was fourfold higher than that of ciprofloxacin. Oral administration of DK-507k to rats achieved higher peak concentrations in serum and higher concentrations in cumulative urine than those achieved with ciprofloxacin. These data indicate the potential advantages of DK-507k over other quinolones for the treatment of a wide range of community-acquired infections.


Treatment of overt meningeal leukaemia in children: results of second MRC meningeal leukaemia trial.
After induction ofmeningeal remission by a course of intrathecal methotrexate patients were randomly allocated to receive either cranial irradiation or craniospinal irradiation. Patients being treated for their first meningeal relapse were randomised separately from those in their second or subsequent relapse. All eight patients in their first relapse who were given cranial irradiation alone developed further meningeal recurrence (median length of remission 15 weeks) compared with only two out of nine given craniospinal irradiation (median length of remission at least 99 weeks). Four of the nine patients given craniospinal irradiation were alive and without further meningeal relapse two and a half to four years after treatment. Craniospinal irradiation produced no such advantage for patients entering the trial in their second or subsequent meningeal relapse.


Effect of Serial Use of Bone Morphogenetic Protein 2 and Fibroblast Growth Factor 2 on Periodontal Tissue Regeneration.
This study evaluates the synergistic effect of serial application of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) on both new bone formation and periodontal tissue regeneration using 1-wall intrabony defect in mongrel dogs. One-wall defects were created at the mesial aspect of the mandibular first molars of 6 male mongrel dogs. Each mandibular defect received 1 of the 2 experimental treatments randomly (BMP2 or BMP2 + FGF2), and it was allowed to heal for either 4 or 8 weeks postoperatively. Histologic and histomorphometric analyses were performed for the evaluation of the overall healing patterns of new bone formation and periodontal tissue regeneration. The results showed that after 8 weeks, serial application of BMP2 and FGF2 significantly improved the periodontal tissue regeneration, whereas application of BMP2 only showed greater new bone formation after 4 weeks. The serial application of BMP2 and FGF2 may have synergistic effects on periodontal tissue regeneration over time.


Infectious, oncologic, and autoimmune comorbidities of psoriasis and psoriatic arthritis: a report from the GRAPPA 2012 annual meeting.
At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) in Stockholm, Sweden, members addressed the infectious, oncologic, and autoimmune comorbidities of psoriasis and psoriatic arthritis (PsA). Members discussing infectious comorbidities asked whether patients with psoriasis or PsA are predisposed to particular types of infections, and whether the use of biologic agents is advisable in patients with certain preexisting infections. Regarding the oncologic comorbidities of psoriasis and PsA, members addressed cutaneous malignancy screening, lymphoproliferative malignancy risk and the need for screening, and treatment of patients with preexisting oncologic history requiring systemic therapy. Finally, GRAPPA members discussed autoimmune comorbidities associated with psoriasis and PsA; they agreed that research is nascent in this field and larger studies are necessary to determine the precise magnitude of these associations.


Assessors assemble: the need for harmonised external quality assessment schemes for emerging diagnostic methodologies in the field of parasitology.
Global travel and migration trends have meant a huge increase in the numbers of people exposed to tropical parasitic diseases. Thus, there is an increasing need for robust, reproducible and reliable diagnostic techniques in the field. Advanced molecular and lateral flow techniques have pushed the boundaries of clinical parasite diagnostics with their enhanced sensitivities and specificities. These emerging technologies are, however, not without their challenges, and recently there has been multiple evidence of a lack of consensus among protocols and results obtained by quality assessment of these novel technologies. This commentary discusses findings from some recent quality assessment studies in the field of blood and faecal parasitology. The article also makes recommendations for a unified and harmonised approach towards delivering high-quality clinical parasitology diagnoses, especially through the use of proficiency testing.


Choosing the correct treatment for acute aortic type B dissection.
Acute type B aortic dissection is a life threatening disease process, which remains a clinical dilemma despite advances in technology, surgical technique and postoperative management. The variability of presenting symptoms, lack of a consensus on indications for treatment and differing opinions about the optimal timing for repair have added to the management confusion. Medical management has been the standard of care for acute uncomplicated type B dissection. Surgical repair and endovascular intervention are reserved for those who present with, or subsequently develop, dissection-related complications. Complicated dissections occur in 25% of cases and may include organ malperfusion, aortic rupture, periaortic hematoma, and uncontrolled hypertension. In the past decade thoracic endovascular aortic repair (TEVAR) has gained widespread acceptance as the modality of choice for the treatment of complicated type B dissection. This transition is representative of advances in technology, physician experience with aortic endografts and lower morbidity and mortality rates associated with TEVAR. The best medical therapy remains the standard of care for uncomplicated dissection, however this strategy fails to prevent long-term aortic-related morbidity and mortality. Recent data suggest that early TEVAR lowers aortic-related events and improves long-term aortic specific survival by covering the entry tear, promoting false lumen thrombosis and inducing aortic wall remodeling. The paucity of supporting data has created controversy surrounding the optimal treatment strategy for acute type B dissection. Nonetheless, recent healthcare trends show a paradigm shift towards the utilization of early TEVAR in acute type B dissection.


Vascular endothelial growth factor expression and cyclosporine toxicity in renal allograft rejection.
The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF-alpha, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow-up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF-alpha expressions (p < 0.001). VEGF expression increased with increasing expression of TNF-alpha (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow-up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.


[Intervening and therapeutic effect of cordyceps mycelia extract on liver cirrhosis induced by dimethylnitrosamine in rats].
To explore the intervening and therapeutic effect of Cordyceps mycelia extract (CME) on liver cirrhosis induced by dimethylnitrosamine (DMN) in rats. Rat liver cirrhosis model was established by peritoneal injection of DMN at a dose of 10 microg/kg, once daily in the first 3 days of every week for 4 successive weeks. Experimental study on CME-intervention was conducted from the beginning of modeling to the end of the 4th week, while the CME-treatment experiment was carried out from the 4th week of modeling, when terminating the modeling factor, to the end of the 8th week, by administering CME at a dose of 0. 74 g/( kg d) once a day. Animals were killed in batches on the 3rd day, the 2nd (T1), 4th (T2), 6th (T3) and 8th (T4) week after modeling, to observe the histopathologic change in liver and the immunohistochemical staining of alpha-smooth muscle actin (alpha-SMA) and collagen type I (Col I), determine the content of hydroxyproline (Hyp) in liver, and the liver function was tested as well. CME-intervention experiment showed that as compared to those in the modeled rats at corresponding time points, in rats at T1 and T2, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity and total bilirubin (TBIL) content were significantly lower, and albumin (Alb) obviously higher; while at T2, Hyp content, ct-SMA and Col I positive expression were significantly lower (P < 0.05), the proliferation of collagen fibre attenuated. CME-treatment experiment showed that as compared to those in the modeled rats at corresponding time points, lower serum ALT, AST activity and TBIL content, and higher serum level of Alb were shown in rats at T1; and lower Hyp content, liver collagen fibre, and alpha-SMA positive expression were shown at T1 and T2; while less Col I positive expression at T2 was also shown in them (all P < 0.05). CME could not only prevent the development of liver cirrhosis induced by DMN in rats, but also effectively promote the reversion of already formed liver cirrhosis, having a favourable prospect of clinical application.


Biphasic regulation of RNA interference during rotavirus infection by modulation of Argonaute2.
RNA interference (RNAi) is an evolutionary ancient innate immune response in plants, nematodes, and arthropods providing natural protection against viral infection. Viruses have also gained counter-defensive measures by producing virulence determinants called viral-suppressors-of-RNAi (VSRs). Interestingly, in spite of dominance of interferon-based immunity over RNAi in somatic cells of higher vertebrates, recent reports are accumulating in favour of retention of the antiviral nature of RNAi in mammalian cells. The present study focuses on the modulation of intracellular RNAi during infection with rotavirus (RV), an enteric virus with double-stranded RNA genome. Intriguingly, a time point-dependent bimodal regulation of RNAi was observed in RV-infected cells, where short interfering RNA (siRNA)-based RNAi was rendered non-functional during early hours of infection only to be reinstated fully beyond that early infection stage. Subsequent investigations revealed RV nonstructural protein 1 to serve as a putative VSR by associating with and triggering degradation of Argonaute2 (AGO2), the prime effector of siRNA-mediated RNAi, via ubiquitin-proteasome pathway. The proviral significance of AGO2 degradation was further confirmed when ectopic overexpression of AGO2 significantly reduced RV infection. Cumulatively, the current study presents a unique modulation of host RNAi during RV infection, highlighting the importance of antiviral RNAi in mammalian cells.


Application of Artificial Intelligence in Early Diagnosis of Spontaneous Preterm Labor and Birth.
This study reviews the current status and future prospective of knowledge on the use of artificial intelligence for the prediction of spontaneous preterm labor and birth ("preterm birth" hereafter). The summary of review suggests that different machine learning approaches would be optimal for different types of data regarding the prediction of preterm birth: the artificial neural network, logistic regression and/or the random forest for numeric data; the support vector machine for electrohysterogram data; the recurrent neural network for text data; and the convolutional neural network for image data. The ranges of performance measures were 0.79-0.94 for accuracy, 0.22-0.97 for sensitivity, 0.86-1.00 for specificity, and 0.54-0.83 for the area under the receiver operating characteristic curve. The following maternal variables were reported to be major determinants of preterm birth: delivery and pregestational body mass index, age, parity, predelivery systolic and diastolic blood pressure, twins, below high school graduation, infant sex, prior preterm birth, progesterone medication history, upper gastrointestinal tract symptom, gastroesophageal reflux disease, Helicobacter pylori, urban region, calcium channel blocker medication history, gestational diabetes mellitus, prior cone biopsy, cervical length, myomas and adenomyosis, insurance, marriage, religion, systemic lupus erythematosus, hydroxychloroquine sulfate, and increased cerebrospinal fluid and reduced cortical folding due to impaired brain growth.


Methodological aspects of minimal residual disease assessment by flow cytometry in acute lymphoblastic leukemia: A French multicenter study.
Background: Minimal residual disease (MRD) assessment provides a powerful prognostic factor for therapeutic stratification in acute lymphoblastic leukemia (ALL). Multiparameter flow cytometry (MFC) has the potential for a rapid and sensitive identification of high risk patients. Our group has previously published that MRD levels analyzed by clone specific Ig/TcR-QPCR and MFC were concordant at a sensitivity of 10-4 . Here we report the MFC methodological aspects from this multi-center experience. Methods: MRD was assessed by MFC in 1030 follow-up samples from 265 pediatric and adult patients with de novo ALL treated in the FRALLE, EORTC or GRALL clinical trials. MRD assessment as applied by the eight participating MFC laboratories is described in detail regarding cell preparation, leukemia-associated immunophenotype (LAIP) markers and data analysis. Samples were obtained from bone marrow (BM) and peripheral blood (PB). Immunostaining was performed after erythrocyte lysis or Ficoll enrichment. Results: This study confirms the applicability of MFC-based MRD assessment in 97% of patients with ALL at the 10-4 cut-off. MRD values after Ficoll enrichment and erythrocyte lysis were found comparable. Higher MRD values were obtained in BM than in PB, especially for B-lineage ALL. Conclusions: Measurement of MRD by MFC at the 10-4 cut-off is applicable within a few hours for almost all patients and using a comparable analytical strategy allows for multicenter collaborative studies. The method can be introduced in a strategy aimed at defining the risk of failure of patients with childhood or adult ALL. © 2014 Clinical Cytometry Society.


Transplantation for colorectal liver metastasis.
Liver transplantation has emerged as a possible treatment for selected patients with nonresectable colorectal liver metastasis, but controversy still exists regarding optimal selection criteria and acceptable outcomes. Univariate analysis in the largest cohorts confirms that metachronous disease, Oslo score = 0-1, metabolic tumor volume (MTV) less than 70 cm3, and tumor burden score less than 9 are positive predictive factors for good overall survival outcomes. Some recent trials might suggest that technical resectability is not a valid exclusion criterion for patients with high tumor load and favorable prognostic scores in the transplant evaluation. Recent developments in circulation DNA technology and liquid biopsy may play a future role in the selection and monitoring of patients. Evaluation for transplant needs multidisciplinary involvement and should not be delayed until the failure of conventional oncological therapy. Larger data sets are needed to refine the selection criteria for liver transplantation in colorectal liver metastasis (CRLM).


Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma.
The phosphoinositide 3-kinase (PI3K) signaling pathway is the most commonly mutated pathway in head and neck squamous cell carcinoma (HNSCC). There are several drugs targeting members of the PI3K signaling pathway in development for HNSCC. In this article, we review the genetic alterations reported in the pathway pertinent to HNSCC, various agents in development targeting various mediators of the pathway, results from clinical trials, and remaining challenges in the development of PI3K pathway inhibitors.


High-Voltage Instability of Vinylene Carbonate (VC): Impact of Formed Poly-VC on Interphases and Toxicity.
Full exhaustion in specific energy/energy density of state-of-the-art LiNix Coy Mnz O2 (NCM)-based Li-ion batteries (LIB) is currently limited for reasons of NCM stability by upper cut-off voltages (UCV) below 4.3 V. At higher UCV, structural decomposition triggers electrode crosstalk in the course of enhanced transition metal dissolution and leads to severe specific capacity/energy fade; in the worst case to a sudden death phenomenon (roll-over failure). The additive lithium difluorophosphate (LiDFP) is known to suppress this by scavenging dissolved metals, but at the cost of enhanced toxicity due to the formation of organofluorophosphates (OFPs). Addition of film-forming electrolyte additives like vinylene carbonate (VC) can intrinsically decrease OFP formation in thermally aged LiDFP-containing electrolytes, though the benefit of this dual-additive approach can be questioned at higher UCVs. In this work, VC is shown to decrease the formation of potentially toxic OFPs within the electrolyte during cycling at conventional UCVs but triggers OFP formation at higher UCVs. The electrolyte contains soluble VC-polymerization products. These products are formed at the cathode during VC oxidation (and are found within the cathode electrolyte interphase (CEI), suggesting an OFP electrode crosstalk of VC decomposition species, as the OFP-precursor molecules are shown to be formed at the anode.


The current situation of Endocrine Surgery in Latin America.
The management of patients with surgical endocrine diseases requires a multidisciplinary team of endocrinologists, radiologists, pathologists and surgeons. As the incidence of surgical endocrine disorders has increased, Endocrine Surgery has emerged as a recognized specialty within general surgery. The number of endocrine surgeons has gradually increased worldwide, however, different from Europe and North America, the specialty has not developed enough in Latin America. We have conducted an extensive research throughout the continent in order to quantify how many trained endocrine surgeons were practicing, how many training programs exist, where we are today and where are we going in the future.


Ender nailing in intertrochanteric fractures of the femur.
A review of 442 patients with intertrochanteric fractures of the femur has confirmed our initial finding in the first 227 patients so treated. Mortality continues at a low 11% at 6 months follow-up. No implant failures have occurred. Fixation failure, as manifested by head penetration or backing out of the nails with subsequent loss of fracture position, can be readily overcome by proper technique. External rotation deformity is controlled by prebending of the nails and early ambulation of the patient. Properly applied, Ender nailing represents a significant advance in the treatment of intertrochanteric fracture of the femur.


Differential roles of AC2 and AC4 of cassava geminiviruses in mediating synergism and suppression of posttranscriptional gene silencing.
Posttranscriptional gene silencing (PTGS) in plants is a natural defense mechanism against virus infection. In mixed infections, virus synergism is proposed to result from suppression of the host defense mechanism by the viruses. Synergistic severe mosaic disease caused by simultaneous infection with isolates of the Cameroon strain of African cassava mosaic virus (ACMV-[CM]) and East African cassava mosaic Cameroon virus (EACMCV) in cassava and tobacco is characterized by a dramatic increase in symptom severity and a severalfold increase in viral-DNA accumulation by both viruses compared to that in singly infected plants. Here, we report that synergism between ACMV-[CM] and EACMCV is a two-way process, as the presence of the DNA-A component of ACMV-[CM] or EACMCV in trans enhanced the accumulation of viral DNA of EACMCV and ACMV-[CM], respectively, in tobacco BY-2 protoplasts. Furthermore, transient expression of ACMV-[CM] AC4 driven by the Cauliflower mosaic virus 35S promoter (p35S-AC4) enhanced EACMCV DNA accumulation by approximately 8-fold in protoplasts, while p35S-AC2 of EACMCV enhanced ACMV-[CM] DNA accumulation, also by approximately 8-fold. An Agrobacterium-based leaf infiltration assay determined that ACMV-[CM] AC4 and EACMCV AC2, the putative synergistic genes, were able to suppress PTGS induced by green fluorescent protein (GFP) and eliminated the short interfering RNAs associated with PTGS, with a correlated increase in GFP mRNA accumulation. In addition, we have identified AC4 of Sri Lankan cassava mosaic virus and AC2 of Indian cassava mosaic virus as suppressors of PTGS, indicating that geminiviruses evolved differently in regard to interaction with the host. The specific and different roles played by these AC2 and AC4 proteins of cassava geminiviruses in regulating anti-PTGS activity and their relation to synergism are discussed.


q-Space imaging using small magnetic field gradient.
q-Space diffusion analysis is a method to obtain the probability density function of the translational displacement of diffusing water molecules. Several quantities can be extracted from the function that indicate a characteristic of the water diffusion in tissue, e.g., the mean displacement of the diffusion, probability for zero displacement, and kurtosis of the function. These quantities are expected to give information about the microstructure of tissues in addition to that obtained from the apparent diffusion coefficient (ADC); however, this method requires high q (i.e., high b) values, which are undesirable in practical applications of the method using clinical magnetic resonance (MR) imaging equipment. We propose a method to obtain certain quantities that indicate a characteristic of the diffusion and that uses low q-value measurements. The quantities we can obtain are the moments of translational displacement, R; the n-th order moment is defined as the average of Rn (n: integer). Kurtosis can also be calculated from the second and fourth moments. We tried to map the moments and kurtosis using clinical MR imaging equipment. We also estimated the inherent errors of the moments obtained. Our method requires precision in measuring spin echo signals and setting q values rather than using high q-value measurements. Although our results show that further error reductions are desired, our method is workable using ordinary clinical MR imaging equipment.


Role of first aid in the management of acute alcohol intoxication: a narrative review.
Acute alcohol intoxication is actually a common admission cause in the Emergency Department and represents an increasing public health burden, in particular among adolescents. It involves possible and significant illness and injury, which can quickly get worse and may need to be managed in the emergency room. We conducted a narrative review of the literature regarding the effectiveness of first aid role of the Emergency Department setting. This review included eighteen studies about alcohol intoxication management in the Emergency Department; most of all highlights the emerging phenomenon in Europe and around the world of acute alcohol intoxication management in first aid. The treatment of acute alcohol intoxication depends on general clinical conditions of the patient, vital signs, hemodynamic stability, cognitive state, alcohol-related complications, which are closely related to the blood alcohol concentration. At the same time, symptoms could be extremely variable due to individual differences in alcohol metabolism. In case of mild-moderate intoxication (blood alcohol concentration < 1 g/L), no drugs are necessary. In case of severe intoxication (blood alcohol concentration > 1 g/L), it is necessary to support with intravenous fluids, treat hypoglycemia, hypotension, hypothermia and electrolyte imbalance, administer complex B and C vitamins and accelerate alcohol elimination from blood with metadoxine. Unlike adults, adolescents are more exposed to the toxic effect of alcohol (because of their immature hepatic alcohol dehydrogenase activity), and then, acute alcohol-related complications are more frequent and dangerous in young people than in adult population. In many cases, patients affected by acute alcohol intoxication referring to an Emergency Department have mild-moderate transitory symptoms that do not require the use of drugs; they can benefit from a clinical observation, with a clinical course often completed within 24 hours with a favorable outcome. Clinical observation with vital signs control is necessary also to evaluate the possible development of the alcohol withdrawal syndrome (that involves a specific treatment) and to evaluate also possible pathological complications of the organism, above all acute liver damage. Patients affected by acute alcohol intoxication are the best candidates to apply the rules of the Temporary Observation Unit in the Emergency Department, because of a clinical course often completed within 24 hours, a favorable outcome and without the need for hospitalization. In many cases, hospitalization could be not necessary, but the patient affected by Alcohol Use Disorder must be referred to an Alcohol Addiction Unit for the follow-up, to reduce the risk of alcohol relapse and complications related to alcohol abuse, and financial costs of hospitalization.


Potential beneficial effects of kefir and its postbiotic, kefiran, on child food allergy.
Food allergies are known as the public health problem, affecting people of all age groups, but more commonly in babies and children, with consequences for nutritional status and quality of life. The increase in the consumption of healthy foods has consequently led to an increased demand for functional foods with specific health benefits. Thus, the pharmaceutical industry's interest in natural products has grown every time and is therefore considered as an alternative to synthetic drugs. Kefir has been outstanding for several years as promising in the manufacture of various pharmaceutical products, due to its nutritional and therapeutic properties for the treatment of many diseases. Currently, a wide variety of new functional foods are appearing on the market, representing an important segment. Postbiotics, for example, has stood out for being a product with action similar to probiotics, without offering side effects. The kefiran is the postbiotic from kefir that promotes potential beneficial effects on food allergy from the intestinal microbiome to the immune system. In this context, it is necessary to know the main promoting component of this functional effect. This review compiles the benefits that kefir, and especially its postbiotic, kefiran, can bring to food allergy. In addition, it serve as a subsidy for studies on the development of innovative nutraceutical products, including the use of kefiran as an alternative therapy in food allergy.


Evidence of weak conscious experiences in the exclusion task.
Exclusion tasks have been proposed as objective measures of unconscious perception as they do not depend upon subjective ratings. In exclusion tasks, participants have to complete a task without using a previously presented prime. Use of the prime is taken as evidence for unconscious processing in the absence of awareness, yet it may also simply indicate that participants have weak experiences but fail to realize that these affect the response or fail to counter the effect on the response. Here, we tested this claim by allowing participants to rate their experience of a masked prime on the perceptual awareness scale (PAS) after the exclusion task. Results showed that the prime was used almost as often when participants reported having seen a "weak glimpse" of the prime as when they claimed to have "no experience" of the prime, thus suggesting participants frequently have weak (possibly contentless) experiences of the stimulus when failing to exclude. This indicates that the criteria for report of awareness is lower (i.e., more liberal) than that for exclusion and that failure to exclude should not be taken as evidence of complete absence of awareness.


Modernizing and transforming medical education at the Kilimanjaro Christian Medical University College.
The Kilimanjaro Christian Medical University (KCMU) College and the Medical Education Partnership Initiative (MEPI) are addressing the crisis in Tanzanian health care manpower by modernizing the college's medical education with new tools and techniques. With a $10 million MEPI grant and the participation of its partner, Duke University, KCMU is harnessing the power of information technology (IT) to upgrade tools for students and faculty. Initiatives in eLearning have included bringing fiber-optic connectivity to the campus, offering campus-wide wireless access, opening student and faculty computer laboratories, and providing computer tablets to all incoming medical students. Beyond IT, the college is also offering wet laboratory instruction for hands-on diagnostic skills, team-based learning, and clinical skills workshops. In addition, modern teaching tools and techniques address the challenges posed by increasing numbers of students. To provide incentives for instructors, a performance-based compensation plan and teaching awards have been established. Also for faculty, IT tools and training have been made available, and a medical education course management system is now being widely employed. Student and faculty responses have been favorable, and the rapid uptake of these interventions by students, faculty, and the college's administration suggests that the KCMU College MEPI approach has addressed unmet needs. This enabling environment has transformed the culture of learning and teaching at KCMU College, where a path to sustainability is now being pursued.


Sexually transmitted infections in Bangladeshis resident in the UK: a case-control study.
To evaluate the prevalence of sexually transmitted infections (STIs) and mode of presentation in patients originating from Bangladesh and resident in the United Kingdom in comparison with non-Bangladeshi patients attending an inner London genitourinary medicine (GUM) clinic. A retrospective, cross sectional study with comparator group was carried out at an open access GUM clinic in east London. 104 consecutive newly attending Bangladeshi men were compared with 199 consecutive newly attending non-Bangladeshi men and 115 consecutive newly attending Bangladeshi women were compared with 218 consecutive newly attending non-Bangladeshi women. Any diagnosed sexually transmitted infections, sexual history characteristics, reasons for presentation, and referral patterns were noted. Bangladeshi men (28.8% compared with 7.5%; p<0.0001) and women (42.7% compared with 12.8%; p<0.0001) were more likely to be referred by their general practitioners or other medical services. Bangladeshi men were more likely to present with sexual dysfunction (12.5% compared with 2.5%; p=0.001). The prevalence of STIs was broadly similar across the study groups; however, syphilis was significantly more common in the Bangladeshi men (10.9% compared with 4%; p=0.04) and nongonococcal urethritis (NGU) in the control men (35% compared with 20.2%; p=0.02). Bacterial vaginosis was an infrequent diagnosis in the Bangladeshi women (3.5% compared with 22.4%; p<0.0001). STI prevalence in Bangladeshis attending GUM services is similar to other populations although patterns of presentation and referral do show variation. Bangladeshi men are more likely to access GUM clinics for psychosexual services. The presence of STIs in Bangladeshis particularly those imported from Bangladesh provides an opportunity for HIV transmission between the United Kingdom and Bangladesh.


The epidemiology of acute endophthalmitis after cataract surgery in an Asian population.
To describe the incidence, risk factors, and clinical outcome of acute endophthalmitis after cataract extraction in a multiethnic Asian population. Prospective case series. All patients with cataract extractions performed at the Singapore National Eye Center from 1996 to 2001. Data on patients with acute endophthalmitis cases presenting within 6 weeks after cataract surgery were prospectively collected in a standardized format. Acute endophthalmitis after cataract surgery. During the study period, 44 803 cataract operations (25 476 phacoemulsification and 19 327 extracapsular cataract extractions) were performed. There were 34 cases of acute endophthalmitis (average annual incidence of 0.076%), 21 of which were culture positive (average annual incidence of 0.040%). In multivariate analysis, risk of endophthalmitis was associated with phacoemulsification technique (relative risk [RR], 1.9; 95% confidence interval [CI], 0.9, 3.9; P = 0.10 for all endophthalmitis cases; RR, 3.1; 95% CI, 1.1, 9.4; P = 0.04 for culture-positive endophthalmitis cases) and the occurrence of intraoperative posterior capsule rupture (RR, 8.0; 95% CI, 3.1, 20.7; P<0.001 for all endophthalmitis cases; RR, 11.0; 95% CI, 3.7, 23.9; P<0.001 for culture-positive endophthalmitis cases). After a median follow-up of 234 days, half of the eyes achieved a final best-corrected visual acuity of 20/40. Predictors of this visual acuity included baseline acuity of counting fingers or better, culture-negative endophthalmitis, or infection caused by coagulase-negative Staphylococcus. The incidence of acute endophthalmitis after cataract extraction in Singapore is consistent with rates reported elsewhere. The phacoemulsification technique is associated with a higher risk of acute culture-positive endophthalmitis compared with extracapsular cataract extraction. Intraoperative posterior capsule rupture is associated with an 8- to 11-fold higher risk of acute endophthalmitis, suggesting that these eyes should be closely monitored for signs of infection in the immediate postoperative period.


Nociceptin prevents stress-induced ethanol- but not cocaine-seeking behavior in rats.
This study examined whether nociceptin/orphanin FQ (NC), the endogenous ligand of the opioid receptor-like1 (ORL1) receptor, can block drug-seeking behavior induced by foot-shock stress. Male Wistar rats were trained to operantly self-administer ethanol or cocaine, and then subjected to daily extinction training until responding ceased. Subsequent exposure to 15 min of intermittent footshock elicited robust reinstatement of responding at the previously drug-paired lever. NC (0.1-2.0 microg; i.c.v.) significantly inhibited the effects of footshock stress on ethanol- but not cocaine-seeking behavior. The results support the hypothesis that the NC system participates in the regulation of behavioral responses to stress, and that drugs interacting with NC receptors may have therapeutic potential for the treatment of stress-induced alcohol-seeking behavior and relapse.


Systematic mutagenesis of the murine gammaherpesvirus 68 M2 protein identifies domains important for chronic infection.
Murine gammaherpesvirus 68 (MHV68) infection of inbred mice represents a genetically tractable small-animal model for assessing the requirements for the establishment of latency, as well as reactivation from latency, within the lymphoid compartment. By day 16 postinfection, MHV68 latency in the spleen is found in B cells, dendritic cells, and macrophages. However, as with Epstein-Barr virus, by 3 months postinfection MHV68 latency is predominantly found in isotype-switched memory B cells. The MHV68 M2 gene product is a latency-associated antigen with no discernible homology to any known cellular or viral proteins. However, depending on experimental conditions, the M2 protein has been shown to play a critical role in both the efficient establishment of latency in splenic B cells and reactivation from latently infected splenic B cells. Inspection of the sequence of the M2 protein reveals several hallmarks of a signaling molecule, including multiple PXXP motifs and two potential tyrosine phosphorylation sites. Here, we report the generation of a panel of recombinant MHV68 viruses harboring mutations in the M2 gene that disrupt putative functional motifs. Subsequent analyses of the panel of M2 mutant viruses revealed a functionally important cluster of PXXP motifs in the C-terminal region of M2, which have previously been implicated in binding Vav proteins (P. A. Madureira, P. Matos, I. Soeiro, L. K. Dixon, J. P. Simas, and E. W. Lam, J. Biol. Chem. 280:37310-37318, 2005; L. Rodrigues, M. Pires de Miranda, M. J. Caloca, X. R. Bustelo, and J. P. Simas, J. Virol. 80:6123-6135, 2006). Further characterization of two adjacent PXXP motifs in the C terminus of the M2 protein revealed differences in the functions of these domains in M2-driven expansion of primary murine B cells in culture. Finally, we show that tyrosine residues 120 and 129 play a critical role in both the establishment of splenic latency and reactivation from latency upon explant of splenocytes into tissue culture. Taken together, these analyses will aide future studies for identifying M2 interacting partners and B-cell signaling pathways that are manipulated by the M2 protein.


Computerized provider order entry systems - Research imperatives and organizational challenges facing pathology services.
Information and communication technologies (ICT) are contributing to major changes taking place in pathology and within health services more generally. In this article, we draw on our research experience for over 7 years investigating the implementation and diffusion of computerized provider order entry (CPOE) systems to articulate some of the key informatics challenges confronting pathology laboratories. The implementation of these systems, with their improved information management and decision support structures, provides the potential for enhancing the role that pathology services play in patient care pathways. Beyond eliminating legibility problems, CPOE systems can also contribute to the efficiency and safety of healthcare, reducing the duplication of test orders and diminishing the risk of misidentification of patient samples and orders. However, despite the enthusiasm for CPOE systems, their diffusion across healthcare settings remains variable and is often beset by implementation problems. Information systems like CPOE may have the ability to integrate work, departments and organizations, but unfortunately, health professionals, departments and organizations do not always want to be integrated in ways that information systems allow. A persistent theme that emerges from the research evidence is that one size does not fit all, and system success or otherwise is reliant on the conditions and circumstances in which they are located. These conditions and circumstances are part of what is negotiated in the complex, messy and challenging area of ICT implementation. The solution is not likely to be simple and easy, but current evidence suggests that a combination of concerted efforts, better research designs, more sophisticated theories and hypotheses as well as more skilled, multidisciplinary research teams, tackling this area of study will bring substantial benefits, improving the effectiveness of pathology services, and, as a direct corollary, the quality of patient care.


The benefit of seat belt legislation in the United Kingdom.
Legislation for compulsory wearing of seat belts by car drivers and front seat passengers has been acclaimed as a major public health advance. Reports from other countries, and two recent evaluative studies in the United Kingdom, have suggested that legislation reduces both deaths and injuries. To assess the effect of the UK law 5 years after its implementation, trends in routine data for 1976-1987 have been reviewed. There were two sources of data: mortality statistics, published by the Office of Population Censuses and Surveys in the quarterly Monitor DH4, and road accident statistics, recorded by the police and published by the Department of Transport. There is a downward trend in deaths over the period, but the data show little impact from the law. One explanation for this lack of effect is the risk compensation hypothesis, which suggests that "safety" improvements are transferred by drivers into increased performance--the amount and speed of travel. Public health policies need to take into account the complex behavioural interactions between travel and safety choices if they are to affect underlying trends.


A colony multiplex quantitative PCR-Based 3S3DBC method and variations of it for screening DNA libraries.
A DNA library is a collection of DNA fragments cloned into vectors and stored individually in host cells, and is a valuable resource for molecular cloning, gene physical mapping, and genome sequencing projects. To take the best advantage of a DNA library, a good screening method is needed. After describing pooling strategies and issues that should be considered in DNA library screening, here we report an efficient colony multiplex quantitative PCR-based 3-step, 3-dimension, and binary-code (3S3DBC) method we used to screen genes from a planarian genomic DNA fosmid library. This method requires only 3 rounds of PCR reactions and only around 6 hours to distinguish one or more desired clones from a large DNA library. According to the particular situations in different research labs, this method can be further modified and simplified to suit their requirements.


Antigenic cross-reactions among herpes simplex virus types 1 and 2, Epstein-Barr virus, and cytomegalovirus.
Polyvalent rabbit antisera against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV), monospecific antisera against affinity-purified HSV-2 glycoproteins gB and gG, and a panel of monoclonal antibodies against HSV and EBV proteins were used to analyze cross-reactive molecules in cells infected with the four herpesviruses. A combination of immunoprecipitation and Western blotting with these reagents was used to determine that all four viruses coded for a glycoprotein that cross-reacted with HSV-1 gB. CMV coded for proteins that cross-reacted with HSV-2 gC, gD, and gE. Both CMV and EBV coded for proteins that cross-reacted with HSV-2 gG. Antigenic counterparts to the p45 nucleocapsid protein of HSV-2 were present in HSV-1 and CMV, and counterparts of the major DNA-binding protein and the ribonucleotide reductase of HSV-1 were present in all the viruses. The EBV virion glycoprotein gp85 was immunoprecipitated by antisera to HSV-1, HSV-2, and CMV. Antisera to CMV and EBV neutralized the infectivity of both HSV-1 and HSV-2 at high concentrations. This suggests that cross-reactivity between these four human herpesviruses may have pathogenic as well as evolutionary significance.


Polythioether Particles Armored with Modifiable Graphene Oxide Nanosheets.
Facile and scalable fabrication methods are attractive to prepare materials for diverse applications. Herein, a method is presented to prepare cross-linked polymeric nanoparticles with graphene oxide (GO) nanosheets covalently attached to the surface. Alkene-modified GO serves as a surfactant in a miniemulsion polymerization, and the alkene functionalities of GO exposed to the oil-phase are incorporated into the polymer particle through thiol-ene reactions, leaving the unreacted alkene functional groups of the other face of GO available for further functionalization. The surface of GO-armored polymer particles is then modified with a small molecule fluorophore or carboxylic acid functional groups that bind to Fe2 O3 and TiO2 nanoparticles. This methodology provides a facile route to preparing complex hybrid composite materials.


Extracellular DNA release, quorum sensing, and PrrF1/F2 small RNAs are key players in Pseudomonas aeruginosa tobramycin-enhanced biofilm formation.
Biofilms are structured microbial communities that are the leading cause of numerous chronic infections which are difficult to eradicate. Within the lungs of individuals with cystic fibrosis (CF), Pseudomonas aeruginosa causes persistent biofilm infection that is commonly treated with aminoglycoside antibiotics such as tobramycin. However, sublethal concentrations of this aminoglycoside were previously shown to increase biofilm formation by P. aeruginosa, but the underlying adaptive mechanisms still remain elusive. Herein, we combined confocal laser scanning microscope analyses, proteomics profiling, gene expression assays and phenotypic studies to unravel P. aeruginosa potential adaptive mechanisms in response to tobramycin exposure during biofilm growth. Under this condition, we show that the modified biofilm architecture is related at least in part to increased extracellular DNA (eDNA) release, most likely as a result of biofilm cell death. Furthermore, the activity of quorum sensing (QS) systems was increased, leading to higher production of QS signaling molecules. We also demonstrate upon tobramycin exposure an increase in expression of the PrrF small regulatory RNAs, as well as expression of iron uptake systems. Remarkably, biofilm biovolumes and eDNA relative abundances in pqs and prrF mutant strains decrease in the presence of tobramycin. Overall, our findings offer experimental evidences for a potential adaptive mechanism linking PrrF sRNAs, QS signaling, biofilm cell death, eDNA release, and tobramycin-enhanced biofilm formation in P. aeruginosa. These specific adaptive mechanisms should be considered to improve treatment strategies against P. aeruginosa biofilm establishment in CF patients' lungs.


Cognitive activity and the cognitive morbidity of Alzheimer disease.
To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter. As part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals. On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale. Mentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.