Complete mitochodrial genome of Bangana decora (Cypriniformes, Cyprinidae).
The complete mitochondrial genome of Bangana decora was determined in this study. The gene composition, arrangement and transcriptional orientation in B. decora mitogenome were identical to most vertebrates. The complete mitogenome of B. decora was 16,607 bp in size with 13 protein-coding genes, 22 tRNA genes and a control region. Two start codon patterns and three stop codon patterns were found in protein-coding genes. Only the tRNA-Ser2 could not fold into a typical clover-leaf secondary structure due to the absence of the dihydrouridine arm. Sequence alignment results suggest that the complete mitogenome of B. decora is an efficient tool to study molecular phylogenetics, biogeography and adaptive evolution of this lineage.


Continuous spinal anesthesia for hip replacement in an elderly patient with an anterior mediastinal mass: a case report.
Incremental dosing of intrathecal local anesthetic for an indefinite duration performed during continuous spinal anesthesia (CSA) allows for better control of adverse effects caused by sympathetic nerve blockade. This case report describes a 91-year-old female with a left intertrochanteric fracture and a large thyroid mass causing contralateral anterior displacement of the trachea and the great vessels. We conducted a detailed investigation of the different techniques that can be used in such circumstances and the consequences each may have on a patient. We concluded that: better control of sympathetic nerve blockade and less adverse effects can be achieved with CSA, optimal management of thrombocytopenia should be done in a patient prior to regional anesthesia, and CSA is an anesthetic alternative to consider on elderly patients with an anterior mediastinal mass undergoing hip fracture surgery.


Recycled poly(ethylene terephthalate) for direct food contact applications: challenge test of an inline recycling process.
Of all the plastics used for packaging, due to its low diffusivity and chemical inertness, poly(ethylene terephthalate) (PET) is one of the favoured candidate plastics for closed-loop recycling for new packaging applications. In the work reported here, a PET-recycling process was investigated with respect to its cleaning efficiency and compliance of the PET recyclate with food law. The key technology of the investigated PET-recycling process to remove contaminants consists of a predecontamination-extruder combination. At the end of the recycling process, there is either a pelletizing system or downstream equipment to produce preforms or flat sheets. Therefore, the process has two process options, an inline production of PET preforms and a batch option producing PET pellets. In the case of possible misuse of PET bottles by the consumer, the inline process produces higher concentrations in the bottle wall of the recyclate containing preforms. Owing to the dilution of the PET output material by large amounts of uncontaminated PET, the batch option is the less critical process in terms of consumer protection. Regarding an appropriate testing procedure for the evaluation of a bottle-to-bottle recycling process, both process options have their own specific requirements with respect to the design of a challenge test. A novel challenge test approach to the inline mode of a recycling process is presented here.


Dose escalation of imatinib after failure of standard dose in Korean patients with metastatic or unresectable gastrointestinal stromal tumor.
We evaluated the results of imatinib dose escalation in patients with advanced gastrointestinal stromal tumors (GISTs) after disease progression on standard-dose imatinib. Clinical data from patients with metastatic or unresectable GISTs whose dose of imatinib was increased after disease progression on imatinib 400 mg/day were retrospectively reviewed. The 24 patients studied had a median age of 52 years. Imatinib dosing was escalated to 600 mg/day in 12 patients, then to 800 mg/day in four patients. The other 12 patients had dose escalation directly to 800 mg/day. Two patients (8.3%) achieved a partial response, and seven (29.2%) had stable disease. Six-month progression-free and overall survival rates were 33.3 and 70.7%, respectively. Dose escalation to 600 or 800 mg/day was generally well tolerated. Imatinib dose escalation is feasible and well tolerated in patients with advanced GIST who progress on standard-dose therapy, producing clinical benefit in approximately 37% of patients.


Second antibody chemically linked to cellulose for the separation of bound and free hormone: an improvement over soluble second antibody in gonadotrophin radioimmunoassay.
Coupling the second antibody to a solid pase (DASP) was found to be a definite improvement over the classical technique of soluble second antibody (DA) separation of bound and free hormone in the radioimmunoassays of gonadotrophins in plasma or in serum. The duration (2.5 to 7.5 min) and the pH (10.5 to 12.5) of the cyanogen bromide activation of microcristalline cellulose did not affect the coupling capacity or the immunoreactivity of the second antibody, nor did it augment aspecific adsorption of free gonadotrophin on the cellulose matrix. Precision of duplicates was comparable for both methods but the accuracy and the detection limit of the solid phase system were higher due to a better separation of bound and free hormone, to the lower blank value and to the absence of aspecific interference of protein concentration. Cost was lower since much less second antibody was needed in the solid phase system than in the soluble system and since the experimental procedures were simplified by the absence of prozoning effect and the solid nature of the cellulose matrix.


Prevalence of dental caries and periodontal disease in a rural area of Faridabad District, Haryana, India.
An oral health survey was conducted in 829 individuals in different age groups in Ballabhgarh, Haryana, India, to estimate the prevalence of Dental caries and Periodontal diseases. A survey tool was modified from WHO's STEPwise approach to surveillance and Oral Health Assessment form 2013 from recently released WHO Oral Health Survey: Basic Methods (5th Edition) keeping in mind the South East Asian region. Out of 28 villages, six villages were randomly selected. A random list of study participants (Age-sex specific) was generated from the pooled list of these 6 villages. Local health workes helped in inviting the specific subjects to one centralized location within each village/ locality. The subjects were examined by trained dental surgeons and recordings were done by trained assistants. The prevalence of dental caries in 5-7 year, 12-15 year, 35-44 year and 65-74 year was 33.2%, 31.3%, 64.9% and 50.1% respectively. The prevalence of Periodontal Disease in 35-44 year and 65-74 year found to be 65.2% and 90.4% respectively. Only 37 participants had mucosal lesions, of which leukoplakia and tobacco pouch keratosis was seen in majority. Using the adopted tool, the prevalence of dental caries was found to be highest in 35-44 year (64.9%) age group and the prevalence of periodontal disease was found to be high in 35-44 year (65.2%) age group and highest in 65-74 year (90.4%) age group. Oral health promotion efforts are required to prevent oro-dental diseases in the studied population.


Folate/vitamin B12 inter-relationships.
Folate deficiency causes anaemia owing to impaired purine and pyrimidine biosynthesis. Vitamin B12 deficiency causes an identical anaemia owing to metabolic trapping of intracellular folate. Vitamin B12 also causes nerve damage. Unlike the anaemia, the nerve damage is probably owing to inhibition of methyltransferase involved in nerve cell biosynthesis. This decreased activity is owing to a reduction in the availability of SAM, the methyl donor, together with product inhibition by its demethylated form, SAH.


Heat shock protein antagonists in early stage clinical trials for NSCLC.
Cancer cells have a higher need of chaperones than normal cells to prevent the toxic effects of intracellular protein misfolding and aggregation. Heat shock proteins (Hsps) belong to these chaperones; they are classified into families according to molecular size. Hsps are upregulated in many cancers and inhibition can inhibit tumor growth by destabilizing proteins necessary for tumor survival. In non-small cell lung cancer (NSCLC), there are three different Hsp antagonist classes that are in (early) clinical trials: Hsp90, Hsp70 and Hsp27 inhibitors. Areas covered: The rationale to use Hsp inhibitors in NSCLC will be summarized and phase I-III trials will be reviewed. Expert opinion: Several Hsp90 inhibitors have been tested in phase I-III trials, until now none was positive in unselected NSCLC; therefore development of AUY922, ganetespib and retaspimycin was halted. Results seem more promising in molecularly selected patients, especially in ALK-rearranged NSCLC. Hsp27 is overexpressed in squamous NSCLC and is a mechanism of chemotherapy resistance. The Hsp27 inhibitor apatorsen is now tested in squamous NSCLC. No phase II/III data are known for Hsp70 inhibitors. Combination of Hsp inhibitors with heat shock transcription factor 1 inhibitors or focal adhesion kinase inhibitors might be of interest for future trials.


Analysis of complex reacting mixtures by time-resolved 2D NMR.
Nuclear magnetic resonance (NMR) spectroscopy is a versatile tool for chemical analysis. Besides the most straightforward application to study a stable sample containing a single compound, NMR has been also used for the analysis of mixtures. In particular, the analyzed mixtures can undergo changes caused by chemical reactions. The multidimensional NMR techniques are especially effective in a case of samples containing many components. Unfortunately, they are usually too lengthy to be applied in time-resolved experiments performed to study mentioned changes in a series of spectral "snapshots." Recently, time-resolved nonuniform sampling (NUS) has been proposed as a straightforward solution to the problem. In this paper, we discuss the features of time-resolved NUS and give practical recommendations regarding the temporal resolution and use of the time pseudodimension to resolve the components. The theoretical considerations are exemplified by the application in challenging cases of fermenting samples of wheat flour and milk.


Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases.
Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.


miRNA-transcription factor interactions: a combinatorial regulation of gene expression.
Developmental processes require a precise spatio-temporal regulation of gene expression wherein a diverse set of transcription factors control the signalling pathways. MicroRNAs (miRNAs), a class of small non-coding RNA molecules have recently drawn attention for their prominent role in development and disease. These tiny sequences are essential for regulation of processes, including cell signalling, cell development, cell death, cell proliferation, patterning and differentiation. The consequence of gene regulation by miRNAs is similar to that by transcription factors (TFs). A regulatory cascade essential for appropriate execution of several biological events is triggered through a combinatorial action of miRNAs and TFs. These two important regulators share similar regulatory logics and bring about a cooperative action in the gene regulatory network, dependent on the binding sites present on the target gene. The review addresses the biogenesis and nomenclature of miRNAs, outlines the mechanism of action and regulation of their expression, and focuses on the combinatorial action of miRNAs and TFs for the expression of genes in various regulatory cascades.


Hepatic acute phase protein synthesis is indirectly regulated by tumor necrosis factor.
It has been proposed that tumor necrosis factor (TNF) is a direct regulator of postinjury hepatic protein synthesis. To test this hypothesis we investigated the total protein and specific acute phase protein synthesis response of murine hepatocytes to stimulation with mu-rTNF-alpha in vivo and in vitro. Total hepatocyte secretory protein synthesis was assessed by incorporation of [35-S] methionine into TCA-precipitated protein; and acute phase protein synthesis was assessed by induction of a 23-kD acute phase protein marker and by suppression of albumin synthesis determined by SDS-PAGE and autoradiography. We found that rTNF in vivo (8,000 units, IP injection) was associated with reduced total hepatocyte secretory protein synthesis (29 +/- 10%), increased synthesis of the 23-kD acute phase reactant (4.1 +/- 1.6-fold), and decreased albumin synthesis (0.68 +/- 0.2-fold) compared to saline-injected control animals. The in vitro stimulation of cultured murine hepatocytes directly with rTNF failed to demonstrate changes in total secretory protein synthesis or 23-kD protein; however, it did result in significant suppression of albumin synthesis (0.82 +/- 0.1-fold). In additional experiments, hepatocytes:nonparenchymal cell co-cultures stimulated with lipopolysaccharide (LPS) demonstrated protein synthesis changes similar to the in vivo TNF response including increased 23-kD protein and decreased albumin synthesis. These co-cultures demonstrated TNF production; however, addition of TNF antiserum during LPS stimulation had no effect on either 23-kD protein or albumin synthesis, despite the complete neutralization of TNF activity in the co-culture supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)


Opinion: the species problem, can we achieve a universal concept?
One of the so called 'species problems' is that no universal concept exists. There is a tendency among microbiologists to criticize the hitherto devised concept. It is considered by some researchers as being too conservative and not suitable to be compared with those for eukaryotes. However, such problem is not only restricted to prokaryotes, but among other taxonomies comparisons seem to be impossible. As it is argued, the underlying cause to this problem is the reductionistic and monistic use of taxonomy. Analyzing the more than 22 devised concepts it seems possible to achieve a universal species concept. However, this might not be pragmatic. For the time being, a pluralistic sense of the species concept might be accepted, and one will have to recognize that any comparison among different taxonomies will be difficult.


Randomized Electronic Promotion of Lung Cancer Screening: A Pilot.
Screening for lung cancer with low-dose computed tomography is endorsed by the US Preventive Services Task Force, but many eligible patients have yet to be offered screening. Major barriers to the implementation of screening are physician and system related-the requirement for a detailed smoking history, including pack-years, to determine eligibility. We conducted this pilot to determine the feasibility of lung cancer screening (LCS) promotion that would offer screening to eligible persons and patient completion of smoking history to estimate the size of the population of former smokers who may be eligible for LCS in a single health care system. Two hundred participants were randomly selected from former smokers who were seen at the University of Minnesota Health in the past 2 years and assigned to control (usual care) and electronic promotion, stratified by age. Electronic messages to promote LCS were sent to an intervention group, including a link to complete a detailed smoking history in the electronic health record. Of 99 participants, 66 (67%) in the intervention group read the message, 24 (36%) of 66 responded, and 19 (79%) of 24 respondents completed the smoking history. Ten intervention participants and 13 usual care participants were eligible for screening on the basis of pack-year history. Four eligible participants underwent screening in the intervention group compared with one participant in the usual care group. Electronic promotion may help identify patients who are eligible for LCS but will not reliably reach all patients because of low response rates. In this sample of former smokers, the majority are ineligible for LCS on the basis of pack-year history. Electronic methods can improve documentation of smoking history.


Vascular endothelial growth factor overexpression increases vascularization by murine but not human endothelial cells in cultured skin substitutes grafted to athymic mice.
Cultured skin substitutes (CSS) consisting of fibroblasts, keratinocytes, and biopolymers are an adjunctive treatment for large burns. Because CSS lack a vascular plexus, they vascularize more slowly than split-thickness autografts. Previously, CSS were prepared with dermal microvascular endothelial cells (ECs), which formed vascular analogs at a low frequency but did not contribute to increased vascularization after grafting. The present study addressed whether keratinocytes genetically modified to overexpress vascular endothelial growth factor (VEGF), an endothelial cell mitogen, could improve the persistence and organization of ECs in CSS. CSS were prepared with control or VEGF-modified keratinocytes, with (CSS + ECs) or without added ECs, and were grafted to full-thickness wounds in athymic mice. Elevated VEGF expression was detected in VEGF-modified CSS and CSS + ECs compared with controls, but no significant difference in EC density in vitro was observed. After grafting, VEGF-modified CSS and CSS + ECs showed enhanced vascularization, and organization of human ECs into multicellular structures in CSS + ECs was observed. However, VEGF overexpression did not significantly enhance the proliferation of human ECs, suggesting that other factors may be required. Improved persistence and organization of human ECs in vitro will likely be required for their participation in vascularization of CSS + ECs after grafting.


An experimental system for spectral line ratio measurements in the TJ-II stellarator.
The chord-integrated emissions of spectral lines have been monitored in the TJ-II stellarator by using a spectral system with time and space scanning capabilities and relative calibration over the entire UV-visible spectral range. This system has been used to study the line ratio of lines of different ionization stages of carbon (C(5+) 5290 A and C(4+) 2271 A) for plasma diagnostic purposes. The local emissivity of these ions has been reconstructed, for quasistationary profiles, by means of the inversion Fisher method described previously. The experimental line ratio is being empirically studied and in parallel a simple spectroscopic model has been developed to account for that ratio. We are investigating whether the role played by charge exchange processes with neutrals and the existence of non-Maxwellian electrons, intrinsic to Electron Cyclotron Resonance Heating (ECRH) heating, leave any distinguishable mark on this diagnostic method.


Unexpected impact of irreversible adsorption on thermal expansion: Adsorbed layers are not that dead.
We investigated the impact of irreversible adsorption on the mechanisms of thermal expansion of 1D confined polymer layers. For spincoated films (polystyrene on aluminum) of constant thickness, the thermal expansion coefficient of the melt drops upon annealing following the kinetics of irreversible adsorption of the chains onto the supporting substrate, while the thermal expansion of the glass is annealing invariant. These perturbations are explained in terms of the reduction in free volume content, upon immobilization of monomers onto the substrate. To shed more light on this phenomenon, we performed an extensive investigation of the thermal expansion of irreversibly adsorbed layers of polystyrene on silicon oxide. We verified that, contrarily to recent speculations, these films cannot be modeled as dead layers - immobilized slabs lacking of segmental relaxation. On the contrary, thin adsorbed layers show an increase in thermal expansion with respect to the bulk, due to packing frustration. Immobilization plays a role only when the thickness of the adsorbed layers overcomes ∼10 nm. Finally, we show that for adsorbed layers the difference in thermal expansion between the melt and the glass is sufficiently high to investigate the glass transition down to 3 nm. Owing to this unique feature, not shared by spincoated films, adsorbed layers are the perfect candidate to study the properties of extremely thin polymer films.


Design and Implementation of a Modular and Scalable Research Platform for Ultrasound Computed Tomography.
Increasing attention has been attracted to the research of ultrasound computed tomography (USCT). This article reports the design considerations and implementation details of a novel USCT research system named UltraLucid, which aims to provide a user-friendly platform for researchers to develop new algorithms and conduct clinical trials. The modular design strategy is adopted to make the system highly scalable. A prototype has been assembled in our laboratory, which is equipped with a 2048-element ring transducer, 1024 transmit (TX) channels, 1024 receive (RX) channels, two servers, and a control unit. The prototype can acquire raw data from 1024 channels simultaneously using a modular data acquisition and a transfer system, consisting of 16 excitation and data acquisition (EDAQ) boards. Each EDAQ board has 64 independent TX and RX channels and 4-Gb Ethernet interfaces for raw data transmission. The raw data can be transferred to two servers at a theoretical rate of 64 Gb/s. Both servers are equipped with a 10.9-TB solid-state drive (SSD) array that can store raw data for offline processing. Alternatively, after processing by onboard field-programmable gate arrays (FPGAs), the raw data can be processed online using multicore central processing units (CPUs) and graphics processing units (GPUs) in each server. Through control software running on the host computer, the researchers can configure parameters for transmission, reception, and data acquisition. Novel TX-RX scheme and coded imaging can be implemented. The modular hardware structure and the software-based processing strategy make the system highly scalable and flexible. The system performance is evaluated with phantoms and in vivo experiments.


Rapid determination of free fatty acid content in waste deodorizer distillates using single bounce-attenuated total reflectance-FTIR spectroscopy.
A simple, rapid, economical, and environmentally friendly analytical method was developed for the quantitative assessment of free fatty acids (FFAs) present in deodorizer distillates and crude oils by single bounce-attenuated total reflectance-FTIR spectroscopy. Partial least squares was applied for the calibration model based on the peak region of the carbonyl group (C=O) from 1726 to 1664 cm(-1) associated with the FFAs. The proposed method totally avoided the use of organic solvents or costly standards and could be applied easily in the oil processing industry. The accuracy of the method was checked by comparison to a conventional standard American Oil Chemists' Society (AOCS) titrimetric procedure, which provided good correlation (R = 0.99980), with an SD of +/- 0.05%. Therefore, the proposed method could be used as an alternate to the AOCS titrimetric method for the quantitative determination of FFAs especially in deodorizer distillates.


Pre-operative staging with positron emission tomography in patients with pelvic recurrence of rectal cancer.
The treatment of pelvic recurrences of rectal cancer is primarily surgical. The substantial morbidity and mortality of such resections warrant stringent patient selection. Recent literature reports PET to be of additional value to CT for the detection of metastases in colorectal cancer patients. We studied the clinical impact of PET in pelvic rectal cancer recurrence. PET findings in 37 pelvic recurrences of rectal cancer were evaluated retrospectively. Comparison was made to CT and MRI findings. It was analyzed whether PET had been decisive in clinical decision making or could have been so. Thirty-two patients had 37 rectal cancer recurrences. PET differed from conventional imaging in 13 cases (35%): seven PET scans showed lesions that were not seen with CT or MRI. PET scans were negative in six lesions detected by CT or MRI. PET alone changed management in five recurrences (14%). Four PET scans were false-positive; this had clinical implications in 2 patients. In a selected population with pelvic rectal cancer recurrences, PET had additional value to conventional imaging, mainly in detecting lymph node metastases. PET findings thus had a significant impact on selection of patients for curative surgery.


Response of elevated Epstein-Barr virus DNA levels to therapeutic changes in pediatric liver transplant patients: 56-month follow up and outcome.
Posttransplant lymphoproliferative disease (PTLD) is a serious complications after liver transplantation. Epstein-Barr virus (EBV) load measured by quantitative competitive polymerase chain reaction (PCR) has been used as an early marker for the development of PTLD and a guide for initiating preemptive therapy. The aim of this study is to report the results of EBV DNA PCR screening in a transplant population and to examine the risk factors for developing elevated EBV DNA PCR and the effect of interventions for reducing EBV DNA levels. Medical records of 44 children who underwent liver transplantation and EBV DNA PCR screening during a 3-year period were reviewed, and the patients were prospectively followed up for another 2 years. Eleven patients who developed elevated EBV DNA PCR levels, defined as >/=40 genomes/105 peripheral blood lymphocytes (PBL) in pretransplant EBV-seronegative patients and >/=200 genomes/105 PBL in pretransplant-seropositive patients, were treated. The initial intervention was reduction of immunosuppression and initiation of anti-viral therapy in all patients, with administration of cytomegalovirus immunoglobulin (CMV-IgG) in two patients. CMV-IgG was then given to five of the patients who did not respond to the initial intervention. The initial intervention resulted in the reduction of EBV DNA PCR levels to below threshold values in 4 of 11 patients. Five patients who did not respond to the initial interventions were subsequently given intravenous CMV-IgG. The EBV DNA PCR level fell in all five of these patients during the course of treatment with CMV-IgG, with a significant reduction (to threshold levels or by two dilutions) in four of the five patients. No episodes of graft rejection were observed. Eleven patients (25%) developed elevated EBV DNA PCR after liver transplantation. There were no identifiable risk factors for developing elevated EBV DNA PCR. A combination of reducing immunosuppression, adding antiviral agents, and initiating CMV-IgG resulted in a significant reduction of EBV DNA levels in nine (82%) patients during the follow-up period.


Influence of material properties on TEM specimen preparation of thin films.
Several factors must be taken into account when deciding which specimen preparation technique(s) to use. These factors include the amount of material available, ease of preparing this material due to its properties and familiarity, location and size of the region of interest, amount of information sought, facilities accessible, and time available by the researcher to devote to the preparation of the specimen. The more popular specimen preparations for thin films, namely, electropolishing, cleaving, crushing, mechanical thinning followed by ion milling, and ultramicrotomy are discussed and the more unusual techniques such as extraction/replication, photochemical etching, lithography and reactive ion etching (RIE), chemically assisted ion beam etching (CAIBE), and precision polishing-based techniques are described. Their advantages and disadvantages in the context of the above factors are discussed. Suggestions for increasing one's success rate in preparing specimens are given. The role of transmission electron microscopy (TEM) analysis is considered since it rarely stands in isolation from other physical analytical techniques, nor is it often used as a quick diagnostic tool. Conservation of material by the minimization of the amount of material used (or destroyed) by TEM specimen preparation, and conservation of one's time by performing TEM analysis only on "worthy" samples should be given maximum consideration.


Conclusions, reflections, and prospects for future research, policy, and programming.
This concluding chapter draws together some of the key themes from the contributions and proposes some recommended areas for future research, policy, and programming. It highlights the artificiality of categorization processes related to both migration and childhood that independent child migrants encounter, and problematizes the vulnerability-agency binary. The author encourages more research into how power relations, relationships, and networks shape migration decisions and suggests the need to analyze comparative experiences of families and siblings who are "left behind." Finally, the chapter draws attention to the need for mixed methodological and disciplinary approaches and greater analysis of the intersection of social age and gender issues.


Toxicity of iron oxides and metabolites of benzo[a]pyrene alone or in combination in cells culture and identification by laser microprobe mass spectrometry.
The goal of the gas-phase studies of well-characterized transition-metal systems is to enhance our understanding of the chemistry and sometimes of the toxic, carcinogenic effects of transition metal oxide clusters and compounds. The analysis of inorganic solids by time of flight laser microprobe mass spectrometry (TOF-LMMS) shows the formation of clusters in the mass spectra which can be used for the identification of inorganic particles. First, we have applied non-resonance ionization (delta = 226 nm) or resonant ionization (delta = 293.7 nm) of iron to study the non stoichiometric Fe1-xO, Fe3O4, Fe2O3 compounds in positive mode by TOF-LMMS. The positive mass spectra are characterized by many differences between the clusters detected and their intensities. Then, we have analysed the benzo[a]pyrene (BaP), the 1-hydroxbenzo[a]pyrene (1-OH-BaP) and the 3-hydroxybenzo[a]pyrene (3-OH-BaP) of TOF-LMMS and by Fourier Transform Irons Cyclotron Resonance Mass Spectrometry (FT-ICR-MS). It is possible to distinguish these different compounds by their respective fingerprint. Later on, we have studied toxic effects of iron oxides (Hematite Fe2O3 and Magnetite Fe3O4), benzo[a]pyrene (BaP) and Pyrene, alone or in combination. The LC50 was appreciated by colony-forming cell culture method. Cells were observed by electron microscopy and the valence of particles was analysed by TOF-LMMS. With Fe2O3 we have observed a significant decrease (20%) at higher concentration (0.5 mmol/l) and smaller quantities of BaP were highly toxic. The association of BaP at the LC10 dose (0.05 mumol/l) with growing doses of Fe2O3 or Fe3O4 (0.0125; 0.025; 0.05; 0.1; 0.2 mmol/l), appeared to increase the toxic effect of BaP 3 to 4 times. These results suggest that Fe2O3 and Fe3O4 alone are not very toxic but the association of one of these compounds with BaP increases the toxicity of the latter. On the other hand, TOF-LMMS seems to show a metabolization of iron oxide into reduced form. But, it is necessary to raise the ambiguity about the iron which is always in the cells present. For that purpose, studies with iron oxides enriched by 54Fe isotope have begun.


Rotational deformity in varus osteoarthritis of the knee: analysis with computed tomography.
Rotational deformities in varus osteoarthritis of the knee were evaluated with computed tomography. Preoperative computed tomography scans of 150 knees (114 patients) having total knee arthroplasty and 31 control knees (20 patients) were included. The femorotibial rotation was quantified using the clinical epicondylar axis of the femur and the tibial tuberosity (patella tendon) as the references. The knees with osteoarthritis were divided into three groups according to the femorotibial angle (Group 1, 0 degrees -9 degrees varus, n = 87; Group 2, 10 degrees -19 degrees varus, n = 51; Group 3, 20 degrees or greater varus, n = 12) and statistically analyzed. Rotational deformities (external rotation of the tibia) existed in knees with osteoarthritis and were larger in knees with increased varus deformities (mean +/- standard deviation, -2.24 degrees +/- 4.19 degrees in Group 1; 0.33 degrees +/- 4.14 degrees in Group 2; and 5.33 degrees +/- 5.71 degrees in Group 3). When the femorotibial rotation of each knee was stratified by the corresponding femorotibial angle, we found a correlation. The information should help minimize the rotational mismatch between the femoral and the tibial components in total knee arthroplasty and elucidate the pathogenesis of varus osteoarthritis of the knee. Diagnostic study, Level III-1 (study of nonconsecutive patients--no consistently applied reference gold standard). See the Guidelines for Authors for a complete description of levels of evidence.


[Effects of Radix Ophiopogonis decoction on embryo-fetal development in rats].
To investigate the potential developmental toxicity of Radix Ophiopogonis decoction in SD rats. Timed-pregnant SD rats were given Radix Ophiopogonis decoction (26.9 g x kg(-1)) or vehicle (distilled water) by gavage on gestation days 6-17. Maternal clinical sign, abortions, premature deliveries, and body weight were monitored throughout gestation. At termination (gestation days 20) pregnant females were evaluated for clinical status and gestational outcome; live fetuses were examined for gender, external, visceral and skeletal malformation and variations. No deaths, premature deliveries or dose-related clinical signs were attributed to Radix Ophiopogonis decoction. Maternal body weight and body weight gain were not affected. There were no effects on fetus weight and viability, incidences of fetal malformation and variation. These results demonstrated that Radix Ophiopogonis decoction had no detectable adverse effects in either the treated F0 female rats or the fetuses.


[Use of modern fixators in trochanteric fractures treatment].
Results of surgical treatment of trochanteric fractures in 225 aged patients are presented. The DHS system was used in 115 (51,5%) patients, core system constructed by A.I. Gorodnichenko was used in 56 (24,9%), PFN and PFN-A fixators used in 45 (20%) and 9 (4%) patients were treated with the use of DCS system. Follow-up results after 1 year were studied in 183 (81,3%) patients. Excellent results achieved in 145 (79,2%) cases, satisfactory outcome registered in 38 (20,8%). Authors recommend PFN and PFN-A fixators, as well as the A.I. Gorodnichenko's core system for the surgical treatment of trochanteric fractures especially in aged patients with concomitant ostheporosis.


Evaluation of Metarhizium brunneum F52 (Hypocreales: Clavicipitaceae) for Control of Japanese Beetle Larvae in Turfgrass.
Experimental and commercial preparations of Metarhizium brunneum (Petch) strain F52 were evaluated for control of Japanese beetle, Popillia japonica Newman (Coleoptera: Scarbaeidae), larvae (white grubs) in the laboratory and under field conditions. Experimental preparations consisted of granule and liquid formulations made using in vitro produced microsclerotia, which are intended to produce infective conidial spores after application. These formulations were compared against commercial insecticides (imidacloprid and trichlorfon), and commercial formulations of M. brunneum F52 (Met 52) containing only conidia. Field-collected grubs were susceptible to infection in a dosage-dependent relationship when exposed to potting soil treated with experimental microsclerotia granules in the laboratory. The LC(50) for field-collected larvae was 14.2 mg of granules per cup (∼15 g granules/m(2)). Field plots treated with experimental and commercial formulations of M. brunneum F52 after 10 September (targeting second and third instar grubs) had significantly lower grub densities compared with untreated plots, providing 38.6-69.2% control, which sometimes equaled levels of control with chemical insecticides. Fungal treatments made prior to 21 August provided 14.3-69.3% control, although grub densities resulting from these treatments were often not significantly lower than those in untreated control plots. By comparison, chemical insecticide treatments provide 68-100% grub control, often providing better control when applied earlier in the season. In conclusion, P. japonica larvae are susceptible to infection by M. brunneum, and grub densities were reduced most consistently by fall applications targeting later instars.


Morbid obesity, absorption, neuroticism, and the high risk model of threat perception.
We studied 70 morbidly obese patients, candidates for gastric exclusion surgery. We found that their mean absorption score was significantly lower and that their mean neuroticism score significantly higher than a matched control group. These results are consistent with predictions from the High Risk Model of Threat Perception (Wickramasekera, 1979, 1986, 1988, 1993a). People high in neuroticism are hypothesized to be hypersensitive to threat and, therefore, at greater risk for stress related psychobiological disorders. But if they are also low in absorption, they are hypothesized to have poor conscious perception of psychosocial threats and, therefore, they develop a very restricted range of psychosocial methods of coping with such threats. Consequently, lows may be mainly restricted to behavioral methods of coping like feeding and drinking to self-soothe unconscious aversive emotions associated with autonomic dysregulation and elevated parasympathetic tone. Their skeptical, rational, pragmatic cognitive style drives them to perceive medical surgical solutions to weight gain as more credible than psychosocial weight reduction programs.


The inhibition of pro-inflammatory cytokines with pentoxifylline in the cardiopulmunary bypass lung.
In addition to preventing tissue energy loss during cardiopulmonary bypass, pentoxifylline (Ptx) prevents the production of pro-inflammatory cytokines as well. The aim of this study was to investigate whether Ptx decreases the inflammatory effects of cardiopulmonary bypass on the lungs during open-heart surgery. The patients in the study group (n = 15) who were going through an open-heart surgery had 500 mg l(-1) of Ptx added to their prime solution, whereas the patients in the control group (n = 10) only received prime solution. Pre-pump and post-pump blood samples were obtained from both groups and assayed for interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNFalpha). Lung tissue samples that were obtained after the pump were examined with light microscopy and stained for tissueTNFalpha. Non-parametric Wilcoxon test was utilized for statistical evaluation. In the post-pump period, the difference in the IL-6, IL-8 and TNFalpha levels of the two groups was found to be statistically significant (P<0.005). The tissue samples from the control group had significant staining with TNFalpha. We think that Ptx has important protective effects on the lungs during cardiopulmonary bypass.


Co-influence of transgene expression in mammalian cells. Mutual influence of transgenes on their expression in mammalian cells.
It becomes increasingly clear that therapeutic gene delivery should provide not only for the sustained high level of gene expression but also, in most cases, for the regulated expression of transgenes as much as it occurs under natural conditions. Over the past few years a variety of different systems have been developed in order to regulate the amounts of transcribed RNA upon administration of exogenous agents, or in autoregulated manner. While efforts were focused on optimizing gene expression at the transcriptional level, other levels are still overlooked. In the meantime, regulation of gene expression is not restricted to transcription, but is also executed at the post-transcriptional level, i.e. mRNA stability, processing, transport, translation, protein stability, and modification. Codon usage is considered to be one of the critical factors that limit the expression rate of heterologous genes in different organisms at the posttranscriptional level. HIV-1 structural genes gag, pol, and env represent one of the most extensively utilized models for studying codon usage-mediated effects on transgene expression. In the current work we demonstrate that the codon content affects not only CMV-driven HIV-1 gag expression but also the expression of luciferase reporter gene transcribed independently from the SV40 promoter. The expression levels of both transgenes co-transfected into the human H1299 were inversely co-dependent. The observed phenomenon may be described as sequence-independent post-transcriptional gene silencing, which reflects the existing limitation of transgene expression in mammalian cells at the post-transcriptional level. Optimization of the codon usage may provide for the additional level of regulation of transgene expression in gene transfer experiments in order to maintain the concentration of the protein at the therapeutic levels.


Fingerprinting of Campylobacter jejuni by using resolution-optimized binary gene targets derived from comparative genome hybridization studies.
The aim of this investigation was to exploit the vast comparative data generated by comparative genome hybridization (CGH) studies of Campylobacter jejuni in developing a genotyping method. We examined genes in C. jejuni that exhibit binary status (present or absent between strains) within known plasticity regions, in order to identify a minimal subset of gene targets that provide high-resolution genetic fingerprints. Using CGH data from three studies as input, binary gene sets were identified with "Minimum SNPs" software. "Minimum SNPs" selects for the minimum number of targets required to obtain a predefined resolution, based on Simpson's index of diversity (D). After implementation of stringent criteria for gene presence/absence, eight binary genes were found that provided 100% resolution (D=1) of 20 C. jejuni strains. A real-time PCR assay was developed and tested on 181 C. jejuni and Campylobacter coli isolates, a subset of which have previously been characterized by multilocus sequence typing, flaA short variable region sequencing, and pulsed-field gel electrophoresis. In addition to the binary gene real-time PCR assay, we refined the seven-member single nucleotide polymorphism (SNP) real-time PCR assay previously described for C. jejuni and C. coli. By normalizing the SNP assay with the respective C. jejuni and C. coli ubiquitous genes, mapA and ceuE, the polymorphisms at each SNP could be determined without separate reactions for every polymorphism. We have developed and refined a rapid, highly discriminatory genotyping method for C. jejuni and C. coli that uses generic technology and is amenable to high-throughput analyses.


PTG-0861: A novel HDAC6-selective inhibitor as a therapeutic strategy in acute myeloid leukaemia.
Dysregulated Histone Deacetylase (HDAC) activity across multiple human pathologies have highlighted this family of epigenetic enzymes as critical druggable targets, amenable to small molecule intervention. While efficacious, current approaches using non-selective HDAC inhibitors (HDACi) have been shown to cause a range of undesirable clinical toxicities. To circumvent this, recent efforts have focused on the design of highly selective HDACi as a novel therapeutic strategy. Beyond roles in regulating transcription, the unique HDAC6 (with two catalytic domains) regulates the deacetylation of α-tubulin; promoting growth factor-controlled cell motility, cell division, and metastatic hallmarks. Recent studies have linked aberrant HDAC6 function in various hematological cancers including acute myeloid leukaemia and multiple myeloma. Herein, we report the discovery, in vitro characterization, and biological evaluation of PTG-0861 (JG-265), a novel HDAC6-selective inhibitor with strong isozyme-selectivity (∼36× ) and low nanomolar potency (IC50 = 5.92 nM) against HDAC6. This selectivity profile was rationalized via in silico docking studies and also observed in cellulo through cellular target engagement. Moreover, PTG-0861 achieved relevant potency against several blood cancer cell lines (e.g. MV4-11, MM1S), whilst showing limited cytotoxicity against non-malignant cells (e.g. NHF, HUVEC) and CD-1 mice. In examining compound stability and cellular permeability, PTG-0861 revealed a promising in vitro pharmacokinetic (PK) profile. Altogether, in this study we identified a novel and potent HDAC6-selective inhibitor (∼4× more selective than current clinical standards - citarinostat, ricolinostat), which achieves cellular target engagement, efficacy in hematological cancer cells with a promising safety profile and in vitro PK.


High-frequency plasma spark discharge assessment in pulse-scanning digital holographic interferometry.
In this paper, we consider the method for observing and detecting of high-frequency pulsed plasma spark discharge by means of stroboscopic digital holographic interferometry to demonstrate the feasibility of the electron concentration assessment in nonthermal plasma. A spark discharge with a 5 kHz frequency and 1250 ns duration has been exited between two electrodes in atmospheric pressure. The sequence of holograms acquired due to the proper synchronization between plasma pulses, laser radiation, and the camera's frame grabbing that ensure the recording of the plasma pulses at different moments of time, and the temporal optical scanning of plasma pulse were realized. We also show that the phase difference contrast variation corresponds to the plasma's instant and indicates a change in the electron concentration in the discharge. The concentration of electrons at different moments of plasma existence has been estimated. The limitations of the proposed method are considered, and its applicability for the study of low-temperature pulsed plasma are discussed.


Hydroxylated gedunin derivatives from Cedrela sinensis.
Four new limonoids, 11alpha-hydroxygedunin (1), 11beta-hydroxygedunin (2), 7-deacetoxy-7alpha,11alpha-dihydroxygedunin (3), and 7-deacetoxy-7alpha,11beta-dihydroxygedunin (4), were isolated from the cortex of Cedrela sinensis, together with three known compounds, gedunin (5), 7-deacetoxy-7alpha-hydroxygedunin (6), and 11-oxogedunin (7). The structures of 1-4 were determined by a combination of 2D NMR experiments and chemical methods and by X-ray crystallography of 1 and 2.


[Prevalence of autoantibodies directed against 1,25(OH)2D3 in patients with systemic lupus erythematosus].
In systemic lupus erythematosus (SLE) patients photosensitivity is considered as a factor which may cause exacerbation of skin lesions and provoke organ damage. Therefore in all therapeutic standards photo protection is recommended which may diminish vitamin D synthesis. Because of the enhanced activity of the humoral immunity which is present in the course of disease one postulates the possibility of the production of antibodies directed against vitamin D, that would be able to intensify this deficiency independently from consequences of photoprotection. THE AIM of the study was to estimate the frequency of occurrence of antibodies directed against 1,25(OH)2D3 in patients with SLE and to assess serum concentration of 25 (OH)D3 in comparison with clinical and laboratory parameters. The study encompassed 45 patients with SLE. The control group in the 25(OH)D3 investigation comprised 49 healthy individuals but in autoantibodies against 1,25(OH)2D3 evaluation involved 30 sera obtained from healthy blood donors. In the determination of autoantibodies directed against 1,25(OH)2D3 ELISA method was employed. The concentration of 25 (OH)D3 in the serum was evaluated with automatized electrochemi-luminescence method on the automatic platform Elecsys 2010 in the control system DEQAS (vitamin D external quality assessment scheme). Serum concentration of 25(OH)D3 was significantly decreased in SLE patients in comparison with the control group (15.03 +/- 8.69 vs 23.37 +/- 12.34 ng/ml, respectively; p = 0.0005). Vitamin D deficit (25(OH)D3 < 10 ng/ml) was ascertained in 16 patients (35.55%), deficiency (10-20 ng/ml) in 16 (35.55%) and hypovitaminosis (20-30 ng/ml) in 10 (22.22%). Values within the recommended range (30-80 ng/ml) were established in 3 (6.66%) patients. The risk for vitamin D deficiency was 3.28 folds higher in SLE patients than in healthy controls (OR = 3.28; p = 0.005). Autoantibodies directed against 1,25(OH)2D3 were found in 4 (8.88%) patients. No statistically significant difference in the concentration of 25 (OH)D3 between SLE anti-1,25(OH)2D3 positive and anti-1,25(OH)2D3 negative patients was disclosed. The study did not reveal the correlations between the presence of antibodies directed against 1,25(OH)2D3 and the occurrence of ascertain clinical and laboratory parameters of SLE. The winter times was found to be the risk factor for vitamin D deficiency (OR = 7.33; p = 0.005). Sunscreen usage was revealed to be the predictor of serum 25(OH) vitamin D, concentration (beta = -0.44; p = 0.04). The low concentration of vitamin D in lupus patients indicates that they are at the essential risk for vitamin D deficiency, however the presence of the antibodies directed against 1,25(OH)2D3 seems not to influence vitamin D status.


White matter lateralization and interhemispheric coherence to auditory modulations in normal reading and dyslexic adults.
Neural activation of slow acoustic variations that are important for syllable identification is more lateralized to the right hemisphere than activation of fast acoustic changes that are important for phoneme identification. It has been suggested that this complementary function at different hemispheres is rooted in a different degree of white matter myelination in the left versus right hemisphere. The present study will investigate this structure-function relationship with Diffusion Tensor Imaging (DTI) and Auditory Steady-State Responses (ASSR), respectively. With DTI we examined white matter lateralization in the cortical auditory and language regions (i.e. posterior region of the superior temporal gyrus and the arcuate fasciculus) and white matter integrity in the splenium of the corpus callosum. With ASSR we examined interhemispheric coherence to slow, syllabic-rate (i.e. 4 Hz) and fast, phonemic-rate (i.e. 20 Hz) modulations. These structural and functional techniques were applied in a group of normal reading adults and a group of dyslexic adults for whom previously reduced functional interhemispheric connectivity at 20 Hz has been reported (Poelmans et al. (2012). Ear and Hearing, 33, 134-143). This sample was chosen since it is hypothesized that in dyslexic readers insufficient hemispheric asymmetry in myelination might relate to their auditory and phonological problems. Results demonstrate reduced white matter lateralization in the posterior superior temporal gyrus and the arcuate fasciculus in the dyslexic readers. Additionally, white matter lateralization in the posterior superior temporal gyrus and white matter integrity in the splenium of the corpus callosum related to interhemispheric coherence to phonemic-rate modulations (i.e. 20 Hz). Interestingly, this correlation pattern was opposite in normal versus dyslexic readers. These results might imply that less pronounced left white matter dominance in dyslexic adults might relate to their problems to process phonemic-rate acoustic information and to integrate them into the phonological system.


Monoclonal antibodies identify individual determinants on mouse mammary tumor virus glycoprotein gp52 with group, class, or type specificity.
Hybrid cell lines producing monoclonal antibodies against the C3H strain of mouse mammary tumor virus (C3H MMTV) were prepared by the fusion of mouse myeloma cells with the lymphocytes of BALB/c mice that were immunized with C3H MMTV. Approximately 10% of the hybrid cells initially plated after cell fusion produced immunoglobulins that reacted in antibody-binding assays with C3H MMTV; 40 of these cells were cloned, and 6 eventually yielded stable cell lines. High concentrations of monoclonal antibodies (5 to 20 mg/ml) were obtained from serum and ascites fluid of syngeneic mice inoculated with the hybrid cells. All of the monoclonal antibodies were directed against the envelope glycoprotein gp52. Three of the hybrid cell lines produced immunoglobulins of the immunoglobulin M subclass and three produced immunoglobulin G2a. The monoclonal antibodies showed limited charge heterogeneity in light and heavy chains when analyzed by high-resolution, two-dimensional gel electrophoresis. Three serologically distinct specificities were observed when these ascites fluids were tested against different strains of MMTV. The antigenic determinants detected were the following: (i) a type-specific determinant unique to the C3H strain of MMTV; (ii) class-specific determinants shared between C3H and GR MMTVs; and (iii) a group-specific determinant found on C3H, GR, RIII, and the endogenous C3H (C3Hf) MMTVs. Because monoclonal antibodies recognize single antigenic determinants, these results demonstrate for the first time that the three patterns of antigenic reactivity for MMTV are related to individual determinants on the gp52 molecule and also clearly show that one strain of MMTV can be distinguished from other strains.


[Influence of T-593 on the recurrence and relapse of cryocautery-induced gastric ulcer in rats: sequential observation with an endoscope and histological evaluation].
We investigated the influence of T-593, a novel anti-ulcer agent, on the recurrence and relapse of cryocautery-induced gastric ulcer in rats, in comparison with the action of famotidine and ranitidine. The drugs were administered from the 7th to the 119th day and then discontinued to the 190th day after induction of gastric ulcer. The healing, recurrence and relapse process of gastric ulcer was sequentially observed with an endoscope. In the control group, the reduction of ulcer index was observed until the 76th day after ulcer induction followed by aggravation, suggesting the recurrence and relapse occurred on cryocautery-induced gastric ulcer in rats. In the famotidine and ranitidine groups, the recurrence and relapse occurred after cessation of administration. The recurrence and/or relapse rate of T-593 was lower than those of other drugs. In the histological measurement, the grades of heterotopic regenerated gland and inflammatory cell infiltration of T-593 was lower than those of the control and other drugs in the ulcer area. From these results, it is concluded that T-593 induces ulcer healing with a lower recurrence and/or relapse rate of ulcers than other conventional H2-antagonists, and T-593 may thus be a useful anti-ulcer drug for clinical therapy.


Influence of dietary energy restriction on the numbers and proportions of Ly-1+ B lymphocytes in autoimmunity-prone mice.
Chronic energy-intake restriction (CEIR) has been shown to increase life-span, delay diseases expression, and inhibit immunological perturbations in all strains of autoimmunity-prone mice studied, including NZB, (NZB x NZW)F1, MRL/Mp-lpr/lpr, BXSB, and kd/kd mice. In (NZB x NZB)F1 mice, increased percentages and increased absolute numbers of Ly-1+ B lymphocytes in spleen, mesenteric lymph nodes, thymus, and bone marrow as revealed by two-color immunofluorescence analysis were greatly reduced by CEIR with a diet high in carbohydrate and low in fat. This influence on a possibly crucial lymphocyte subpopulation was associated with delayed onset of disease and with greatly prolonged life-span. In the present investigation, the percentages and absolute number of Ly-1+ B lymphocytes in the spleen, peritoneal exudate, and peripheral blood were found to be increased in each autoimmunity-prone strain studied. CEIR decreased the absolute and relative numbers of the Ly-1+ B lymphocytes in mice of each of the autoimmunity-prone strains and returned the number and proportions of Ly-1+ B cells close to levels present in the same locations in genetically long-lived C57BL/6, DBA/2, or BALB/c mice fed a standard commercial diet ad libitum.


Heat strain at high levels does not degrade target detection and rifle marksmanship.
A recent investigation found no degradation in rifle marksmanship due to mild heat strain (up to a 1 degrees C increase in core temperature) even though the subjective sensation of discomfort was significant. The present study was conducted to determine if, and at what level of heat strain would degradation in both target detection and marksmanship (TD&M) occur. Degradation in TD&M performance is expected in individuals who reach a level of high heat strain. There were 11 subjects (mean +/- SD of 28.9 +/- 6.0 yr, 177 +/- 10 cm, and 81.2 +/- 18.8 kg) who participated in 3 counterbalanced trials: control (CN); heat with hydration (HH); and heat without hydration (HD). Core temperature was increased through a combination of exercise and passive heating over 4 h. Measures of shooting performance every half hour included target detection and engagement times, friend-foe discrimination, and shooting accuracy using a small arms trainer. All physiological measures and indices indicated that a significantly elevated heat strain was attained during HH and HD compared with CN. Mean heart rates and core temperatures approached 150 bpm and 39 degrees C, respectively, at the end of the heated trials. Aside from minor differences in target detection and identification owing to target type, no detrimental impact on TD&M due to heat strain, whether hydrated or dehydrated, was observed. High levels of heat strain do not adversely affect target detection and rifle marksmanship performance, at least for a period of time not exceeding 4 h in a non-threatening environment.


Modest inflammation enhances diclofenac hepatotoxicity in rats: role of neutrophils and bacterial translocation.
Idiosyncratic adverse drug reactions (IADRs) represent an important human health problem, yet animal models for preclinical prediction of these reactions are lacking. Recent evidence in animals suggests that some IADRs arise from drug interaction with an inflammatory episode that renders the liver sensitive to injury. Diclofenac (DCLF) is one of those drugs for which the clinical use is limited by idiosyncratic liver injury. We tested the hypothesis that modest inflammation triggered in rats by a small dose of lipopolysaccharide (LPS) renders a nonhepatotoxic dose of DCLF injurious to liver. Cotreatment of rats with nonhepatotoxic doses of LPS and DCLF resulted in elevated serum alanine aminotransferase activity and liver histopathologic changes 6 h after DCLF administration. Neither LPS nor DCLF alone had such an effect. Gene array analysis of livers revealed a unique gene expression pattern in the LPS/DCLF-cotreated group compared with groups given either agent alone. Antiserum-induced neutrophil (PMN) depletion in LPS/DCLF-cotreated rats protected against liver injury, demonstrating a role for PMNs in the pathogenesis of this LPS/DCLF interaction. Gut sterilization of LPS/DCLF-treated rats did not protect against liver injury. In contrast, gut sterilization did attenuate liver injury caused by a large, hepatotoxic dose of DCLF, suggesting that hepatotoxicity induced by large doses of DCLF is caused in part by its ability to increase intestinal permeability to endotoxin or other bacterial products. These results demonstrate that inflammation-DCLF interaction precipitates hepatotoxicity in rats and raise the possibility of creating animal models that predict human IADRs.


Serum Follistatin Levels are Independently Associated with Exercise Tolerance in Patients with Obesity.
Follistatin (FST)/myostatin (MST) myokine-signaling axis is important for muscle metabolism and pathogenesis of obesity. FST, mainly secreted by skeletal muscle and liver, inhibits MST and affects skeletal muscle synthesis. This study aimed to identify the characteristics of myokines and independent predictors of serum FST levels in patients with obesity. In this retrospective cross-sectional study, 226 patients (mean age, 46.6 years; men, 35.4%) with obesity who initially visited an outpatient clinic between June 2014 and September 2020, were included and classified into obesity (25.0 ≤ body mass index (BMI) < 35.0 kg/m2) and severe obesity (BMI ≥35 kg/m2) groups based on the guidelines of the Japan Society for the Study of Obesity. Body composition was measured using bioelectrical impedance analysis and computed tomography. Muscle strength, exercise tolerance, metabolic parameters, and myokines were measured, including serum levels of FST, MST, irisin, and brain-derived neurotrophic factor. Serum FST levels were significantly higher in the severe obesity group than in the obesity group (median: 768.4 vs. 895.1 pg/mL, P = 0.020). However, the levels of other myokines showed no significant differences between the groups. In Model 1, which included factors that significantly correlated with FST levels, stepwise multivariate regression analysis revealed peak oxygen uptake (VO2) as an independent predictor of FST levels based on the significance of the univariate analysis. Additionally, Model 2 was analyzed by adding myokine level to Model 1, revealing that peak VO2, MST, and irisin levels were independent predictors of FST levels. Serum FST levels were higher in patients in the severe obesity group compared to those in the obesity group. There was an independent association between low exercise tolerance and elevated serum FST levels.


Assessment of cerebral circulation in a porcine model of intravenously given E. coli induced fulminant sepsis.
The aim of the present work was to assess cerebral hemodynamic changes in a porcine model of E.coli induced fulminant sepsis. Nineteen healthy female Hungahib pigs, 10-12 weeks old, randomly assigned into two groups: Control (n = 9) or Septic Group (n = 10). In the Sepsis group Escherichia coli culture suspended in physiological saline was intravenously administrated in a continuously increasing manner according to the following protocol: 2 ml of bacterial culture suspended in physiological saline was injected in the first 30 min, then 4 ml of bacterial culture was administered within 30 min, followed by infusion of 32 ml bacterial culture for 2 h. Control animals received identical amount of saline infusion. Systemic hemodynamic parameters were assessed by PiCCo monitoring, and cerebral hemodynamics by transcranial Doppler sonography (transorbital approach) in both groups. In control animals, systemic hemodynamic variables and cerebral blood flow velocities and pulsatility indices were relatively stable during the entire procedure. In septic animals shock developed in 165 (IQR: 60-255) minutes after starting the injection of E.coli solution. Blood pressure values gradully decreased, whereas pulse rate increased. A decrease in cardiac index, an increased systemic vascular resistance, and an increased stroke volume variation were observed. Mean cerebral blood flow velocity in the middle cerebral artery did not change during the procedure, but pulsatility index significantly increased. There is vasoconstriction at the level of the cerebral arterioles in the early phase of experimental sepsis that overwhelmes autoregulatory response. These results may serve as additional pathophysiological information on the cerebral hemodynamic changes occurring during the septic process and may contribute to a better understanding of the pathomechanism of septic encephalopathy.


1H-NMR study of the quadruplex [d(TGGGT)]4 containing a modified thymine.
A NMR structural study of quadruplex [d(TGGGT)]4 containing a modified thymine is reported. The three dimensional structure of the complex is very similar to those of other parallel stranded quadruplexes. The modified thymines (T*) are able, at least in the minimised structures, to form a tetrad containing extra H-bonds through the hydroxyl groups. Nevertheless, in this new tetrad the modified thymines are slightly open towards the solvent respect to the unmodified T-tetrad.


[Micromorphological observation of bacterial biofilms on ciliated epithelia of chronic rhinosinusitis].
To observe the micromorphological characteristic of bacterial biofilm on mucosa of chronic rhinosinusitis (CRS). Mucosa samples of middle turbinate were obtained from 4 patients of CRS during ESS. The size of each sample was about 4 mm x 4 mm. The samples were fixed in 4% paraformaldehyde for 24 hours, then fixed in 1% osmium tetroxide for 2 hours, graded dehydration with ethanol, dried with carbon dioxide and sputter coated with gold. The ultrastructure of these samples was observed by scanning electron microscope. Bacterial biofilms were found on samples in all 4 patients. The biofilms were mainly formed on the surface of cilia. The bacterial flagella and cilia were intertwined. The biofilms could be found in a lot kinds of bacterial infections or mixed infections which were caused by multiple bacteria and fungi. Bacterial biofilm could be formed on ciliated epithelia.


Verbal and gestural communication in children with bilateral perisylvian polymicrogyria.
We assessed intelligence and receptive and expressive language skills in 6 children, ages 7 years 9 months to 12 years 4 months, with bilateral perisylvian polymicrogyria of variable extent and with dysarthria of different severity. In view of the recent findings of a close relationship between word and gesture, we also examined the communicative use of gesture. We found that mental retardation was related to the extent of cortical malformation; lexical comprehension, but not morphosyntactic comprehension, and verbal production were more compromised than expected from nonverbal intellectual abilities; lack of verbal language was not compensated by the use of referential gestures. Results are discussed suggesting that compromised verbal and gestural communication in bilateral perisylvian polymicrogyria are not due simply to mental retardation and/or dysarthria but also to dysfunction of Sylvian fissure areas concerned with the totality of language processing.


Functions and Potential Applications of Circular RNAs in Cancer Stem Cells.
Circular RNAs (circRNAs) were discovered in the 1970s, but they have drawn increasing attention in recent years. Currently, we know that circRNAs are not "wrongly spliced" during transcription but play important roles in the initiation and development of various diseases, including cancers. Recently, a growing number of studies have suggested that cancer stem cells (CSCs) may contribute to the origination and maintenance of cancers. This review briefly introduces the major functions of circRNAs, including interacting with other noncoding RNAs, competing with pre-mRNA splicing, binding with proteins to form a scaffold, promoting protein nuclear translocation and even translating proteins in a cap-independent manner. Furthermore, we describe the regulatory mechanism of circRNAs in CSC phenotypes and discuss the potential clinical applications of circRNAs in CSC-targeted therapy, including functioning as new biomarkers, acting as vaccines and breaking the therapeutic resistance of CSCs. Finally, we discuss the major limitations and challenges in the field, which will be beneficial for the future clinical use of circRNAs.


Studies of the toxicological potential of capsinoids: X. Safety assessment and pharmacokinetics of capsinoids in healthy male volunteers after a single oral ingestion of CH-19 Sweet extract.
The safety and pharmacokinetics of capsinoids, physiologically active ingredients of CH-19 Sweet extract, were investigated in 16 healthy male volunteers following a single oral ingestion of CH-19 Sweet extract. The study subjects consumed soft gel capsules containing either capsinoids (15 or 30 mg/person) or placebo. Capsinoids were well tolerated, and no clinically significant changes in physical examinations, blood pressure, heart rate, body temperature, electrocardiogram, hematology, blood chemistry, and urinalysis were observed at either the 15 or 30 mg dose. Body temperature tended to increase after the ingestion of capsinoids, but remained within the normal range. Plasma levels of capsinoids and their metabolite, vanillyl alcohol, were below the lower limit of quantitation. In addition, some study subjects showed increases in urinary excretion of 3-methoxy-4-hydroxyphenylglycol that, when compared to the group receiving the placebo, did not achieve statistical significance.


What Does It Take to Be an Effective National Steward of Digital Health Integration for Health Systems Strengthening in Low- and Middle-Income Countries?
Digital innovations have evolved over the last 15 years to support health activities, and their introduction in low- and middle-income countries has shown the potential to catalyze gains in health systems and service delivery. Despite widespread efforts to roll out these technologies, standardized approaches for formalizing national stewardship responsibilities and ensuring that digital health is a routine, mature, sustainable, and country-owned component of the health system are lacking. In this paper, we define digital health stewardship, with a focus on the ministry of health's role; describe practices undertaken to date; and identify gaps where increased attention could improve sustainability, impact, and local ownership. We conducted a purposeful review of peer-reviewed and gray literature. Of the 404 identified resources from the peer-reviewed literature, 12 met all of the inclusion criteria. After searching various online gray literature repositories, we identified 6 sources based on their quality, source, and relevance. Selected resources were abstracted for relevance to our stewardship themes and synthesized. Findings are presented in 4 broad thematic areas: strategic direction, policies and procedures, roles and responsibilities, and health service delivery implications. Evidence related to strategic direction offers guidance on the main responsibilities under digital health stewardship, including regulations and incentives to promote compliance with standards, mechanisms for oversight, and structures to support evidence-based decisions, and the potential institutional structures and goals that could be used to achieve them. A number of examples of high-level policies and implementation-oriented procedures, such as from the European Commission and the World Health Organization, demonstrate how to operationalize the strategic direction. Available evidence for the remaining themes was sparse, drawing attention to key areas for future work. Despite the importance of country-owned stewardship of digital health, the guidance available is limited and aspirational. Concrete recommendations, including how to adapt existing innovations to the local context, are needed. In particular, the role of external partners needs to be oriented toward building and supporting country capacity to achieve digital health stewardship's potential to support health systems into the future.


Best Location and Reader Role in Usage of Emergency Manuals During Critical Events: Experienced Emergency Manual Users' Opinion.
Introduction Emergency manuals (EM) are an essential component of the response to critical events by healthcare providers, and there is strong evidence to support the benefits of utilizing EMs in crisis management. Despite the widespread utilization of EMs by providers, there is currently no national standardized protocol for EM usage, accompanied by a deficit in research on EM usage. To develop a protocol for EM utilization, factors such as the best location for EMs to be placed and the EM reader role must be determined. Methods Anesthesiologists with experience in EM use from seven hospitals participated in a survey questionnaire that was distributed to all participants through WeChat using the WenJianxen software. Survey response numbers were converted into percentages and were used to summarize the categorical variables. Results Results showed the best location of EMs used during critical events was in the anesthesia station of the operating room and that the preferred reader of EMs during critical events is the senior physician. Conclusion Our study suggests that placing EMs within close reach of the health care providers may be most efficient and that the reader of EMs should be the leader of the clinical team. These results may be applicable to the development and implementation of a national protocol for EM usage.


Blood Pressure, Sexual Activity, and Erectile Function in Hypertensive Men: Baseline Findings from the Systolic Blood Pressure Intervention Trial (SPRINT).
Erectile function, an important aspect of quality of life, is gaining increased research and clinical attention in older men with hypertension. To assess the cross-sectional association between blood pressure measures (systolic blood pressure [SBP]; diastolic blood pressure [DBP]; and pulse pressure [PP]) and (i) sexual activity and (ii) erectile function in hypertensive men. We performed analyses of 1,255 male participants in a larger randomized clinical trial of 9,361 men and women with hypertension aged ≥50 years. The main outcome measures were self-reported sexual activity (yes/no) and erectile function using the 5-item International Index of Erectile Function (IIEF-5). 857 participants (68.3%) reported being sexually active during the previous 4 weeks. The mean (SD) IIEF-5 score for sexually active participants was 18.0 (5.8), and 59.9% of the sample reported an IIEF-5 score <21, suggesting erectile dysfunction (ED). In adjusted logistic regression models, neither SBP (adjusted odds ratio = 0.998; P = .707) nor DBP (adjusted odds ratio = 1.001; P = .929) was significantly associated with sexual activity. In multivariable linear regression analyses in sexually active participants, lower SBP (β = -0.04; P = .025) and higher DBP (β = 0.05; P = .029) were associated with better erectile function. In additional multivariable analyses, lower PP pressure was associated with better erectile function (β = -0.04; P = .02). Blood pressure is an important consideration in the assessment of erectile function in men with hypertension. Assessments of blood pressure and clinical and psychosocial variables were performed using rigorous methods in this multi-ethnic and geographically diverse sample. However, these cross-sectional analyses did not include assessment of androgen or testosterone levels. Erectile dysfunction was highly prevalent in this sample of men with hypertension, and SBP, DBP, and PP were associated with erectile function in this sample. Foy CG, Newman JC, Berlowitz DR, et al. Blood Pressure, Sexual Activity, and Erectile Function in Hypertensive Men: Baseline Findings from the Systolic Blood Pressure Intervention Trial (SPRINT). J Sex Med 2019;16:235-247.


Therapeutic potential of S179D prolactin--from prostate cancer to angioproliferative disorders: the first selective prolactin receptor modulator.
Increasing evidence suggests an important role for autocrine/paracrine prolactin in breast and prostate cancers and other disease states. Prolactin production in these extrapituitary sites is not governed by dopamine agonists, a finding that has spurred the production of prolactin receptor antagonists. This review focuses on one such antagonist, S179D prolactin, which was produced by mimicking a natural antagonist, phosphorylated prolactin. S179D prolactin is a very effective growth antagonist, partly because it inhibits signalling from unmodified prolactin and partly because it produces its own intracellular signal. This signal results in cell differentiation, cell-cycle arrest or apoptosis depending on dose, duration of treatment and cellular context. S179D prolactin is also a potent antiangiogenic and initial studies have shown it to be a potent anti-inflammatory agent. In light of these additional modes of action, it is suggested that S179D prolactin should now be more aptly referred to as a selective prolactin receptor modulator.


Novel Highly Pathogenic Avian Influenza A(H5N6) Virus in the Netherlands, December 2017.
A novel highly pathogenic avian influenza A(H5N6) virus affecting wild birds and commercial poultry was detected in the Netherlands in December 2017. Phylogenetic analysis demonstrated that the virus is a reassortant of H5N8 clade 184.108.40.206 viruses and not related to the Asian H5N6 viruses that caused human infections.


[Association between loneliness and risks of depressive episode among rural older people].
To investigate association between loneliness and depressive episode among rural older people. Methods: A total of 839 rural adults (aged over 60 years) from Liuyang in Hunan were enrolled by using multi-stage cluster sampling method. The Short-form of the UCLA Loneliness Scale, the Social Support Rating Scale, the Life Events Scale for the Elderly, Quality of Life Scale, and the Activity of Daily Living Scale were used to assess loneliness, the social support condition, the stimulating quantity of negative life events, the quality of life, and the abilities of daily life activities, respectively. The Structured Clinical Interview for DSM-IV-TR Axis I Disorders questionnaire survey was performed by a face-to-face interview. Results: The prevalence rate of depressive episode among the rural older people was 6.8%. Multivariable analysis showed that the elderly who were with stronger loneliness were the risk factor of depression (OR=1.126, 95%CI 1.038 to 1.221). Conclusion: Loneliness is positively associated with an increased risk of depressive episode.


Stimulation of renin release from rat kidney cortical slices by vitamin E-deficiency.
Effect of vitamin E-deficiency on renin release was examined with rat kidney cortical slices. Male Wistar rats were fed either a control or a vitamin E-deficient diet for 4 weeks. When kidney cortical slices were incubated in a Krebs-Ringers' bicarbonate solution (pH 7.4) at 37 degrees C, the rate of renin release into the incubation medium in vitamin E-deficient group was significantly higher than that in the control group. However, dietary supplementation of alpha-tocopheryl acetate (TOCA) or N,N'-diphenyl-p-phenylenediamine (DPPD) to the vitamin E-deficient rats for 5 d suppressed the stimulation of renin release from kidney cortical slices by vitamin E-deficiency. On the other hand, the release of protein, acid phosphatase and alkaline phosphatase during incubation of kidney cortical slices was not affected by vitamin E-deficiency or supplementations of TOCA and DPPD. These findings indicate that vitamin E-deficiency specifically stimulates renin release from kidney cortical slices and this effect is attenuated by the dietary supplementation of TOCA or DPPD.


Clusters of Behavioral Health and Psychosocial Risk for Childbearing Women in Four Virginia Communities.
Introduction Four Virginia communities participated in a community services enhancement pilot to centralize intake and referral for childbearing women eligible for home visiting support through the Maternal, Infant and Early Childhood Home Visiting (MIECHV) program. Methods As an aspect of the study, project-trained intake workers administered behavioral health and psychosocial risk screening (including emotional health, substance use, interpersonal violence, and smoking) during intake eligibility assessment. Participants identified as at-risk were referred for community intervention concurrently with referral to MIECHV services. Results In the study sample (N = 1515), emotional health was identified as the most common single risk factor (n = 326, 21.5%) and clusters of 2 or more behavioral health risks were identified for 223 (14.7%) of women. Among those with two or more behavioral health risks, smoking was significantly related to all other areas of behavioral health risk. Conclusion Findings from this multi-site pilot emphasize concomitant behavioral health and psychosocial risks in childbearing women and reinforce the importance of embedding comprehensive public health interventions in community systems of care.


[Study on the molecular epidemiology and antibiotic resistance of Salmonella enterica serovar Pomona].
To study the epidemiological characteristics and antibiotic resistance of Salmonella enterica serovar Pomona (S. Pomona). Antimicrobial susceptible testing (AST) and pulsed field gel electrophoresis (PFGE) methods were used to analyze on S. Pomona strains that were isolated from diarrhea cases through the diarrhea network monitoring program, environment and food samples in Shanghai as well as from reptiles in Guangxi Zhuang Autonomous Region. 4 553 clinic Salmonella (S.) strains were isolated from the Shanghai network laboratories from 2005 to 2012. The top 10 serotypes would include 20 serotypes all belonged to A-F groups, while S. Pomona was next to S. Wandsworth, according to the non- A-F groups. Young children seemed to be susceptible to S. Pomona, and might cause bloody stools and super-infection. The top 10 serotypes from 1 805 foodborne Salmonella strains were significantly more extensive than those from the human S. Pomona strains, followed by those rare serotypes which were mostly isolated from turtle, sea-shellfish and reptiles. Antibiotic resistance of S. Pomona strains from other sources were significantly more severe than those from human samples, and belonged to A and B clones by means of PFGE. Clone A strains were non-epidemic strains which showed multi-drug resistance (MDR) to antimicrobials. Clone B was the main epidemic-causing strain that not resistant to drugs, which consisting B- I from young-age-groups and B-II were from the seniors. B-I strains were homologous to those from shellfish, tortoises and lizards, while B-II strains only showing homology to those from shellfish. One S. Pomona strain-MDR, isolated from human was homologous to 8 antimicrobials. S. Pomona was a quite common serotype among those rare serotypes, which showed higher pathogenicity to infants while genetic evolution might take place when comparing them with the strains isolated from the clinics in 2005. Surveillance programs should be intensified along with the early warnings systems on infections which were from seafood and reptiles.


Double-blind pretreatment of exercise-induced asthma with sequential inhalations of fenoterol from an aerosol and as a powder (second of two parts).
Eighteen adult asthmatics participated in a placebo controlled, double-blind, randomised study comparing the efficacy of pretreatment with fenoterol administered by pressurized aerosol and as a dry powder on exercise-induced asthma. The dosages used were 0.6 mg and 1.0 mg as both pressurized aerosol and dry powder. The pretreatment was given over a period of 10 min. Six min of treadmill-running was performed in a climate chamber 30 min after pretreatment on five successive days. The lung function was assessed by peak expiratory rate. The decrease in lung function following pretreatment with placebo was 32% (average +/- (SEM) (2). Falls of 9% (2) and 8% (1) were seen after pretreatment with 0.6 and 1.0 mg from a pressurized aerosol. The falls following pretreatment with 0.6 and 1.0 mg of dry powder were 8% (2) and 8%, respectively. It is concluded that pretreatment of exercise-induced asthma with a beta-2-agonist is equally effective whether dosed from a pressurized aerosol as when given as a dry powder. A dose of 0.6 mg is just as effective as a dose of 1.0 mg when inhaled over a period of ten min.


Influence of age and disease severity on high resolution CT lung densitometry in asthma.
Low attenuation areas (LAA) on computed tomographic (CT) scans have been shown to represent emphysematous changes in patients with chronic obstructive pulmonary disease (COPD). However, the significance of LAA is still controversial in patients with asthma. This study was undertaken to assess the usefulness of lung CT densitometry in the detection of airspace enlargement in association with asthma severity. Forty five asthmatic subjects and 15 non-smoking controls were studied to determine the influence of age, pulmonary function, and asthma severity on mean lung density (MLD) and the relative area of the lung showing attenuation values less than -950 HU (RA(950)) on high resolution CT (HRCT) scans. In asthmatic patients both MLD and RA(950) correlated with parameters of airflow limitation (%FEV(1), FEV(1)/FVC, %FEF(25-75)) and lung volume (%TLC, %FRC, %RV), but not with lung transfer factor (%TLCO, %TLCO/VA). The results of HRCT lung densitometry also correlated with patient age and severity of asthma. Decreased CT lung density in non-smoking asthmatics is related to airflow limitation, hyperinflation and aging, but not with lung transfer factor.


Differential impairment of positive and negative schizotypy in list-method and item-method directed forgetting.
Schizophrenia is characterized by cognitive impairment and this impairment is expected to occur, albeit to a lesser degree, in people putatively at risk for schizophrenia. Two experiments assessed the relationship between directed forgetting (DF) and schizotypy, which is a multidimensional construct that reflects the expression of the underlying vulnerability for schizophrenia. Experiment 1 involved item-method DF and Experiment 2 involves list-method DF study. The schizotypy dimensions exhibited differential patterns of impairment across the 2 methods that suggest different underlying processes. Positive schizotypy showed impairment in item-method DF that was driven by reduced ability to forget forget-cued items, whereas performance on remember-cued items was unaffected in positive schizotypy. Despite the deficit in item-method DF, positive schizotypy participants showed preserved performance in list-method DF. The opposite pattern was found in negative schizotypy participants, who showed impairment in list-method DF, despite preserved performance in item-method DF. Negative schizotypy was previously associated with deficits in context processing and, consistent with context-change account of list-method DF, showed deficits in list-method DF task. Positive schizotypy is characterized by deficits in inhibitory control and, consistent with inhibitory account of item-method DF, showed deficits in item-method DF task. Collectively, these results (a) suggest that different DF methods involve different underlying mechanisms, (b) support the context-account of list-method DF and an inhibitory account of item-method DF, and (c) support the multidimensional model of schizotypy by showing differential impairment in positive and negative schizotypy across the 2 DF tasks. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Mirror exposure for the treatment of body image disturbance.
Body image disturbance is a risk factor for the development and persistence of eating disorders. Limitations of current treatments for body image disturbance prompted the development of a mirror exposure (ME) treatment. ME involves deliberate, planned, and systematic exposure to body image. The approach is nonjudgmental, holistic in focus, and mindful of present emotional experience. Complementary behavioral assignments aim to reduce avoidance and excessive checking. The current study evaluated the effectiveness of ME therapy (in a three-session format) compared with a nondirective (ND) therapy for 45 women with extreme weight and shape concerns. ME resulted in significant improvements at termination and follow-up in body checking and avoidance, weight and shape concerns, body dissatisfaction, dieting, depression, and self-esteem. As hypothesized, ME was significantly better than ND on many of the outcome measures. ME is an effective treatment for body image disturbance and should be evaluated in the context of treatments for eating disorders.


Application of a Machine Learning Algorithm for Structural Brain Images in Chronic Schizophrenia to Earlier Clinical Stages of Psychosis and Autism Spectrum Disorder: A Multiprotocol Imaging Dataset Study.
Machine learning approaches using structural magnetic resonance imaging (MRI) can be informative for disease classification; however, their applicability to earlier clinical stages of psychosis and other disease spectra is unknown. We evaluated whether a model differentiating patients with chronic schizophrenia (ChSZ) from healthy controls (HCs) could be applied to earlier clinical stages such as first-episode psychosis (FEP), ultra-high risk for psychosis (UHR), and autism spectrum disorders (ASDs). Total 359 T1-weighted MRI scans, including 154 individuals with schizophrenia spectrum (UHR, n = 37; FEP, n = 24; and ChSZ, n = 93), 64 with ASD, and 141 HCs, were obtained using three acquisition protocols. Of these, data regarding ChSZ (n = 75) and HC (n = 101) from two protocols were used to build a classifier (training dataset). The remainder was used to evaluate the classifier (test, independent confirmatory, and independent group datasets). Scanner and protocol effects were diminished using ComBat. The accuracy of the classifier for the test and independent confirmatory datasets were 75% and 76%, respectively. The bilateral pallidum and inferior frontal gyrus pars triangularis strongly contributed to classifying ChSZ. Schizophrenia spectrum individuals were more likely to be classified as ChSZ compared to ASD (classification rate to ChSZ: UHR, 41%; FEP, 54%; ChSZ, 70%; ASD, 19%; HC, 21%). We built a classifier from multiple protocol structural brain images applicable to independent samples from different clinical stages and spectra. The predictive information of the classifier could be useful for applying neuroimaging techniques to clinical differential diagnosis and predicting disease onset earlier.


Assent and permission rejoinder.
We share Roberts and Buckloh's (this issue) concern about issues of assent and permission in research with children and agree that our research cannot conclude legitimately that (a) researchers failed to obtain permission/assent, (b) children were put at risk, or (c) failure to report permission/assent procedures was, in any way, unethical. We never made these conclusions. Rather, we argue that publishing assent and permission would enhance compliance with ethical standards, sensitize researchers and readers to its importance, and shift publishing priorities in an appropriate direction.


Posterior dopamine D2/3 receptors and brain network functional connectivity.
Recent studies suggest that dopaminergic tone influences resting state activity in multiple brain networks. Although dopamine receptors and transporters have been identified in the posteromedial and parietal cortices, which are linked to functional networks such as the default mode network (DMN), the relationship between dopamine receptor distribution in these posterior regions and resting-state connectivity has yet to be explored. Here, we used a multi-modal neuroimaging strategy, combining resting-state functional magnetic resonance imaging (rsfMRI) and [18 F]-fallypride high-resolution positron emission tomography (PET), to examine the association between within-network functional connectivity and the dopamine D2/3 receptor distribution in the posterior portion of the brain in 13 healthy adults. Our results indicate that the posterior distribution of D2/3 receptors coincides primarily with the posterior portion of the DMN. Furthermore, in the posterior portion of the brain, the level of [18 F]-fallypride binding in the posteromedial cortex correlated positively with the functional connectivity strength of the DMN and sensorimotor network, and negatively with the functional connectivity strength of the dorsal attention network, the salience network, and a network that included the anterior part of the temporo-parietal junction. On the basis of these findings, we propose that posterior brain dopamine influences the configuration of the posterior DMN and several other functional brain networks. The posterior distribution of D2/3 receptors binding (hot colour spectrum) coincides with the functional connectivity of the posterior portion of the default mode network (green colour spectrum). The mean BPND in a posteromedial cortex and the mean ICA-Z score in the precuneus showed significant positive correlation.


Graphene nanoparticle strain sensors with modulated sensitivity through tunneling types transition.
Highly sensitive strain sensors show great potential for use in wearable health monitoring, autonomous intelligent robots and biomimetic prosthetics. The current resistive strain sensors mainly work through piezoresistors. Here, the robust tunneling mechanism based nanoscale strain sensors with high sensitivity are reported. The strain sensors are fabricated from graphene nanoparticle film. The sensitivity of graphene nanoparticle strain sensors could be tunable through the modulation of tunneling type, suggesting a theoretical support in performance optimization of tunneling strain sensors. The output characterization indicates the direct tunneling (DT) and Fowler-Nordheim tunneling (FNT) are dominant for charge carrier transport in the low voltage and high voltage regions, respectively. It is found that gauge factors are ∼79 at low voltage of 0-4 V, and ∼110 at high voltage of 20-40 V, showing profound dependence on DT and FNT types. The strain sensor bearing 0.3% strain shows a great stability over 100 cycles at bias voltage of 1 V and 40 V, respectively. An integrated strain sensor array with 5 × 5 patterned graphene nanoparticle film on a polyethylene terephthalate substrate is fabricated and demonstrates great spatial strain distribution, guiding the design for flexible and transparent strain sensor e-skins.


Demographic features and natural history of intermediate-risk multifocal versus unifocal intraductal papillary mucinous neoplasms.
This study compares the progression of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs) to unifocal (UF) lesions. We performed a retrospective review of demographics, risk factors, and cyst characteristics of a prospectively maintained database of 999 patients with pancreatic cysts. Patients included had IPMN under surveillance for 12 months or more. Those with high-risk stigmata were excluded. Cyst size progression and development of worrisome features were compared between MF and UF cohorts. We evaluated whether the dominant cyst in MF-IPMN had more significant growth than did the other cysts. Seventy-seven patients with MF-IPMN and 54 patients with UF-IPMN, with mean follow-up of 27 and 34 months, met the criteria. There were no significant differences between demographics, risk factors, or initial cyst sizes. Fifty-seven percent of MF dominant cysts and 48% of UF cysts increased in size (P = 0.31). Progression in MF was more likely in the dominant cyst (P < 0.05). There were no significant differences in the development of mural nodules or increase in cyst size to more than 3 cm. Demographics of both cohorts were similar, as was the overall incidence of worrisome features. Because meaningful size progression primarily occurred in the dominant cyst, our findings support surveillance based on the dominant cyst in MF disease.


Use of reamed locked intramedullary nailing in the treatment of aseptic diaphyseal tibial non-union.
Tibial fractures have been associated with the highest rates of bone union disturbances for many years. Stabilization of the tibial shaft with a reamed intramedullary nail is now being increasingly recommended as a treatment of choice. The aim of this study was to evaluate the outcomes of treatment of tibial shaft non-union with reamed intramedullary nails locked distally and proximally. Thirty-three patients (11 females and 22 males) with tibial shaft non-union were treated by locked intramedullary nailing. There were twelve patients with a biologically active non-union, while in the remaining 21 the non-union was biologically non-active. The diagnosis was based on case history, physical examination and X-ray data. The average non-union time was 26.96. An intramedullary nail was inserted according to the technique recommended by AO/ASIF. Follow-up examinations were performed at six-week intervals until bone union was obtained. The diagnosis of bone union was based on physical examination and X-ray evidence. The functional outcome was assessed according to the Johner-Wruhs scale. Treatment failure was defined as the absence of clinical and radiological signs of bone union 12 months after surgery. Bone union was achieved in 94% patients following an average time of 37.2 weeks. The functional outcome was classified as good or very good according to the Johner and Wruhs scale in 60% of the patients, while 18% of the patients were diagnosed to have a poor functional outcome. An infection of the non-union site was found in 6 patients, of whom two developed a chronic infection (in one patient bone union was not achieved). The treatment of an aseptic non-union of the tibial shaft with an intramedullary nail is an effective procedure. This conclusion must be regarded as tentative in view of the small sample size.