Matrix GLA protein gene polymorphisms: clinical correlates and cardiovascular mortality in chronic kidney disease patients.
Increased vascular calcification plays an important role in the pathogenesis of cardiovascular events in chronic kidney disease (CKD) patients. It is the result of an active ossification process counteracted by 'protective' proteins, such as matrix GLA protein (MGP). Polymorphisms of MGP have been identified. The aim of this study was to define the distribution of two MGP polymorphisms (-7, -138) in 99 hemodialysis (HD) patients, in 26 patients with CKD stage 3 and in 135 age- and sex-matched healthy controls. Patients were followed up for 12 months to record any cardiovascular deaths. The cause of death was determined by medical doctors, considering the medical history of each patient. The primers were designed with Primer Express software. MGP -138TT homozygotes were more frequent in the HD group versus controls (p = 0.0004). Additionally, the frequency of the T allele was significantly higher in the HD group (p = 0.0006). The frequency of the A allele of MGP-7 was significantly higher both in the HD group (p = 0.033) and in the CKD group (p = 0.0017) versus controls. MGP-7 GG homozygotes were significantly less common in the CKD group than in controls (p = 0.037). Combination -138TT -7AA was significantly more frequent in both CKD patients (p = 0.001) and in HD patients (p = 0.029) than in controls. Seventeen out of 99 HD patients experienced fatal cardiovascular events. Sixteen (94.1%) were -138TT homozygotes and either -7AA homozygotes or -7GA heterozygotes. This study suggests that CKD and HD patients have a different distribution of MGP gene polymorphism as compared with the normal population. Altered MGP gene polymorphism may be a negative prognostic factor for the progression to end-stage renal disease and for cardiovascular events in CKD patients.


Effect of acclimation on resting energy expenditure measurements.
Development of an acclimation protocol for use when measuring resting energy expenditure (REE) would simplify and standardize data collection. The purpose of this study was to determine if our 2 metabolic carts could be used interchangeably and to determine if excluding the first 3 or 5 minutes of data collected as an acclimation period would significantly improve the coefficients of variation (CVs) for oxygen consumed (VO(2)) and carbon dioxide produced (VCO(2)) when performing REE assessments with our metabolic cart systems. Thirteen healthy, nonsmoking adults ranging in age from 32 to 45 years, with activity levels ranging from sedentary to highly active, participated. Indirect calorimetry was performed twice in the morning after 30 minutes of supine resting. Subjects had fasted for 12 hours, and did not exercise within the last 24 hours. The system order for testing was randomized for the first measurement. When the first measurement was completed, subjects were crossed over for measurement using a second metabolic cart. The CVs for VO(2) and VCO(2) were significantly lower when excluding the first 3 (VO(2), p = .0005), (VCO(2), p = .0024) or 5 minutes (VO(2), p = .0001, VCO(2), p = .0021) of data compared with no exclusions. No significant differences in CVs between the 3- and 5-minute exclusions were found for VO(2) (p = .3224) or VCO(2) (p = .2255). Clearly, our machines cannot be used interchangeably within a study. An acclimation period improves CVs of VO(2) and VCO(2.) The similarities in CVs led us to adopt a 3-minute acclimation period for measuring REE.


Molecular Design of Magnetic Resonance Imaging Agents Binding to Amyloid Deposits.
The ability to detect and monitor amyloid deposition in the brain using non-invasive imaging techniques provides valuable insights into the early diagnosis and progression of Alzheimer's disease and helps to evaluate the efficacy of potential treatments. Magnetic resonance imaging (MRI) is a widely available technique offering high-spatial-resolution imaging. It can be used to visualize amyloid deposits with the help of amyloid-binding diagnostic agents injected into the body. In recent years, a number of amyloid-targeted MRI probes have been developed, but none of them has entered clinical practice. We review the advances in the field and deduce the requirements for the molecular structure and properties of a diagnostic probe candidate. These requirements make up the base for the rational design of MRI-active small molecules targeting amyloid deposits. Particular attention is paid to the novel cryo-EM structures of the fibril aggregates and their complexes, with known binders offering the possibility to use computational structure-based design methods. With continued research and development, MRI probes may revolutionize the diagnosis and treatment of neurodegenerative diseases, ultimately improving the lives of millions of people worldwide.


Modeling deoxyribonucleic acid and ribonucleic acid damage in the gas phase.
This short review outlines the tandem mass spectrometric methods for the generation and analysis of transient nucleobase radicals relevant to deoxyribonucleic acid and ribonucleic acid damage. Radical hydrogen atom adducts to uracil, adenine, cytosine and N-methylcytosine were generated by femtosecond electron transfer to the corresponding gas-phase cations in fast beams at 8 keV kinetic energy. Radical unimolecular dissociations were monitored by product analysis following collisional ionization to cations or anions using neutralization-reionization mass spectrometry. The radical energetics and dissociation kinetics were further analyzed by mapping the potential energy surfaces by high-level ab initio calculations in combination with Rice-Remsberger-Kassel-Marcus calculations of unimolecular rate constants. This first- principles-based approach allows one to model radical dissociations occurring from doublet ground electronic states of radical intermediates, assign reaction mechanisms and derive quantitative branching ratios for dissociation channels that are in agreement with experiments. Theoretical analysis also provides distinction between radical dissociations occurring on the ground and excited electronic state potential energy surfaces. Specific characterization of excited state dissociations of nucleobase and other polyatomic radicals remains a challenging topic for both experimentalists and computational chemists.


The distribution of keratin type intermediate filaments in human breast cancer. An immunohistological study.
Antibodies to different intermediate filament proteins can be used to distinguish cells of epithelial, mesenchymal, muscle, glial and neuronal origin. Antibodies to prekeratin which characterize cells of epithelial origin, and antibodies to vimentin which recognize cells of mesenchymal origin have been used to study twenty cases of breast carcinoma (sixteen infiltrating ductal carcinomas and four infiltrating intraductal carcinomas), two cases of cystic breast disease, two fibroadenomas and one case of benign cystosarcoma phylloides. The prekeratin and vimentin were detected using specific antibodies to these proteins by immunofluorescence microscopy using alcohol fixed paraffin-embedded tissues. In eighteen out of the twenty carcinomas the tumor cells were strongly and specifically stained by antibodies to prekeratin. DIfferent tumors gave different patterns of prekeratin staining. In contrast, when the same specimens were tested with the vimentin antibody, the tumor cells were unstained, and instead only the usual strong staining to fibroblasts and blood vessels in the stroma was observed. In cystic breast disease, fibroadenomas, and benign cystosarcoma phylloides, cells of epithelial origin were strongly stained by the prekeratin but not by the vimentin antibody.


Genetic characterization of T-DNA insertions in the genome of the Arabidopsis thaliana sumo1/2 knock-down line.
Sumoylation is an essential post-translational modification in Arabidopsis thaliana, which entails the conjugation of the SUMO protein onto lysine residues in target proteins. In Arabidopsis, 2 closely related genes, SUMO1 and SUMO2, act redundantly and are in combination essential for plant development, i.e. the combined loss of SUMO1 and SUMO2 results in embryo-lethality. To circumvent this lethality, SUMO2 was previously knocked down in a sumo1 knockout background by expressing an artificial microRNA that targets SUMO2 (amiR-SUMO2). This sumo1/2KD line with low SUMO2 levels represents a valuable genetics tool to investigate SUMO function in planta. Here, we re-sequenced the whole-genome of this sumo1/2KD line and identified 2 amiR-SUMO2 insertions in this line, which were confirmed by PCR-genotyping. Identification of these 2 insertions enables genetics with this tool.


Structural characterization of the catalytic site of a Nilaparvata lugens delta-class glutathione transferase.
Glutathione transferases (GSTs) are a major class of detoxification enzymes that play a central role in the defense against environmental toxicants and oxidative stress. Here, we studied the crystal structure of a delta-class glutathione transferase from Nilaparvata lugens, nlGSTD, to gain insights into its catalytic mechanism. The structure of nlGSTD in complex with glutathione, determined at a resolution of 1.7Å, revealed that it exists as a dimer and its secondary and tertiary structures are similar to those of other delta-class GSTs. Analysis of a complex between nlGSTD and glutathione showed that the bound glutathione was localized to the glutathione-binding site. Site-directed mutagenesis of nlGSTD mutants indicated that amino acid residues Ser11, His52, Glu66, and Phe119 contribute to catalytic activity.


[Toxicological evaluation of pesticide and chemical residues in control of biological processes in vegetables under glass and plastics].
The cultivation of vegetables under glass and plastics is one of the most intensive application fields of pesticides and chemicals for regulation of biological processes. Therefore it may potentially occur a relatively high residues contamination of the crops. The author reveals in a survey the residue situation of usual insecticides, acaricides, fungicides, and chemicals for regulation of biological processes on tomatoes, cucumbers, and lettuce in comparison with the maximum residue limit after cold fogging application. The residues of benomyl, carbendazim, and ethylen-bis-dithiocarbamate are detailed discussed in the light of the latest toxicological findings. The results the residues of 11 agents on the crops show that after the corresponding preharvest interval the residues constitute 1.7-78% of the maximum residue limit. The conclusion is drawn that the cold fogging application of the agents under glass and plastics does not result in food hygienic toxicological problems.


The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective.
The use of stem-cell therapies for the treatment of various musculoskeletal conditions, especially knee osteoarthritis (OA), is rapidly expanding, despite only low-level evidence to support its use. Centers offering these therapies are often marketing and charging patients out-of-pocket costs for such services. Therefore, the purpose of this study was to determine the current marketed: (1) prices and (2) clinical efficacy of stem-cell therapies for knee OA. This was a prospective cross-sectional study which queried 317 U.S. centers that offered direct-to-consumer stem-cell therapies for musculoskeletal conditions. A total of 273 of 317 centers were successfully contacted via phone or e-mail, using a simulated 57-year-old male patient with knee OA. Scripted questions were asked by the simulated patient to determine the marketed prices and clinical efficacy. Centers generally reported the proportion of patients who had "good results" or "symptomatic improvement." The mean price of a unilateral (same-day) stem-cell knee injection was $5,156 with a standard deviation of $2,446 (95% confidence interval [CI]: $4,550-5,762, n = 65). The mean proportion of claimed clinical efficacy was 82% with a standard deviation of 9.6% (95% CI: 79.0-85.5%, n = 36). Most American stem-cell centers offer therapies for knee OA. The cost of these therapies averages about $5,000 per injection, and centers claim that 80% of the patients had "good results" or "symptomatic improvement," denoting a gap between what is documented in the published literature and the marketing claims. These findings offer both patients and physicians insight into the current stem-cell market for knee OA. We hope that with this information, providers can more optimally make patients aware of discrepancies between what is being marketed versus the current evidence-based landscape of these therapies for knee OA.


Cyclic stretch modulates the cell morphology transition under geometrical confinement by covalently immobilized gelatin.
Fibroblasts geometrically confined by photo-immobilized gelatin micropatterns were subjected to cyclic stretch on the silicone elastomer. By using covalently micropatterned surfaces, the cell morphologies such as cell area and length were quantitatively investigated under a cyclic stretch for 20 hours. The mechanical forces did not affect the cell growth but significantly altered the cellular morphology on both non-patterned and micropatterned surfaces. It was found that cells on non-patterns showed increasing cell length and decreasing cell area under the stretch. The width of the strip micropatterns provided a different extent of contact guidance for fibroblasts. The highly extended cells on the 10 μm pattern under static conditions would perform a contraction behavior once treated by cyclic stretch. In contrast, cells with a low extension on the 2 μm pattern kept elongating according to the micropattern under the cyclic stretch. The vertical stretch induced an increase in cell area and length more than the parallel stretch in both the 10 μm and 2 μm patterns. These results provided new insights into cell behaviors under geometrical confinement in a dynamic biomechanical environment and may guide biomaterial design for tissue engineering in the future.


Fine-mapping additive and dominant SNP effects using group-LASSO and fractional resample model averaging.
Genomewide association studies (GWAS) sometimes identify loci at which both the number and identities of the underlying causal variants are ambiguous. In such cases, statistical methods that model effects of multiple single-nucleotide polymorphisms (SNPs) simultaneously can help disentangle the observed patterns of association and provide information about how those SNPs could be prioritized for follow-up studies. Current multi-SNP methods, however, tend to assume that SNP effects are well captured by additive genetics; yet when genetic dominance is present, this assumption translates to reduced power and faulty prioritizations. We describe a statistical procedure for prioritizing SNPs at GWAS loci that efficiently models both additive and dominance effects. Our method, LLARRMA-dawg, combines a group LASSO procedure for sparse modeling of multiple SNP effects with a resampling procedure based on fractional observation weights. It estimates for each SNP the robustness of association with the phenotype both to sampling variation and to competing explanations from other SNPs. In producing an SNP prioritization that best identifies underlying true signals, we show the following: our method easily outperforms a single-marker analysis; when additive-only signals are present, our joint model for additive and dominance is equivalent to or only slightly less powerful than modeling additive-only effects; and when dominance signals are present, even in combination with substantial additive effects, our joint model is unequivocally more powerful than a model assuming additivity. We also describe how performance can be improved through calibrated randomized penalization, and discuss how dominance in ungenotyped SNPs can be incorporated through either heterozygote dosage or multiple imputation.


Current surgical trends in Japan for managing chronic pancreatitis.
The main aims of surgery for treating chronic pancreatitis are to relieve the patient's persistent pain and to preserve pancreatic functioning. The indications for surgery include treating complications, such as the presence of pancreatic pseudocysts or biliary stenosis associated with chronic pancreatitis or both. A resection, ductal drainage, or both, may commonly be required. Furthermore, some surgeons recommend pancreatic denervation. We analyze the details of 2,936 patients with chronic pancreatitis who were treated surgically and were listed in the 1985 National Statistics in Japan. We have also evaluated the present surgical methods for treating chronic pancreatitis in Japan. In addition, we discuss a new surgical method being used to treat chronic pancreatitis. This is a recently improved technique involving a complete duodenum-preserving resection of the head of the pancreas, which also preserves the biliary and alimentary tracts.


Two Landmark Studies Published in 1976/1977 Paved the Way for the Recognition of Human Papillomavirus as the Major Cause of the Global Cancer Burden.
Two groundbreaking reports were published in Acta Cytologica at the transition of 1976 to 1977. One appeared in the last issue of 1976 [Meisels and Fortin: Acta Cytol 1976;20:505-509] and the other in the first issue of 1977 [Purola and Savia: Acta Cytol 1977;21:26-31]. Today, 40 years later, it is not an overstatement to conclude that these are the two most influential studies ever published in this journal. Two reports with a similar content being published so close together (in the same journal) raised the question "Which of the two reports was truly submitted first?" In this commentary, this enigma is clarified beyond reasonable doubt, based on the well-considered testimonial of Prof. Leopold G. Koss, the reviewer of one of the two papers. To fully appreciate the significance of the novel discovery made in these two reports, it is essential to align them in the right context, both retrospectively and prospectively. This commentary will assist the reader by summarizing the existing knowledge on human papillomavirus (HPV) before these two milestone papers appeared, and describe the incredibly rapid progress that they evoked during the subsequent decades, which made HPV the single most important human tumor virus. As the final proof of virus-cancer causality, prophylactic HPV vaccines have been effective in preventing (a) virus transmission and HPV infection, (b) benign HPV-induced tumors (genital warts), and (c) cervical intraepithelial neoplasia (CIN). Formal evidence of the prevention of cervical cancer by these HPV vaccines still awaits confirmation, and the same applies to the eventual prevention of human cancers at other anatomic sites, part of the global burden of oncogenic HPVs.


Prostate Cancer Survivors: Physical, Emotional and Practical Concerns from the LIVESTRONG Survey.
To determine whether a relationship exists between types of treatment received and/or survivorship status of prostate cancer survivors with physical, emotional, and practical concerns that they experience with the hypothesis that no such relationship exists. We analyzed data from the 2010 LIVESTRONG survey for cancer survivors which queried their physical, emotional, and practical concerns. This previously tested survey was administered between June 20, 2010 and March 31, 2011 on the LIVESTRONG.org website. Survivorship status was categorized as reported by the respondents: currently on treatment; living with cancer as a chronic condition; finished treatment less than 1 year ago; 1-5 years ago and; more than 5 years ago. Four categories were established for the types of treatment received: surgery, radiation, hormonal, and combination therapies. One-way ANOVA's were conducted to detect differences between groups and descriptive statistics were reported. Of 2,307 respondents overall, only 281 males were included in this study based on self-reported primary diagnosis of prostate cancer and US residency status. The mean age of respondents was 60 years (SD = 8.54 years) and majority were white (90%). One-way ANOVA detected significant differences between the number of physical (p = 0.02), emotional (p = 0.04), and practical (p = 0.00) concerns for patients receiving different treatments. When compared across the survivorship trajectory, only number of practical concerns (p = 0.00) experienced by prostate cancer survivors were significantly different. Study findings highlight significant differences in number of concerns experienced by the patients based on their survivorship stage and the type of treatment received. Incorporating strategies to address the differences in physical, emotional, and practical concerns are essential to help physicians and clinical team members provide high quality post treatment survivorship care.


Accessory right hepatic artery branched from gastroduodenal artery.
The right hepatic artery usually branches from the common hepatic artery, however, there are cases showing anatomic variations. We present 41-year-old female patient with gallbladder cancer. In this case, the accessory right hepatic artery branched from the gastroduodenal artery, passed in front of the common bile duct and fed into the anterior segment of the liver. Cholecystectomy and resection of the extrahepatic bile duct with hepaticoenterostomy were performed successfully, preserving the accessory right hepatic artery. There are few reports presenting such an extremely rare anomaly of hepatic arteries in the English literature. Additionally, we herein present a review of the English literature regarding anatomic variations of right hepatic artery.


Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo.
The present study investigates the effect of an oxidized nanocrystalline diamond (O-NCD) coating functionalized with bone morphogenetic protein 7 (BMP-7) on human osteoblast maturation and extracellular matrix mineralization in vitro and on new bone formation in vivo. The chemical structure and the morphology of the NCD coating and the adhesion, thickness and morphology of the superimposed BMP-7 layer have also been assessed. The material analysis proved synthesis of a conformal diamond coating with a fine nanostructured morphology on the Ti6Al4V samples. The homogeneous nanostructured layer of BMP-7 on the NCD coating created by a physisorption method was confirmed by AFM. The osteogenic maturation of hFOB 1.19 cells in vitro was only slightly enhanced by the O-NCD coating alone without any increase in the mineralization of the matrix. Functionalization of the coating with BMP-7 resulted in more pronounced cell osteogenic maturation and increased extracellular matrix mineralization. Similar results were obtained in vivo from micro-CT and histological analyses of rabbit distal femurs with screws implanted for 4 or 12 weeks. While the O-NCD-coated implants alone promoted greater thickness of newly-formed bone in direct contact with the implant surface than the bare material, a further increase was induced by BMP-7. It can be therefore concluded that O-NCD coating functionalized with BMP-7 is a promising surface modification of metallic bone implants in order to improve their osseointegration.


Acute Monoblastic Leukemia as a Second Malignancy After Doxorubicin and Cisplatin Treatment for Osteosarcoma.
Secondary or therapy-related acute myeloid leukemia (t-AML) occurs as a complication of various chemotherapy regimens. In pediatric age group, leukemia as a second malignancy after osteosarcoma treatment with doxorubicin and cisplatin is relatively rare. A 15-year-old girl was admitted to our hospital with signs and symptoms of leukemia. She had been treated one-year earlier with doxorubicin and cisplatin for osteosarcoma of the left femur. The patient was diagnosed with acute monoblastic leukemia on the basis of bone marrow examination and immunophenotype analysis. There were no cytogenetic abnormalities. The patient's father had been diagnosed with pelvic chondrosarcoma, which suggested a familial susceptibility to cancer. We interpreted this as a rare case of t- AML with normal cytogenetic analysis, and believe the disease was induced by the addition of platinum compounds to a regimen including topoisomerase II inhibitors.


Electron microscopic localization of acetylcholinesterase and nonspecific cholinesterase at the neuromuscular junction by the gold-thiocholine and gold-thiolacetic acid methods.
By means of the gold-thiocholine (AuThCh) and gold-thiolacetic acid (AuThAc) methods, it has been demonstrated electron microscopically that acetylcholinesterase (AChE) is located at the prejunctional axoplasmic membrane and the postjunctional sarcoplasmic membrane, including the full lengths of its invaginations, at the motor end plate of mouse intercostal muscle. Nonspecific cholinesterase (ChE) is present in relatively low concentrations at the same sites, and in greater concentrations in the teloglial Schwann sheath cells. Significant amounts of reaction product appeared in the junctional cleft only after prolonged incubation with both methods. The identification of AChE and ChE was confirmed by the use of appropriate concentrations of several selective inhibitors. In confirmation of previous studies by light microscopy, the AuThCh method is more specific for AChE and ChE, whereas the AuThAc method allows greater accuracy of localization.


Benzyl ions from 1,1-(2,2'-dimethoxyphenyl)-substituted 2-methylpropanes under electron ionization.
The electron ionization (EI)-induced fragmentations of a series of 1,1-(2,2'-dimethoxyphenyl)-substituted 2-methylpropanes (1-20) in both 70 eV and mass-analyzed ion kinetic energy (MIKE) spectra have been investigated. The EI-MS spectra of these compounds are characterized by the presence of abundant benzyl ions. These ions result from competitive hydrogen migration from the 2- and 2'-methoxy groups on the carbenium center of the diphenylmethyl cations formed by benzylic cleavage of the molecular ions. The relative abundances of the benzyl ions arising from such competitive processes are discussed and rationalized. The steric effect of the 3- or 3'-substituents is the main discriminating factor between the two competitive processes. The structural information, arising either from the 70 eV or the MIKE spectra, is discussed.


Added Value of Patient-Reported Outcome Measures in Stroke Clinical Practice.
There is uncertainty regarding the clinical utility of the data obtained from patient-reported outcome measures (PROMs) for patient care. We evaluated the incremental information obtained by PROMs compared to the clinician-reported modified Rankin Scale (mRS). This was an observational study of 3283 ischemic stroke patients seen in a cerebrovascular clinic from September 14, 2012 to June 16, 2015 who completed the routinely collected PROMs: Stroke Impact Scale-16 (SIS-16), EQ-5D, Patient Health Questionnaire-9, PROMIS Physical Function, and PROMIS fatigue. The amount of variation in the PROMs explained by mRS was determined using r2 after adjustment for age and level of stroke impairment. The proportion with meaningful change was calculated for patients with ≥2 visits. Concordance with change in the other scales and the ability to discriminate changes in health state as measured by c-statistic was evaluated for mRS versus SIS-16. Correlation between PROMs and mRS was highest for SIS-16 (r=-0.64, P<0.01). The r2 ranged from 0.11 (PROMIS fatigue) to 0.56 (SIS-16). Change in scores occurred in 51% with mRS and 35% with SIS-16. There was lower agreement and less ability to discriminate change in mRS than in SIS-16 with change in the other measures. PROMs provide additional valuable information compared to the mRS alone in stroke patients seen in the ambulatory setting. SIS-16 may have a better ability to identify change than mRS in health status of relevance to the patient. PROMs may be a useful addition to mRS in the assessment of health status in clinical practice.


Analytical ultracentrifugation for analysis of doxorubicin loaded liposomes.
Analytical ultracentrifugation (AUC) is a powerful tool for the study of particle size distributions and interactions with high accuracy and resolution. In this work, we show how the analysis of sedimentation velocity data from the AUC can be used to characterize nanocarrier drug delivery systems used in nanomedicine. Nanocarrier size distribution and the ratio of free versus nanoparticle-encapsulated drug in a commercially available liposomal doxorubicin formulation are determined using interference and absorbance based AUC measurements and compared with results generated with conventional techniques. Additionally, the potential of AUC in measuring particle density and the detection of nanocarrier sub-populations is discussed as well. The unique capability of AUC in providing reliable data for size and composition in a single measurement and without complex sample preparation makes this characterization technique a promising tool both in nanomedicine product development and quality control.


Trigeminal neuralgia: a comparison of the results of percutaneous rhizotomy and microvascular decompression.
Seventy-five patients were treated between March 1976 and June 1980 for classical idiopathic tic douloureux. Fifty-five patients underwent percutaneous trigeminal rhizotomy (PTR) and twenty-four had posterior fossa microvascular decompression (MVD) of the trigeminal nerve. Four patients had both procedures. In the PTR group, 4% were immediate failures, 42% had a delayed recurrence of pain, while 54% remained totally pain free with an average follow-up of 30 months. In the MVD group, 12% were immediate failures, 17% had a delayed recurrence of pain, and 71% have remained free of pain with a average follow-up of 28 months. Neither procedure can be regarded as ideal surgical treatment for patients with pain refractory to medical treatment. Percutaneous rhizotomy has an established place because of its safety, particularly in elderly patients. A high rate of recurrent pain is to be expected. Microvascular decompression has appeal in younger patients because of its non-destructive nature but the long term efficacy of the procedure is not known.


Stimuli-Responsive Dual-Color Photon Upconversion: A Singlet-to-Triplet Absorption Sensitizer in a Soft Luminescent Cyclophane.
Reversible emission color switching of triplet-triplet annihilation-based photon upconversion (TTA-UC) is achieved by employing an Os complex sensitizer with singlet-to-triplet (S-T) absorption and an asymmetric luminescent cyclophane with switchable emission characteristics. The cyclophane contains the 9,10-bis(phenylethynyl)anthracene unit as an emitter and can assemble into two different structures, a stable crystalline phase and a metastable supercooled nematic phase. The two structures exhibit green and yellow fluorescence, respectively, and can be accessed by distinct heating/cooling sequences. The hybridization of the cyclophane with the Os complex allows near-infrared-to-visible TTA-UC. The large anti-Stokes shift is possible by the direct S-T excitation, which dispenses with the use of a conventional sequence of singlet-singlet absorption and intersystem crossing. The TTA-UC emission color is successfully switched between green and yellow by thermal stimulation.


Hydatid cyst of the infraspinatus muscle.
Muscle hydatidosis is rare accounting only for 3%-5% of cases. Until now, only one case of muscular hydatidosis involving the infraspinatus muscle has been recorded. Hereby, we present a case report of primary hydatidosis of infraspinatus muscle in a 32-year-old woman from Central India who presented with painful soft-tissue swelling. Ultrasonography appearance was consistent with that of hydatid cyst; while serology was negative, pericystectomy was performed, and the diagnosis was confirmed. The patient was followed up for a period of 6 months, and no recurrence was noted. Hydatid cysts should be considered in the differential diagnosis of soft-tissue swellings, particularly in endemic regions.


Exploring the material basis and mechanism of action of clinacanthus nutans in treating renal cell carcinoma based on metabolomics and network pharmacology.
Clinacanthus nutans (for abbreviation thereafter) is often used as medicine in the form of fresh juice in the folk to treat many kinds of cancers, including renal cell carcinoma (RCC). It is speculated that its active ingredient may have heat sensitivity, but there are currently no reports on this aspect. Therefore, based on the folk application for fresh juice of C nutans, this study used metabonomics and network pharmacology to explore the material basis and mechanism of action of C nutans against RCC. Firstly, untargeted metabolomics profiling was performed by Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to screen the metabolites down-regulated by heat in the extract of C nutans. Secondly, we collected the targets of metabolites in the Swiss Target Prediction platform. In addition, the targets of RCC were obtained in the GeneCards database. The "component-target-disease" network was established by Cytoscape3.9.0 software. Then we constructed a protein-protein interaction network in the STRING network platform to screen core targets. The gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis of core targets were carried out to predict the relevant pathway of C nutans in the treatment of RCC. Finally, the molecular docking verification of the core targets were carried out. In this study, 35 potential active ingredients and 125 potential targets were obtained. And the core targets were Cellular tumor antigen p53, Signal transducer and activator of transcription 3, and so on. Then, 48 biological processes, 30 cell components, and 36 molecular functions were obtained by gene ontology enrichment analysis. Besides, 44 pathways were obtained by Kyoto encyclopedia of genes and genomes enrichment analysis, including Pathway in cancer, PI3K-Akt signal pathway, P53 signal pathway, and so on. The docking model between the core target and its corresponding components was stable. This research is based on the folk application of C nutans, showed its potential active ingredients by metabonomics, and predicted the potential mechanism of C nutans in the treatment of RCC by network pharmacology. It provides new references for follow-up research and new drug development.


Identification of mRNA transcript and screening of amino acids in response to interaction of salinity and nitrate in aquatic fern Azolla caroliniana.
The mechanisms by which Azolla caroliniana respond to salt stress in absence and presence of nitrate is investigated. Screening of amino acid and differential display is used to compare overall differences in gene expression between salinity-stressed and unstressed Azolla caroliniana by quantitative reverse transcriptase polymerase chain reaction (RT-PC R). Results showed that under saline conditions, aspartic acid, glutamic acid, alanine and leucine were the amino acids found to be abundant in Azolla caroliniana, accounting for 11.26%, 8.66%, 9.43%, and 12.36%, respectively. Following salinity stress, a decrease in free glutamate concomitant with a parallel decrease in free proline was indeed evident. Interaction between nitrate and salinity stress increased proline content significantly. By screening a cDNA library, we have identified protein products by homology with known proteins. The RNA transcripts encoding protein influencing secondary metabolites and vacuolar Na+/H+ antiporter that facilitate the transport system. The databasematched under interaction of nitrate and 50 mM NaCl were associated with wall biosynthesis, disease resistance, metabolite transport and protein regulator, other gene for metabolism of steroids and secondary transport. Results obtained from this research could represent a key step in understanding the molecular mechanism of salt tolerance of Azolla caroliniana in the presence and absence of nitrate.


Optogenetic Control of TGF-β Signaling.
Cells employ signaling pathways to make decisions in response to changes in their immediate environment. The Transforming Growth Factor β (TGF-β) signaling pathway plays pivotal roles in regulating many cellular processes, including cell proliferation, differentiation, and migrations. In order to manipulate and explore the dynamic behavior of TGF-β signaling at high spatiotemporal resolution, we developed an optogenetic system (the optoTGFBRs system), in which light is used to control TGF-β signaling precisely in time and space. Here, we describe about experimental details of how to build the optoTGFBRs system and utilize it to manipulate TGF-β signaling in a single cell or a cell population using microscope or LED array, respectively.


Pharmacological treatment of tardive dyskinesia: recent developments.
Tardive dyskinesia (TD) occurs in patients receiving antipsychotic treatment with dopamine receptor antagonists. Despite the prevalence of TD and its negative impact on patients' lives, there has been a lack of approved treatments and limited evidence from controlled trials of pharmacological treatment. Areas covered: PubMed was searched for English-language papers published during 2007-2016 using terms 'tardive dyskinesia' or 'drug-induced movement disorder', and 'treatment'. Studies evaluating pharmacological agents for the treatment of TD were selected. A total of 26 studies (five meta-analyses, twelve randomized controlled trials, and nine open-label observational studies) are reviewed. Expert commentary: Treatment of TD necessitates a stepwise approach. Optimization of antipsychotic therapy should be considered before initiation of antidyskinetic therapies. Data from some recent studies indicate possible improvements in TD after switching antipsychotics or with the use of amantadine, levetiracetam, piracetam, zonisamide, propranolol, vitamin B6, or certain unregulated herbal medicines; although significance of these improvements is unclear and require further investigation in randomized controlled trials. By contrast, recent evidence from Phase III trials of novel vesicular monoamine transporter-2 inhibitors demonstrates they could have a significant effect on TD symptom severity and suggests these agents may have the potential to transform treatment of TD in coming years.


Clinical presentation of women readmitted with postpartum severe preeclampsia or eclampsia.
To identify symptoms that prompted a group of women readmitted for postpartum severe preeclampsia or eclampsia to seek medical care. Retrospective, case-control. Tertiary-care teaching hospital. The study group consisted of 53 women readmitted in the postpartum period with severe preeclampsia or eclampsia. The control group was matched two-to-one with an index study participant and consisted of 106 women who had intrapartum severe preeclampsia or eclampsia. Patient symptoms, physical findings, laboratory assays. Neurologic complaints, malaise, and nausea and vomiting were reported more often in women who were readmitted than in mothers with intrapartum preeclampsia (all p values less than .001). Headaches were positively correlated with systolic, diastolic, and mean arterial blood pressure in women who were readmitted (all p values less than .05), although there was no relationship between blood pressure and headaches in the control group. In addition, multivariate analysis revealed that study participants were more likely to deliver at full term, have headaches and malaise, have normal platelet values, and develop seizures than mothers in the control group, chi 2 = 155.7, p < .001. Women readmitted for postpartum severe preeclampsia or eclampsia have a clinical presentation that differs from that of intrapartum preeclampsia or eclampsia.


[Body composition analysis among adults with different body weights].
To explore the characteristics of body composition among male and female adults with different body weights. A total of 61 379 healthy adults (39 855 males and 21 527 females) were referred to our health examination center between May 2005 and February 2011. Body mass index (BMI) and body composition contents of fat, water, muscle, protein and mineral salt were measured by anthropometric measurements and bioelectrical impedance analysis (BIA). The data were analyzed among groups divided by gender, age and BMI. (1) The prevalence of overweight and obesity defined by BMI was significantly higher in the male group than the female of the same age group under 70 years old (all P < 0.01). (2) Within a certain age range (< 60 in males, < 70 in females), the prevalence of both overweight and obesity defined by BMI increased with age (all P < 0.01). (3) The fat mass percentage was significantly higher in females than in males of the same age group. The difference became more and more significant with advancing age. And the most significant difference was found in the upper 70 years old group (fat mass rate of males vs females, 24% ± 7% vs 36% ± 6%, P < 0.01). (4) Body fat mass percentage progressively elevated with increases of BMI while there was a decreasing trend of other body composition contents. The total male subjects had higher percentage of muscle, water and mineral salt than females (percentage of muscle, water and mineral salt of males vs females, 0.708 ± 0.066 vs 0.664 ± 0.063, 0.520 ± 0.044 vs 0.474 ± 0.042, 0.040 ± 0.004 vs 0.036 ± 0.004, all P < 0.01) while the percentage of protein was higher in the total female group (P < 0.01). Females has more fat mass than males under the same BMI. So it is more reasonable to introduce adiposity for the evaluation of obesity, especially in females.


Culturally-Tailored Education Programs to Address Health Literacy Deficits and Pervasive Health Disparities among Hispanics in Rural Shelbyville, Kentucky.
This investigation was conducted to evaluate the impact of culturally-tailored education on health knowledge among Hispanic residents of rural, Shelbyville, KY. The program identified specific pathways to address health literacy deficits and disparities identified through a community-wide health assessment completed in 2010. A total of 43 Hispanic males who shared deficiencies in community-wide health infrastructure were enrolled in the program. The curriculum included an introductory session followed by five, subject-specific, sessions offered on a weekly basis from February to April 2011. Pre/post-test assessments showed marked improvement in knowledge base for all participants after each session, most notably related to cardiovascular disease, diabetes and metabolic syndrome. The group reconvened in January 2012 for follow-up instruction on cardiovascular disease and diabetes, as well as global assessment of knowledge retention over a nine-month period. Comparisons of pre/post testing in cardiovascular disease and diabetes, as well as global health-related knowledge showed significant gains for all parameters. Health education programs that embrace perceptions of the community of their own health, and that integrate knowledge into culturally-sensitive education, significantly improved health knowledge among Hispanic residents in rural Kentucky. Such gains may translate into sustainable improvements in health literacy and help reduce health disparities.


Association of the BDNF C270T polymorphism with schizophrenia: updated meta-analysis.
Brain-derived neurotrophic factor (BDNF) has been suggested to play a role in the pathophysiology of schizophrenia. The C270T polymorphism (rs56164415) in the BDNF 5'-non-coding region has been extensively investigated for an association with schizophrenia, but with conflicting results. An updated meta-analysis was therefore performed of 13 case-control association studies (3505 patients and 3992 controls). An association was found between the T allele and schizophrenia. The association was significant in the East Asian population, but not in the Caucasian population. It is suggested that the BDNF C270T polymorphism contributes to schizophrenia susceptibility, especially in East Asian subjects.


Notoginsenoside R1 Ameliorates Cardiac Lipotoxicity Through AMPK Signaling Pathway.
Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5'monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway. Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining. Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor. Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.


Atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats.
Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (iNOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an iNOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through iNOS expression.


"War Epidemiology" Versus "Peace Epidemiology": A Personal View.
Epidemiology can be considered as a responsible public health science the aim of which is to control health problems. One of the most important public health problems is "war". The aim of the present paper, therefore, is threefold: firstly, to determine to what extent war has been investigated from an epidemiological point of view; secondly, what the definition and scope of "war epidemiology" would be; and thirdly, if it would be possible to introduce a new branch of epidemiology entitled "peace epidemiology". In the present study, I have tried to fulfill the aims of the study based on my experiences in war and peace epidemiology and also by reviewing the most relevant websites, documents and papers. Evidence suggests that enough epidemiological studies have not been carried out to determine the sheer public health consequences of war. "War epidemiology" can be defined as "the study of the distribution and determinants of war-related events in specified populations, and the application of this study to the control of war". "Peace epidemiology" is a new branch of epidemiology which "highlights how peace could positively shape our world". Epidemiologists need to produce more scientific evidence about the negative public health consequences of wars and also the positive public health consequences of peace. The ultimate aim of "war epidemiology" is to control war, usually by secondary and tertiary prevention activities. However, the ultimate aim of "peace epidemiology" is to reinforce peace by primary and/or primordial prevention activities.


Stress response of the tibial cortex: a longitudinal radiographic study.
The influence of physical exercise on bone tissue was studied in a sample of 30 conscripts, who served in the coast commando battalion . A repeated roentgen examination of the lower legs was performed after 10, 20 and 40 weeks' service. In the anterior cortex of mid-diaphysis of the tibia a structural change in bone could be regularly observed. In the first examination (after 10 weeks) the cortical bone was longitudinally striated. In the next control (after 20 weeks) the finding was less pronounced. After 40 weeks the bone structure was quite homogenous and solid. The cortical thickness did not change significantly during the 40 weeks follow-up. Most of the diagnosed stress lesions (73%) in bone were developed during the first 10 weeks.


The mystery of phospholipid flip-flop in biogenic membranes.
Phospholipid flip-flop is required for bilayer assembly and the maintenance of biogenic (self-synthesizing) membranes such as the eukaryotic endoplasmic reticulum and the bacterial cytoplasmic membrane. Due to the membrane topology of phospholipid biosynthesis, newly synthesized phospholipids are initially located in the cytoplasmic leaflet of biogenic membranes and must be translocated to the exoplasmic leaflet to give uniform bilayer growth. It is clear from many studies that phospholipid flip-flop in biogenic membranes occurs very rapidly, within a period of a few minutes. These studies also reveal that phospholipid translocation in biogenic membranes occurs bi-directionally, independently of the phospholipid head group, via a facilitated diffusion process in the absence of metabolic energy input, and that this type of transport requires specific membrane proteins. These translocators have been termed biogenic membrane flippases, and they differ from metabolic energy-dependent transporters (ABC transporters and MDR proteins). No biogenic membrane flippases have been characterized. This review briefly discusses the importance of biogenic membrane flippases, the various assay methods used for measuring the rate of phospholipid flip-flop, and the progress that has been made towards identifying these proteins.


Noninvasive radiofrequency field destruction of pancreatic adenocarcinoma xenografts treated with targeted gold nanoparticles.
Pancreatic carcinoma is one of the deadliest cancers with few effective treatments. Gold nanoparticles (AuNP) are potentially therapeutic because of the safety demonstrated thus far and their physiochemical characteristics. We used the astounding heating rates of AuNPs in nonionizing radiofrequency (RF) radiation to investigate human pancreatic xenograft destruction in a murine model. Weekly, Panc-1 and Capan-1 human pancreatic carcinoma xenografts in immunocompromised mice were exposed to an RF field 36 hours after treatment (intraperitoneal) with cetuximab- or PAM4 antibody-conjugated AuNPs, respectively. Tumor sizes were measured weekly, whereas necrosis and cleaved caspase-3 were investigated with hematoxylin-eosin staining and immunofluorescence, respectively. In addition, AuNP internalization and cytotoxicity were investigated in vitro with confocal microscopy and flow cytometry, respectively. Panc-1 cells demonstrated increased apoptosis with decreased viability after treatment with cetuximab-conjugated AuNPs and RF field exposure (P = 0.00005). Differences in xenograft volumes were observed within 2 weeks of initiating therapy. Cetuximab- and PAM4-conjugated AuNPs demonstrated RF field-induced destruction of Panc-1 and Capan-1 pancreatic carcinoma xenografts after 6 weeks of weekly treatment (P = 0.004 and P = 0.035, respectively). There was no evidence of injury to murine organs. Cleaved caspase-3 and necrosis were both increased in treated tumors. This study demonstrates a potentially novel cancer therapy by noninvasively inducing intracellular hyperthermia with targeted AuNPs in an RF field. While the therapy is dependent on the specificity of the targeting antibody, normal tissues were without toxicity despite systemic therapy and whole-body RF field exposure.


Fluorocytometric analysis of anti-HLA class 2 autoantibodies in patients with lupus nephritis.
Systemic lupus erythematosus (SLE) patients are known to produce a variety of autoantibodies (AAb), some of which may be directed against immunocompetent cells. Anti-B cell autoimmunity may encompass reactivity against HLA-class 2 molecules, which are also expressed on kidney tissue. We studied 15 patients with moderate to severe renal involvement and 5 lupus patients with no clinical renal disease, in order to detect the presence of anti-HLA class 2 AAb. Flow cytometry was employed in an inhibitory assay using patient sera, autologous cells and two anti-class 2 monoclonals, to establish the specificity of anti-B cell AAb. Seven out of 15 nephritis patients had detectable anti-class 2 AAb with an epitopic heterogeneity, as demonstrated by different degrees of inhibition on the binding of non-overlapping monoclonals. The specificity of the reaction was confirmed by the lack of inhibition of non-class 2 antibody binding. The presence of such AAb was not correlated with disease activity but with the presence of a diffuse proliferative glomerulonephritis on renal biopsy. Anti-class 2 AAb may be a marker of SLE diffuse proliferative nephritis.


In vitro effects of N-acetylcysteine on the mutagenicity of direct-acting compounds and procarcinogens.
N-Acetylcysteine (NAC), reduced (GSH) and oxidized (GSSG) glutathione were negative in the Ames test with 7 Salmonella strains, while L-cysteine was activated by rat liver S-9 fractions to metabolites mutagenic to strains TA102, TA97 and TA100. The mutagenic response in S. typhimurium strains (TA1535, TA98, TA100, TA102) and the levels of enzyme activities, responsible for NADP+ or GSSG reduction and for the utilization of NADPH or GSH in rat liver S-9 fractions, were investigated following in vitro preincubation of NAC with four direct-acting mutagens and six procarcinogens. Treatment with this nucleophilic and reducing compound resulted in a dose-related decrease of the direct mutagenicity of epichlorohydrin, hydrogen peroxide and, sharply, of 4-nitroquinolino-N-oxide and sodium dichromate. The mutagenicity of these compounds, both in the absence and in the presence of NAC, was decreased by rat liver S-9 fractions and to some extent by lung S-9 fractions. A diphasic effect was observed in the case of procarcinogens (cyclophosphamide, 2-aminofluorene, cigarette smoke condensate, Trp-P-2, aflatoxin B1 and benzo[a]pyrene), i.e., an enhancement of S-9 requiring mutagenicity at intermediate NAC doses, which could be ascribed to metabolic factors acting in vitro, and a loss of mutagenicity at high NAC doses, which could be ascribed to trapping of electrophilic metabolites. Out of the five S-9 enzyme activities under study, i.e., glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme, GSH peroxidase and GSSG reductase, only the last one showed significant changes following mutagen and/or NAC treatment.


Video-assisted sympathectomy for essential hyperhidrosis: effects on cardiopulmonary function.
Essential hyperhidrosis is characterized by overactivity of the sympathetic fibers passing through the upper-dorsal ganglia (second and third thoracic ganglia [D2-D3]), and the treatment of choice is video-assisted thoracoscopy sympathectomy. Alterations in cardiopulmonary function after treatment have been reported. To evaluate cardiopulmonary function impairment after sympathectomy in patients with essential hyperhidrosis. Prospective controlled trial at a pulmonary function unit of a university hospital. Twenty patients (2 men and 18 women) with essential hyperhidrosis. Pulmonary function tests, including spirometry and thoracic gas volume, bronchial challenge with methacholine, and maximal exercise, were performed before and 3 months after D2-D3 sympathectomy. Video-assisted sympathectomy was performed using a one-stage bilateral procedure with electrocoagulation of D2-D3 ganglia. Pulmonary function values (spirometrics and volumes) were not statistically different in the two groups. The maximal midexpiratory flow was the only variable that showed significant changes, from 101% (SD, 26%) to 92% (SD, 27%) [p < 0.05]. Ten patients had positive bronchial challenge test results that remained positive 3 months after surgery, and 2 patients whose challenge test results were negative before surgery became positive after sympathectomy. Significant reductions in maximal heart rate (HR) and oxygen and carbon dioxide uptakes were observed during the maximal exercise test. Video-assisted thoracoscopy is a safe treatment, and the observed modifications in cardiopulmonary function only suggest a minimal small airway alterations in the presence of positive bronchial hyperresponsiveness and mild sympathetic blockade in HR. The clinical importance of these findings is not significant.


Interplay between density and superconducting quantum critical fluctuations.
We consider the case of a density-driven metal-superconductor transition in the proximity of an electronic phase separation. In particular, we investigate the interplay between superconducting fluctuations and density fluctuations, which become quantum critical when the electronic phase separation vanishes at zero temperature into a quantum critical point. In this situation, the critical dynamical density fluctuations strongly affect the dynamics of the Cooper-pair fluctuations, which acquire a more singular character with a z = 3 dynamical critical index. This gives rise to a scenario that possibly rules the disappearance of superconductivity when the electron density is reduced by electrostatic gating at the LaAlO3/SrTiO3 interface.


Attitudes, barriers and facilitators to the conduct of research in government hospitals: a cross-sectional study among specialists in government hospitals, northern states of Malaysia.
Specialists constitute a major 'driving force' and catalyst for growth of research in their speciality. A clearer understanding is required as to what motivates their participation in research as well as the barriers they faced. This research aims to study the attitudes, barriers and facilitators faced by specialists and to identify strategies to promote and sustain research activities in their hospitals. A cross-sectional survey using selfadministered questionnaires was conducted among all specialists working in government specialist hospitals in the northern states of Malaysia. Out of 733 questionnaires distributed, 467 were returned giving a response rate of 63.7%. Ninety-nine percent of the respondents believed that research benefits patients while 93.3% think research helps in their professional development. However, 34.8% think that under their present working conditions, it is unlikely they will participate in research. The major barriers identified were lack of funds for research (81%); lack access to expertise, software or statistical analysis (78.4%); interference with daily work schedule (75.1%) and inconsistent manpower in their department (74.2%). There are three barriers with statistically significant difference between hospitals with CRC compared to hospitals without CRC; lack of funds, mentors and access to expertise, software or statistical analysis. The demographic factors, attitudes and barriers contributing to involvement in research also investigated. The main facilitators for the conduct of research are potential to benefit patients and potential for professional development. Taking note of the findings, the Ministry of Health can implement appropriate strategies to improve specialist participation in research.


Serum pseudocholinesterase activity during experimental fattening.
The exact role of serum pseudocholinesterase (PSCE) is not known. Its main role probably consists in the degradation of butyril-choline, an intermediate of lipid metabolism. Decreased values have been described in liver cirrhosis as an index of diminished proteosynthetic function. An increased activity of this enzyme was reported in obesity, diabetes mellitus, nephrosis, hyperthyroidism and in hyperlipemic subjects without obesity. A significant correlation was found between serum cholesterol, triglycerides and PSCE, as an expression of lipid metabolism. In view of assessing the possible change of this enzyme during fattening, the authors investigated PSCE activity during fattening in pigs (the same breed). The results indicate a statistically significant increase of PSCE during fattening, from 30.4 +/- 1.7 to 43.6 +/- 1.7 (p less than 0.001). These results together with those reported in a previous paper concerning blood lipids and cholesterol, show a positive correlation between these parameters and PSCE during fattening in pigs, which might be due to an adaptative increase of the hepatic synthesis of this enzyme in response to the increased lipid metabolism.


Is Very High Thyroid Stimulating Hormone Level Required in Differentiated Thyroid Cancer for Ablation Success?
Remnant ablation with radioactive iodine (I-131) is a successful form of treatment that aims to destroy the remaining residual tissue and/or metastatic tissue after total thyroidectomy in differentiated thyroid cancer (DTC) patients. High level of thyroid stimulating hormone (TSH) (≥30 mIU/L) is recommended for success of ablation treatment. In this retrospective study, our aim was to investigate whether the TSH levels at the time of ablation effect the success of radioactive iodine remnant ablation. Patients who were diagnosed with DTC, treated with bilateral total/near total thyroidectomy and who were referred for I-131 remnant ablation were included in this study. Patients with undetectable TSH-stimulated serum thyroglobulin (Tg) level, normal physical examination, negative results on whole body scan with I-131, and no evidence of neck lymph node metastasis on ultrasound were defined as disease-free. The correlation between TSH level at the time of ablation and ablation success was assessed. Two hundred sixty one consecutive patients were included in the present study. Mean TSH level was 19.47±6 mIU/L in the 34 patients with TSH <30 mIU/L, while mean TSH level was 73.65±27 mIU/L in the 227 patients with TSH ≥30 mIU/L during I-131 remnant ablation. Ablation was unsuccessful in only one patient with TSH <30 mIU/L who had lung metastasis. Ablation was unsuccessful in 5.1% of patients with TSH ≥30 mIU/L. The effect of TSH level was not significant on ablation success (p=0.472). In conclusion, we think that a high TSH serum level alone is not a factor for the success of ablation. Age, presence of metastasis, extent of residual thyroid mass should also be considered. Especially, in the presence of metastatic tissue, obtaining adequate increase in TSH level is not always possible. The success of ablation at lower levels of TSH elevations may be sufficient for patients, and long-term hypothyroidism may not be required.


Successful 72-hour cold storage of dog kidneys with UW solution.
Effects of three cold-storage solutions on kidney function in dogs were examined with the isolated perfused (IPK) kidney model and the autotransplant model. EuroCollins' (EC) solution, phosphate-buffered sucrose solution, and a new solution developed at the University of Wisconsin (UW) were studied. Kidneys were cold-stored for 48 hr or 72 hr. With the IPK model, cold storage for 48 hr or 72 hr in each of the three solutions caused creatinine clearance to decrease by 80%-90%. More protein was excreted by kidneys stored for 48 hr in PBS solution than by kidneys stored in EC or UW solution; protein excretion after 72 hr of storage was similar for kidneys stored in EC or UW solution. Sodium reabsorption decreased after 48 hr or 72 hr of storage, but was higher in kidneys stored in UW solution (83% and 56%, respectively) than in EC solution (52% and 22%, respectively). With the autotransplant model, 40% of the kidneys were viable after 48-hr storage in PBS solution, but 80% viable when stored in EC solution and 100% were viable when stored in UW solution. All kidneys were viable when stored for 72 hr in UW solution; none were viable when stored for 72 hr in EC solution. These results suggest that UW solution effectively preserves kidneys for 72 hr. We previously reported successful 72-hr pancreas preservation. Recently UW solution was able to preserve canine livers for 30 hr. Thus, this single solution appears to be effective for preserving all intraabdominal organs and may simplify cold storage of organs for transplantation.


Collaborative multihop transmission of distributed sensor imagery.
We consider a network of imaging sensors. We address the problem of energy-efficient communication of the measurements of the sensors. A novel algorithm is presented for the purpose of exploiting intersensor and intrasensor correlation, which is inherent in a network of imaging sensors. The collaborative algorithm is used in conjunction with a cooperative multihop routing strategy to maximize the lifetime of the network. The algorithm is demonstrated to achieve an average gain in the lifetime as high as 3.2 over previous methods.


[Chemotherapy of the elderly patients with advanced non-small cell lung cancer].
Chemotherapy of the elderly patients with III B/IV stage non-small cell lung cancer till remains controversial. We retrospectively reviewed the recent literatures, and conclude that single-agent chemotherapy should be the standard therapy of the elderly patients with IIIB/IV stage non-small cell lung cancer.


Age estimation by dental developmental stages in children and adolescents in Iceland.
Studies have shown that it is necessary to create a database for dental maturity for every population and compare it to others. The present study is the first one for dental development in the Icelandic population the age range being 4-24 years. It will help in forensic dental age estimation and will also help dentists, physicians, anthropologists, archaeologists and other professionals who rely on developmental age assessment in children and adolescents. In this present retrospective cross-sectional study, dental maturity was determined in 1100 Icelandic children and adolescents from orthopantomograms (OPGs). The first 100 were used for a pilot study and the remaining 1000 for the main study. A total of 23 subjects were excluded. The sample consisted of 508 girls and 469 boys from the age of 4-24 years and a dental developmental scoring system was used as a standard for determination of dental maturity stages. A total of 200 OPGs were studied both on the left and right side and the remaining on the right side. Dental maturity was established for all teeth and both genders, when the sample permitted, from the beginning of crown formation to the root apex closure. The Cronbach's Alpha reliability test showed high reliability, R=0.982. Girls in Iceland reach dental maturity root completed (stage 10, Rc) at 17.81 years of age for the maxillary and at 18.47 years for the mandibular teeth. Boys reach dental maturity root completed (stage 10, Rc) at 18.00 years of age in the maxilla and 17.63 in the mandible. There was no significant difference between left and right side (r=0.95-1.00) and there was no gender difference, except in root formation in maxillary and mandibular canines where girls reached root completed earlier than boys. A reliable database has been established in Iceland for tooth development in the age range of 4-24 years, which is compatible with international studies. These results will help forensic odontologists and other professionals to estimate with high accuracy both age and dental maturity in Icelandic children and adolescents.


Adherence to guidelines for the prescribing of double and triple combinations of antithrombotic agents.
To prevent cardiovascular complications, sometimes double and triple therapy with a vitamin K antagonist (VKA), clopidogrel and/or acetylsalicylic acid (ASA) are indicated. These combinations increase the patient's risk of serious bleeding events. Therefore, adherence to clinical guidelines is of the utmost importance when these high-risk therapies are prescribed. We performed a retrospective cohort study of 238 cases in a community pharmacy that were treated with a combination of VKA, clopidogrel and/or ASA between January 2006 and December 2009. Hospital records and community pharmacy records were used to obtain the indication(s), the duration of combination therapy, the presence of risk-increasing and risk-decreasing co-medications and any relevant co-morbidities. The cardiologists' attitudes towards the prescribing of antithrombotic combinations and their self-reported adherence to guidelines were assessed by a brief questionnaire. We found there was no guideline-based indication for 22 of the 146 cases (14%) on ASA plus clopidogrel and 19 of the 82 cases (23%) on VKA plus ASA. Of the 238 cases given antithrombotic combination therapies, 77 (32%) were placed at an additional increased risk of serious gastrointestinal events, yet 43 (56%) of these did not receive adequate gastric protection. Out of the 19 of 60 cardiologists (32%) who responded to our questionnaire; 17 (90%) and 13 (68%) stated that a strict indication is very important when initiating therapy with ASA plus clopidogrel or ASA plus VKA, respectively. There is room to further develop adherence to guideline-based prescribing of antithrombotic combination therapies and to improve prescription of gastric protection for patients receiving these high-risk combinations.


Synthesis of a chemically reactive analog of the nonsense codon U-G-A. Its reaction with ribosomes of Escherichia coli.
Nitrophenylated 5'-uridylic acid could be employed as primer in a polyribonucleotide nucleotidyltransferase (Micrococcus luteus) reaction to yield 5'-nitrophenylated Pu-G-A. After reduction of the nitrophenyl moiety and subsequent bromoacetylation, a 5'-bromoacetamido-phenyl-phosphorylated U-G-A was obtained, which could be used as an affinity label for the ribosomal binding site of the nonsense codon. If freshly prepared active ribosomes were employed in the incubation mixtures, the U-G-A analog reacted exclusively with one protein, which is tentatively identified as protein S18. Exposure of ribosomes to low temperatures gave rise to a reaction of the U-G-A label with another protein, which was identified as protein S4, the ram gene product. The results of the affinity labeling experiments with the chemically reactive U-G-A derivative are very similar to that obtained with a corresponding derivative of the initiation codon A-U-G (O. Pongs and E. Lanka (1975) Proc. Natl. Acad. Sci. U.S.A. 75, 1505-1509), which suggests that 70S ribosomes have one preferential codon binding site.


The effect of the Senior Citizens' Freedom to Work Act of 2000 on employer-provided pension and medical plans.
On April 7, 2000 President Clinton signed the Senior Citizens' Freedom to Work Act. The act reduces the Social Security retirement benefit penalties previously imposed on 65- through 69-year-old workers who earned more than nominal incomes after enrolling in the program. This article analyzes the impact that the act will have on retirement decisions of the affected cohorts of older workers and closes with an analysis of how the act may affect employer-provided pension, medical and paid leave plans.


Application of three-dimensional digital models for the morphometric analysis of predentition plasters: accuracy and precision.
This study aimed to test the accuracy and precision of measurements of three-dimensional (3D) digital models from the pre-dentition period using a noncontact 3D measurement system (3D scanner) versus the gold standard method of direct measurements using a digital caliper on plaster models. Ten pairs of plaster models were obtained from children during the predentition period. Linear measurements were performed using both methods. Three operators were trained in the use of both methods for this study. Measurements were performed with a minimum 2-week interval between measurements in a randomly chosen order. The mean difference between the measured values using the two methods was <0.2 mm for each measurement. There was no linearity in the measurements using pre-dentition digital models. An ANOVA Gage R&R analysis revealed that there was no significant operator difference (P < 0.307). The rate of variation of the 3D scanner over the total variation was 2.8%. The ICC was 0.982 (P< 0.001), suggesting excellent interoperator agreement. The results suggest that measurements of digital 3D pre-dentition models are highly accurate and precise, and also comparable to measurements using the gold standard method.


Free and total putrescine in cerebrospinal fluid quantified by reversed-phase liquid chromatography.
This is a simple, rapid, sensitive method for routine quantification of the polyamine putrescine (1,4-diaminobutane) in cerebrospinal fluid. Sample preparation involves protein precipitation, acid hydrolysis for 18 h (if total putrescine is to be measured), pre-column derivatization with o-phthalaldehyde, and extraction into acetonitrile. The derivative is separated and quantified by "high-performance" liquid chromatography on a reversed-phase C18 radial-compression column. A single chromatographic run takes less than 18 min. Putrescine concentrations as low as 50 nmol/L in cerebrospinal fluid can be detected.


[Chlorhexidine: the ideal antiseptic].
This article is a extensive bibliographical review about the characteristics of chlorhexidine as a cutaneous antiseptic. This antiseptic belongs to the biguanides (metformin) group and is very active against a large number of micro-organisms. Its systemic absorption is practically null, thus, it lacks any systemic toxicity. As a cutaneous antiseptic it has a rapid, long-lasting effect and is not inactive in the presence of organic matter and, due to its transparency it does not hide the evolution of wounds. Due to these properties, its recommendations for use have grown and consolidated over time until it has converted into one of the most effective, active and safe antiseptics for daily clinical practice.


BMI, sex, and antidepressant response.
Investigators have examined potential mechanisms for the observed differences between men and women in antidepressant response. However, to date no studies have measured the impact of body mass index (BMI) on men's and women's response to selective serotonin re-uptake inhibitors or placebo. We evaluated the response to antidepressants and placebo of 274 non-obese (BMI<30) and obese (BMI>30) depressed outpatients participating in Phase II-IV clinical trials. After categorizing men and women into their respective BMI groups, we measured the amount of change each group experienced from baseline to the final visit using the HAM-D-17 and MADRS ratings scales. Compared to women, men assigned to an antidepressant had a significantly lower mean total change on both the HAM-D-17 [non-obese, F(1,88)=5.292, p=0.024; obese, F(1,39)=7.040; p=0.012] and the MADRS [non-obese, F(1,66)=4.049, p=0.048; obese, F(1,27)=8.631, p=0.007]. In fact, obese men showed the smallest difference in antidepressant-placebo response. The results of the ANCOVAs indicated significant main effects of treatment (placebo vs. antidepressant), sex of the patient, and BMI category as well as a significant interaction between all three variables. Patients participating in clinical trials are not necessarily representative of the entire depressed population. In addition, our results include only SSRIs, not other antidepressants. Compared to the rest of the depressed sample the subgroup of depressed obese men (n=40) showed little or no therapeutic benefit with SSRI antidepressants. Although our findings may have important clinical implications, replication and further research is warranted in order to understand their underlying mechanisms and their pertinence to dosing strategies.


Two-dimensional droplet spreading over random topographical substrates.
We examine theoretically the effects of random topographical substrates on the motion of two-dimensional droplets via statistical approaches, by representing substrate families as stationary random functions. The droplet shift variance at both early times and in the long-time limit is deduced and the droplet footprint is found to be a normal random variable at all times. It is shown that substrate roughness inhibits wetting, illustrating also the tendency of the droplet to slide without spreading as equilibrium is approached. Our theoretical predictions are verified by numerical experiments.


Chromosome fragility in New Zealand black mice: effect of ultraviolet and gamma radiations on fetal fibroblasts in vitro.
The sensitivity of fibroblasts cultured from New Zealand Black (NZB) and BALB/c mouse fetuses to UV and gamma radiations was tested with two methods: 1) colony-forming ability and 2) chromosome abnormalities. When compared with BALB/c cells, NZB cells had reduced colony-forming ability and increased chromosome abnormalities after UV irradiation. However, no differences were seen in colony formation or frequency of chromosome abnormalities between NZB and BALB/c cells after exposure to gamma radiation. This apparent UV specificity strengthens the suggestion that NZB mice might be used as a model to study the relationship between chromosome abnormalities and cancer in human syndromes such as xeroderma pigmentosum, which is characterized by chromosome instability.


Mutating both relA and spoT of enteropathogenic Escherichia coli E2348/69 attenuates its virulence and induces interleukin 6 in vivo.
Here, we report for the first time that disrupting both relA and spoT genes in enteropathogenic Escherichia coli E2348/69 can attenuate its virulence and significantly induce interleukin 6 (IL-6) in vivo. Our experimental analyses demonstrated that an E2348/69 ΔrelAΔspoT double mutant strain derepressed the expression of type IV bundle forming pilus (BFP) and repressed the expression of glutamate decarboxylase (GAD) and locus of enterocyte effacement (LEE). Whole genome-scale transcriptomic analysis revealed that 1,564 EPEC genes were differentially expressed in the ΔrelAΔspoT double mutant strain (cut-off > two-fold). Such depletion of relA and spoT attenuated the virulence of E2348/69 in a Caenorhabditis elegans infection model. Surprisingly, IL-6 was highly induced in porcine macrophages infected with the ΔrelAΔspoT double mutant strain compared to those with its wildtype strain. Coinciding with these in vitro results, in vivo murine peritoneal challenge assays showed high increase of IL-6 and improved bacterial clearance in response to infection by the ΔrelAΔspoT double mutant strain. Taken together, our data suggest that relA and spoT play an essential role in regulating biological processes during EPEC pathogenesis and that their depletion can affect host immune responses by inducing IL-6.


Heterogeneity of memory T cells in aging.
Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population. Here we review how T cell memory is influenced by age. T cell memory is maintained by a dynamic population of T cells that are heterogeneous in their kinetic parameters under homeostatic condition and their function. Durability of T cell memory can be influenced not only by the loss of a clonal progeny, but also by broader changes in the composition of functional states and transition of T cells to a dysfunctional state. Genome-wide single cell studies on total T cells have started to provide insights on the influence of age on cell heterogeneity over time. The most striking findings were a trend to progressive effector differentiation and the activation of pro-inflammatory pathways, including the emergence of CD4+ and CD8+ cytotoxic subsets. Genome-wide data on antigen-specific memory T cells are currently limited but can be expected to provide insights on how changes in T cell subset heterogeneity and transcriptome relate to durability of immune protection.


Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species.
When long-lasting, balancing selection can lead to "trans-species" polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees-more generally, for pairs of species with low genetic diversity levels-these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa.


The effect of anthropogenic and natural factors on the prevalence of physicochemical parameters of water and bacterial water quality indicators along the river Białka, southern Poland.
This study was aimed to determine the anthropogenic and natural factors affecting spatial and temporal changes in the physicochemical parameters and bacterial indicators of water quality in the river Białka. The impact of intensive development of the tourist infrastructure on the quality of river water and the potential health threats to tourists was also assessed. Water samples were collected over a period of 2.5 years, once per each month in four sites along the river. Temperature, electrolytic conductivity, pH, and water level were measured onsite; flow rate data were acquired from the Institute of Meteorology and Water Management; chemical analyses allowed to determine the amount of fourteen ions, while microbiological indicators included total and thermotolerant coliforms, total and thermotolerant Escherichia coli, and mesophilic and psychrophilic bacteria. The combination of hydrological, hydrochemical, and microbiological methods generated large amount of data, which were processed by multivariate statistical analysis. A downstream cumulative effect was observed in the contamination of the river water. Fecal coliforms and E. coli were detected in all sites, suggesting the source of fecal contamination even in the protected areas. Intensive development of a ski resort and the related infrastructure, together with the need to accommodate numerous tourists in the examined region, has an evident environmental impact. The resulting deterioration of water quality poses health risks to tourists, as water from the Białka river is used for a variety of purposes, including as a raw drinking water or for artificial snowing of ski slopes. The seasonal changes in the physicochemical parameters mainly result from varying natural factors that shape the water quality in the studied region. The differences in the number of analyzed microorganisms result from seasonal variation in touristic activity and are affected mostly by point sources of sewage inflow.


[Species of the genus Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) in dairy goats maintained in intensive system in the São José do Rio Preto region, São Paulo State, Brazil].
Were examined 58 dairy goats, 41 kids and 17 adults, Saanen and Alpine breeds, males and females, in intensive system, in the São José do Rio Preto region, São Paulo state, for detection and identification of Eimeria spp. oocysts. The 58 feces samples analyzed by the Centrifugal-flotation technique, were positive for, at least, one Eimeria species. The Eimeria species found in this research were: E. ninakohlyakimovae (77,6%), E. jolchijevi (72,4%), E. alijevi (63,8%), E. christenseni (63,8%), E. arloingi (62,1%), E. caprovina (56,9%), E. hirci (50,0%) and E. caprina (48,3%). It follows that the high rate of the positive animals and the high frequency of the Eimeria species among the animals demonstrated that the disease is common in dairy goats, kids and adults, in intensive system.


3-Amino-6-nitroamino-tetrazine (ANAT)-based energetic salts.
The synthesis and properties of several new high-nitrogen materials with 3-amino-6-nitroamino-tetrazine (ANAT) as the anion are reported; all salts were fully characterized by IR and NMR spectroscopy, and elemental analysis.


Impact of Alternaria toxins on CYP1A1 expression in different human tumor cells and relevance for genotoxicity.
The Alternaria toxins alternariol (AOH) and alternariol monomethyl ether (AME) have been reported previously to act as activators of the aryl hydrocarbon receptor (AhR) in murine hepatoma cells, thus enhancing the expression of cytochrome P450 (CYP) 1A monooxygenases. Concomitantly, both benzopyrones represent substrates of CYP1A, giving rise to catecholic metabolites. The impact of AOH and AME on CYP1A expression in human cells of different tissue origin colon (HT29), esophagus (KYSE510), liver (HepG2) and their effects on cell viability, generation of reactive oxygen species (ROS) and DNA integrity were investigated. ROS production was induced by both mycotoxins in all cell lines with AOH exhibiting the highest potency in esophageal cells concomitant with the most prominent CYP1A induction level. Of note, altertoxin-II (ATX-II), the more potent DNA-damaging mutagen formed by Alternaria alternata, induces CYP1A even at significant lower concentrations. AhR-siRNA knockdown in human esophageal cells supported the hypothesis of AhR-mediated CYP1A1 induction by AOH. However, DNA damage was minor at CYP1A1-inducing AOH concentrations. AhR-depletion did not affect the DNA-damaging properties of AOH indicating no substantial impact of AhR in this regard. However, in combination with xenobiotics prone to metabolic activation by CYP1A the induction of CYP1A by Alternaria toxins deserves further attention.


Submillimeter ionoacoustic range determination for protons in water at a clinical synchrocyclotron.
Proton ranges in water between 145 MeV to 227 MeV initial energy have been measured at a clinical superconducting synchrocyclotron using the acoustic signal induced by the ion dose deposition (ionoacoustic effect). Detection of ultrasound waves was performed by a very sensitive hydrophone and signals were stored in a digital oscilloscope triggered by secondary prompt gammas. The ionoacoustic range measurements were compared to existing range data from a calibrated range detector setup on-site and agreement of better than 1 mm was found at a Bragg peak dose of about 10 Gy for 220 MeV initial proton energy, compatible with the experimental errors. Ionoacoustics has thus the potential to measure the Bragg peak position with submillimeter accuracy during proton therapy, possibly correlated with ultrasound tissue imaging.


[Author and time of writing of Shanghanlun Jujie].
Li Wenjin (courtesy name of Xiangyi, the styled names as Zhian and Shujingtang Zhuren), lived in Xu Village, south of Tianyin Mountain, Jinling. He was born on the 47(th) year of the Kangxi Period (1708) and died approximately at the end of the Qianlong Period. Bold and generous, he liked making friends and practising medicine, divination, astrology, and also writing poetry and painting. Later he devoted himself to medicine and wrote Shanghanlun Jujie and Yijia 24 ze. Shanghanlun Jujie included Shanghanzabinglun Shujingtangqinjie (14 volumes) and Siwenji (7 volumes). The former one was written in 1768 and was his annotation of Shanghanlun. Siwenji included Shujingtang Gaidingzhushi Hanrewenpingyaoxingfu (4 volumes), Shujingtang Shenyizazhu (1 volume), Yiyao Zhenyan (1 volume) and Shujingtang Yiyaojian (1 volume) and was finished in 1765.


Degree of hydrolysis, functional and antioxidant properties of protein hydrolysates from Grass Turtle (Chinemys reevesii) as influenced by enzymatic hydrolysis conditions.
Grass turtle muscle was hydrolyzed with papain enzyme to produce protein hydrolysate (PH) and the degree of hydrolysis (DH) was determined. Under optimal conditions, the highest DH was 19.52% and the yield was recorded as 17.26%. Protein content of the hydrolysates was ranged from 73.35% to 76.63%. Total amino acids were more than 96.77% for each PH. The PH obtained at DH 19.52% achieved excellent solubility and emulsifying activity which were 95.56% and 108.76 m2/g, respectively at pH 6. Foam capacity amounted 100% in PH of DH 19.52% at pH 2, and water-holding capacity was 4.38 g/g. The antioxidant activity showed the strongest hydroxyl radical scavenging activity (95.25%), ABTS (84.88%), DPPH (75.89%), iron chelating (63.25%), and cupper chelating (66.90%) at DH 11.96%, whereas reducing power (0.88) at DH 19.52%. Thus, the findings indicated that utilization of grass turtle muscle protein hydrolysate is a potential alternative protein resource to improve the nutritional and functional properties in food ingredients and product formulations.


Use of tissue plasminogen activator for reopening of clotted dialysis catheters.
The use of central venous catheters as permanent vascular access in chronic hemodialysis is complicated by clotting. We have tried a nonallergenic thrombolytic agent, tissue plasminogen activator (t-PA), to dissolve catheter luminal thrombosis. Eight patients, 7 in chronic hemodialysis and 1 treated by immune adsorption had 18 treatments with locally applied t-PA (2 mg/2 cm3). Fifteen out of 16 treatments with longer bolus dwell than 60 min were successful. No side effects occurred. t-PA dissolves clot formation efficiently and safely, the drug is nonallergenic and can therefore be given repeatedly.


High mortality in lower salaried Norwegian men: the healthy worker effect?
This study aimed to examine whether the high mortality in lower salaried men in Norway was related to an inflow into this group of unskilled workers with high mortality. Individual information on occupation was derived from the 1970 and the 1980 censuses and linked to mortality data for the period 1980-5 by the official, individual identification numbers. The study population included Norwegian men aged 20-64 years in 1980. All men enumerated in the 1980 census (and who were registered in the 1970 census) within the two occupational groups, unskilled workers and lower salaried employees, were included. The subjects were allocated to the two occupational groups according to the official Norwegian classification of socioeconomic status. Mortality was measured by standardised mortality ratios (SMR). The findings suggest that a fairly large number of unskilled workers with high mortality move into the lower salaried employee group. This transition produces a higher SMR in lower salaried employees and, simultaneously, an artificially but modestly lower SMR in unskilled workers. The difference in SMR between the two groups is thereby exaggerated by 44%. The difference among the elderly was smaller. Occupational mobility consistent with "the healthy worker effect" increases the SMR of lower salaried men and, at the same time, reduces slightly the SMR of unskilled workers.


[Central precocious puberty in girls: prediction of the etiology].
Precocious puberty (PP) is defined in girls by the occurrence of pubertal development before the age of 8. This development raises 3 questions: 1) Is it abnormal puberty or variant of the normal? 2) If abnormal puberty, is it of central, hypothalamic-pituitary, or peripheral, ovarian or adrenal origin? 3) If central, is it idiopathic or due to a lesion, and is there indication to treat it? The PP in a girl with no previous medical history is usually of central and idiopathic origin. However, isolated central PP may reveal a CNS lesion, particularly an optic glioma with its risk of blindness. Two independent predictors of CNS lesion are the age at PP onset of less than 6 years old, and increased plasma estradiol concentration. The selection of the girls for neuroradiological imaging should be based on these two parameters. However, neuroradiological imaging remains necessary until the prospective confirmation of their predictive value.


Cylindroma of the breast of skin adnexal type: a study of 4 cases.
Four cases of solitary cylindroma of the breast of skin adnexal type are described. The tumors were morphologically and immunophenotypically identical to their dermal counterparts. They arose in close proximity to the nipple, such as the retroareolar area of the breast and in intimate association with the lactiferous ducts, suggesting an origin from the latter structures. One case occurred in a woman with hereditary multiple cylindromatosis (Brooke-Spiegler syndrome). This is the second reported case of this hereditary syndrome with extracutaneous manifestations and the first case in which the breast is involved.


Is quality of care a key predictor of perinatal health care utilization and patient satisfaction in Malawi?
The Malawi government encourages early antenatal care, delivery in health facilities, and timely postnatal care. Efforts to sustain or increase current levels of perinatal service utilization may not achieve desired gains if the quality of care provided is neglected. This study examined predictors of perinatal service utilization and patients' satisfaction with these services with a focus on quality of care. We used baseline, two-stage cluster sampling household survey data collected between November and December, 2012 before implementation of CARE's Community Score Card© intervention in Ntcheu district, Malawi. Women with a birth during the last year (N = 1301) were asked about seeking: 1) family planning, 2) antenatal, 3) delivery, and 4) postnatal care; the quality of care received; and their overall satisfaction with the care received. Specific quality of care items were assessed for each type of service, and up to five such items per type of service were used in analyses. Separate logistic regression models were fitted to examine predictors of family planning, antenatal, delivery, and postnatal service utilization and of complete satisfaction with each of these services; all models were adjusted for women's socio-demographic characteristics, perceptions of the closest facility to their homes, service use indicators, and quality of care items. We found higher levels of perinatal service use than previously documented in Malawi (baseline antenatal care 99.4%; skilled birth attendance 97.3%; postnatal care 77.5%; current family planning use 52.8%). Almost 73% of quality of perinatal care items assessed were favorably reported by > 90% of women. Women reported high overall satisfaction (≥85%) with all types of services examined, higher for antenatal and postnatal care than for family planning and delivery care. We found significant associations between perceived and actual quality of care and both women's use and satisfaction with the perinatal health services received. Quality of care is a key predictor of perinatal health service utilization and complete patient satisfaction with such services in Malawi. The current heightened attention toward perinatal health services and outcomes should be coupled with efforts to improve the actual quality of care offered to women in this country.