Validation of the Health-Related Productivity Questionnaire Diary (HRPQ-D) on a sample of patients with infectious mononucleosis: results from a phase 1 multicenter clinical trial.
The objective of this work was to assess the performance of the newly developed Health-Related Productivity Questionniare-Diary (HRPQ-D). Patients completed the HRPQ-D daily for 1-week periods during weeks 1, 2, 4, and 8 of a clinical trial for infectious mononucleosis. Productivity data were collected on a daily basis in terms of absenteeism, presenteeism, and combined lost productivity for three work venues (work outside home, housework, and classes/homework). These were then correlated with patient symptom scores. Symptom scores were positively correlated with lost work hours because of absenteeism and combined lost productivity scores. However, negative correlations were observed between symptom scores and the lost work hours due to presenteeism. The HRPQ-D demonstrated good construct validity, making it a useful tool for determining productivity levels across different work venues within clinical trial or survey research applications.


Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes.
Previous functional magnetic resonance imaging (fMRI) studies have identified brain systems underlying different components of working memory (WM) in healthy subjects. The aim of this study was to compare the functional integrity of these neural networks in children with self-limited childhood epilepsy with centro-temporal spikes (ECTS) as compared to healthy controls, using a verbal working memory task (WMT). Functional MRI of WM in seventeen 6-to-13 year-old children, diagnosed with ECTS, and 17 sex- and age-matched healthy controls were conducted at 3 T. To estimate BOLD responses during the maintenance of low, medium, and high WMT loads, we used a Sternberg verbal WMT. Neuropsychological testing prior to scanning and behavioral data during scanning were also acquired. Behavioral performances during WMT, in particular accuracy and response time, were poorer in children with ECTS than in controls. Increased WM load was associated with increased BOLD signal in all subjects, with significant clusters detected in frontal and parietal regions, predominantly in the left hemisphere. However, under the high load condition, patients showed reduced activation in the frontal, temporal and parietal regions as compared to controls. In brain regions where WM-triggered BOLD activation differed between groups, this activation correlated with neuropsychological performances in healthy controls but not in patients with ECTS, further suggesting WM network dysfunction in the latter. Children with ECTS differ from healthy controls in how they control WM processes during tasks with increasing difficulty level, notably for high WM load where patients demonstrate both reduced BOLD activation and behavioral performances.


Chromosome-level genome assembly of grass carp (Ctenopharyngodon idella) provides insights into its genome evolution.
The grass carp has great economic value and occupies an important evolutionary position. Genomic information regarding this species could help better understand its rapid growth rate as well as its unique body plan and environmental adaptation. We assembled the chromosome-level grass carp genome using the PacBio sequencing and chromosome structure capture technique. The final genome assembly has a total length of 893.2 Mb with a contig N50 of 19.3 Mb and a scaffold N50 of 35.7 Mb. About 99.85% of the assembled contigs were anchored into 24 chromosomes. Based on the prediction, this genome contained 30,342 protein-coding genes and 43.26% repetitive sequences. Furthermore, we determined that the large genome size can be attributed to the DNA-mediated transposable elements which accounted for 58.9% of the repetitive sequences in grass carp. We identified that the grass carp has only 24 pairs of chromosomes due to the fusion of two ancestral chromosomes. Enrichment analyses of significantly expanded and positively selected genes reflected evolutionary adaptation of grass carp to the feeding habits. We also detected the loss of conserved non-coding regulatory elements associated with the development of the immune system, nervous system, and digestive system, which may be critical for grass carp herbivorous traits. The high-quality reference genome reported here provides a valuable resource for the genetic improvement and molecular-guided breeding of the grass carp.


Geometrical and total efficiencies of CdZnTe rectangular parallelepiped detector using arbitrary positioned point, plane, and volumetric sources.
Gamma-ray detectors are widely used in many fields like environmental measurements, medicine, space science, and industry, where the detector geometrical, total, photopeak efficiencies and peak-to-total ratio could be required. The calculation of the detector efficiency depends mainly on the value of the geometrical efficiency, which depends on the solid angle subtended by the source-detector system. The present work introduces a direct analytical method to calculate the geometrical and total efficiencies of CdZnTe gamma-ray detector using off-axis isotropic radiating γ-ray [point, disk, and cylindrical] sources. To test the validity of the present work, the results are compared with some published data and also to prove how much it is important to determine the efficiency of difficult gamma-ray detection arrangement.


Immature bovine cartilage wear is due to fatigue failure from repetitive compressive forces and not reciprocating frictional forces.
Wear of articular cartilage is not well understood. We hypothesize that cartilage wears due to fatigue failure in repetitive compression instead of reciprocating friction. This study compares reciprocating sliding of immature bovine articular cartilage against glass in two testing configurations: (1) a stationary contact area configuration (SCA), which results in static compression, interstitial fluid depressurization, and increasing friction coefficient during reciprocating sliding, and (2) a migrating contact area configuration (MCA), which maintains pressurization and low friction while producing repetitive compressive loading in addition to reciprocating sliding. Contact pressure, sliding duration, and sliding distance were controlled to be similar between test groups. SCA tests exhibited an average friction coefficient of μ=0.084±0.032, while MCA tests exhibited a lower average friction coefficient of μ=0.020±0.008 (p<10-4). Despite the lower friction, MCA cartilage samples exhibited clear surface damage with a significantly greater average surface deviation from a fitted plane after wear testing (Rq=0.125±0.095 mm) than cartilage samples slid in a SCA configuration (Rq=0.044±0.017 mm, p=0.002), which showed minimal signs of wear. Polarized light microscopy confirmed that delamination damage occurred between the superficial and middle zones of the articular cartilage in MCA samples. The greatest wear was observed in the group with lowest friction coefficient, subjected to cyclical instead of static compression, implying that friction is not the primary driver of cartilage wear. Delamination between superficial and middle zones implies the main mode of wear is fatigue failure under cyclical compression, not fatigue or abrasion due to reciprocating frictional sliding.


[Transcommissural afferent projections of the lemniscal and spino-reticulo-thalamic systems].
In cats with section of classic, contralateral somatosensory pathways of the fore-leg at the midbrain level an instrumental defensive reflex "to this leg" can be elaborated. This fact suggests that the intact ipsilateral afferent somatosensory pathways of the brain-stem transmit kinsthetic excitations. The electrophysiological study (acute experiments under nembutal anesthesia) of somatosensory projections of the fore-leg, contralateral to the midbrain section, revealed bilateral evoked responses in the somato-sensory cortical areas with a latency of 18-20 msec. These responses evidence bilateral afferent projections of the ipsilateral part of the spinoreticulo-thalamic system. They constitute the functional basis for the formation of this conditioned instrumental defensive reflex. The lemniscal system as well as the ipsilateral part of spino-reticulo-thalamic system send bilateral afferent projections to the somatosensory structures of the brain.


Chimeric derivatives of functionalized amino acids and α-aminoamides: compounds with anticonvulsant activity in seizure models and inhibitory actions on central, peripheral, and cardiac isoforms of voltage-gated sodium channels.
Six novel 3″-substituted (R)-N-(phenoxybenzyl) 2-N-acetamido-3-methoxypropionamides were prepared and then assessed using whole-cell, patch-clamp electrophysiology for their anticonvulsant activities in animal seizure models and for their sodium channel activities. We found compounds with various substituents at the terminal aromatic ring that had excellent anticonvulsant activity. Of these compounds, (R)-N-4'-((3″-chloro)phenoxy)benzyl 2-N-acetamido-3-methoxypropionamide ((R)-5) and (R)-N-4'-((3″-trifluoromethoxy)phenoxy)benzyl 2-N-acetamido-3-methoxypropionamide ((R)-9) exhibited high protective indices (PI=TD50/ED50) comparable with many antiseizure drugs when tested in the maximal electroshock seizure test to mice (intraperitoneally) and rats (intraperitoneally, orally). Most compounds potently transitioned sodium channels to the slow-inactivated state when evaluated in rat embryonic cortical neurons. Treating HEK293 recombinant cells that expressed hNaV1.1, rNaV1.3, hNaV1.5, or hNaV1.7 with (R)-9 recapitulated the high levels of sodium channel slow inactivation.


Nutrient and productivity relations of the dune grasses Ammophila arenaria and Elymus mollis : II. Growth and patterns of dry matter and nitrogen allocation as influenced by nitrogen supply.
The purpose of this research was to investigate the influence of nitrogen availability on growth and the patterns of dry matter and nitrogen allocation of the dune grasses Ammophila arenaria and Elymus mollis. Plants were grown from rhizome segments under near-ambient coastal conditions and received either high or low supplies of nitrogen. Sequential harvests, and the separation of plant material into live blade, dead blade, tiller, rhizome, and root fractions were made during the exponential phase of growth. The concentrations of total nitrogen in these fractions were ascertained by the micro-Kjeldahl method.Despite similar relative rates of dry matter accumulation over the entire period of growth, Ammophila rates eventually surpassed those of Elymus due to a higher rate of blade area development under both nitrogen regimes. This was the result of allocating a larger proportion of daily assimilate to the production of new blades and a lower rate of blade area senescence, rather than a greater net assimilation rate. Low nitrogen availability decreased mean relative growth rate, mean leaf area ratio, mean leaf area expansion rate, and the leaf area partitioning coefficient but tended to increase mean net assimilation rate in both species.Studies of dry matter allocation revealed a "shoot-oriented" pattern of Ammophila growth, with an emphasis on the live blade fraction and a correspondingly diminished root fraction. Conversely, Elymus allocated more dry matter to roots and less to live blades. Allometric plots showed that twice as much live blade area was supported per gram of root by Ammophila than by Elymus. These differences were maintained despite changes in the availability of nitrogen.Although the patterns of dry matter and nitrogen partitioning were somewhat independent within a species (i.e. they were not tightly coupled), a general correspondence between the allocation of these resources was observed when the two species were compared. Ammophila allocated more nitrogen to live blades and less to tillers and roots than did Elymus. These characteristics of growth and resource allocation of Ammophila are thought to contribute to its greater above-ground productivity along the Pacific coast of North America compared to the native Elymus.


A network of Wnt, hedgehog and BMP signaling pathways regulates tooth replacement in snakes.
Most dentate vertebrates, from fish to humans, replace their teeth and yet the molecular basis of tooth replacement is poorly understood. Canonical Wnt signaling regulates tooth number in mice and humans, but it is unclear what role it plays in tooth replacement as it naturally occurs. To clarify this, we characterized Wnt signaling activity in the dental tissues of the ball python Python regius. This species replaces teeth throughout life (polyphyodonty) and in the same manner as in humans, i.e., sequential budding of teeth from the tip of the dental lamina. From initiation stage onwards, canonical Wnt read-out genes (Lef1 and Axin2) are persistently expressed by cells in the dental lamina tip and surrounding mesenchyme. This implies that molecular signaling at work during dental initiation carries over to tooth replacement. We show that canonical Wnt signaling promotes cell proliferation in python dental tissues and that by confining Wnt activity in the dental lamina the structure extends instead of thickens. Presumably, lamina extension creates space between successive tooth buds, ensuring that tooth replacement occurs in an ordered manner. We suggest that hedgehog signaling confines Wnt activity in the dental epithelium by direct planar repression and, during tooth replacement stages, by negatively regulating BMP levels in the dental mesenchyme. Finally, we propose that Wnt-active cells at the extending tip of the python dental lamina represent the immediate descendents of putative stem cells housed in the lingual face of the lamina, similar to what we have recently described for another polyphyodont squamate species.


Clinical and haemodynamic correlates of heart rate variability in children with congenital heart disease.
Heart rate variability (HRV) represents a noninvasive parameter for studying the autonomic control of the heart. Cardiac patients have a complex autonomic disturbance. The relation of HRV to this abnormality in children with congenital heart disease (CHD) has not yet been examined. The present study examined HRV indices from 24 h Holter recordings in 258 children with an operated or non-operated CHD, to determine their differences as an indicator of the severity of heart disease. The latter was defined clinically as New York Heart Association (NYHA) functional classes I to IV and haemodynamically by invasive parameters. Five time-domain measures (SDNN, SDNNi, SDANNi, rMSSD and pNN50) and three frequency-domain measures (LF, HF and balance LF/HF) were compared with normal ranges. HRV was reduced in children with CHD, except in patients of NYHA class I. The level of reduction depended on the NYHA functional class. None of the measures was significantly related to haemodynamic data. Heart rate variability is reduced in children with Congenital heart disease depending on the functional limitation but not on haemodynamic disturbances. Heart rate variability indices are sensitive markers of the clinical state.


Digital subtraction angiography in the evaluation of neoplasms.
Intravenous and intraarterial DSA studies were performed in patients being evaluated for possible neoplastic disease. DSA studies were obtained of the head, neck, chest, abdomen and extremities to evaluate the potential use of this technique in the cancer patient's workup. The results of this study suggest that many cancer patients can have the extent of tumor involvement defined using intravenous digital subtraction angiography. However, due to the number of false negative examinations, this study should not be relied upon as the only screening procedure. The current best application of DSA appears to be its use in conjunction with intraarterial injections as a faster and more economical alternative to angiography and in following up these neoplasms with intravenous DSA after appropriate therapy to evaluate possible recurrence or metastatic spread. Hybrid subtraction techniques and/or the development of new contrast media may greatly facilitate the use of intravenous DSA in conjunction with cancer diagnosis.


Theatre without theatres: Investigating access barriers to mediatized theatre and digital liveness during the covid-19 pandemic.
In each stage of the Covid-19 pandemic, we have witnessed initiatives that, through digital technologies, have attempted to ensure the presence of theatre and to nurture the relationship with audiences. Our research asks which entry barriers to the artistic field have been strengthened or weakened by implementing theatre initiatives for online audiences and how these initiatives have affected the regional performing arts scene. The study consists of three parts. In the first part, analysis of Italian calls for digital performance projects was carried out to investigate the institutional construction of beneficiaries and imagined audiences. In the second part, we analysed the case of the digital-theatre season MPA - Marche Palcoscenico Aperto. The MPA project provided funding for artists from the Marche region in Italy to realize online performances between February and May 2021. Eleven focus groups were conducted with 41 of the 60 participating companies. In the third phase, four in-depth interviews were conducted with the project's organisers. Findings show how the increased dependence of theatre artists on the artistic system imposed by Covid has simultaneously produced an increase in the collective awareness of the artistic class, but also a stronger distinction between professionalism and amateurism.


Comparison of an automated chemiluminescent assay to a manual ELISA assay for determination of von Willebrand Factor collagen binding activity on VWD plasma patients previously diagnosed through molecular analysis of VWF.
The correct diagnosis and classification of VWD (von Willebrand disease) is crucial and must be optimized by including the collagen binding assay (VWF:CB). VWF:CB remains an under-recognized tool, not fully automated. The objective of this study was to evaluate and to compare the previously evaluated automated chemiluminescent assay (HemosIL AcuStar VWF:CB) to the ELISA ASSERACHROM® assay used routinely in our laboratory in patients with molecular diagnosis of VWD. A plasma sample from 49 patients previously diagnosed with VWD (type 1; type 2A, type 2M, type 2B) through phenotype and VWF (von Willebrand factor) analysis and 15 healthy controls was analysed. The VWF ristocetin cofactor activity (VWF:Rco) and VWF antigen (VWF:Ag) were performed simultaneously on the VWD plasma samples, and VWF:CB/VWF:Ag ratios were calculated. The AcuStar VWF:CB assay was quickly performed with Pearson's correlation coefficient (r²) of .9571 between assays and a bias of +5.1U/dL (AcuStar > ELISA). Discrepancies of VWF:CB/VWF:Ag ratio were observed in type 2M-2A-like VWD (ratio <0.6 with AcuStar assay in 4/5 samples). The AcuStar VWF:CB assay has demonstrated good performance to detect VWF mutational changes with capacity to discriminate quickly principal types of VWD.


Breast milk iron--a declining concentration during the course of lactation.
The present investigation is the first longitudinal study of the concentration of iron in breast milk and is based on 229 milk samples obtained from 27 mothers during their period of lactation up to 9 months. The samples were collected at the beginning and at the end of each feed during a 24-h period to reflect as accurately as possible the actual concentration of iron. The median value declined during the course of lactation from 0.6 to 0.3 mg/l with a large range of values. The results indicate that the concentration is lower than is generally stated or is unusually low in Finnish mothers. As a consequence some infants may require iron supplementation during prolonged breast feeding although in general, the high bioavailability of breast milk iron prevents the development of iron deficiency.


Heterogeneity of chicken photoreceptors as defined by hybridoma supernatants. An immunocytochemical study.
Immune cells producing antibodies to chicken photoreceptor membranes were fused with myeloma cells and supernatants of the resulting hybridoma cells were used to test various types of photoreceptor cells in the chicken retina by means of immunocytochemistry. A polyclonal antibody raised against the protein component of bovine rhodopsin was also used. Outer segments of various photoreceptor cells were labelled by the following antibodies: rods were positive with the anti-rhodopsin antibody, both members of the double cones were stained by supernatant A1, while one type of single cones (designated as type A) was specifically labelled by supernatants A5, B3 and D6. The other type of single cones (type B) reacted with anti-rhodopsin and supernatant A1. The results indicate that there are distinct differences in the molecular structure of various photoreceptor outer segments.


Challenges associated with prolonged survival of patients with thalassemia: transitioning from childhood to adulthood.
Thalassemia is a chronic condition that presents a range of clinical and psychosocial challenges. Although recent advances in the treatment of thalassemia can prolong patient life spans, problems may arise when patients are transferred from pediatric health care settings to adult health care settings. These issues and our recommendations for handling them are discussed.


The hairless mouse in skin research.
The hairless (Hr) gene encodes a transcriptional co-repressor highly expressed in the mammalian skin. In the mouse, several null and hypomorphic Hr alleles have been identified resulting in hairlessness in homozygous animals, characterized by alopecia developing after a single cycle of relatively normal hair growth. Mutations in the human ortholog have also been associated with congenital alopecia. Although a variety of hairless strains have been developed, outbred SKH1 mice are the most widely used in dermatologic research. These unpigmented and immunocompetent mice allow for ready manipulation of the skin, application of topical agents, and exposure to UVR, as well as easy visualization of the cutaneous response. Wound healing, acute photobiologic responses, and skin carcinogenesis have been extensively studied in SKH1 mice and are well characterized. In addition, tumors induced in these mice resemble, both at the morphologic and molecular levels, UVR-induced skin malignancies in man. Two limitations of the SKH1 mouse in dermatologic research are the relatively uncharacterized genetic background and its outbred status, which precludes inter-individual transplantation studies.


Simultaneous determination of limonin, dictamnine, obacunone and fraxinellone in rat plasma by a validated UHPLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cortex Dictamni extract.
A rapid and selective ultra high performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of four major ingredients in Cortex Dictamni extract, including limonin, dictamnine, obacunone and fraxinellone in rats plasma. Nimodipine was used as the internal standard. Following extraction by methyl tert-butyl ether, the analytes were separated on a Thermo Syncronis C18 column by a gradient elution within a runtime of 9min. The mobile phase consisted of A (methanol) and B (2mmol/L ammonium acetate in water). The detection was accomplished by using positive ion electrospray ionization in multiple reaction monitoring mode. The method was linear for all analytes over investigated range with all correlation coefficients greater than 0.998. The lower limits of quantification were 9.18ng/mL for limonin, 12.0ng/mL for dictamnine, 16.05ng/mL for obacunone and 4.59ng/mL for fraxinellone. The intra- and inter-day precision (RSD%) was within 10% and the accuracy (RE%) ranged from -12.9% to 9.7%. This rapid and sensitive method was fully validated and successfully applied to the pharmacokinetic study of limonin, dictamnine, obacunone and fraxinellone in the rat plasma after oral administration of Cortex Dictamni extract.


Leucine and its transporter provide protection against cigarette smoke-induced cell death: A potential therapy for emphysema.
Cigarette smoke (CS) is a major risk factor for emphysematous changes in the lungs and the underlying mechanism involves CS-induced cell death. In the present study we investigated the ability of nutrients to rescue CS-induced cell death. We observed that pre-treatment with excess leucine can partially rescue CS extract-induced cell death in Saccharomyces cerevisiae and alveolar epithelial A549 cells. Excess dietary leucine was also effective in alleviating effects of CS in guinea pig lungs. Further investigation to understand the underlying mechanism showed that CS exposure causes downregulation of leucine transporter that results in inactivation of mTOR, which is a positive regulator of protein synthesis and cell proliferation. Notably, leucine supplemented diet ameliorated even existing CS-induced emphysematous changes in guinea pig lung, a condition hitherto thought to be irreversible. Thus the current study documents a new mechanism by which CS affects cellular physiology wherein leucine transporter is a key target.


New genes encoding subunits of a cytochrome bc1-analogous complex in the respiratory chain of the hyperthermoacidophilic crenarchaeon Sulfolobus acidocaldarius.
The soxL gene from Sulfolobus acidocaldarius (DSM 639) encodes a Rieske iron-sulfur protein. In this study we report the identification of two open reading frames in its downstream region. The first one, named soxN, codes for a membrane protein bearing a resemblance to the b-type cytochromes of the cytochrome bc1 and b6f complexes. The protein is predicted to contain at least 10 transmembrane helices and features the two conserved histidine pairs coordinating the heme groups of these cytochromes. The second open reading frame, named odsN, encodes a soluble protein of unknown function. The genomic region displays a complex transcription pattern. Northern blot and RT-PCR analyses revealed the presence of mono- and bi-cistronic transcripts as well as a tri-cistronic transcript of soxL and cbsAB, encoding the mono-heme cytochrome b558/566. Phylogenetic analyses of the genes of the soxLN pair and of other archaeal gene pairs encoding Rieske iron-sulfur proteins and b-type cytochromes revealed an identical branching patterns for both protein families, suggesting an evolutionary link of these genes provided by the functional interaction of the proteins. On the basis of the findings of this study and the previously studied properties of the soxL and cbsA proteins, we propose the occurrence of a novel cytochrome bc1-analogous complex in the membranes of Sulfolobus, consisting of the cytochrome b homolog soxN, the Rieske protein soxL, the high potential cytochrome cbsA, as well as the non-redox-active subunits cbsB and odsN.


Neurally mediated cardiovascular responses to stimulation of cell bodies in the hypothalamus of the rat.
To study the cardiovascular responses to selective activation of neuronal cell bodies in the hypothalamus, DL-homocysteate (5-50 nl of a 0.15-M solution, pH 7.4) was injected into 417 histologically verified sites in the hypothalamus of 46 urethan-anesthetized, paralyzed and artificially ventilated rats. Injections resulted in depressor responses (-5 to -32 mm Hg) in 271 sites, in pressor responses (5-47 mm Hg) in 77 sites and 69 sites were not responsive. Depressor effects had a shorter latency (85% started within 5 s) than pressor effects (42% started within 5 s). Control injections of 0.15 M NaCl into 126 of the responsive sites were ineffective. Arterial pressure (AP) responses showed a positive correlation (r = 0.61, P less than 0.001) with changes in heart rate (HR). Analysis of the anatomical distribution of responsive sites showed that in all hypothalamic subdivisions depressor responses predominated except in the paraventricular nucleus, where mainly pressor effects and tachycardia were elicited. These results demonstrate that excitation of cell bodies in most hypothalamic regions elicits neurally mediated changes in AP and HR and that the traditional functional division of the hypothalamus into a rostral depressor and a caudal pressor area is probably based on the combined excitation of fibers of passage and cell bodies.


A multiuser system for whole body plethysmographic measurements and interpretation.
A multiuser system for whole body plethysmographic measurements and interpretation which has been developed under clinical conditions is described. The following measurements can be carried out in a rapid way and in one session with the patient: specific airway resistance during spontaneous breathing, determination of functional residual capacity, static lung volumes, and maximal forced expiratory data. Each section is normally measured twice and can be repeated up to ten times. The final results are displayed and printed together with a consistent system of normal reference values. All values and selected original curves are stored automatically in an integrated data base system. Obstructive patients are measured again after the inhalation of a bronchodilator. All results are evaluated by an automatic interpretation program. This analyzes and graduates airway obstruction, lung volumes, and pharmacological airway reversibility using standardized texts which are written below all numerical printouts and graphical plots. The interpretation algorithm is tree structured and uses the normal reference values as a knowledge base. The system supports up to four online laboratories with their own A/D converter and up to 20 video terminals, printers, plotters, and modems. Our laboratory performs 8,297 such complete measurements on 4,671 different patients per year with one body box.


The Vertebral Fracture Cascade: Etiology and Clinical Implications.
A vertebral fracture is a marker of bone fragility and is associated with a downward spiral of recurrent fractures known as the vertebral fracture cascade. Etiology of this unfortunate cascade includes bone and muscle loss from immobility, changes in spinal mechanics causing increased loading on adjacent vertebrae, and the development of an increased thoracic kyphosis (hyperkyphosis [HK]). Degenerative disc disease, common in osteoporotic patients, can also cause HK. HK of any etiology has been associated with decreased thoracic extensor muscle strength, unstable gait, increased body sway, decreased physical and pulmonary functions, chronic pain, and increased spinal loads contributing to the vertebral fracture cascade. Preventing this downward spiral requires a multidisciplinary approach that includes early identification, consideration of pharmacologic treatment, early mobilization of the fracture patient, appropriate exercise, and back protection. Exercise should include weight-bearing and muscle-strengthening activities, but caution is needed to avoid undue stress on the back. Physical therapy can be particularly helpful by teaching the patient how to safely perform daily activities and can assist the patient in establishing a safe exercise program that avoids flexion but promotes back extension and weight-bearing activities. Hopefully, these measures will decrease pain, prevent falls, improve posture, prevent additional bone and muscle loss, and potentially abort the devastating downward spiral of the vertebral fracture cascade.


Occupational risk factors for brain tumors: results from a population-based case-control study in Germany.
In a population-based case-control study in the Rhein-Neckar-Odenwald area (containing 1.3 million inhabitants) of the Federal Republic of Germany (FRG), risk factors were assessed for brain tumor development in 226 cases with primary brain tumors (ICD-9 191, 192.1, 192.0) and 418 population controls, interviewed by a standardized questionnaire. The analysis of occupational risk factors and smoking is presented. No elevated risk was found for smoking. Similarly, no significant effects were found for most occupations. Five specific occupational groups were examined because of a priori determination that they were of interest. Some categories showed slightly elevated risks but in none was the elevation statistically significant. A significant increase in risk for brain tumor development was found associated with working in electrical occupations for women (relative risk [RR] = 5.2; 95 percent confidence interval [CI] 1.4-20.1) but not for men (RR = 0.9, 95 percent CI 0.3-2.3).


A Novel Colorimetric and Fluorometric Dual-Channel Chemosensor based on A Conjugated Perylene-Benzothiazole System for Highly Selective Detection of Cyanide in Aqueous Media.
A novel cyanine compound based on the conjugated perylene-benzothiazole system (PBI) as a colorimetric and fluorometric dual-channel sensor for cyanide (CN- ) detection was synthesized and characterized via UV-vis and fluorescence spectroscopy. PBI exhibited a high sensitivity and rapid optical response for CN- due to the intramolecular charge transfer (ICT) mechanism. The detection limit of PBI for CN- was 1.15×10-7 M in the mixture of DMSO/H2 O (1 : 1, v/v). Moreover, probe PBI demonstrated high selectivity and sensitivity for CN- over other common anions, including Cl- , Br- , F- , I- , AcO- , ClO4 - , HSO4 - , SO4 2- , NO2 - , NO3 - and SCN- . This work provided a simple and effective approach to trace the toxic CN- ion with rapid response, high selectivity, and sensitivity that is possibly applied in environmental control and agricultural management.


Molecular evidence for a clonal relationship between lymphomatoid papulosis and Ki-1 positive large cell anaplastic lymphoma.
Currently, considerable controversy surrounds questions about the clonal evolution of lymphomas in patients with lymphomatoid papulosis. In order to analyze a possible clonal relationship between lesions of lymphomatoid papulosis and a Ki 1+ large cell anaplastic lymphoma in the same patient, a highly specific molecular probe for the malignant lymphoid clone of the large cell anaplastic lymphoma was developed. As a clone specific molecular marker, highly variable junctional sequences of rearranged T-cell receptor-gamma genes were used. An oligonucleotide primer complementary to these sequences was synthesized and, using the polymerase chain reaction, clone specific DNA was detected in all lesions of lymphomatoid papulosis of the patient. These results provide evidence for a clonal relationship between lesions of lymphomatoid papulosis and large cell anaplastic lymphoma developing in the same patient.


Altered small bowel motility in irritable bowel syndrome is correlated with symptoms.
The pathogenesis of irritable bowel syndrome (IBS) has been related more to dysmotility of the colon than to abnormalities of the small intestine. To look for small bowel abnormalities, we recorded ultraluminal pressures in 16 patients with IBS. All patients complained of abdominal pain, and diarrhea (n = 8) or constipation (n = 8) were also prominent symptoms. Comparable studies were performed on 16 age-matched controls. The observations include diurnal and nocturnal fasting recordings and the response to a fatty meal. Periodicities of the interdigestive migrating myoelectric complexes were shorter in IBS (p less than 0.05); this was due to much shorter diurnal cycles in patients with diarrhea (77 +/- 10 min) than those with constipation (118 +/- 15 min) or controls (113 +/- 10 min, both p less than 0.05). All groups exhibited circadian changes, with nocturnal cycles being more frequent. Two specific patterns of small bowel motor activity were more common in IBS--ileal propulsive waves and clusters of jejunal pressure activity (both p less than 0.05 compared to controls). Moreover, cramping abdominal pain was usually noted in IBS when ileal motility was propulsive; jejunal bursts were also sometimes associated with abdominal symptoms. We conclude that motility of the small intestine is modified in some patients with IBS and that certain motor patterns are related to their symptoms.


A rapid and efficient method for testing immunohistochemical reactivity of monoclonal antibodies against multiple tissue samples simultaneously.
A flexible, efficient and rapid method was developed whereby a small volume of monoclonal antibody could be used to immunohistochemically stain many different tissues, simultaneously, on one standard glass slide. This method is based on the preparation of 'cores' of paraffin-embedded tissue from standard histology blocks. The paraffin cores are straightened, inserted into a casing cut from an ordinary drinking straw, mounted in a paraffin block and sectioned. Over 120 individual tissue samples can be organized on a slide and stained for screening or characterization with 0.25 ml of diluted primary antibody. Advantages of this paraffin core method include: great economies in time, reagents, tissue specimens and antibodies; ease of producing multiple, regular, stable, easily handled tissue core samples; direct identification of intratissue regions of interest for inclusion; efficient use of rare tissue samples; versatility for rapid construction of multiple tissue slides containing any combination of relevant tissues from a 'library' of tissue cores; and, no need for deparaffinization and reembedding of tissues.


Graphene Oxide Nanoparticels Interaction with Jurkat Cell Line in Cell-IQ System.
In recent years, materials based on graphene oxide (GO) have been actively studied for their use in biomedicine. The aim of our study was to investigate the increase in cell mass and viability of Jurkat tumor line T cells during 24 h of contact with GO nanoparticles in the Cell-IQ system of intravital observation. We used nanoparticles of different sizes coated with linear or branched polyethylene glycol (PEG) at concentrations of 5 and 25 μg/mL. It was shown for the first time that direct contact with GO nanoparticles reduced the growth in cell mass at the visualization points by more than twofold, regardless of nanoparticle size and concentration. Moreover, the number of live cells in the culture decreased by 5-9% after 24 h of monitoring. Thus, PEG-coated GO nanoparticles were found to suppress the proliferation and viability of Jurkat cell line T lymphocytes.


Model Species to Investigate the Origin of Flowers.
The angiosperms, or flowering plants, arose at least 135 million years ago (Ma) and rapidly diversified to form over 300,000 species alive today. This group appears, however, to have separated from its closest living relatives, the extant gymnosperms, much earlier: over 300 Ma. Representatives of basally-diverging angiosperm lineages are of key importance to studies aimed at reconstructing the most recent common ancestor of living angiosperms, including its morphological, anatomical, eco-physiological and molecular aspects. Furthermore, evo-devo comparisons of angiosperms with living gymnosperms may help to determine how the many novel aspects of angiosperms, including those of the flower, first came about. This chapter reviews literature on the origin of angiosperms and focusses on basally-diverging angiosperms and gymnosperms that show advantages as potential experimental models, reviewing information and protocols for the use of these species in an evo-devo context. The final section suggests a means by which data from living and fossil groups could be integrated to better elucidate evolutionary events that took place on the long stem-lineage that apparently preceded the radiation of living angiosperms.


Evaluation of intensive rehabilitation under continuous suprascapular nerve blockade for the treatment of refractory adhesive shoulder capsulitis. Case series.
Treatment of refractory adhesive shoulder capsulitis is a challenge. This observational retrospective study evaluated the long-term effectiveness of intensive physiotherapy protocol under a continuous peripheral blockade of the suprascapular nerve (cSSNB). We reviewed 29 medical records of patients suffering from adhesive capsulitis and treated with intensive physiotherapy under cSSNB during 10 days. The "disabilities of the arm, shoulder and hand" outcome questionnaire (DASH score) and shoulder movements were recorded at the beginning, 10 days after local anesthetic infusion and three months after. Twenty six patients significant improved shoulder movements after 10 days of treatment. Sixteen patients were followed completely until 3 months after rehabilitation program. Range of four shoulder motion compatible with a normal daily life was acquired in nine patients at three months. There is no significant difference in shoulder motion between the end of LA infusion and at three months. At the end of infusion, DASH score is significantly decreased to 59.3 (n = 26), and persists three months 42.1 (n = 16). At three months, 33% of the initial population objectively reach the 4 goals, compatible with a correct quality of life. Rehabilitation under cSSNB is associated with a significant long term improvement in shoulder motion and quality of life in patients with adhesive capsulitis. Randomized controlled trials will be necessary to demonstrate our encouraging results.


Bone marrow transplantation for Fanconi anemia.
Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.


Experimental study of dermal grafts for reconstruction of oral mucosa.
Mucosal defects in the oral cavities of 35 dogs were repaired with reversed dermal grafts, full-thickness skin grafts, and dermal grafts. Comparative observations were made for up to two years to analyze the healing processes. The reversed dermal grafts were covered by surrounding mucosal epithelium and formed normal mucosal tissue that maintained its characteristics for two years. Histologic and scanning electron microscopic examination revealed that the epithelial appendages underwent degeneration, presumably through being embedded by the grafting of the dermis inside out. Epithelialization of the dermal grafts occurred from both surrounding mucosal epithelium and ancillary skin appendages. The full-thickness skin grafts maintained their original structure and function over the two-year observation period. It appears from this investigation that the reversed dermal graft method has definite advantages over full-thickness skin grafting and dermal grafting.


Thermo-mechanical properties of the composite made of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) and acetylated chitin nanocrystals.
Acetylated chitin nanocrystals were prepared through surface modification, and biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/chitin nanocrystals films were produced via solution-casting method. Transmission electron microscopy observations and X-ray diffraction profiles revealed that the rod-like morphology and crystal structure of chitin nanocrystals were maintained. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy results showed that the hydroxyl groups were partly replaced by the acetyl groups on the surface of chitin nanocrystals. The hydrophobic performance of the acetylated chitin nanocrystals was significantly increased according to the contact angle measurements. Differential scanning calorimeter results indicated that the influence of chitin nanocrystals on the crystallization behaviors of PHBV matrix was changed from suppression to assistance after the surface modification. Tensile test showed that the tensile strength and Young's modulus of PHBV/acetylated chitin nanocrystals composites were improved by 44% and 67%, comparing to the improvement of 24% and 43% for PHBV/chitin nanocrystals composites with the addition of 5.0 wt.% nanocrystals into PHBV.


Efficient and selective capture of uranium by polyethyleneimine-modified chitosan composite microspheres from radioactive nuclear waste.
Uranium extraction from radioactive nuclear waste is vital for sustainable energy supply and ecological security. Herein, a polyethyleneimine-chitosan composite microspheres n-PEI/ECH-CTS (n = 0.1, 0.2, 0.3, 0.4, 0.5) were synthetized for efficient and selective uranium adsorption. The prepared chitosan microspheres with uniform size, uniform dispersion and good mechanical strength combine cost-effectiveness and environmental benefits. The 0.4-PEI/ECH-CTS exhibits the highest adsorption capacity of 380.65 mg g-1 within only 4 h due to high nitrogen content of 6.57 mol kg-1. The DFT calculations confirms that the optimal coordination mode of UO22+ and 0.4-PEI/ECH-CTS is one UO22+ chelated with two -NH2 from two adsorption units, respectively. Adsorption efficiency of U(VI) from simulated nuclear wastewater achieves to 100%, and the Kd value is up to 1.1 × 104 mL g-1, which is 1.7 × 104-6.1 × 104 times that of coexisting ions. The CU(VI) reduces in simulated wastewater from 10.98 mg L-1 to 1 μg L-1, which is well below the US Environmental Protection Agency uranium limits for drinking water (30 μg L-1). Besides, 0.4-PEI/ECH-CTS still maintains above 95% adsorption efficiency after seven cycles. In short, the 0.4-PEI/ECH-CTS microspheres integrate high performance, practicality and cost-effectiveness, which has great advantages in practical industrial applications.


Analysis of Long-Term 4-Dimensional Computed Tomography Regional Ventilation After Radiation Therapy.
To determine whether regional ventilation, as measured using 4-dimensional computed tomography (4D-CT), declines after radiation therapy (RT). We analyzed pretreatment 4D-CT scans associated with 2 RT courses. We quantified regional pulmonary function over equivalent dose in 2 Gy (EQD2α/β=3) intervals of 0 to 5 Gy, 5 to 20 Gy, 20 to 40 Gy, and >40 Gy using percentile-normalized intensity-based (VentInt) and Jacobian-based (VentJac) ventilation metrics. We modeled the impact of dose on mean ventilation (Vent¯) and regional tidal volume (rTV: tidal volume [TV] within a dose interval normalized to total lung TV). We also identified clinical and dosimetric factors that affected regional ventilation changes (ΔVent¯ and ΔrTV) after RT for the >20 Gy dose interval. After RT, Vent¯Int exhibited statistically significant dose-dependent declines within the 20 to 40 Gy (-5.0%; P=.03) and >40 Gy (-6.8%; P<.01) intervals. Vent¯Jac exhibited a declining trend after RT only for the >40 Gy interval (-4.6%; P=.07). Factors associated with ΔVent¯Int for the >20 Gy dose interval included airway stenosis progression (P=.03) and gross tumor volume (P=.09). Both rTVInt and rTVJac were associated with small (<2%) but significant declines after RT for 20 to 40 Gy and >40 Gy intervals. Factors associated with declining rTVInt (P<.05) for the >20 Gy dose interval included airway stenosis progression, greater V20 (volume of lung receiving >20 Gy), and smaller fraction of emphysema in V20. The association between the absence of chronic obstructive pulmonary disease and declining rTV trended toward significance (P=.09). Regional ventilation, as measured using 4D-CT, demonstrates a dose-dependent decline after RT. Our results support the use of 4D-CT ventilation imaging for monitoring regional pulmonary function change after RT.


Lipoperoxidation in human and rat brain tissue: developmental and regional studies.
Lipoperoxidation in human and rat brain was studied on the basis of formation in vitro of thiobarbituric acid positive (TBA) materials. In rats aged 1--540 days, the endogenous pools of reactive material were unchanged but on subsequent incubation of their homogenates the level of TBA-positive materials fell by 3 fold (fresh weight basis) and 5.4 fold (protein basis). In human brain, there was a distinct regional distribution of reactive materials in the endogenous pools with highest levels in the cerebellar vermis, and lower levels in thalamus, cortical regions, substantia nigra, caudate nucleus, pallidum, putamen, and hypothalamus. Only trace levels were detected in the pineal gland. On incubation all values rose 13--25 fold within 3 h at 37 degrees C except for cerebellar vermis which was increased 6 fold, and pineal gland 9 fold. Four TBA-positive materials were separated from rat brain by TLC, three of which were identical to malonyldialdehyde and its polymers. Lipoperoxidation in rat homogenates was inhibited 75--90% by sera from several different sources. The inhibitory properties were unaffected by dialysis and were not reproduced by addition of a large number of low and high mol. wt. components including vitamin E when added in concentrations equal to or exceeding that of native serum.


GraphFind: enhancing graph searching by low support data mining techniques.
Biomedical and chemical databases are large and rapidly growing in size. Graphs naturally model such kinds of data. To fully exploit the wealth of information in these graph databases, a key role is played by systems that search for all exact or approximate occurrences of a query graph. To deal efficiently with graph searching, advanced methods for indexing, representation and matching of graphs have been proposed. This paper presents GraphFind. The system implements efficient graph searching algorithms together with advanced filtering techniques that allow approximate search. It allows users to select candidate subgraphs rather than entire graphs. It implements an effective data storage based also on low-support data mining. GraphFind is compared with Frowns, GraphGrep and gIndex. Experiments show that GraphFind outperforms the compared systems on a very large collection of small graphs. The proposed low-support mining technique which applies to any searching system also allows a significant index space reduction.


Laparoscopic Nissen fundoplication: report of first 15 cases.
Performance of a Nissen fundoplication laparoscopically for gastroesophageal reflux disease offers significant advantages such as reduction in hospital stay, postoperative recovery time, and return to work time. Early experience with laparoscopic Nissen fundoplication is presented.


Replica plating of colonies from Listeria-selective agars to blood agar to improve the isolation of Listeria monocytogenes from foods.
Bacterial colonies from Listeria-selective agars were replica plated to sheep blood agar to screen for beta-hemolysis. By using the replica plating method to test for the beta-hemolytic characteristic of all the colonies growing on Listeria-selective agars instead of picking 3 to 10 suspected colonies for further testing, we recovered Listeria monocytogenes from 59 of 142 Listeria-selective agar plates which contained colonies of hemolytic and nonhemolytic Listeria species and were negative when tested by conventional colony picks.


American Diet Quality: Where It Is, Where It Is Heading, and What It Could Be.
Diet quality is critically important to the prevention of many types of chronic disease. The federal government provides recommendations for optimal diet quality through the Dietary Guidelines for Americans, and sets benchmarks for progress toward these recommendations through the Healthy People objectives. This analysis estimated recent trends in American diet quality and compared those trends to the quality of diets that would meet the Healthy People 2020 objectives and the 2010 Dietary Guidelines for Americans in order to measure progress toward our national nutrition goals. This analysis used 24-hour recall data from the cross-sectional National Health and Nutrition Examination Survey, between the years of 1999-2000 and 2011-2012, to determine mean intakes of various dietary components for the US population over time. Mean intakes were estimated using the population ratio method, and diet quality was assessed using the Healthy Eating Index 2010 (HEI-2010). The mean HEI-2010 total score for the US population has increased from 49 in 1999-2000 to 59 in 2011-2012; continuing on that trajectory, it would reach a score of 65 by 2019-2020. A diet that meets the Healthy People 2020 objectives would receive a score of 74 and, by definition, a diet that meets the 2010 Dietary Guidelines for Americans would receive a score of 100. Trends in HEI-2010 component scores vary; all HEI-2010 component scores except sodium have increased over time. Diet quality is improving over time, but not quickly enough to meet all of the Healthy People 2020 objectives. Whole fruit and empty calories are the only HEI-2010 components on track to meet their respective Healthy People 2020 targets. Furthermore, the country falls short of the 2010 Dietary Guidelines for Americans by a large margin in nearly every component of diet quality assessed by the HEI-2010.


HuC:Kaede, a useful tool to label neural morphologies in networks in vivo.
A simple and efficient procedure for labeling neurons is a prerequisite for investigating the development of neural networks in zebrafish. To label neurons we used Kaede, a fluorescent protein with a photoconversion property allowing conversion from green to red fluorescence following irradiation with UV or violet light. We established a zebrafish stable transgenic line, Tg(HuC:Kaede), expressing Kaede in neurons under the control of the HuC promoter. This transgenic line was used to label a small number of neurons in the trigeminal ganglion. Also, using embryos injected with the transgene, we labeled peripheral axon arbors of a Rohon-Beard neuron at 4 days postfertilization and observed the dendrite development of a tectal neuron for 3 days. These data indicate that Kaede is a useful tool to selectively label neural networks in zebrafish.


The risk of nerve injury during anatomical and reverse total shoulder arthroplasty: an intraoperative neuromonitoring study.
This study compared the incidence and pattern of potential nerve injuries between reverse shoulder (RSA) and total shoulder arthroplasty (TSA) using intraoperative neuromonitoring. Our hypothesis was that RSA has a greater risk of nerve injury than TSA due to arm lengthening. We reviewed 36 consecutive patients who underwent RSA (n = 12) or TSA (n = 24) with intraoperative neuromonitoring. The number of nerve alerts was recorded for each stage of surgery. Neurologic function was assessed preoperatively and postoperatively at routine follow-up visits. Predictive factors for increased intraoperative nerve alerts and clinically detectable neurologic deficits were determined. There were nearly 5 times as many postreduction nerve alerts per patient in the RSA cohort compared with the TSA cohort (2.17 vs. 0.46). There were 17 unresolved nerve alerts postoperatively, with only 2 clinically detectable nerve injuries, which fully resolved by 6 months postoperatively. A preoperative decrease in active forward flexion and the diagnosis of rotator cuff arthropathy were independent predictors of intraoperative nerve alerts. RSA has a higher incidence of intraoperative nerve alerts than TSA during the postreduction stage due to arm lengthening. Decreased preoperative active forward flexion and the diagnosis of rotator cuff arthropathy are predictors of more nerve alerts. The clinical utility of routine intraoperative nerve monitoring remains in question given the high level of nerve alerts and lack of persistent postoperative neurologic deficits.


CaO nanocrystals grown over SiO2 microtubes for efficient CO2 capture: organogel sets the platform.
Materials that can capture and store CO2 are important. Though CaO is a cheap sorbent, it is inefficient for practical purposes due to sintering and poor diffusion of CO2 through the surface-CaCO3 layer. We have developed a high performance, sintering-resistant CaO-based sorbent by uniformly nanofabricating the CaO nanocrystals on SiO2 microtubes made by organogel templated polymerization.


Adenylate cyclase activity in cyanobacteria: activation by Ca(2+)-calmodulin and a calmodulin-like activity.
An adenylate cyclase activity was partially characterized in the cyanobacterium Anabaena sp. The enzyme activity is found in soluble cell fractions and shows an apparent molecular weight of about 183,400. This adenylate cyclase is activated by Ca2+ and bovine brain or spinach calmodulin and it is inhibited by EGTA and some phenothiazine derivatives. Furthermore, Anabaena sp. extracts contain a calmodulin-like activity which stimulates bovine brain cyclic AMP phosphodiesterase and the Anabaena adenylate cyclase. EGTA and phenothiazine derivatives block the cyanobacterial modulator effect.


Anti-inflammatory and immunoregulatory effects of Yupingfeng powder on chronic bronchitis rats.
To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng (, YPF) Powder and its components in rats. A rat chronic bronchitis (CB) model was developed using lipopolysaccharide (LPS) combined with bacillus Calmette Guerin (BCG). YPF, simple recipe Astragalus membranaceus (Fisch.) Bge (AM) and Astragalus membranaceus (Fisch.) Bge plus rhizome of Atractylodes macrocephala Koidz (AM+RA) decoction were administered (intragastric administration, once a day for 21 days) to rats, to prevent and treat CB. Immunoregulatory and anti-inflammatory effects of YPF, AM and AM+RA were tested by serum pharmacology in vitro on splenic lymphocytes of normal rats and alveolar macrophages of CB rats. Inflammation in the pulmonary tissue and the bronchus of CB rats was significantly reduced in the YPF-treatment groups, AM and AM+RA groups demonstrating the efficacy of YPF. Serum samples collected at different times from rats after administration of YPF, AM and AM+RA demonstrated increased proliferation of splenic lymphocytes with area under the effect curve (AUE) of 552.6%, 336.3% and 452.0%, respectively. Treatment of alveolar macrophages with serum samples in YPF, AM or AM+RA group inhibited interleukin-8 (IL-8) in the cell culture media, and the effect was much better in the YPF group compared with AM or AM+RA group, with a higher maximal effect (Emax, P<0.05) and larger AUE (P <0.01 and P<0.05). Moreover, serum from rats treated with AM or AM+RA had similar efficacy, while the efficiency was lower than that treated with YPF. YPF demonstrated anti-inflammatory and immunoregulatory effects in a rat model of CB, and timedependent relationships were demonstrated in vitro.


Immunohistochemical versus biochemical estrogen-receptor and progesterone-receptor analysis: correlation with histological parameters.
Human breast carcinomas were evaluated for estrogen and progesterone receptors by immunohistochemistry using monoclonal anti-receptor antibodies (n = 267) and by cytosol steroid-binding assays (n = 212). The estrogen and progesterone receptor contents of the tumors correlated with histological features of differentiation, such as histological and nuclear grade, and with the amount of tumor necrosis and lymphoid infiltration. The correlation of immunohistochemically determined steroid receptor values with histological characteristics was somewhat better than that of biochemically assessed concentrations.


Pan-Cancer Landscape Analysis Reveals Recurrent KMT2A-MAML2 Gene Fusion in Aggressive Histologic Subtypes of Thymoma.
Thymomas are epithelial neoplasms that represent the most common thymic tumors in adults. These tumors have been shown to harbor a relatively low mutational burden. As a result, there is a lack of genetic alterations that may be used prognostically or targeted therapeutically for this disease. Here, we describe a recurrent gene rearrangement in type B2 + B3 thymomas. A single index case of thymoma was evaluated by an RNA-based solid fusion assay. Separately, tissues from 255,008 unique advanced cancers, including 242 thymomas, were sequenced by hybrid capture-based next-generation DNA sequencing/comprehensive genomic profiling of 186 to 406 genes, including lysine methyltransferase 2A (KMT2A) rearrangements, and a portion were evaluated for RNA of 265 genes. We characterized molecular and clinicopathologic features of the pertinent fusion-positive patient cases. We identified 11 patients with thymomas harboring a gene fusion of KMT2A and mastermind-like transcriptional coactivator 2 (MAML2). Fusion breakpoints were identified between exon 8, 9, 10, or 11 of KMT2A and exon 2 of MAML2. Fifty-five percent were men, with a median age of 48 years at surgery (range, 29-69 years). Concurrent genomic alterations were infrequent. The 11 thymomas were of B2 or B3 type histology, with 1 case showing foci of thymic carcinoma. The frequency of KMT2A-MAML2 fusion was 4% of all thymomas (10 of 242) and 6% of thymomas of B2 or B3 histology (10 of 169). KMT2A-MAML2 represents the first recurrent fusion described in type B thymoma. The fusion seems to be specific to type B2 and B3 thymomas, the most aggressive histologic subtypes. The identification of this fusion offers insights into the biology of thymoma and may have clinical relevance for patients with disease refractory to conventional therapeutic modalities.


Tumor promoting phorbol diesters stimulate release of radioactivity from [3H]-arachidonic acid labeled- but not [14C]linoleic acid labeled-cells. Indomethacin inhibits the stimulated release from [3H] arachidonate labeled cells.
The tumor promoting phorbol diester, 12-O-tetradecanoyl-phorbol-13-acetate, stimulates MDCK cells to deacylate cellular phospholipids and to produce prostaglandins when measured as the release of arachidonic acid and its metabolites into the culture fluid. Indomethacin, at levels of 2.8 x 10(-8) to 2.8 x 10(-6) M, inhibits the release of radioactivity from [3H]arachidonate labeled cells stimulated by 12-O-tetradecanoyl-phorbol-13-acetate treatment in a concentration dependent manner. At these concentrations, the conversion of released [3H]arachidonic acid into prostaglandins E2 and F2alpha and the production of PGE2 measured serologically also is suppressed in a concentration dependent manner. Indomethacin, at these levels, has no effect on the acylation of [3H]arachidonic acid into cellular lipids. The tumor promoting phorbol diester does not stimulate the release of radioactive materials from MDCK cells labeled with [14C]linoleic acid, although prostaglandin production by these cells is stimulated.


Delayed presentation of traumatic diaphragmatic rupture with herniation of the left kidney and bowel loops.
Rupture of the diaphragm mostly occurs following major trauma. We report a case of delayed presentation of traumatic diaphragmatic hernia on the left side in a 44-year-old male who presented two weeks after a minor blunt trauma. Left kidney and intestinals coils were found to herniate through the diaphragmatic tear. This case demonstrates the importance of considering the diagnosis in all cases of blunt trauma of the trunk. It also illustrates the rare possibility of herniation of kidney through the diaphragmatic tear.


Mosquito and tick repellency of two Anthemis essential oils from Saudi Arabia.
The essential oils (EOs) of Anthemis melampodina (Am) and Anthemis scrobicularis (As) (Asteraceae) were extracted from the aerial parts of the plants by hydrodistillation, and their chemical compositions were analyzed using GC-FID and GC-MS. Fifty-six components representing 85.5% of the oil composition of Anthemis melampdina were identified, and the major components were α-pinene (17.1%) and β-eudesmol (13.8%). Forty-one components representing 86% of the oil composition of Anthemis scrobicularis were identified, and the major component was β-eudesmol (12.8%). Laboratory bioassays were conducted to determine repellency of Am and As EOs against the yellow fever mosquito Aedes aegypti L. and the lone star tick Amblyomma americanum L. The minimum effective doses (MEDs) of the Am and As EOs against mosquitoes were 0.187 ± 0.000 and 0.312 ± 0.063 mg/cm2 respectively, which were significantly higher than that of DEET (0.023 ± 0.000 mg/cm2) in human-based repellent bioassays. The As EO was more repellent than Am EO against nymphal ticks but was less effective than DEET in vertical paper bioassays.


Integration of hepatitis B virus DNA into the myeloid/lymphoid or mixed-lineage leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular carcinoma.
Integration of hepatitis B virus (HBV) DNA into host DNA is detected in about 90% of HBV-related hepatocellular carcinoma (HCC), but the preferential sites of the viral integration etiologically relevant to oncogenesis have been controversial. By using an adaptor-ligation/suppression-PCR, we identified four integrations into the myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4) gene from 10 HCC patients with positive HBV surface antigen (HBsAg). Determination of the cellular-virus DNA junction demonstrated that various lengths of the virus were integrated within 300 bp of intron 3 flanked by the Alu element of MLL4. Chimeric hepatitis B virus X gene (HBx)/MLL4 transcripts and the HBx fusion proteins were detected. DNA microarray revealed that HBx/MLL4 fusion proteins suppressed unique genes in HepG2 cells. Finally, chromosomal translocations of intron 3 of MLL4 to the specific region of chromosome 17p11.2 in 22 out of 32 HCC patients were observed, showing that the intron 3 region of MLL4 gene would be a target of translocation breakpoint. In conclusion, the present data suggest that the translocation breakpoint of MLL4 gene is one of the preferential targets for HBV DNA integration into the MLL4 gene and the HBV DNA integration may be involved in liver oncogenesis.


Electrochemical investigation of the voltammetric determination of hydrochlorothiazide using a nickel hydroxide modified nickel electrode.
The preparation and electrochemical characterization of a nickel hydroxide modified nickel electrode as well as its behavior as electrocatalyst toward the oxidation of hydrochlorothiazide (HCTZ) were investigated. The electrochemical behavior of the modified electrode and the electrooxidation of HCTZ were explored using cyclic voltammetry. The voltammetric response of the modified electrode in the detection of HCTZ is based on the electrochemical oxidation of the Ni(II)/Ni(III) and a chemical redox process. The analytical parameters for the electrooxidation of HCTZ by the nickel hydroxide modified nickel electrode were obtained in NaOH solution, in which the linear voltammetric response was in the concentration range from 1.39×10(-5) to 1.67×10(-4)mol L(-1) with a limit of detection of 7.92×10(-6)mol L(-1) and a sensitivity of 0.138 μA Lmmol(-1). Tafel analysis was used to elucidate the kinetics and mechanism of HCTZ oxidation by the modified electrode.


[The role of alternative lengthening of telomeres mechanisms in carcinogenesis and prospects for using an anti-telomerase drugs in malignant tumors treatment].
The review analyzes telomere lengthening mechanisms in cancer cells of two different tumor types--carcinomas and sarcomas. Basic attention is given to sarcomas which cells lengthen their telomeres through alternative mechanisms for lengthening telomeres (ALT). The features of ALT mechanisms functioning in these cells have been examined in detail. Moreover, the actually existing anti-telomerase drugs and their efficiency in carcinomas treatment were analyzed. The experimental data showing that, contrary to theoretical expectations, activation of ALT was not observed on a background of such anti-telomerase, are presented. This portends a good prognosis in the treatment of the patients with carcinoma. Finally, on the basis of the data analyzed the candidates for a role of targets are proposed for development of anti-ALT antineoplastic therapy. Expected efficiency and toxicity of such drugs are considered in detail.


Copper(II) complexes of tridentate pyridylmethylethylenediamines: role of ligand steric hindrance on DNA binding and cleavage.
Copper(II) complexes of three linear unsymmetrical tridentate ligands viz. N-methyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L1), N,N-dimethyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L2) and N,N-dimethyl-N'-((6-methyl)pyrid-2-ylmethyl)ethylenediamine (L3) have been isolated and characterized by elemental analysis, electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes [Cu(L2)Cl2] and [Cu(L3)Cl2] have been structurally characterized by X-ray crystallography. The [Cu(L2)Cl2] complex crystallizes in the monoclinic space group P2(1)/n with a=11.566(2) A, b=7.369(1) A, c=15.703(3) A, alpha=90 degrees , beta=109.68(8) degrees , gamma=90 degrees and Z=4 while [Cu(L3)Cl2] crystallizes in the triclinic space group P1 with a=9.191(2) A, b=12.359(3) A, c=14.880(3) A, alpha=79.61(13) degrees , beta=86.64(13) degrees , gamma=87.28(8) degrees and Z=2. The coordination geometries around copper (II) in these two complexes are best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). The distorted CuN3Cl basal plane in them is comprised of three nitrogen atoms of the meridionally coordinated ligand and a chloride ion and the axial position is occupied by the other chloride ion. The interaction of these complexes with Calf Thymus DNA (CT DNA) has been studied by using absorption, emission and circular dichroic spectral methods, thermal denaturation studies, viscometry and cyclic and differential pulse voltammetry. A strong blueshift in the ligand field band and a redshift in the ligand based bands of the copper(II) complexes on binding to DNA imply a covalent mode of DNA binding of the complexes, which involves coordination of most possibly guanine N7 nitrogen of DNA to form a CuN4 chromophore. This is supported by studying the interaction of the complexes with N-methylimidazole (N-meim), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine (cytd) by ligand field and EPR spectral methods, which indicate the formation of a CuN4 chromophore only in the case of the more basic N-meim and GMP. The DNA melting curves obtained in the presence of copper(II) complexes reveal a monophasic and irreversible melting of the DNA strands and the high positive DeltaTm values (12-21 degrees C) also support the formation of strong Cu-N bonds by the complexes with DNA, leading to intra- and/or interstrand crosslinking of DNA. Competitive ethidium bromide (EthBr) binding studies show that the L2 and L3 complexes are less efficient than the L1 complex in quenching EthBr emission, which is consistent with their forming DNA crosslinking preventing the displacement of the DNA-bound EthBr. A very slight decrease in relative viscosity of DNA is observed on treating the L1 and L2 complexes with CT DNA; however, a relatively significant decrease is observed for the L3 complex suggesting that the length of the DNA fiber is shortened. DNA cleavage experiments show that all the complexes induce the cleavage of pBR322 plasmid DNA, the complex of L1 being more efficient than those of sterically hindered L2 and L3 ligands.


Association Between Single-Nucleotide Polymorphism (SNP) in miR-146a, miR-196a2, and miR-499 and Risk of Ischemic Stroke: A Meta-Analysis.
BACKGROUND The association between 3 well known SNPs - miR-146a C/G (rs2910164), miR-196a2 T/C (rs11614913), and miR-499 A/G (rs3746444) - in pre-miRNA sequences and ischemic stroke (IS) are still conflicting and inconclusive. This meta-analysis aimed to pool previous studies get a more precise assessment of the association between these 3 SNPs and the risk of IS. MATERIAL AND METHODS Relevant studies were searched in online databases. The strength of the association between the SNPs and IS were estimated by pooling odds ratios (OR) and 95% confidence intervals (CI) using Review Manager (version 5.3). RESULTS Rs2910164 C allele was associated with lower IS risk. But this trend was only observed in Koreans under the allele model (OR=0.81, 95% CI=0.68-0.95, p=0.009), dominant model (OR=0.68, 95% CI=0.50-0.93, p=0.02), recessive model (OR=0.79, 95% CI=0.63-1.00, p=0.05), and homozygous model (OR=0.63, 95%CI=0.45-0.88, p=0.007). Rs11614913 T allele might be associated with higher IS risk under the dominant model (OR=1.45, 95% CI=1.19-1.78, p=0.0003), while rs3746444 A allele might be associated with decreased IS risk under the homozygous model (OR=0.48, 95% CI=0.23-0.98, p=0.04) only in Chinese, but not in Koreans. CONCLUSIONS Although the 3 SNPs might be associated with IS, the association varied significantly in different countries.


Escape of a leaflet from a St. Jude Medical prosthesis in the mitral position.
Twenty-three months after mitral valve replacement for mitral stenosis with a St. Jude Medical heart valve prosthesis size 31, a 29-year-old man suddenly went into a profound cardiogenic shock and pulmonary edema due to escape of one of the leaflets from the prosthesis. At emergency operation the valve was replaced with another type of prosthesis. The escaped leaflet was retrieved from the abdominal aorta and was found to be intact. The cause of the escape was found to be a fracture in the pivot area. Further examination with optic and scanning electron microscopy revealed an old fracture at the base of the pivot covered with organic material and another fracture at the top of the pivot area not covered with organic material and therefore probably very recent and responsible for the break-off of part of the area and subsequent escape of the leaflet. The cause of the primary fracture is unknown.


Developing valid test bank of surveillance case study scenarios for inter-rater reliability.
Case studies are utilized for training on National Healthcare Safety Network (NHSN) healthcare associated infection surveillance definitions. Item discrimination and item analysis were applied to case studies to identify questions that most accurately assess infection preventionists (IPs) application of surveillance definitions.


Exploring the relation between preoperative physical functioning and the impact of major complications in patients following pancreatic resection.
This study aimed to evaluate the association between preoperative level of physical functioning and time to recovery of physical functioning, postoperative complications, and the impact of postoperative major complications in patients undergoing elective pancreatic resection. Additionally, prediction models to identify high-risk patients for developing a major complication were externally validated. Perioperative data of patients who underwent pancreatic resection were analysed. Primary outcomes were time to recovery of physical functioning and postoperative major complications. Impact of a major complication was explored by evaluating its effect on time to recovery of physical functioning. Risk-prediction models were retrieved following a systematic review. Multivariable analysis (n = 63) showed that ASA grade III (OR 3.498) and preoperative platelet count (OR 1.005) were associated with major complications, whereas aerobic capacity (OR 0.347) was associated with time to recovery of physical functioning. Age, preoperative aerobic capacity, functional mobility, and perceived level of functional capacity were associated with the impact of a major complication. The AUC of two risk prediction models were 0.556 and 0.701. Preoperative parameters of physical function were associated with postoperative outcomes and may be useful in outcome prediction, although future approaches should not only register the incidence of major complications but also take the impact of a complication on a patient's physical functioning into account.


Antiviral activity of palmitic acid via autophagic flux inhibition in zebrafish (Danio rerio).
Fatty acids (FAs) are key elements that affect not only growth but also different immune functions, and therefore, nutrition is important for growing healthy fish. Zebrafish (Danio rerio) is a good model for assessing the beneficial effects of immunostimulants, including FAs, before applying them in aquaculture. Accordingly, this study evaluated the effects of palmitic acid (PA) treatment on different immune parameters of zebrafish and on the mortality caused by the spring viremia of carp virus (SVCV). The results suggest that PA modulates the infection outcome in vivo, which benefits zebrafish and results in reduced mortality and viral titres. The antiviral protection elicited by this FA seems to be associated with the inhibition of autophagy and is independent of other immune processes, such as neutrophil proliferation or type I interferon (IFN) activity. The use of PA as an immunostimulant at low concentrations showed great potential in the prevention of SVCV infections; therefore, this FA could help to prevent the mortality and morbidity caused by viral agents in aquacultured fish. Nevertheless, the potentially detrimental effects of suppressing autophagy in the organism should be taken into account.


[Evaluation of endometrial carcinoma using hysteroscopy and transvaginal echography].
To compare transvaginal ultrasound and hysteroscopy in the diagnosis of endometrial cancer in women with postmenopausal bleeding. Sixty postmenopausal women with abnormal uterin bleeding underwent to transvaginal ultrasound, hysteroscopy and endometrial biopsy. USG and hysteroscopy demonstrate respectively a sensitivity of 96% and 90%, specificity of 88% and 94%, positive predictive value of 86% and 92% and negative predictive value of 92% and 96% and accuracy of 89% and 94%. The accuracy of hysteroscopy is significantly higher than transvaginal sonography for the detection of endometrial cancer.


Minimization of chloroplast contamination in 16S rRNA gene pyrosequencing of insect herbivore bacterial communities.
Chloroplast sequence contamination in 16S ribosomal RNA gene (16S) analyses can be particularly problematic when sampling microbial communities in plants and folivorous arthropods. We previously encountered high levels of plastid contamination in herbivorous insect samples when we used the predominant 454 pyrosequencing 16S methodologies described in the literature. 799F, a primer previously found to exclude chloroplast sequences, was modified to enhance its efficacy, and we describe, in detail, our methodology throughout amplicon pyrosequencing. Thirteen versions of 799F were assessed for the exclusion of chloroplast sequences from our samples. We found that a shift in the mismatch between 799F and chloroplast 16S resulted in significant reduction of chloroplast reads. Our results also indicate that amplifying sequences from environmental samples in a two-step PCR process, with the addition of the multiplex identifiers and 454 adapters in a second round of PCR, further improved primer specificity. Primers that included 3' phosphorothioate bonds, which were designed to block primer degradation, did not amplify consistently across samples. The different forward primers do not appear to bias the bacterial communities detected. We provide a methodological framework for reducing chloroplast reads in high-throughput sequencing data sets that can be applied to a number of environmental samples and sequencing techniques.


Smoking Cessation Interventions and Abstinence Outcomes for People Living in Rural, Regional, and Remote Areas of Three High-Income Countries: A Systematic Review.
Tobacco smoking rates in high-income countries are greater in rural, regional, and remote (RRR) areas compared to cities. Yet, there is limited knowledge about interventions targeted to RRR smokers. This review describes the effectiveness of smoking cessation interventions for RRR smokers in supporting smoking abstinence. Seven academic databases were searched (inception-June 2022) for smoking cessation intervention studies to include if they reported on RRR residents of Australia, Canada, or the United States, and short- (<6 months) or long-term (≥6 months) smoking abstinence outcomes. Two researchers assessed study quality, and narratively summarized findings. Included studies (n = 26) were primarily randomized control (12) or pre-post (7) designs, from the United States (16) or Australia (8). Five systems change interventions were included. Interventions included cessation education or brief advice, and few included nicotine monotherapies, cessation counseling, motivational interviewing, or cognitive behavioral therapy. Interventions had limited short-term effects on RRR smoking abstinence, decreasing markedly beyond 6 months. Short-term abstinence was best supported by contingency, incentive, and online cessation interventions, and long-term abstinence by pharmacotherapy. Cessation interventions for RRR smokers should include pharmacotherapy and psychological cessation counseling to establish short-term abstinence, and identify effective means of maintaining abstinence beyond 6 months. Contingency designs are a suitable vehicle for psychological and pharmacotherapy support for RRR people who smoke, and intervention tailoring should be explicitly considered. Smoking disproportionately harms RRR residents, who can encounter access barriers to smoking cessation support. High-quality intervention evidence and outcome standardization are still required to support long-term RRR smoking abstinence.


Low-dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5-y prospective cohort study.
Introduction Aspirin is an effective antiplatelet drug for preventing cardiovascular events in high-risk subjects. However, for patients with chronic kidney disease and undergoing hemodialysis (HD), its preventive efficacy remains controversial. The present study aimed to determine whether aspirin therapy reduces the risk of cardiovascular disease (CVD) and all-cause mortality in patients on HD. Methods We conducted a 5-y prospective cohort study involving patients on HD. Major exposure variables included prescription of aspirin (100 mg/d) and no aspirin (nonaspirin). The primary outcomes included all-cause death, cardiovascular events, hemorrhage, and ischemic stroke. The secondary outcome included bleeding events defined by the requirement of hospitalization. Findings In this study, 406 patients on regular HD were involved during a 5-y follow-up. Among these, 152 and 254 propensity-matched patients were enrolled in the aspirin and nonaspirin cohort, respectively. The cumulative survival rate was not significantly higher in the aspirin than in the nonaspirin users (log rank χ2 = 1.080, P = 0.299). Aspirin use was not significantly associated with reduced all-cause mortality, fatal and nonfatal congestive heart failure, as well as acute myocardial infarction and ischemic stroke. The risk of fatal cerebral hemorrhage was not significantly increased in the aspirin users (HR = 1.795, 95% CI 0.666-4.841, P = 0.174). After adjustment for other confounders, aspirin use was also not associated with decreased risk of all-cause mortality and CVD. Discussion The present prospective cohort study suggests that low-dose aspirin use is not associated with a significant decrease in the risks of all-cause mortality, CVD, and stroke in population undergoing HD (ClinicalTrials.gov number, NCT02261025).


Coincident presence of thyro-gastric autoimmunity at onset of type 1 (insulin-dependent) diabetes.
We have determined thyroid microsomal and gastric parietal cell autoantibodies in 972 patients with onset of Type 1 (insulin-dependent) diabetes before age 20 years. In a cross sectional study, the frequencies of these autoantibodies did not change significantly over the ensuing 20 years following diagnosis of diabetes. In a longitudinal study of 424 patients with Type 1 diabetes followed up to 5.3 years, few new patients with thyro-gastric autoantibodies were identified. Whereas the frequencies of these autoantibodies among the diabetic patients were more than fivefold greater than for age, sex and race matched controls, they resembled those seen in the non-diabetic general population (n = 1524) for the over 60 year age group. We conclude that in patients with thyro-gastric autoantibodies and Type 1 diabetes, the onset of autoimmune processes affecting the thyroid, gastric mucosa and pancreatic islets tend to be simultaneous, although the resultant diseases have different natural histories.


NEAT1 induces osteosarcoma development by modulating the miR-339-5p/TGF-β1 pathway.
The long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been recognized as a tumor oncogene involved in the development of multiple cancers. However, the function of NEAT1 and its molecular mechanism in osteosarcoma (OS) remain unclear. First, we detected the NEAT1 expression in OS cell lines by performing quantitative reverse-transcription polymerase chain reaction. Next, the effects of NEAT1 on OS cell growth, apoptosis, migration, and invasion were tested by lentivirus-mediated downregulation. We observed that inhibition of NEAT1 restrained OS cell progression greatly. Interestingly, in the last few years, increasing studies have shown that some lncRNAs can act as miRNA sponges and reduce the amount of the same. Here, we found that NEAT1 can modulate OS development via sponging miR-339-5p. MiR-339-5p was significantly decreased in OS cells, and its overexpression can remarkably repress the OS proliferation. These results indicated that NEAT1 could function as a tumor oncogene in OS by inhibiting miR-339-5p in vitro. Then, the following assays validated that transforming growth factor β1 (TGF-β1) can act as a functional target of miR-339-5p in OS cells. Finally, we indicated that NEAT1 could mediate TGF-β1 expression by competitively sponging miR-339-5p. NEAT1 induced OS cell proliferation and cell mobility by binding to miR-339-5p and increasing TGF-β1 in OS. It was demonstrated in our study that lncRNA NEAT1 could impede miR-339-5p expression to maintain the expression of TGF-β1, which led to the development of OS. Our findings implied that the novel identified NEAT1/miR-339-5p/TGF-β1 axis might be a new molecular pathway or therapeutic target for OS diagnosis and treatment.


A Human Factors Approach to Surgical Patient Safety.
This article explores the role of human factors engineering in patient safety in surgery. The authors discuss the history and evolution of human factors and the role of human factors in patient safety and provide a description of human factors methods used to study and improve patient safety.


Optimizing pregnancy outcomes in intrauterine insemination cycles by stratifying pre-wash total motile count and patient-specific factors: a patient counseling tool.
The purpose of this study is to clarify which pre-wash total motile count are associated with improved clinical pregnancy rate (CPR) and live birth rate (LBR) based on maternal age, AMH level, stimulation regimen, and infertility diagnosis. This was a retrospective cohort study of first completed IUI cycles at two academic fertility centers from 5/2015 to 9/2019. Cycles were stratified by pre-wash TMC, maternal age, AMH level, stimulation regimen, and infertility diagnosis. The primary outcome was CPR and secondary outcomes were live birth and miscarriage. One thousand one hundred fifty-four cycles were analyzed. Of the 162 cycles that resulted in a CPR (14.0%), most had an insemination TMC > 20 million. Compared to TMC > 20 million, there was no difference in CPR or LBR for lower TMC categories, excluding the TMC < 2 million group, in which there were no pregnancies. When TMC was stratified by deciles, there was also no difference in CPR and LBR, including within the lowest decile (TMC 0.09-8.6 million). Younger age and higher ovarian reserve parameters were associated with higher pregnancy and LBR when stratified by TMC. There was no difference in pregnancy and LBR when considering different stimulation protocols. Our data suggest that pregnancy and LBR are equivalent above a TMC of 2 million. Data stratified by TMC and patient parameters can be used to counsel patients pursuing ART.


Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part II--proposals for DSM-V and ICD-11.
In the Diagnostic and Statistical Manual of Mental Disorders (DSM), a descriptive definition for premature ejaculation (PE) that was based on historical assumptions has been accepted. To formulate a new functional definition of PE in the DSM. A "syndrome" approach instead of a "complaint" approach is applied and evidence-based data from epidemiological and clinical studies are used. A new functional definition of PE should pertain to a cluster of "symptoms" of a distinct "syndrome." A syndrome rather than a descriptive definition should distinguish Lifelong and Acquired PE variants. Evidence-based data also suggest another PE type "Natural Variable PE," which is not a typical syndrome but rather a cluster of inconsistent symptoms of rapid ejaculation. Moreover, in "Natural Variable PE" the occurrence of rapid ejaculation is not based on neurobiological or psychological pathology, but belongs to the normal variability of sexual performance. Its prevalence is probably much higher than that of Lifelong and Acquired PE. We propose three separate operationalized definitions of these three PE types for the pending DSM-V and ICD-11, which include a quantification of the ejaculation time (intravaginal ejaculation latency time), inability of ejaculatory control, and a description of severity of PE in terms of psychological distress. The use of the intravaginal ejaculation latency time into the DSM-V and ICD-11 would mean that statistical evidence becomes accepted as one of the mainstays for establishing an evidence-based definition of the three PE types.


Competence at graduation: implications for assessment.
Assessment of clinical competence is an integral component of veterinary medical and medical programs. Assessing competence is not straightforward, however, and there have been many studies in the medical education literature on the subject. This article seeks to review developments and current thinking in this important area.


Tspan15-ADAM10 signalling enhances cancer stem cell-like properties and induces chemoresistance via Notch1 activation in ICC.
Notch1 activation promotes ICC progression and is associated with chemoresistance; however, therapies directly targeting Notch1 showed severe adverse effects. Notch1 activation is mediated by ADAM10, a molecular scissor that separates the target protein from its substrates in the cell membrane. Tspan15 regulates ADAM10 function, but the role of Tspan15 in ICC progression is unclear. Tspan15, ADAM10, and Notch1 expression and activation in fresh surgical specimens from 80 ICC patients and ICC cells were evaluated by immunohistochemistry, RT-PCR, western blotting, and flow cytometry. Tspan15 expression was increased in ICC compared with adjacent liver tissue, and high Tspan15 expression was an independent factor for poor prognosis. In ICC with high Tspan15 expression, vascular invasion, lymph node metastasis, and haematogenous recurrence were increased. Tspan15 was co-expressed with ADAM10 in ICC, and associated with the expression of stemness and EMT markers. In ICC cells, Tspan15 induced ADAM10 activation by mediating the translocation of activated m-ADAM10 from the cytoplasm to the surface of the cell membrane, which further activated Notch1 by separating the intracellular domain of Notch1 from its extracellular domain, leading to enhancement of CSC-like properties and EMT. This signalling was associated with enhanced chemoresistance against gemcitabine and cisplatin. Inhibition of Tspan15 or ADAM10 is a promising therapeutic strategy in ICC, as Tspan15 or ADAM10 knockdown or treatment with ADAM10 inhibitor reduced chemoresistance and invasiveness by suppressing Notch1-mediated CSC-like properties and EMT. Tspan15-ADAM10-Notch1 signalling is associated with aggressive tumour progression and poor prognosis in ICC.


Entorhinal cortex MRI assessment in temporal, extratemporal, and idiopathic generalized epilepsy.
We previously showed a reduction in the volume of the entorhinal cortex (EC) ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy (TLE). The purpose of this study was to examine the specificity of EC atrophy in epilepsy. We performed volumetric measurement of the EC on high-resolution magnetic resonance imaging (MRI) in patients with TLE (n = 70), extratemporal lobe epilepsy (ETE; n = 18), and idiopathic generalized epilepsy (IGE; n = 20). EC volumes of epilepsy patients were compared with those of 48 age- and sex-matched normal controls. Within the TLE group, 63 patients were selected prospectively with hippocampal atrophy ipsilateral to the seizure focus. The remaining seven patients were chosen retrospectively based on normal volumetric MRI of the hippocampus and amygdale, as well as normal histopathologic examination of the resected tissue. Compared with normal controls, EC volume was smaller ipsilateral but not contralateral to the seizure focus in patients with TLE (p < 0.001). No difference in the EC volumes ipsilateral and contralateral to the seizure focus was seen in patients with ETE and IGE compared with normal controls. The individual analysis showed that the EC was atrophic in 73% of TLE patients with hippocampal atrophy. Three of the seven TLE patients with normal volumetric MRI of the hippocampus and amygdala and normal histopathologic examination had EC atrophy ipsilateral to the seizure focus. In no patient with ETE or IGE was the EC found to be atrophic. EC atrophy ipsilateral to the seizure focus appears to be specific to mesial temporal lobe structural damage associated with TLE.


The drug titration paradox: something obvious finally understood.
The drug titration paradox is an emerging concept in clinical pharmacology. The paradox refers to the observation that when drug is titrated to a specified level of effect in a population of patients, the expected positive correlation between dose and effect is reversed. That is, when titration rather than fixed dosing is used, greater drug exposure is associated with lesser effect, and vice versa. The drug titration paradox may have important implications for study design and data interpretation in anaesthesiology investigations, particularly in big data studies.


Seasonal changes in radiocesium and potassium concentrations in current-year shoots of saplings of three tree species in Fukushima, Japan.
We studied seasonal changes in radiocesium (137Cs) activity and potassium concentrations in current-year leaves and branches of Pinus densiflora (naturally regenerated saplings), Cryptomeria japonica (planted saplings) and Quercus serrata (planted saplings and coppice shoots) in Fukushima, Japan. We collected current-year shoots from 10 individuals of each species over two growing seasons at intervals of 1-4 months, between June 2016 and December 2017. For the deciduous species Q. serrata, we also collected dead leaves that remained attached to branches in December to investigate reabsorption of 137Cs. All collected shoots were divided into leaves and branches, oven-dried, and ground; dry weights of each sample were recorded. 137Cs activity concentrations were measured using a germanium semiconductor detector. Potassium concentrations were quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Increases in dry weight were observed in both leaves and branches between May/June and August; growth then slowed considerably and virtually ceased after October. Clear seasonal changes in 137Cs activity concentrations were observed in both 2016 and 2017, regardless of tree species. Concentrations were higher in young leaves and branches during May and June, then decreased and changed relatively little from August to winter. Reduced 137Cs activity concentrations in dead leaves of Q. serrata were observed only in December 2017 (approximately 15% lower than in October). This reduction may indicate reabsorption of 137Cs in leaves prior to shedding. The changes in potassium concentrations were similar to those in 137Cs in both years. Potassium concentrations were higher in young leaves than in mature leaf and branch samples collected later in the year. A reduction of about 50% in the potassium concentrations in dead leaves of Q. serrata was also observed in December. A positive relationship between 137Cs and potassium concentrations in leaves and branches was observed in all species, except for planted Q. serrata. This relationship may indicate that 137Cs moves in tree shoots with potassium. Leaf and branch weight correlated negatively with 137Cs and potassium concentrations. Reduced concentrations may indicate dilution of these elements as a result of biomass increases over the growing season. Our results imply that irrespective of species, 137Cs exhibits seasonal variations resulting from dilution; these variations correspond with trends in potassium, with higher levels in young organs and decreased levels in older organs.