AIScore chemically diverse empirical scoring function employing quantum chemical binding energies of hydrogen-bonded complexes.
In this work we report on a novel scoring function that is based on the LUDI model and focuses on the prediction of binding affinities. AIScore extends the original FlexX scoring function using a chemically diverse set of hydrogen-bonded interactions derived from extensive quantum chemical ab initio calculations. Furthermore, we introduce an algorithmic extension for the treatment of multifurcated hydrogen bonds (XFurcate). Charged and resonance-assisted hydrogen bond energies and hydrophobic interactions as well as a scaling factor for implicit solvation were fitted to experimental data. To this end, we assembled a set of 101 protein-ligand complexes with known experimental binding affinities. Tightly bound water molecules in the active site were considered to be an integral part of the binding pocket. Compared to the original FlexX scoring function, AIScore significantly improves the prediction of the binding free energies of the complexes in their native crystal structures. In combination with XFurcate, AIScore yields a Pearson correlation coefficient of R P = 0.87 on the training set. In a validation run on the PDBbind test set we achieved an R P value of 0.46 for 799 attractively scored complexes, compared to a value of R P = 0.17 and 739 bound complexes obtained with the FlexX original scoring function. The redocking capability of AIScore, on the other hand, does not fully reach the good performance of the original FlexX scoring function. This finding suggests that AIScore should rather be used for postscoring in combination with the standard FlexX incremental ligand construction scheme.


Recovery Assessment Scale - Domains and Stages (RAS-DS): Its feasibility and outcome measurement capacity.
A self-report instrument of mental health recovery is needed both to facilitate collaborative, recovery-oriented practice and measure recovery-focused outcomes. The Recovery Assessment Scale - Domains and Stages (RAS-DS) has been developed to simultaneously fulfill these goals. The aim of this study was to test the feasibility and measurement properties of the RAS-DS. Feasibility was examined by 58 consumer-staff pairs volunteering from 3 non-government organisations. Consumers completed the RAS-DS, discussed it with staff, and then both completed Usefulness Questionnaires. The psychometric properties were examined using Rasch analysis with the data from these consumer participants and from additional participants recruited from two Partners in Recovery programs (N=324). Over 70% of consumers reported taking 15 minutes or less to complete the RAS-DS and rated the instrument as easy or very easy to use. Qualitative data from both consumers and staff indicated that, for most, the RAS-DS was an easy to use, meaningful resource that facilitated shared understandings and collaborative goal setting. However, for a very small number of consumers, the instrument was too confronting and hard to use. Rasch analysis demonstrated evidence for excellent internal reliability and validity. Raw scores were highly correlated with Rasch-generated overall scores and thus no transformation is required, easing use for clinicians. Preliminary evidence for sensitivity to change was demonstrated. The results provide evidence of the feasibility and psychometric strengths of the RAS-DS. Although further research is required, the RAS-DS shows promise as a potential addition to the national suite of routine outcome measures.


[Effectiveness of PCR analysis in the diagnostics of tuberculosis].
To discover DNA of mycobacterium and evaluate chemotherapy efficiency of pulmonary tuberculosis Polimerize Chain Reaction (PCR) analysis was performed. Different pathological materials of patients with pulmonary tuberculosis and those with nonspecific lung diseases had been examined. Phlegm sample had been carried out regularly by means of PCR analysis and traditional microbiological methods. PCR analysis demonstrated 94% sensibility, specificity 100%; investigation of different pathological materials demonstrated 54% sensibility of molecular - genetic method. Discontinuance of bacterium secretion at PCR analysis positively correlated with clinical rontgenologic dynamics of disappearance of tubercular process.


The association between fingolimod and mental health outcomes in a cohort of Multiple Sclerosis patients with stress.
The primary objective was to study the association between fingolimod and the frequency of depression, anxiety, and insomnia symptoms among a cohort of Multiple Sclerosis (MS) patients with stress. The secondary objective was to examine the association between patient characteristics and these psychiatric symptoms. Patients with MS and stress were recruited according to the Arabic version of the Perceived Stress Scale (PSS). Psychiatric outcomes were measured by validated scales. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Data from 324 participants were analyzed. Fingolimod was associated with a significantly lower adjusted odds ratio for depression (aOR 0.58, 95% CI 0.35-0.97, p<0.05) but less associated with anxiety (aOR 0.63, 95% CI 0.35-1.01, p=0.05) and insomnia (aOR 0.88, 95% CI 0.52-1.51, p=0.64). Close monitoring of mental health is required for patients with MS using disease-modifying therapies.


Genetically-modified Stem Cell in Regenerative Medicine and Cancer Therapy; A New Era.
Recently, genetic engineering by various strategies to stimulate gene expression in a specific and controllable mode is a speedily growing therapeutic approach. Genetic modification of human stem or progenitor cells, such as Embryonic Stem Cells (ESCs), Neural Progenitor Cells (NPCs), Mesenchymal Stem/Stromal Cells (MSCs), and Hematopoietic Stem Cells (HSCs) for direct delivery of specific therapeutic molecules or genes has been evidenced as an opportune plan in the context of regenerative medicine due to their supported viability, proliferative features, and metabolic qualities. On the other hand, a large number of studies have investigated the efficacy of modified stem cells in cancer therapy using cells from various sources, disparate transfection means for gene delivery, different transfected yields, and wide variability of tumor models. Accordingly, cell-based gene therapy holds substantial aptitude for the treatment of human malignancy as it could relieve signs or even cure cancer succeeding expression of therapeutic or suicide transgene products; however, there exist inconsistent results in this regard. Herein, we deliver a brief overview of stem cell potential to use in cancer therapy and regenerative medicine and importantly discuss stem cells based gene delivery competencies to stimulate tissue repair and replacement in concomitant with their potential to use as an anti-cancer therapeutic strategy, focusing on the last two decades' in vivo studies.


Linking the orthopaedic office-hospital continuum: results before and after implementation of an automated patient health history project.
This article introduces an innovative collaboration between an orthopaedic surgeon's office and the hospital to assure complete and accurate admission information without duplication. With the use of point-of-care software, the assessment process was re-tooled. This change involved the patient/family assuming responsibility for completing paper and pencil in-depth history and systems review that was then used as part of the evaluation process and inputted into the database allowing for more effective outcomes assessment. In this re-tooling process, the concept of "sharing" information with the partnering hospital was explored. In collaborative discussions, the nursing admission assessment was targeted as a process where there was significant duplication. In fact, much of the information required on the 4-page form was already assessed and documented in the office setting. Consequently it was agreed that the majority of the inpatient nursing history/admission assessment form would be replaced with the assessment completed by the professional office staff. Because of incompatible software, the systems could not be linked but a printed copy of the form was sent to the hospital. Results measuring satisfaction, timesaving, and compliance with JCAHO documentation standards were part of the evaluation. Patients and clinicians were satisfied with the process. There was a significant timesaving for the in-patient RN which facilitated more direct contact with the patient and family.


Measuring the agreement between brain connectivity networks.
Investigating the level of similarity between two brain networks, resulting from measures of effective connectivity in the brain, can be of interest from many respects. In this study, we propose and test the idea to borrow measures of association used in machine learning to provide a measure of similarity between the structure of (un-weighted) brain connectivity networks. The measures here explored are the accuracy, Cohen's Kappa (K) and Area Under Curve (AUC). We implemented two simulation studies, reproducing two contexts of application that can be particularly interesting for practical applications, namely: i) in methodological studies, performed on surrogate data, aiming at comparing the estimated network with the corresponding ground-truth network; ii) in applications to real data, when it is necessary to compare the structure of a network obtained in a specific subject with a reference (e.g. a baseline condition or normative data). In the simulations, the level of similarity between two networks was manipulated through different factors. We then investigated the effect of such manipulations on the measures of association. Results showed how the three parameters modulated their values according to the level of similarity between the two networks. In particular, the AUC provided the better performances in terms of its capability to synthetize the similarity between two networks, showing high dynamic and sensitivity.


Low-volume jet injection for intradermal immunization in rabbits.
This study tested a low-volume (20-30 microl/20-30 microg DNA) jet injection method for intradermal delivery of a DNA vaccine. Jet injection offers the advantages of a needle-less system, low-cost, rapid preparation of the injected DNA solution, and a simple delivery system. More than one construct can be injected simultaneously and the method may be combined with adjuvants. Low-volume jet injection targeted delivery of a DNA solution exclusively to the dermis and epidermis of rabbits. A three injection series of plasmid DNA, encoding the Hepatitis B Surface Antigen stimulated a humoral immune response in 2/5 rabbits. One rabbit developed a significant rise in antibody titer after 1 injection and one following 2 injections. There were no significant differences between jet injection and particle bombardment in the maximal antibody titers or number of injections before response. A three injection series of the same plasmid DNA by particle bombardment elicited a significant rise in antibody titer in 3/5 rabbits. One rabbit developed antibody after 1 injection and two after 3 injections. In contrast, 0/5 rabbits receiving DNA by needle and syringe injection responded. In the jet injection and particle bombardment groups, gene expression levels in the skin did not predict response. While immune responses were similar, luciferase gene expression levels in the skin following particle bombardment were 10-100 times higher than jet injection. Low-volume jet injection is a simple, effective methodology for intradermal DNA immunization.


Preliminary characterization of a placental factor inhibiting breathing in fetal sheep.
Previous studies have revealed a placental extract that inhibits breathing in fetal sheep. In the present study of 29 chronically instrumented sheep at 132+/-1 days of gestation, infusion of the 1-10 kDa extract inhibited breathing in 76% of the experiments whereas Krebs' solution inhibited it in 24%. It retained this activity after 6 months of freezing, after lyophilization, and upon lowering the pH during purification from 8.0 to 4.0, but it inhibited breathing in only 35% when the pH was lowered to 2.0. A significant dose-dependent effect was observed from a 16-fold dilution to a 4-fold concentration. Treatment of the extract with proteinase K or boiling reduced the activity to 30% or 26% inhibition, respectively. The activity was not adsorbed to an ion-exchange column at pH 7.0 or 8.0, but it was at pH 9.0 and it eluted with increasing NaCl concentrations. On a polyacrylamide gel the activity was eluted at a K(av) of 0.66 (82% inhibition), corresponding to between 2.5 and 4.5 kDa. These findings suggest that a peptide produced by the placenta, with a molecular mass between 2.5 and 4.5 kDa, inhibits fetal breathing.


TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types.
Immunotherapy with checkpoint inhibitors, such as PD-1/PD-L1 blockage, is becoming standard of practice for an increasing number of cancer types. However, the response rate is only 10%-40%. Thus, identifying biomarkers that could accurately predict the ICI-therapy response is critically important. We downloaded somatic mutation data for 46,697 patients and tumor-infiltrating immune cells levels data for 11070 patients, then combined TP53 and BRAF mutation status into a biomarker model and found that the predict ability of TP53/BRAF mutation model is more powerful than some past models. Commonly, patients with high-TMB status have better response to ICI therapy than patients with low-TMB status. However, the genotype of TP53MUTBRAFWT in high-TMB status cohort have poorer response to ICI therapy than the genotype of BRAFMUTTP53WT in low-TMB status (Median, 18 months vs 47 month). Thus, TP53/BRAF mutation model can add predictive value to TMB in identifying patients who benefited from ICI treatment, which can enable more informed treatment decisions.


Apoptosis, neurotrophic factors and neurodegeneration.
Apoptosis is an active process of cell death characterized by distinct morphological features, and is often the end result of a genetic programme of events, i.e. programmed cell death (PCD). There is growing evidence supporting a role for apoptosis in some neurodegenerative diseases. This conclusion is based on DNA fragmentation studies and findings of increased levels of pro-apoptotic genes in human brain and in in vivo and in vitro model systems. Additionally, there is some evidence for a loss of neurotrophin support in neurodegenerative diseases. In Alzheimer's disease, in particular, there is strong evidence from human brain studies, transgenic models and in vitro models to suggest that the mode of nerve cell death is apoptotic. In this review we describe the evidence implicating apoptosis in neurodegenerative diseases with a particular emphasis on Alzheimer's disease.


Varietal differences among the phenolic profiles and antioxidant properties of four cultivars of spine grape (Vitis davidii Foex) in Chongyi County (China).
Spine grape (Vitis davidii Foex) is an important wild plant species in South China. To provide sufficient experimental evidence for the strong antioxidant activity of spine grapes, four cultivars from Chongyi County, China, including three red varieties (Junzi #1, Junzi #2, and Liantang) and one white variety (Baiyu) were evaluated. The Junzi #1 had the highest phenolic content (total phenolic, flavonoids, flavanols, and anthocyanins) and the strongest antioxidant capacity (DPPH radical-scavenging capacity, cupric-reducing capacity and hydroxyl radical-scavenging activity) among the four varieties. HPLC analysis of spine grapes revealed that the (+)-catechin was the most abundant phenolics and the hydroxycinnamic acids were the major phenolic acids in the four varieties. Hierarchical cluster analysis showed that the Junzi #1 belongs to the group with high phenolic content and strong antioxidant power. The results suggest the Junzi #1 has the best health promoting properties, and the higher utilization value and potential for development.


Open versus arthroscopic surgical treatment for anterior shoulder dislocation: a comparative systematic review and meta-analysis over the past 20 years.
The purpose of this study was to perform a meta-analysis comparing open and arthroscopic surgery for the treatment of anterior shoulder instability by analyzing comparative studies during 2 different time intervals during the last 20 years. We conducted a systematic review of MEDLINE, Embase, Scopus, and Google Scholar. Two groups were created by dividing studies according to the year of publication, those published from 1995 to 2004 or from 2005 to 2015. Publication bias and risk of bias were assessed using the Cochrane Collaboration's tools. Heterogeneity was assessed using the I2 statistics. A total of 22 studies (n = 1633) met the eligibility criteria. Comparison of the pooled estimate for all of these studies demonstrated no significant differences (P = .64) in clinical outcomes between open and arthroscopic shoulder stabilization. However, studies published from 1995 through 2004 demonstrated significant differences (P = .015) in recurrence rates favoring open surgery. In contrast, no significant differences (P = .09) in recurrence rates were observed for studies published from 2005 through 2015. The pooled estimate for all studies in both groups demonstrated significant differences (P = .001) in external rotation deficits between open and arthroscopic shoulder stabilization favoring arthroscopic surgery. Despite advances in surgical techniques and devices during the last 20 years, either open or arthroscopic surgical treatment of anterior shoulder dislocation results in similar clinical outcomes. The recurrence rate for arthroscopic surgical stabilization has only marginally decreased, from 16.8% to 14.2%. However, during the earlier decade from 1995 through 2004, patients treated with arthroscopic surgery had twice the risk of recurrence compared with an open procedure.


BRICseq Bridges Brain-wide Interregional Connectivity to Neural Activity and Gene Expression in Single Animals.
Comprehensive analysis of neuronal networks requires brain-wide measurement of connectivity, activity, and gene expression. Although high-throughput methods are available for mapping brain-wide activity and transcriptomes, comparable methods for mapping region-to-region connectivity remain slow and expensive because they require averaging across hundreds of brains. Here we describe BRICseq (brain-wide individual animal connectome sequencing), which leverages DNA barcoding and sequencing to map connectivity from single individuals in a few weeks and at low cost. Applying BRICseq to the mouse neocortex, we find that region-to-region connectivity provides a simple bridge relating transcriptome to activity: the spatial expression patterns of a few genes predict region-to-region connectivity, and connectivity predicts activity correlations. We also exploited BRICseq to map the mutant BTBR mouse brain, which lacks a corpus callosum, and recapitulated its known connectopathies. BRICseq allows individual laboratories to compare how age, sex, environment, genetics, and species affect neuronal wiring and to integrate these with functional activity and gene expression.


From racemic precursors to fully stereocontrolled products: one-pot synthesis of chiral α-amino lactones and lactams.
Substituted racemic lactols or cyclic hemiaminals were directly used as nucleophiles in enamine-based asymmetric amination reactions to access enantioenriched α-amino lactones or lactams via a one-pot sequence. The desired products, which are very important building blocks in organic synthesis but difficult to be prepared in the optically enriched form, could be afforded with two stereogenic centers in high yields with excellent enantioselectivities. Moreover, starting from the racemic precursors and catalyzed by the enantiomeric pair of the catalyst, all possible stereoisomeric products were discretely provided only after simple column chromatography. Additionally, this protocol provides facile access to several novel bicyclic carbamates, and such drug-like heterocyclic compounds should be potentially useful in medicinal chemistry.


Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition.
Over-expression of thrombin in ovarian cancer cells is associated with poor prognosis. In this study, we investigated the role of thrombin in inducing epithelial-mesenchymal transition (EMT) in SKOV3 epithelial ovarian cancer cells. After thrombin treatment SKOV3 cells were subjected to western blots, reverse-transcription PCR, and enzyme-linked immunosorbent assay to quantify EMT-related proteins, mRNA expression of SMAD2, DKK1, and sFRP1, and the secretion of matrix metalloproteinases (MMPs) and cytokines. Meanwhile, invasion ability was evaluated using transwell assays. The results indicated a dose- and time-dependent down-regulation of E-cadherin and upregulation of N-cadherin and vimentin in thrombin-treated SKOV3 cells, compared with the thrombin-free control group (p<0.05). There was a dose- and time-dependent increase in the levels of SMAD2 and DKK1 mRNAs and a decrease in the levels of sFRP1 mRNA in thrombin-treated SKOV3 cells compared to control cells (p<0.05). Thrombin-treated SKOV3 cells exhibited increased secretion of MMP-9, MMP-2, interleukin (IL)-8, and IL-6 and increased invasion compared to untreated cells (p<0.05). Thrombin altered the morphology of SKOV3 cells to a spindle-like phenotype. Addition of hirudin to thrombin-treated cells reversed the effects of thrombin. Thrombin induced EMT and promoted the invasion of SKOV3 cells, possibly via distinct signaling pathways. Hirudin inhibited the effects of thrombin, suggesting that anticoagulant therapy could be a novel therapeutic strategy for ovarian carcinoma.


Clathrin regenerates synaptic vesicles from endosomes.
Ultrafast endocytosis can retrieve a single, large endocytic vesicle as fast as 50-100 ms after synaptic vesicle fusion. However, the fate of the large endocytic vesicles is not known. Here we demonstrate that these vesicles transition to a synaptic endosome about one second after stimulation. The endosome is resolved into coated vesicles after 3 s, which in turn become small-diameter synaptic vesicles 5-6 s after stimulation. We disrupted clathrin function using RNA interference (RNAi) and found that clathrin is not required for ultrafast endocytosis but is required to generate synaptic vesicles from the endosome. Ultrafast endocytosis fails when actin polymerization is disrupted, or when neurons are stimulated at room temperature instead of physiological temperature. In the absence of ultrafast endocytosis, synaptic vesicles are retrieved directly from the plasma membrane by clathrin-mediated endocytosis. These results may explain discrepancies among published experiments concerning the role of clathrin in synaptic vesicle endocytosis.


Echinococcosis of the liver.
Echinococcosis, also known as hydatid disease, is an infection of larval stage animal tapeworm, Echinococcus. The larvae reside in the liver and lungs, producing multiloculated fluid-filled cysts. Imaging findings of Echinococcosis caused by E. granulosus are single, unilocular cyst or multiseptated cysts, showing "wheel-like", "rosette-like" or "honeycomb-like" appearances. There may be "snow-flakes" sign, reflecting free floating protoscoleces (hydatid-sand) within the cyst cavity. Degenerating cysts show wavy or serpentine bands or floating membranes representing detached or ruptured membranes. Degenerated cysts show heterogeneous, solid-looking pseudotumor that may show "ball of wool sign". Dead cysts show calcified cyst wall. Echinococcosis caused by E. multilocularis produces multilocular alveolar cysts with exogeneous proliferation, progressively invading the liver parenchyma and other tissues of the body. Imaging findings are ill-defined infiltrating lesions of the liver parenchyma, consisting of multiple small clustered cystic and solid components. On sonography, lesions are heterogeneous with indistinct margins, showing "hailstorm appearance" or "vesicular or alveolar appearance". CT and MR imaging displays multiple, irregular, ill-defined lesions. Multiple small round cysts with solid components are frequent. Large lesions show "geographical map" appearance. Calcifications are very frequent, appearing as peripheral calcification or punctuate scattered calcific foci. Invasion into the bile ducts, portal vein or hepatic vein may occur. Direct spread of infected tissue may result in cysts in the peritoneal cavity, kidneys, adrenal gland or bones.


Treatment of type C pilon fractures by external fixator combined with limited open reduction and absorbable internal fixation.
This study was conducted to evaluate the clinical outcome of the treatment of type C pilon fractures by using an external fixator combined with limited open reduction and absorbable internal fixation. Twenty-five type C pilon fractures, including 4 open fractures, were included in this retrospective study. The procedure of first-stage manipulation and external fixation spanning the ankle joint was conducted as early as possible. For the second stage, the tibial and fibular fractures were reduced and fixed with absorbable screws or rods through a limited incision. Clinical and radiographic evaluations were performed. The American Orthopaedic Foot & Ankle Society score (AOFAS) was obtained for evaluation of function. Twenty-one patients were followed postoperatively for a minimum of 18 months. The mean time of union was 4.8 months. Delayed union of the distal tibia occurred in 1 patient. Minor infection occurred in 8 patients and deep infection in 1 patient. No skin necrosis, malunion, loss of reduction, nonunion, or fixation failure was observed during the follow-up period. No hardware removal was needed, nor was adverse tissue reaction to the implants observed. An excellent or good AOFAS outcome was obtained in 81% (17/21) of the patients. External fixator combined with limited open reduction and absorbable internal fixation was a reliable treatment for closed and open AO/OTA type C pilon fractures of the distal tibia.


Multiple sclerosis and myasthenia gravis. A case report with single fiber electromyography.
A 34-year-old woman with long-standing multiple sclerosis had a 2-year history and physical signs of myasthenia gravis. The edrophonium chloride (Tensilon) test was positive. Repetitive stimulation of the ulnar nerve at 3 Hz did not show evidence of myasthenic response; however, a single-fiber electromyography demonstrated evidence of neuromuscular block as seen in myasthenia gravis, which was reversed to normal after intravenously administered edrophonium. The patient improved on anticholinesterase medication. It is suggested that patients with multiple sclerosis who have unusual features such as in the patient reported here should be investigated for the presence of myasthenia gravis to ensure proper treatment.


Draft genome sequences of 14 Lacticaseibacillus spp. strains, representatives of a collection of 200 strains.
Lactobacilli have a fundamental role in the food industry as starters and probiotics, therefore, requiring special attention concerning food safety. In this work, 14 strains selected accordingly to their genetic fingerprint and physiologic characteristics are presented as representatives of a collection of 200 strains.


Giant Cell Tumor of Flexor Pollicis Longus Tendon Sheath: An Uncommon Case Report and Literature Review.
Giant cell tumors of tendon sheath are benign, rarely malignant, soft-tissue tumors arising from tenosynovial sheath and periarticular soft tissue. They usually present as painless masses with some restriction of movement. Histopathological diagnosis is gold standard although pre-operative fine-needle aspiration cytology (FNAC), plain radiographs, and MRI help in narrowing down the differentials. Giant cell tumor of the tendon sheath (GCTTS) although benign is notorious for having a high rate of recurrences, with most important risk factors being adjacency to joint and incomplete excision. Adequate marginal excision forms the mainstay for managing these tumors. Adjuvant radiotherapy has found some role in treating and decreasing the chances of recurrences. A 55-year-old lady was brought to the outpatient department with a history of painless, gradually progressive swelling on volar aspect of thumb. Swelling was well defined with a smooth surface. Overlying skin showed no signs of local inflammation or adherence. Pain radiographs showed soft-tissue shadow with some articular bony erosions. A ultrasound-guided FNAC and MRI showed a picture of GCTTS. An excisional biopsy was done and confirmed the diagnosis. GCTTS is a benign entity with a slow course of evolution, although uncommon, and should be kept as differential for swellings of hand and feet. Complete excision with no evidence residual tumor is diagnostic as well as curative. A regular follow-up is essential on account of high rates of recurrences.


A genetic risk tool for obesity predisposition assessment and personalized nutrition implementation based on macronutrient intake.
There is little evidence about genetic risk score (GRS)-diet interactions in order to provide personalized nutrition based on the genotype. The aim of the study was to assess the value of a GRS on obesity prediction and to further evaluate the interactions between the GRS and dietary intake on obesity. A total of 711 seekers of a Nutrigenetic Service were examined for anthropometric and body composition measurements and also for dietary habits and physical activity. Oral epithelial cells were collected for the identification of 16 SNPs (related with obesity or lipid metabolism) using DNA zip-coded beads. Genotypes were coded as 0, 1 or 2 according to the number of risk alleles, and the GRS was calculated by adding risk alleles with such a criterion. After being adjusted for gender, age, physical activity and energy intake, the GRS demonstrated that individuals carrying >7 risk alleles had in average 0.93 kg/m(2) of BMI, 1.69 % of body fat mass, 1.94 cm of waist circumference and 0.01 waist-to-height ratio more than the individuals with ≤7 risk alleles. Significant interactions for GRS and the consumption of energy, total protein, animal protein, vegetable protein, total fat, saturated fatty acids, polyunsaturated fatty acids, total carbohydrates, complex carbohydrates and fiber intake on adiposity traits were found after adjusted for confounders variables. The GRS confirmed that the high genetic risk group showed greater values of adiposity than the low risk group and demonstrated that macronutrient intake modifies the GRS association with adiposity traits.


SPECT/CT: Standing on the Shoulders of Giants, It Is Time to Reach for the Sky!
Twenty years ago, SPECT/CT became commercially available, combining the strengths of both techniques: the diagnostic sensitivity of SPECT and the anatomic detail of CT. Other benefits initially included attenuation correction of SPECT reconstructions, ultimately evolving to correction techniques that would enable absolute tracer uptake quantification. Recent developments in SPECT hardware include solid-state digital systems with higher sensitivity and resolution, using novel collimator designs based on tungsten. Similar advances in CT technology have been introduced in hybrid SPECT/CT systems, replacing low-end x-ray tubes with high-end multislice CT scanners equipped with iterative reconstruction, metal artifact reduction algorithms, and dual-energy capabilities. More recently, the design of whole-body SPECT/CT systems has taken another major leap with the introduction of a ring-shaped gantry equipped with multiple movable detectors surrounding the patient. These exciting developments have fueled efforts to develop novel SPECT radiopharmaceuticals, creating new chelators and prosthetic groups for radiolabeling. Innovative SPECT radionuclide pairs have now become available for radiolabeling with the potential for use as theranostic agents. The growth of precision medicine and the associated need for accurate radionuclide treatment dosimetry will likely drive the use of SPECT/CT in the near future. In addition, expanding clinical applications of SPECT/CT in other areas such as orthopedics offer exciting opportunities. Although it is true that the SPECT/CT ecosystem has seen several challenges during its development over the past 2 decades, it is now a feature-rich and mature tool ready for clinical prime time.


A questionnaire study of sexological problems following urinary diversion in the female patient.
A questionnaire study was conducted to evaluate the sexological problems after urinary diversion, using the continent Kock reservoir or the ileal conduit diversion. Thirty-seven female patients completed the questionnaire: 17 patients had a continent and 20 an ileal conduit diversion, with a median follow-up of 0.8 year (range 0.5-4.4) and 4.6 years (range 2.8-12.0), respectively. Data from only 33 patients were eligible for analysis, but no significant between-group differences were found. Coital frequency remained unchanged or increased among 44% of patients with a continent reservoir and among 18% of ileal conduit patients (p = 0.11). Among those reporting other than unchanged/increased activity almost one-third gave physical problems or decreased desire as the reason, and 30% felt less sexually attractive, with cystectomized patients reporting a higher percentage than others. A higher frequency of dyspareunia among patients with a continent reservoir was an unexpected finding (p = 0.06), and merits further investigation in a larger sample. Here it may be due to the shorter follow-up of these patients. Thirty per cent of all patients would have like more sexological counselling.


Synthesis of a Cyclophane Bearing Two Benz[a]anthracene Units Connected at the 5 and 7 Positions with Two Naphth-1,4-diyl Groups.
A synthetic pathway to a cyclophane bearing two benz[a]anthracene units connected at the 5 and 7 positions through two naphth-1,4-diyl groups was developed, and its structure was confirmed by X-ray structure analysis. Because of structural constraints, the two naphthyl groups are distorted from planarity and the bonds connecting them to the benz[a]anthracene units are bent significantly. The UV-vis and fluorescence spectra of the cyclophane are red-shifted from those of 7-(1-naphthalenyl)benz[a]anthracene, which is the corresponding monomeric polycyclic aromatic hydrocarbon.


A histologic study of age changes in the adult human periodontal joint (ligament).
This study evaluated the histological age changes in 80 periodontal joints from 24 human cadavers ranging in age from 20 to 90 years. The limitations of such a descriptive study were reviewed to prevent overextrapolation of the findings to whole populations. In the young speciments, the bone surface of the tooth socket was smooth and regular with the insertion of Sharpey's fibers evenly distributed in the woven bone. Interstitial lamellae were found between secondary osteons in the alveolar bone. Copious periodontal fibers passed around small vascularized interstitial spaces to insert evenly into the cementum as Sharpey's fibers. Numerous cells, probably fibroblasts, were present within and between the fiber bundles. Like the bone surface, the cemental surface was smooth and regular. Both cellular and acellular cementum were present. Cemental splits were found both intracementally and at the cemento-dentinal junction. In the older specimens, the periodontal surface of the alveolar bone was jagged and uneven with Sharpey's fibers inserting irregularly into the woven bone. Subjectively an increased amount of internal remodeling was seen in the periodontal bone. A relative decrease in both suspensory fibers and cellular content was noted in the periodontal ligaments of the older specimens. Large vascularized interstitial spaces encroached upon areas formerly occupied by periodontal fibers and bone. Fat cells also were observed replacing the suspensory fibers. The cementum showed an irregular surface into which Sharpey's fibers were unevenly inserted. Both cellular and acellular cementum were present, and cemental splits were seen with the same frequency as in the young specimens. There was a tendency for greater cemental apposition, particularly in the apical region of the tooth. In many respects the aging periodontal joint showed atrophic and degenerative changes similar to those in cranio-facial sutures. However, these changes did not include either bony ankylosis or osteoporosis related to increasing age. In summary, the periodontal joints of the younger specimens were well organized while those of the older specimens showed a more irregular structure and a decrease in fiber and cellular content. Intermediate changes were seen in the intermediate age groups.


Opinions about potential causes and triggers of intimate partner violence against women: a population-based study among married men from Kermanshah city, Iran.
This cross-sectional study forms part of a community-based social diagnosis in an Iranian city where different community members were approached regarding their opinions about what can cause and trigger intimate partner violence against women (IPVAW). The study deals with the opinions of married men and looks for patterns of opinions and how those patterns relate to individual socio-demographic characteristics. It also discusses opinions expressed concerning the consequences of IPVAW. A workplace-based convenient sample of men from Kermanshah city filled in a standardised, self-administered questionnaire (n = 480, response rate 93%). By means of cluster analysis, four patterns of answers emerged: (1) regarding most items proposed as potential causes or triggers (33.3% of respondents); (2) not regarding them as potential causes or triggers (18.9%); (3) being ambivalent about their role (20.3%); (4) having mixed opinions but mainly not regarding them as potential causes and triggers (27.4%). Being less educated and a blue-collar worker were prominent attributes of those men inclined not to agree with the potential role played in IPVAW by the items proposed (class 2). Moreover, individual ethnicity and perpetration of non-physical violence against one's spouse had very little association with the patterns observed.


Magnetic resonance imaging as a monitor of kidney enlargement and regression in experimental diabetes in rats.
The aim of the present study was to use magnetic resonance imaging as a non-invasive measure of renal enlargement and regression in experimental diabetes in rats. Rats were randomized into three groups: (1) non-diabetic control animals, (2) diabetic animals, untreated for 30 days after streptozotocin treatment and (3) diabetic animals treated with insulin from day 21 to day 30 after streptozotocin administration. Magnetic resonance images were obtained from anaesthetized rats and kidney, cortex, medulla and pelvis volumes were calculated throughout the experiment until day 30. In untreated diabetic animals, a marked increase in kidney volume was seen 4 days after the induction of diabetes (P < 0.05) and after 30 days this increase amounted to 73%, with similar increases in the cortex (63%) and medulla (69%). No change was seen in the pelvis volume. Insulin administration on day 21 to untreated diabetic rats abruptly reduced kidney volume by 21%, cortex volume by 27% and medulla volume by 18%, and after 4 days all three parameters were similar to those seen in non-diabetic controls. In conclusion, the present study has demonstrated the applicability of magnetic resonance imaging as a non-invasive measure of renal enlargement and regression in experimental diabetes in rats. In untreated hyperglycaemic diabetic rats, with manifest diabetic renal enlargement, acute regression in renal volume was observed concomitant with insulin-induced normoglycaemia.


The value of dual-source multidetector-row computed tomography in determining pulmonary blood supply in patients with pulmonary atresia with ventricular septal defect.
Primary evaluation of patients with pulmonary atresia with ventricular septal defect (PA-VSD) traditionally relies upon echocardiography and conventional cardiac angiography (CCA). Cardiac angiography is considered the gold standard for delineation of anatomy in children with PA-VSD. Data comparing CCA and dual-source multidetector-row computed tomography angiography (MDCT) in PA-VSD patients is limited. The objective of this study was to test the hypothesis that MDCT is equivalent to CCA for anatomic delineation in these patients. Twenty-eight patients with PA-VSD underwent CCA and MDCT in close proximity to each other without interval therapy. A retrospective review of these 28 patients was performed. All MDCT data of pulmonary artery morphology, major aortopulmonary collateral arteries (MAPCAs) and type of blood supply (dual vs. single supply) were evaluated by blinded experts and results were compared with CCA. Twenty-eight patients had adequate size right and left pulmonary arteries (21 confluent and 7 non-confluent). Seven patients had complete absence of native pulmonary artery and 3 patients had stenosis of distal branches of pulmonary arteries; all had MAPCAs from descending thoracic aorta and/or subclavian arteries. Sensitivity, specificity, positive and negative predictive value of MDCT for detecting confluent of pulmonary arteries, absence of native pulmonary artery and stenosis of pulmonary arteries were all 100%. Moreover, accuracy of detecting MAPCAs was excellent. These results suggest that MDCT and CCA are equivalent in their ability to delineate pulmonary artery anatomy and MAPCAs. Dual source MDCT provides high diagnostic accuracy in evaluation of pulmonary blood supply in patients with PA-VSD and allows precise characterisation of the condition of pulmonary arteries and MAPCAs which is of paramount importance in managing patients with PA-VSD. (Folia Morphol 2018; 77, 1: 116-122).


Role of nitric oxide in leukotriene C4-induced increases in microvascular transport.
The goal of this study was to determine the role of nitric oxide in alterations in macromolecular transport of the hamster cheek pouch in vivo in response to leukotriene C4. We used intravital fluorescent microscopy to examine the transport of macromolecules across the hamster cheek pouch in response to leukotriene C4 before and after application of an enzymatic inhibitor of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 1.0 microM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC-dextran; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increase in the number of venular leaky sites and clearance of FITC-dextran-70K. Superfusion of L-NMMA (1.0 microM) significantly decreased leukotriene C4-induced increases in venular leaky sites and clearance of FITC-dextran-70K. In addition, superfusion of LY-83583 (10 microM) significantly decreased leukotriene C4-induced increases in venular leaky sites. In contrast, superfusion of NG-monomethyl-D-arginine (D-NMMA; 1.0 microM), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-20 mg/kg iv) did not significantly alter leukotriene C4-induced increases in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play an important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4.


Comparison of alternative methods of collection of service use data for the economic evaluation of health care interventions.
Economic evaluation of health care interventions usually requires the collection of service use data to estimate the total cost of participants in an evaluation. There are a number of methods available to measure the quantity of services used but little is known about the relative accuracy of alternative methods. In a multicentre randomised controlled trial of interventions for the treatment of adults with recurrent episodes of deliberate self-harm (the POPMACT trial), health service data were collected by patient self-report after six and twelve months and also from GP records by independent investigators. Agreement for overall costs was relatively high. However, this hides substantial variation in agreement between the two sources of information for different services. The results suggest that GP records provide more accurate data on the use of general practice-based contacts than patient report, but less reliable information on contacts with other health services. Thus reliance on GP records for data on hospital services and other community health services based outside of general practice surgeries is not recommended. Future research should explore the level of agreement between patient report and other providing sector records, such as hospital records.


High on Walking: Conquering Everyday Life.
The aim of this study is to discuss the meaning of walking impairment among people who have previously been able to walk on their own. The study is based on findings from three different life situations: older people recovering after admission in intermediate care, people who have lost a leg, and people who live with Parkinson's disease. The analysis of the data is inspired by Paul Ricoeur's philosophy of interpretation. Four themes were identified: (a) I feel high in two ways; (b) Walking has to be automatic; (c) Every Monday, I walk with the girls in the park; and (d) I dream of walking along the street without sticks and things like that. The findings demonstrate that inability to walk profoundly affected the participants' lives. Other problems seemed small by comparison because walking impairment was at the same time experienced as a concrete physical limit and an existential deficit.


Diagnostic aspects and follow-up of 174 cases of hepatocellular carcinoma. Second report.
From June 1981 to June 1989 we diagnosed 174 cases of hepatocellular carcinoma (HCC) at our institution (Piacenza, Northern Italy). Average age was 65.6 years; male to female ratio 3.4. 149 patients were cirrhotic (85.6%); alcohol abuse was present in 88/169 (52.1%); in 53/145 patients all hepatitis B virus markers were negative. Alpha-fetoprotein showed a low diagnostic sensitivity (values above 500 ng only in 49/169 or 29.0%). We used ultrasound (US) examination with a very high identification rate in all cases; pathological diagnosis was achieved by US guided fine-needle aspiration biopsy in 135 patients; in 13, by laparoscopy-histology. Metastases were found in 24/169 cases (14.2%); a second malignancy was diagnosed in 13/169 (7.7%): the most common association was HCC-non-Hodgkin lymphoma. Only 14 patients could be referred to surgery, which significantly improved prognosis.


A Comparison of Pediatric vs. Adult Patients with the Ewing Sarcoma Family of Tumors.
This study sought to identify differences in clinical characteristics, outcomes, and treatments between adult and pediatric patients with the Ewing sarcoma family of tumors (ESFT). By using the Surveillance, Epidemiology, and End Results database from 1983 to 2013, 1,870 patients were analyzed (n = 976 pediatric, n = 894 adult). Between the two groups, demographic, tumor, and treatment characteristics were collated and compared. The chi-square test determined differences in proportions of the variables between groups. Survival analysis was performed using the Kaplan-Meier method; distributions were compared using the log-rank test. Univariate and multivariate analyses were performed to examine variables correlating with overall survival (OS), the primary endpoint. Adult patients had a poorer prognosis and were more likely to present with primitive neuroectodermal tumor (PNET) histology, along with distant metastasis and soft tissue primary site. In patients undergoing surgery, radiation therapy (RT) was not associated with higher OS in either children or adults. If no surgery was performed, receipt of RT was associated with higher OS in adults but not children. Adulthood negatively correlated with OS on multivariate analysis when adjusting for potential confounding factors. Other salient factors associated with OS were male gender, metastatic disease, non-extremity bone location, treatment era, and PNET histology. However, when examining the most recent subset (patients treated from 2004 to 2013), RT was associated with improved OS in both pediatrics and adults, which was an independent predictor on multivariate analysis. Adult patients with ESFT have inferior survival compared to pediatric patients, likely related to earlier clinical detection in the latter.


Discovery of powerful uranyl ligands from efficient synthesis and screening.
New tripodal gem-(bis-phosphonates) uranophiles were discovered by a screening method that allowed for the selection of ligands with strong uranyl-binding properties in a convenient microtiter-plate format. The method is based on competitive uranium binding by using Sulfochlorophenol S as chromogenic chelate. This dye compound was found to present high uranyl complexation properties and allowed to highlight ligands presenting association constants for UO(2+)(2) up to 10(18) at pH 7.4 and 10(20) at pH 9. A collection of 40 known ligands including polycarboxylate, hydroxamate, catecholate, hydroxypyridonate and hydroxyquinoline derivatives was tested. Also screened was a combinatorial library prepared from seven amine scaffolds and eight acrylates bearing diverse chelating moieties. Among these 96 tested candidates, a tripod derivative bearing gem-bis-phosphonates moieties was found to present the highest complexation properties over a wide range of pH and was further studied.


Extensive gene acquisition in the extremely psychrophilic bacterial species Psychroflexus torquis and the link to sea-ice ecosystem specialism.
Sea ice is a highly dynamic and productive environment that includes a diverse array of psychrophilic prokaryotic and eukaryotic taxa distinct from the underlying water column. Because sea ice has only been extensive on Earth since the mid-Eocene, it has been hypothesized that bacteria highly adapted to inhabit sea ice have traits that have been acquired through horizontal gene transfer (HGT). Here we compared the genomes of the psychrophilic bacterium Psychroflexus torquis ATCC 700755(T), associated with both Antarctic and Arctic sea ice, and its closely related nonpsychrophilic sister species, P. gondwanensis ACAM 44(T). Results show that HGT has occurred much more extensively in P. torquis in comparison to P. gondwanensis. Genetic features that can be linked to the psychrophilic and sea ice-specific lifestyle of P. torquis include genes for exopolysaccharide (EPS) and polyunsaturated fatty acid (PUFA) biosynthesis, numerous specific modes of nutrient acquisition, and proteins putatively associated with ice-binding, light-sensing (bacteriophytochromes), and programmed cell death (metacaspases). Proteomic analysis showed that several genes associated with these traits are highly translated, especially those involved with EPS and PUFA production. Because most of the genes relating to the ability of P. torquis to dwell in sea-ice ecosystems occur on genomic islands that are absent in closely related P. gondwanensis, its adaptation to the sea-ice environment appears driven mainly by HGT. The genomic islands are rich in pseudogenes, insertional elements, and addiction modules, suggesting that gene acquisition is being followed by a process of genome reduction potentially indicative of evolving ecosystem specialism.


The astrocyte surface NAAG receptor and NAAG peptidase signaling complex as a therapeutic target.
There is evidence that schizophrenia and other neuropathies may involve malfunction of a unique N-acetylaspartylglutamate (NAAG) receptor and its associated NAAG peptidase, a receptor and enzyme found together on the astrocyte surface. NAAG is a peptide neurotransmitter released by stimulated neurons and specifically targeted to the group II metabotropic glutamate receptor 3 (mGlu(3)), activation of which initiates astrocyte Ca(2+) waves responsible for astrocyte-astrocyte and astrocyte-vascular system signaling and induction of vascular hyperemic responses that increase energy supplies to stimulated neurons. In this review, it is hypothesized that the receptor and enzyme exist as a cytostructural unit on the astrocyte surface, and the nature of this proposed mGlu(3)-NAAG peptidase complex is considered in terms of its physiological signaling role, and of the effect of drugs on this role. The mGlu(3) receptor has been the target of extrinsic antagonists and agonists that mimic NAAG structure and compete with natural NAAG for the receptor site. NAAG metabolism has also been the target of extrinsic NAAG-like substances that inhibit NAAG peptidase, competing with NAAG for the enzyme active site. Several drugs that affect the mGlu(3) receptor or NAAG peptidase have reached a stage of human testing. Two are agonists of the mGlu(3) receptor, and another is an NAAG peptidase inhibitor. These substances appear to have potential for treating schizophrenia and other cognitive neuropathies by interfering with a homeostatic NAAG activated neuron-astrocyte-vascular energy supply system.


Effect of neoadjuvant treatment combined with radical gastrectomy on postoperative complications and prognosis of gastric cancer patients.
To investigate the occurrence of postoperative complications in and factors influencing the prognosis of patients undergoing radical gastrectomy after neoadjuvant chemotherapy. A total of 238 patients with gastric cancer were enrolled in this study. There were 194 patients who underwent neoadjuvant chemotherapy before surgery and 44 patients who underwent concurrent radiochemotherapy before surgery. The clinical data of patients and the incidence of postoperative complications were collected. Postoperative complications were graded based on the Clavien-Dindo classification. The impact of postoperative complications on the prognosis of patients was analysed. (1) The overall incidence of postoperative complications was 17.2% (41/238) among all patients. A total of 49 patients experienced postoperative complications, including 12 cases of grade I, 15 cases of grade II, seven cases of grade IIIa, three cases of grade IIIb, seven cases of grade IV, and four cases of grade V complications. A total of 21 patients experienced severe complications. Multivariate analysis indicated that age, body mass index (BMI), and scope of gastrectomy were independent risk factors for postoperative complications (p < .05). (2) The five-year survival rate for the entire group of patients was 58.4%. The five-year survival rate for the complication group and non-complication group were 31.7% and 51.7%, respectively, with a significant difference between the two groups (χ2=15.41p = .000). Based on the severity of complications, the subgroup analysis indicated that the five-year survival rate for patients with severe postoperative complications was 21.1% and that for patients with non-severe complications was 40.9%; the difference was significant (χ2=21.70, p = .000). (3) Multivariate analysis indicated that age, pathological tumour, node, and metastasis (ypTNM) stages II-III, operation time >3.5 h, total gastrectomy, and postoperative complications were independent risk factors affecting the prognosis of patients undergoing radical gastrectomy after neoadjuvant chemotherapy. Postoperative adjuvant therapy was an independent protective factor for patient prognosis (p < .05). The incidence of complications in patients undergoing radical gastrectomy after neoadjuvant chemotherapy is closely correlated with patient age and the scope of surgical resection, and the occurrence of severe complications has a significant adverse effect on patient prognosis.


[Epidemiological surveillance of grippe and dengue. Réunion, 1996].
The local Welfare and Health Authorities together with the country council of Reunion Island set up a medical supervision network for influenza and dengue fever in March 1996. Influenza of which the spreading over the island has never been well-researched is anticipated by a vaccination campaign organised in an empirical way after a model from the mother country (France). Dengue fever of which one of the vectors is omnipresent on the island ranged in an epidemic way in 1978. The aim of this network based on watching doctors, the laboratories of the island as well as the Pasteur Institute of Madagascar, is to adapt the prevention (Flu) and alert the Health Authorities in case of epidemic (Dengue). The article shows the results of 1996 observation and touches on the future of this type of supervision in a tropical environment.


Alpha-2 adrenergic modulation of norepinephrine secretion in the perfused rabbit iris-ciliary body.
Clonidine and other selective alpha-2 adrenergic agonists have been found to lower intraocular pressure in the eyes of rabbits and primates, including humans. It has been suggested that the ocular hypotensive response to alpha-2 agonists may be mediated, in part, by prejunctional inhibition of norepinephrine secretion at intraocular synapses. In this study, we have investigated the effects of adrenergic agonists and antagonists on field-stimulated, Ca++-dependent release of 3H-norepinephrine (3H-NE) from isolated, perfused rabbit iris-ciliary bodies and have utilized radioligand binding methods to identify prejunctional adrenoceptors in this tissue. Clonidine (10(-9)-10(-5) M) produced a dosage-dependent inhibition of stimulation-evoked 3H-NE secretion (EC50 approximately equal to 3 X 10(-8) M), but did not alter basal secretion. Other adrenergic agonists capable of activating alpha-2 adrenoceptors (e.g., epinephrine, norepinephrine and xylazine) also significantly depressed 3H-NE secretion, whereas selective alpha-1 adrenergic or beta adrenergic agonists were without effect. Clonidine-mediated inhibition of 3H-NE release was reversed by the selective alpha-2 antagonist yohimbine (10(-7) M), but was unaffected by prazosin or timolol. Yohimbine alone markedly enhanced 3H-NE secretion, indicating tonic activation of prejunctional alpha-2 adrenoceptors by endogenous released norepinephrine. Forskolin or 8-bromo-cAMP, which alone enhanced norepinephrine secretion, failed to attenuate the inhibitory responses to alpha-2 agonists. 3H-rauwolscine binding measurements showed a small decrease in alpha-2 receptor sites in iris-ciliary body membranes following surgical sympathetic denervation. It is concluded that the rabbit iris-ciliary body contains functional, prejunctional alpha-2 adrenoceptors which may play an autoregulatory role in vivo and contribute to the ocular effects of adrenergic drugs.


Bypass surgery versus palliative pancreaticoduodenectomy in patients with advanced ductal adenocarcinoma of the pancreatic head, with an emphasis on quality of life analyses.
In some centers, palliative resection (PR; partial pancreaticoduodenectomy) is, in selected cases, promoted in preference to double loop bypass (DLB) surgery for advanced pancreatic cancer. This prospective study compares PR with DLB, placing particular focus on patients' quality of life (QoL). From 01/1993 to 09/2004, 167 patients were analyzed in a prospective single center study of palliative surgical treatment of advanced ductal adenocarcinoma of the pancreatic head. Thirty-eight underwent PR and 129 underwent palliative DLB. Patients undergoing DLB were divided into: (1) locally advanced disease (LAD-subgroup; n = 61; 47%) and (2) metastasized disease (MD-subgroup; n = 68; 53%). QoL was assessed using the EORTC QLQ-C30 questionnaire supplemented by a pancreatic cancer specific module. QoL data were collected pre-operatively and for up to 12 months after surgery. Median survival was 7.0 months (95% CI 4.09; 9.91) in PR patients and 6.0 months (95% CI 5.39; 6.61) in patients who received DLB. Mortality and morbidity were, respectively, 7.8 and 58% for PR, and 2.6 and 42% for DLB. QoL decreased more after PR than after DLB. The DLB-group recovered quicker, reaching pre-operative QoL levels after 3 months, and were less impaired when discharged. The LAD-subgroup and the MD-subgroup presented with equal levels of QoL. QoL analysis revealed favorable QoL data after DLB. Additionally, the survival rates of the two groups did not differ significantly, but morbidity and mortality rates in the PR group were elevated. Therefore, the use of PR for advanced pancreatic cancer needs to be carefully evaluated.


Enhanced myogenic response in the afferent arteriole of spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHRs) have normal glomerular capillary pressure even though renal perfusion pressure is higher, suggesting that preglomerular vessels exhibit abnormally high resistance. This may be due to increased superoxide (O(2)(-)) production, which contributes to the vasoconstriction in hypertension. We tested the hypothesis that the myogenic response of the afferent arteriole (Af-Art) is exaggerated in SHRs because of increased levels of reactive oxygen species (ROS). Single Af-Arts were microdissected from kidneys of SHRs and Wistar-Kyoto (WKY) rats and microperfused in vitro. When perfusion pressure in the Af-Art was increased stepwise from 60 to 140 mmHg, the luminal diameter decreased by 8.4 + or - 2.9% in WKY Af-Arts but fell by 29.3 + or - 5.6% in SHR Af-Arts. To test whether ROS production is enhanced during myogenic response in SHRs, we measured chloromethyl-dichlorodihydrofluorescein diacetate acetyl ester (CM-H(2)DCFDA) florescence before and after increasing intraluminal pressure from 60 to 140 mmHg. Pressure-induced increases in ROS were fourfold greater in SHR Af-Arts compared with WKY Af-Arts (SHR, 48.0 + or - 2.2%; and WKY, 12.2 + or - 0.3%). To test whether O(2)(-) contributes to the myogenic response in SHRs, either the membrane-permeant O(2)(-) scavenger Tempol or the nox2-based NADPH oxidase (NOX2) inhibitor gp91ds-tat were added to the Af-Art lumen and bath and the myogenic response was tested before and after treatment. Both Tempol (10(-4) M) and gp91ds-tat (10(-5) M) significantly attenuated the pressure-induced constriction in SHR Af-Arts but not in WKY Af-Arts. We conclude that 1) pressure-induced constriction is exaggerated in SHR Af-Arts, 2) NOX2-derived O(2)(-) may contribute to the enhanced myogenic response, and 3) O(2)(-) exerts little influence on the myogenic response under normotensive conditions.


The impact of coronary artery disease on outcomes after liver transplantation.
The aim of this study is to assess the impact of obstructive coronary artery disease (CAD) on outcomes after liver transplantation. Patients considered for liver transplantation are at an increased risk for CAD. Obstructive CAD is a contraindication for liver transplantation at most centres. However, the association between severity of CAD and liver transplantation outcomes remains poorly characterized. We retrospectively reviewed 386 consecutive liver transplantations performed between January 2001 and December 2005 at Northwestern Memorial Hospital (NMH). A comparative analysis was conducted for a national cohort (n = 23 820) from the United Network for Organ Sharing database. Outcome measures included patient and graft survival, rates of acute myocardial infarction and heart failure. Patient survival remained similar irrespective of CAD severity or cardiovascular risk index (CRI) in the NMH cohort. The CRI closely correlated with the presence of CAD in the NMH cohort [CRI 0, odds ratio (OR) 0.125, 95% confidence interval (95% CI) 0.02-0.61, P = 0.01; CRI 1, OR 1 reference; CRI ≥2, OR 2.28, 95% CI 1.09-4.75, P = 0.02]. In the national cohort using Cox regression, high (≥2) CRI (reference 0, hazard ratio 1.376, 95% CI 1.271-1.488, P < 0.0001) predicted patient mortality and exceeded established risk factors, including Hepatitis C virus (HCV) (hazard ratio 1.321, 95% CI 1.242-1.403, P < 0.0001), hepatocellular carcinoma (HCC) (hazard ratio 1.27, 95% CI 1.181-1.370, P < 0.0001) and diabetes (hazard ratio 1.241, 95% CI 1.160-1.326, P < 0.0001). Liver transplantation in patients with CAD is not associated with prohibitive risk for cardiac events and patient mortality. Appropriately treated CAD should therefore not represent a contraindication to liver transplantation.


Thoracoscopy for correction of adult thoracic scoliosis.
The endoscopic technique of instrumentation, correction, and fusion for scoliosis has undergone radical modifications since the first surgery. Some key factors conducive to successful fusion, such as thorough discectomy and end plate removal, are common to endoscopic and non-endoscopic procedures. There are indeed special technical features in our endoscopic approach that clearly affect outcome, however, and their enumeration rightly chronicles the evolution of our experimental undertaking.


Systematic Literature Review of the Take-Home Route of Pesticide Exposure via Biomonitoring and Environmental Monitoring.
Exposure to pesticides via take-home can be an important pathway for farmworkers' families. The aim of this review was to summarize and analyze the literature published during the last decade of exposure to pesticides via take-home pathway in farmworkers' families. We conducted a systematic review to identify peer-reviewed articles of interest; only articles related to take-home pathway that included some sort of pesticide monitoring were considered for inclusion. Systematic reviews, literature reviews, and meta-analyses were excluded, resulting in a total of 39 articles elected for analysis. The articles were summarized based on the location of the study, population (sample size), pesticide analyzed, and type of sample. The majority of the reviewed studies were conducted in the U.S., but there seems to be an increase in literature on pesticide take-home pathway in developing countries. Most of the articles provided evidence that farmworkers' families are exposed to pesticides at higher levels than non-farmworkers' families. The levels may depend on several factors such as seasonality, parental occupation, cohabitation with a farmworker, behavior at work/home, age, and gender. Community-based interventions disrupting the take-home pathway seem to be effective at reducing pesticide exposure. The take-home pathway is an important contributor to overall residential exposures, but other pathways such as pesticide drift, indoor-residential applications, and dietary intake need to be considered. A more comprehensive exposure assessment approach is necessary to better understand exposures to pesticides.


Alexithymia and reaching group consensus.
One characteristic of human nature is the ability to align our behavior with others. Previous research has linked poor communication skills to alexithymia. This may suggest the possibility that individuals with high alexithymia do not adhere to the principles of social alignment. One form of cognitive alignment is consensus with a group. So far, little research attention has been given to the possible link between alexithymia and this form of cognitive social alignment. In this study, we address this gap by investigating the association between consensus-reaching abilities and alexithymia. A sample comprising of 122 participants completed the Toronto Alexithymia Scale and then played a specially designed game called "Consensus under a deadline". In each game, a participant played with either seven bots designed to act rationally and always seek a consensus, or with seven other participants. The participants were unaware who they were playing with. The results of the study confirm the link between alexithymia and impaired cognitive social alignment, showing that the alexithymia cognitive component (EOT) is associated with a deficit in reaching a consensus with humans (that sometimes act irrationally). However, this association was not evident when group members were bots (that always act rationally).


Mimicking Cardiac Fibrosis in a Dish: Fibroblast Density Rather than Collagen Density Weakens Cardiomyocyte Function.
Cardiac fibrosis is one of the most devastating effects of cardiac disease. Current in vitro models of cardiac fibrosis do not sufficiently mimic the complex in vivo environment of the cardiomyocyte. We determined the local composition and mechanical properties of the myocardium in established mouse models of genetic and acquired fibrosis and tested the effect of myocardial composition on cardiomyocyte contractility in vitro by systematically manipulating the number of fibroblasts and collagen concentration in a platform of engineered cardiac microtissues. The in vitro results showed that while increasing collagen content had little effect on microtissue contraction, increasing fibroblast density caused a significant reduction in contraction force. In addition, the beating frequency dropped significantly in tissues consisting of 50% cardiac fibroblasts or higher. Despite apparent dissimilarities between native and in vitro fibrosis, the latter allows for the independent analysis of local determinants of fibrosis, which is not possible in vivo.


Insights into photodissociation dynamics of benzamide and formanilide from ab initio calculations.
In the present study, the five lowest electronic states that control the UV photodissociation of formanilide and benzamide have been characterized using the complete active space self-consistent field theory. The mechanisms for the initial relaxation and subsequent dissociation processes have been determined on the basis of the calculated potential energy surfaces and their intersections. It was found that the S(1)/T(1)/T(2) three-surface intersection plays an important role in the photodissociation processes of benzamide. However, the dissociation behavior of formanilide and benzamide was found to be quite different from that for aliphatic amides. The present study provides several insights into the photodissociation dynamics of formanilide and benzamide.


Janus nanostructures based on Au-TiO2 heterodimers and their photocatalytic activity in the oxidation of methanol.
Au-TiO2 snowman-like heterodimer nanoparticles were prepared by a surface sol-gel process based on gold Janus nanoparticles whose surface-protecting monolayers consisted of a hemisphere of hydrophobic 1-hexanethiolates and the other of hydrophilic 2-(2-mercaptoethoxy)ethanol. Transmission electron microscopic measurements showed that the resulting TiO2 nanoparticles (diameter 6 nm) exhibited well-defined lattice fringes that were consistent with the (101) diffraction planes of anatase TiO2. The heterodimer nanoparticles displayed apparent photoluminescence that was ascribed to electronic transitions involving trap states of TiO2 particles, and the photocatalytic activity was manifested by the oxidative conversion of methanol into formaldehyde, which was detected quantitatively by the Nash method. The enhanced photocatalytic performance, as compared to that of the TiO2 nanoparticles alone, was ascribed to the charge separation of photogenerated electrons and holes at the Au-TiO2 interface that was facilitated by the close proximity of the gold nanoparticles. These results suggested that (i) there were at least two possible pathways for photogenerated electrons at the TiO2 conduction band, decay to the trap states and transfer to the gold nanoparticles, and (ii) energy/electron transfer from the trap states to gold nanoparticles was less efficient. In essence, this study showed that the snowman-like heterodimers might be exploited as a homogeneous photocatalytic system for the preparation of functional molecules and materials.


Pomegranate Seed Oil Exerts Synergistic Effects with trans-Resveratrol in a Self-nanoemulsifying Drug Delivery System.
Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields.


The multiple facets of multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory and degenerative entity that may involve the brain, optic nerve, and/or the spinal cord. We reviewed 137 patients, aged 4-54 years old at the time of the diagnosis and will report on the vision, different motility disorders found, visual fields, optic neuritis and RAPD, return of vision following the neuritis, visual evoked potential, nerve fiber layer analysis, and systemic problems such as Uhthoff phenomenon, L'Hermitte sign, urinary urgency, and constipation. One hundred thirty-seven patients were given full ophthalmologic and orthoptic evaluations. Particular attention was given to subtle relative afferent pupillary defects (RAPD), oscillopsia, pain with eye movement, and other specialty testing including visual evoked potentials and nerve fiber layer assessment. The immunology, pediatric MS, clinical courses, and treatment are also discussed. Treatment included medication, orthoptic modalities, strabismus procedures, and cooling devices. Motiltiy disorders included exophoria, unilateral Internuclear Ophthalmoplegia (INO), esophoria, and various types of nystagmus. The majority of nonmotility ophthalmic entities included optic neuritis, RAPD, and abnormal nerve fiber layer studies. Most patients were diagnosed based on white matter lesions on the MRI and oligoclonal bands in the spinal fluid after lumbar puncture. The majority of systemic signs were numbness, Uhthoff sign, and balance difficulties. Thirty-four percent of the patients were helped with either convergence therapy, prisms for all kinds of diplopia, and field manipulation. MS is a multi-factorial entity. It is important to emphasize how important a few extra history questions are, including: any pain with eye movement, any bouncing of the images, and is vision or balance any worse in the heat? The Visual Evoked Potential (VEP) and nerve fiber layer studies are important in the diagnosis of MS. Seventy percent of patients with had eye complaints as their initial symptom. Finally, one-third of all patients were helped with some form of orthoptic therapy.


IL-10 regulation by HIV-Tat in primary human monocytic cells: involvement of calmodulin/calmodulin-dependent protein kinase-activated p38 MAPK and Sp-1 and CREB-1 transcription factors.
The anti-inflammatory cytokine, IL-10 plays an important role in HIV immunopathogenesis. The HIV accessory protein, Tat is not only critical for viral replication, but affects the host immune system by influencing cytokine production including IL-10. During HIV infection, IL-10 production by monocytic cells is up-regulated, representing a critical pathway by which HIV may induce immunodeficiency. Herein, we show that extracellular Tat-induced IL-10 expression in normal human monocytes. To understand the signaling pathways underlying HIV-Tat induced IL-10 transcription, we investigated the involvement of MAPK as well as calcium signaling and the downstream transcription factor(s). Our results suggest that Tat-induced calcium influx regulated IL-10 transcription in monocytic cells. The experiments designed to further understand the molecules involved in the calcium signaling suggested that calmodulin and calmodulin-dependent protein kinase-II (CaMK-II)-activated p38 MAPK played a role in extracellular Tat-induced IL-10 expression in primary human monocytes. Furthermore, Tat-induced IL-10 expression was regulated by p38 MAPK- and CaMK II-activated CREB-1 as well as Sp-1 transcription factors. Taken together, our results suggest that extracellular HIV-Tat induced IL-10 transcription in primary human monocytes is regulated by CREB-1 and Sp-1 transcription factors through the activation of calmodulin/CaMK-II-dependent p38 MAPK.


Side effects of terazosin in the treatment of symptomatic benign prostatic hyperplasia.
In this report, we assess the safety of terazosin in the treatment of patients with symptomatic benign prostatic hyperplasia. We analyzed seven prospectively designed placebo-controlled trials involving 3,080 patients, 1,689 of whom received the study drug in doses ranging from 1 mg to 20 mg daily for a total of 1,282 patient-years of exposure. The most common side effects seen in treated patients were dizziness (10.7%), asthenia (7.5%), and peripheral edema (4.0%). These side effects were generally reported as mild and improved after cessation of therapy. The incidence of withdrawal from the study due to side effects was 14.5% in the treatment arm versus 11.4% in the placebo control arm. Also noted was a statistically significant decreased risk of urinary tract infection and myocardial infarction in the terazosin-treated group. This updated report confirms that terazosin can be administered safely to a population of men with symptomatic benign prostatic hyperplasia with minimal clinically significant side effects.


Viability of Clostridium sporogenes spores after CaO hygienization of meat waste.
The occurrence of the pathogenic species C. perfringens and C. botulinum spores in animal by-products poses a potential epidemiological hazard. Strong entero- and neurotoxins produced by these bacteria adversely affect human health. To inactivate pathogens present in animal by-products, waste must be subjected to various methods of sanitization. The aim of the presented study was to estimate the effect of different doses of CaO on the viability of spores Clostridium sporogenes in meat wastes category 3. During the research, two doses of burnt lime were added to the poultry mince meat and meat mixed with swine blood contaminated with Clostridium sporogenes spore suspension. Half of the samples collected for microbiological analyses were buffered to achieve the pH level ~7, the other were examined without pH neutralization. To estimate the spore number, 10-fold dilution series in peptone water was prepared and heat-treated at 80 °C for 10 min. After cooling-down, one milliliter of each dilution was pour-plated onto DRCM medium solidified with agar. Statistical analysis were performed using the Statistica software. Application of 70% CaO caused complete inactivation of Clostridium spores in meat wastes after 48 hours. The highest temperature achieved during the experiment was 67 °C. Rapid alkalization of the biomass resulted in increasing pH to values exceeding 12. The effect of liming was not dependent on the meat wastes composition nor CaO dose. The experiment proved the efficiency of liming as a method of animal by-products sanitization. Application of the obtained results may help reduce the epidemiological risk and ensure safety to people handling meat wastes at each stage of their processing and utilization.


Hormetic Effects of Mixtures of Dimethachlone and Prochloraz on Sclerotinia sclerotiorum.
Previous studies showed that dimethachlone has significant hormetic effects on phytopathogenic fungus Sclerotinia sclerotiorum. The present study investigated hormetic effects of mixtures of dimethachlone and prochloraz on mycelial growth and virulence of two dimethachlone-resistant isolates of S. sclerotiorum. The stimulatory dimethachlone dosage range was around 1 to 100 μg/ml in potato dextrose agar (PDA) medium for mycelial growth of the two isolates, and dimethachlone at 10 and 50 μg/ml had the maximum percent stimulations of 80.6 and 19.3% for isolates JMS14 and HLJ4, respectively. Prochloraz at 0.0003 and 0.002 μg/ml had the maximum percent stimulations of 9.3 and 11.1% for isolates JMS14 and HLJ4, respectively. However, dimethachlone and prochloraz mixed at their respective stimulatory concentrations had the maximum percent stimulations of 48.1 and 9.3% for isolates JMS14 and HLJ4, respectively. After the mycelia with increased and inhibited growth on fungicide-amended PDA were subcultured on PDA without fungicide, mycelial growth for the second generation increased compared with the nontreated control. After the mycelia grown on fungicide-amended PDA were inoculated on rapeseed leaves, the amplitude of virulence stimulation was much greater than that of mycelial growth on PDA amended with fungicide, and the inhibited mycelia also showed substantially increased virulence on leaves. The mixture of dimethachlone at 100 μg/ml and prochloraz at 0.03 μg/ml in PDA inhibited mycelial growth of isolate JMS14 by 59.4%; however, after the inhibited mycelia were inoculated on rapeseed leaves, virulence was stimulated by 69.0%. Spraying sublethal doses of dimethachlone and prochloraz on rapeseed leaves also exhibited significant stimulatory effects on virulence. For isolate JMS14, the stimulatory concentration ranges for dimethachlone and prochloraz were around 1 to 600 μg/ml and 0.0003 to 0.18 μg/ml, respectively. The fitted curve of virulence stimulation for the mixture of dimethachlone and prochloraz shifted to the left on the x axis, denoting dose-additive interactions between the two fungicides with regard to virulence stimulation. Spraying dimethachlone alone at 10 to 50 μg/ml had significant stimulations on virulence, whereas prochloraz alone at 10 to 50 μg/ml had significant inhibitory effects on virulence, and the mixture of dimethachlone and prochloraz at the concentration ratio of 1:1 had greater inhibitory effects than prochloraz alone, indicating dose-additive interactions for the inhibitory effects. Dimethachlone and prochloraz and their mixtures increased tolerance of mycelia to hydrogen peroxide. Dimethachlone significantly increased, whereas prochloraz reduced mycelial cell membrane permeability, and the mixture of the two fungicides had effect-additive interactions with respect to effects on cell membrane permeability. These studies will advance our understanding of hormesis of fungicide mixtures.


Effect of exogenous selenium on the testicular toxicity induced by ethanol in rats.
The effects of supplementation of selenium at a dose of 10 microg/ kg body weight were investigated on ethanol induced testicular toxicity in rats. In the present study, four groups of male albino rats were maintained for 60 days, as follows: (1) Control group (normal diet) (2) Ethanol group (4g/kg body weight) (3) Selenium (10 microg/kg body weight) (4) Ethanol + Selenium (4g/kg body weight + 10 microg/kg body weight). Results revealed that ethanol intake caused drastic changes in the sperm count, sperm motility and sperm morphology. It also reduced the levels of testosterone and fructose. The activities of 3betaHSD, 17betaHSD in the testis and SDH in the seminal plasma were also reduced. Lipid peroxidation was also enhanced as the lipid peroxidation products were increased and the activities of the scavenging enzymes were reduced. But on coadministration of selenium along with alcohol all the biochemical parameters were altered to near normal levels indicating a protective effect of selenium. These results were reinforced by the histopathological studies.


[A distinct whole nucleus stain pattern of gamma H2AX induced by N-methyl-No-nitro-N-nitrosoguanidine].
To characterize the DNA damage property represented by the distinct whole nucleus stain pattern of gammaH2AX induced by N-methyl-No-nitro-N-nitrosoguanidine (MNNG). MNNG-induced gammaH2AX foci formation in human amnion FL cells was observed by immunofluorescent microscopy. DNA double-stranded breaks (DSBs) were detected by neutral comet assay. General DNA damages were detected by alkaline comet assay. A distinct whole nucleus stain pattern of gammaH2AX was induced by high concentration MNNG (10 mg/L). 1 mg/L MNNG also induced this type of stain pattern in a small fraction of cells, although the effect was transient. Neutral comet assay did not detect any significant DSBs formation in this type of cells, while alkaline comet assay revealed the presence of DNA damage. Although normal gammaH2AX foci were regarded as a biomarker for DSBs, the whole nucleus stain pattern might represent DNA damage other than DSBs.


Antioxidant potential of buffalo and cow milk Cheddar cheeses to tackle human colon adenocarcinoma (Caco-2) cells.
The aim of present study was to assess the anti-oxidant potential of water-soluble peptides (WSPs) extract derived from buffalo and cow milk Cheddar cheeses at different stages of ripening. The antioxidant potential of WSPs extract was assessed through 2,2'-azinobis-3-ethylbenzothiazoline-6sulfonic acid (ABTS)-radical scavenging activity. In addition, impact of WSPs extract on cell viability and production of reactive oxygen species (ROS) in human colon adenocarcinoma Caco-2 (tert-butylhydroperoxide-induced) cell lines was also evaluated. The ABTS-radical scavenging activity increased progressively with ripening period and dose-dependently in both cheeses. However, peptide extract from buffalo milk Cheddar cheese demonstrated relatively higher activity due to higher contents of water-soluble nitrogen. Intracellular ROS production in Caco-2 cells decreased significantly (p<0.05) till 150th day of cheese ripening and remained constant thereafter. Additionally, dose-dependent response of WSPs extract on antioxidant activity was noticed in the Caco-2 cell line. On the basis of current in vitro study, the Cheddar cheese WSPs extract can protect intestinal epithelium against oxidative stress due to their antioxidant activity.


Global dynamic routing for scale-free networks.
Traffic is essential for many dynamic processes on networks. The efficient routing strategy [G. Yan, T. Zhou, B. Hu, Z. Q. Fu, and B. H. Wang, Phys. Rev. E 73, 046108 (2006)] can reach a very high capacity of more than ten times of that with shortest path strategy. In this paper, we propose a global dynamic routing strategy for network systems based on the information of the queue length of nodes. Under this routing strategy, the traffic capacity is further improved. With time delay of updating node queue lengths and the corresponding paths, the system capacity remains constant, while the travel time for packets increases.


An adulticidal sticky ovitrap for sampling container-breeding mosquitoes.
The efficacy of a standard ovitrap and an ovitrap featuring an internal wall covered by a polybutylene adhesive was compared in field studies in Cairns, Australia. The sticky ovitrap was as effective as the standard ovitrap in detecting Aedes aegypti, with 67.5% and 64% of traps positive for Ae. aegypti, respectively. Significantly higher numbers of Ae. aegypti were collected by traps set outside rather than inside premises. Sticky ovitraps also readily collected Ochlerotatus notoscriptus and, especially, Culex quinquefasciatus. With a 10X hand lens, mosquitoes of these species could readily be identified in traps set for 3 and 7 days. The sticky ovitraps were comparable in cost and as time efficient as standard ovitraps. The greatest advantage of the sticky ovitrap is the collection of adult female mosquitoes, negating the need to rear larvae for identification and providing a faster, more direct measure of the effectiveness of ovipositional attractants than egg counts. Finally, we demonstrated that sticky ovitraps, being adulticidal, have potential as a supplementary control measure, especially for quarantine programs designed to prevent the import and export of container-breeding vector mosquitoes at sea- and airports.


Electron microscopic radioautographic study on protein synthesis in hepatocyte mitochondria of aging mice.
For the purpose of studying the aging changes of intramitochondrial protein synthesis in mouse hepatocytes, 10 groups of aging mice, each consisting of 3 individuals (total 30), from fetal day 19 to postnatal month 24, were injected during development with 3H-leucine, a protein precursor, sacrificed 1 h later, and the liver tissues processed for electron microscopic (EM) radioautography. On EM radioautograms obtained from each animal, the number of mitochondria, the number of labeled mitochondria, and the mitochondrial labeling index labeled with silver grains due to 3H-leucine showing protein synthesis in each mononucleate hepatocytes were counted and the averages in respective aging groups were compared. From the results, it was demonstrated that the numbers of mitochondria, the numbers of labeled mitochondria, and the labeling indices of intramitochondrial protein syntheses in mononucleate hepatocytes of mice at various ages from embryonic day 19 to postnatal month 24 increased and decreased due to development and aging of animals.


Why do some children have good hearing results following type III and IV tympanoplasty? Current theories of middle ear mechanics.
Middle ear reconstruction in children following tympanomastoidectomy for cholesteatoma is commonly limited to a Wullstein type III or IV reconstruction owing to ossicular erosion. The hearing outcomes of this procedure have been unpredictable. Nevertheless, there are children who have remarkably good hearing results despite having extensive and aggressive cholesteatoma surgery and limited reconstruction. The current theories of middle ear mechanics following tympanoplasty and ossicular reconstruction are reviewed. In addition, a selective retrospective chart review of pediatric type III and IV tympanoplasty at The Hospital for Sick Children between 1998 and 2003 is presented. Nine patients were reconstructed with a type III (n = 3) or IV (n = 6) tympanoplasty. The mean pre- and postoperative air-bone gaps were 43.6 and 24.9 dB. Speech reception threshold improved from 37.5 to 22.8 dB. The changes were statistically significant (p < .05). This series of patients demonstrated a statistically significant hearing improvement at long-term follow-up. The improvements are consistent with optimal hearing outcomes predicted by current theories of middle ear mechanics.


Aberrant PI3Kδ splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers.
PI3K/AKT signaling pathway is upregulated in a broad spectrum of cancers. Among the class I PI3Ks (PI3Kδ/β/δ isoforms), PI3Kδ has been implicated in hematologic cancers and solid tumors. Alternative splicing is a post-transcriptional process for acquiring proteomic diversity in eukaryotic cells. Emerging evidence has highlighted the involvement of aberrant mRNA splicing in cancer development/progression. Our previous studies revealed that PIK3CD-S is an oncogenic splice variant that promotes tumor aggressiveness and drug resistance in prostate cancer (PCa). To further evaluate the potential of utilizing PI3Kδ-S (encoded from PIK3CD-S) as a cancer biomarker and/or drug target, comprehensive analyses were performed in a series of patient samples and cell lines derived from endocrine/solid tumors. Specifically, IHC, immunofluorescence, western blot and RT-PCR assay results have demonstrated that PI3Kδ isoforms were highly expressed in endocrine/solid tumor patient specimens and cell lines. Differential PIK3CD-S/PIK3CD-L expression profiles were identified in a panel of endocrine/solid tumor cells. SiRNA knockdown of PIK3CD-L or PIK3CD-S differentially inhibits AKT/mTOR signaling in PCa, breast, colon and lung cancer cell lines. Moreover, siRNA knockdown of PTEN increased PI3Kδ levels and activated AKT/mTOR signaling, while overexpression of PTEN reduced PI3Kδ levels and inhibited AKT/mTOR signaling in cancer cells. Intriguingly, PI3Kδ-S levels remained unchanged upon either siRNA knockdown or overexpression of PTEN. Taken together, these results suggested that PTEN negatively regulates PI3Kδ-L and its downstream AKT/mTOR signaling, while PI3Kδ-S promotes AKT/mTOR signaling without regulation by PTEN. Lastly, PI3Kδ inhibitor Idelalisib and SRPK1/2 inhibitor SRPIN340 were employed to assess their efficacies on inhibiting the PI3Kδ-expressing endocrine/solid tumors. Our results have shown that Idelalisib effectively inhibited PI3Kδ-L (but not PI3Kδ-S) mediated AKT/mTOR signaling. In contrast, SRPIN340 reversed the aberrant mRNA splicing, thereby inhibiting AKT/mTOR signaling. In-vitro functional assays have further demonstrated that a combination of Idelalisib and SRPIN340 achieved a synergistic drug effect (with drastically reduced cell viabilities/growths of tumor spheroids) in inhibiting the advanced tumor cells. In summary, our study has suggested a promising potential of utilizing PI3Kδ-S (an oncogenic isoform conferring drug resistance and exempt from PTEN regulation) as a prognostic biomarker and drug target in advanced endocrine cancers.


PET-based geometrical calibration of a pinhole SPECT add-on for an animal PET scanner.
We developed SPECT imaging capability on an animal PET scanner to provide a cost effective option for animal SPECT imaging. The SPECT add-on sub-system was enabled by mechanically integrating a multiple-pinhole collimator in the PET detector ring. This study introduces a method to calibrate the geometrical parameters of the SPECT add-on using the PET imaging capability of the scanner. The proposed PET imaging-based calibration method consists of two steps: (1) paint the pinhole apertures of the collimator with a positron emitting radioactive solution; and (2) image the collimator inside the scanner in PET mode. The geometrical parameters of the multi-pinhole SPECT add-on can then be derived directly from a set of PET images by simple linear calculation and used in defining the SPECT system. The method was compared to our implementation of a SPECT calibration approach with model-based fitting of SPECT projection data. The procedure for carrying out the PET imaging-based calibration method is simpler and faster than that of our implementation of the SPECT model-based calibration method. Since it does not require model fitting, the uniqueness of the calibration result is warranted. Better quality SPECT images were reconstructed using the PET-derived calibration parameters rather than our implementation of the SPECT model-based calibration parameters. We conclude that the proposed PET imaging-based calibration method provides a highly effective means for enabling SPECT imaging on a PET scanner.


Synthesis and structure of nongeminally substituted cyclic phosphazenes with haloalkyl and thioester functional groups.
Nongeminally substituted cyclic phosphazenes with various haloalkyl substituents were prepared using deprotonation-substitution reactions at the methyl groups of the cis isomers of nongeminally substituted cis-[Me(Ph)P=N]3, 2. Treatment of 2 with n-BuLi followed by reaction with organic halogenated reagents (RX=C2Cl6, BrC(O)CMe2Br, and ICH2COOEt) at low temperature afforded the various cyclic derivatives cis-[(XCH2)(Ph)PN]3 (3, X=Cl, 4, Br, and 5, I). The mono- and dibromoalkyl derivatives, cis-[Ph3(BrCH2)Me2P3N3], 6, and [Ph3(BrCH2)2MeP3N3], 7, were also isolated along with 4 when the electrophile was dibromoethane. Reaction of cis-[Ph(BrCH2)PN]3, 4, with KSC(O)Me gave cis-[Ph(MeC(O)SCH2)PN]3, 8. The structures of all the cis cyclic phosphazenes were determined by NMR spectroscopy and X-ray diffraction. All retained the basketlike shape with the hydrophobic phenyl groups opposite the haloalkyl groups on the P3N3 ring. Thermal analysis of the new cyclic trimers indicates that ring-opening polymerization does not occur. The melting points and the thermal stabilities of haloalkyl cyclophosphazenes were higher than those of the parent compound 2.


Imaging mass spectrometry: Towards clinical diagnostics.
Imaging MS (IMS) has emerged as a powerful tool for biomarker discovery. A key advantage of this technique is its ability to probe the proteome directly from a tissue section with preservation of the spatial relationships of the sample and minimal sample preparation. This allows for direct correlation of protein expression with histology. Here, we present the latest developments in imaging MS and their relevance to clinical mass spectral analysis. IMS allows for high throughput analysis of tissue samples and is fully compatible with biostatistical analysis without prior knowledge of protein expression. Several studies are presented of applications in which direct tissue mass spectral analysis has provided insight into clinical questions not readily available by other means. Examples include the determination of lymph node status from investigation of primary breast tumors, prediction of response of breast tumors to chemotherapy, classification and prediction of progression of lung lesions, and exploration of 'molecular' margins in invasive disease.