Biological properties of human periodontal ligament cell spheroids cultivated on chitosan and polyvinyl alcohol membranes.
Multicellular spheroid cultures have attracted increasing attention in the field of periodontal regeneration. However, very few studies have reported the periodontal ligament (PDL) cell spheroid formation via biomaterials-induced processes. This study investigated the biological characteristics of human PDL cell spheroids formed on two hydrophilic polymer-based biomaterials, namely chitosan and polyvinyl alcohol. The expressions of periostin, paxillin, hypoxia-inducible factor 1-α (HIF-1α), and vascular endothelial growth factor (VEGF) were analyzed. Cell migration ability was assessed using a scratch assay. Furthermore, PDL cell spheroids were cultured in 3D-printed polylactic acid scaffolds to evaluate mineralizing capability. Western blot analysis revealed increased expressions of periostin, HIF-1α, and VEGF in the 3D spheroids. After the spheroids were reseeded, the cells gradually migrated outward from the spheroids and time-dependent distribution of paxillin was observed. The cells migrating outward from the 3D spheroids demonstrated greater migration ability than that of 2D monolayer cells. Compared to the dissociated cells from a monolayer culture, the cell spheroids formed on the chitosan membrane exhibited elevated alkaline phosphatase activity and an increase in mineralized matrix deposition. The biomaterial-induced formation of PDL cell spheroids suggests a novel strategy for cell delivery in research and clinical applications of periodontal regeneration.


Ovarian myxoma.
A case of primary ovarian myxoma is reported. The tumor is rare as there are only two previously reported cases in the literature.


Fragmented QRS complexes are not hallmarks of myocardial injury as detected by cardiac magnetic resonance imaging in patients with acute myocardial infarction.
Q waves on a 12-lead electrocardiography (ECG) are considered to be classic hallmarks of prior myocardial infarction. However, one study suggested that the fragmented QRS complex (fQRS) on ECG is a highly sensitive and specific marker of myocardial scarring on a nuclear stress test. The study aimed to investigate the diagnostic accuracy of fragmented QRS complexes compared with Q waves for myocardial injury detected by delayed contrast-enhanced cardiovascular magnetic resonance imaging (DE-CMRI) in subjects with acute myocardial infarction. Electrocardiograms of 190 subjects with myocardial infarction who underwent DE-CMR were analyzed. fQRS was defined by the presence of an additional R wave (R″), or notching of the S wave, or more than one R' in two contiguous leads. Delayed enhancement was observed in 180 (94.7%) patients. Transmural enhancement was noted in 78 (43.3%) and subendocardial enhancement in 102 (56.7%) patients. The sensitivity and specificity of Q waved and fQRS for diagnosing delayed enhancement were 59.4% vs. 66.7% and 90.0% vs. 40.0%. The area under the receiver-operator characteristics curve of delayed enhancement was 0.75 for Q waves and 0.53 for fQRS (p=0.04). The areas under the ROC curves of the transmurality of delayed enhancement were 0.44 for fQRS and 0.58 for Q waves (p=0.73). fQRS has poor accuracy for the detection of myocardial injury compared with Q waves. fQRS and Q waves are not valuable tools for the diagnosis transmural irreversible myocardial injury in acute myocardial infarction.


The correlations between C-reactive protein and MRI-detected inflammation in patients with axial spondyloarthritis: a systematic review and meta-analysis.
C-reactive protein (CRP) and magnetic resonance imaging (MRI) are widely used to monitor inflammation in patients with axial spondyloarthritis (axSpA), but the relationship between CRP and MRI-detected inflammation is incompletely understood. The present study was undertaken to assess correlations between CRP and MRI-detected inflammation in axSpA. A systematic literature search was performed (Medline, Embase, and Cochrane Library) to identify relevant studies concerning CRP and MRI-detected inflammation in axSpA patients. The MRI-detected inflammation was evaluated by MRI-based disease activity score (DAS). The correlation between CRP and MRI-based DAS was integrated by random-effect models. Eighteen studies reported a total of 1392 axSpA patients which were included in this meta-analysis. CRP was significantly associated with spinal MR DAS (r=0.226, 95%CI [0.149, 0.291], p<0.001, I2=23%). We also found a moderate correlation between CRP change and spinal MR DAS change (r[ASspiMRI-a]=0.354, 95%CI [0.282, 0.422], p<0.001, I2=48%; r[SPARCC]=0.544, 95%CI [0.345, 0.701], p<0.001, I2=19%). CRP at baseline was negatively associated with improvement in spinal MR DAS (r= - 0.327, 95%CI [-0.397, -0.264], p<0.001, I2=0%). However, no significant association was found between CRP and sacroiliac joint (SIJ) MR DAS. In axSpA patients, CRP is associated with MRI-detected inflammation in the spine but not in SIJ. We speculate that CRP could be a reasonable index to reflect spinal inflammation. Therefore, we suggest it is not essential to repeat spinal MRI in a short term, while SIJ MRI may be necessary to provide additional information on inflammation. Key Points • CRP is associated with MRI-detected inflammation in the spine but not in sacroiliac joints. • CRP at baseline was negatively associated with improvement in spinal MR DAS. • It was not essential to repeat spinal MRI frequently, while SIJ MRI may be necessary to provide additional information on inflammation.


Concentrations, sources, fluxes, and absorption properties of carbonaceous matter in a central Tibetan Plateau river basin.
Carbonaceous matter (CM) (such as water-insoluble organic carbon (WIOC), black carbon (BC), and water-soluble organic carbon (WSOC)) has a significant impact on the carbon cycle and radiative forcing (RF) of glacier. Precipitation samples and glacier's snow/ice samples (snowpit, surface snow, and granular ice) (Xiao dongkemadi Glacier) were collected at the Dongkemadi River Basin (DRB) in the central Tibetan Plateau (TP) between May and October 2016 to investigate the characteristics and roles of CM in the TP River Basin. WIOC, BC, and WSOC concentrations in precipitation were relatively higher than that in snowpit, but lower than that in surface snow/ice, with the wet deposition fluxes of 0.10 ± 0.002, 0.04 ± 0.001, and 0.12 ± 0.002 g C m-2 yr-1 at DRB, respectively. The positive matrix factorization model identified four major sources (biomass burning source, secondary precursors, secondary aerosol, and dust source) of CM in precipitation at DRB. Two source areas (South Asia and the interior of TP) contributing to the pollution at DRB were identified using a potential source contribution function model, a concentration-weighted trajectory method, and the back-trajectory model. Moreover, the light-absorption by WSOC in the ultraviolet region was 23.0%, 12.1%, and 3.4% relative to the estimated total light-absorption in precipitation, snowpit, and surface snow/ice, respectively. Optical indices analysis revealed that WSOC in snowpit samples presented higher molecular weight, while presented higher aromatic and higher molecule sizes in surface snow/ice and precipitation samples, respectively. RF by WSOC relative to that of BC was estimated to be 17.6 ± 17.6% for precipitation, 10.9 ± 5.8% for snowpit, and 10.7 ± 11.6% for surface snow/ice, respectively, during the melt season in the central TP River Basin. These results help us understand how CM affects glaciers, and they can be utilized to create policies and recommendations that efficiently reduce emissions.


Inclined relative magnetic field analysis of Brinkman type dusty fluid through fluctuating upright parallel plates.
Due to the widespread use of magnetohydrodynamic (MHD) in electromagnetic targeted therapy, malignant tumor therapy, magnetic microscopy, regulating blood circulation following operations, and fluid pumping in industrial and technical processes. The main goal of the article investigates the analysis of a dusty Brinkman fluid flowing through fluctuating parallel plates with an inclined relative magnetic field. The study aims to analyze the relative magnetic phenomena which is fixed relative to the fluid (MFFRF) or plate (MFFRP), and its impact on fluid and particle motion. The mathematical modelling of the fluid is established through a conventional partial differential equations, and Buckingham's pi theorem is utilized to obtain dimensionless variables. Poincare-Lighthill perturbation technique (PLPT) is employed to derive the solution, with the aid of the program Mathcad-15, the findings are displayed graphically for both velocities. The study indicates that the relative magnetic field significantly influences fluid and particle motion which can be utilized to control fluid pumping in industrial operations and blood flow during surgery.


Digitalization and entrepreneurial firms' resilience to pandemic crises: Evidence from COVID-19 and the German Mittelstand.
While stressing the relevance of context, the organizational resilience literature has so far not extensively examined resilience in times of healthcare crises such as the ongoing COVID-19 pandemic. The Parasite Stress Theory of Values suggests that such pandemic crises have detrimental impacts on entrepreneurial activity due to social distancing and its effects on interaction, collaboration, and innovation. However, alternatives to personal contact now available thanks to digitalization, have not yet been examined. We expect entrepreneurial firms with more digitalized business models to show higher resilience to pandemic crises, especially those highly affected by globalization and more for non-family businesses than for family businesses. Based on a survey of German Mittelstand firms in the midst of the crisis induced by COVID-19, our findings broadly support our expectations and thus help qualify the Parasite Stress Theory of Values and contribute to a better understanding of organizational resilience in times of pandemic crises.


A TOGgle for Tension at Kinetochores.
Differential stability of kinetochore-microtubule attachments at low versus high tension is critical for accurate chromosome segregation. Miller et al. find that a TOG domain microtubule-binding protein imparts intrinsic tension selectivity to kinetochore-microtubule attachments.


Isolation and characterization of the porcine growth hormone gene.
A cosmid clone containing the entire porcine growth hormone (PGH) gene has been isolated using a full-length PGH cDNA as the hybridization probe. The gene within the cosmid was subcloned into plasmids and completely sequenced. The coding, promoter, and both 5'- and 3'-noncoding sequences of the PGH gene were found to be highly conserved when compared to the previously sequenced genes coding for rat, human and bovine growth hormones, and also to the human placental lactogen gene. The high degree of conservation between the 5'- and 3'-noncoding regions of the genes from these different species indicates that growth hormone genes may be evolving by some unusual mechanism. The PGH gene was found to contain the unusual variant GC donor splice site.


[Effect of fructose-1,6-diphosphate and trental on the erythrocyte aggregating capacity in ischemic heart disease].
It was shown that fructose-1.6-diphosphate was capable of marked suppression of the aggregation power of the blood erythrocytes of patients with acute myocardial infarction and angina of effort. The antiaggregation effect of the drug was dose-related and enhanced with an increase in the time of its contact with erythrocytes. The antiaggregation effect of pentoxifylline was not of distinct dose-related nature. Its antiaggregation power did not considerably depend on the time of incubation with erythrocytes.


Adrenergic neurons: are they present on microvessels in cheek pouches of hamsters?
Catecholaminergic innervation was investigated in the cheek pouch, mesentery, and cremaster muscle of the hamster. These tissues were removed from normal hamsters after anesthetization with sodium pentobarbital. They were prepared immediately for visualization of catecholamines by using a glyoxylic acid fluorescent technique. Visualization was accomplished via a Zeiss fluorescent microscope with a 470-nm barrier and a 420-nm excitation filter. No fluorescence was observed in or around the microvessels of the cheek pouch; however, intense fluorescence was demonstrated around and along microvessels in the mesentery and cremaster muscle. Thus, within the limitations of this technique, this study demonstrates that local catecholamines, either as a component of adrenergic neurons or a part of the local tissue milieu, are nondetectable in the microvessels within the cheek pouch as compared to mesenteric and muscle tissue of the hamster.


Understanding the trajectory of research efforts in atypical teratoid rhabdoid tumors: a bibliometric analysis of the 50 most impactful studies to date.
Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the central nervous system (CNS) that occurs predominantly in children. More is being discovered about this disease to improve understanding and outcomes. The aim of this analysis was to evaluate citation and other bibliometric characteristics of the 50 most cited articles in the contemporary literature in order to better model the trajectory of our current efforts. Elsevier's Scopus database was searched for the 50 most cited articles about ATRT. To look for trends, earliest 25 articles were separated from the latest 25 articles and then were compared. Various bibliometric parameters were summarized and compared using Pearson's chi-square and Mann-Whitney U tests. The 50 most cited articles were published between 1990 and 2016, from 5 unique countries in 29 unique journals, with genetic and retrospective observational cohort studies the most common design (n = 11 each). Overall median values were as follows: citation count, 145.4 citations (range, 67-626); citation rate per year, 11.7 (range, 3.5-51.4); number of authors 12 (range, 1-95); with 32 (64%) originating from the USA. Compared with older articles, newer articles had statistically lower citation counts (101.8 vs 189.0; P < 0.01), higher number of authors (17.3 vs 6.6; P < 0.01), and were less likely published from the USA (40% vs 88%; P < 0.01) CONCLUSIONS: The 50 most cited articles about ATRT were characterized in this analysis. There was a distinct focus in these studies on the genetic composition and consequences of these tumors. Trends over time suggest greater impact will be had in highly collaborative efforts worldwide. Moving forward, it will be of great interest to see how the findings of these basic science finding will translate into future clinical studies.


Upper normal threshold of serum alanine aminotransferase in identifying individuals at risk for chronic liver disease.
Serum alanine aminotransferase (ALT) is an easily available, low-cost screening tool for detecting silent chronic liver disease. Recent studies have suggested that the currently accepted healthy ALT thresholds be lowered. In this retrospective cross-sectional study, we determined upper thresholds for ALT values in a nationally representative healthy cohort (n = 3337) from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV). Sensitivity and specificity of the currently used ALT threshold (40 IU/L, regardless of gender) was compared against study-derived, gender-specific ALT thresholds for detecting individuals at risk for chronic liver disease in 27 913 health check-up participants. The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free KNHANES participants were 34 IU/L for men and 25 IU/L for women. The prevalence of ALT elevation among health check-up participants was 11.0% in currently used thresholds, and increased to 22.6% with study-derived, gender-specific thresholds. Of the population who were additionally defined to have elevated ALT levels under new ALT threshold, 65.7% were at risk for chronic liver disease. Sensitivity for detecting individuals at risk for chronic liver disease improved from 18 to 33% with new thresholds whereas a trade-off in specificity (from 96 to 88%) was observed. It is recommendable to lower the current ALT thresholds to better identify individuals at risk for chronic liver disease.


Comprehensive understanding of electrochemical treatment systems combined with biological processes for wastewater remediation.
The presence of toxic pollutants in wastewater discharge can affect the environment negatively due to presence of the organic and inorganic contaminants. The application of the electrochemical process in wastewater treatment is promising, specifically in treating these harmful pollutants from the aquatic environment. This review focused on recent applications of the electrochemical process for the remediation of such harmful pollutants from aquatic environments. Furthermore, the process conditions that affect the electrochemical process performance are evaluated, and the appropriate treatment processes are suggested according to the presence of organic and inorganic contaminants. Electrocoagulation, electrooxidation, and electro-Fenton applications in wastewater have shown effective performance with high removal rates. The disadvantages of these processes are the formation of toxic intermediate metabolites, high energy consumption, and sludge generation. To overcome such disadvantages combined ecotechnologies can be applied in large-scale wastewater pollutants removal. The combination of electrochemical and biological treatment has gained importance, increased removal performance remarkably, and decreased operational costs. The critical discussion with depth information in this review could be beneficial for wastewater treatment plant operators throughout the world.


CPR in COVID-19: Should We Use the PAPR to Keep the Savior Safe?
Saran S. CPR in COVID-19: Should We Use the PAPR to Keep the Savior Safe? Indian J Crit Care Med 2021;25(8):950.


Study protocol: high-dose mizoribine with prednisolone therapy in short-term relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse (JSKDC05 trial).
Eighty percent of children with steroid-sensitive nephrotic syndrome (SSNS) relapse within 2 years and 40-50% patients show frequently-relapsing nephrotic syndrome (FRNS). Patients showing a relapse within 6 months after initial remission are at high risk of FRNS. Since frequent prednisolone treatment for FRNS induces severe prednisolone side effects, development of a treatment to prevent patients from shifting to FRNS is desirable. Mizoribine is an immunosuppressive drug with fewer side effects than prednisolone. Recent studies reported the efficacy of high-dose mizoribine in children with FRNS. We conduct a multicenter, open, randomized controlled trial to investigate the efficacy and safety of standard prednisolone plus high-dose mizoribine therapy in children with SSNS showing a relapse within 6 months after an initial remission. Patients are allocated to either standard prednisolone alone treatment group, or standard prednisolone plus high-dose mizoribine group. For the former group, mizoribine is administered at a dose of 10 mg/kg/day once daily and continued for 2 years. The primary endpoint is the duration to frequent relapse. The results provide important data on use of high-dose mizoribine to prevent SSNS patients from shifting to FRNS. Since blood concentrations of mizoribine have not been investigated in detail until now, there is a possibility that mizoribine is underestimated in favor of other immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to prevention of relapse in children at high risk of FRNS, and to decreased total dose of prednisolone. UMIN000005103 , (Prospectively registered 1st March 2011).


Stepwise evolution of Elk-1 in early deuterostomes.
Metazoans have multiple ETS paralogues with overlapping or indiscriminate biological functions. Elk-1, one of three mammalian ternary complex factors (TCFs), is a well-conserved, ETS domain-containing transcriptional regulator of mitogen-responsive genes that operates in concert with serum response factor (SRF). Nonetheless, its genetic role remains unresolved because the elk-1 gene could be deleted from the mouse genome seemingly without adverse effect. Here we have explored the evolution of Elk-1 to gain insight into its conserved biological role. We identified antecedent Elk-1 proteins in extant early metazoans and used amino acid sequence alignments to chart the appearance of domains characteristic of human Elk-1. We then performed biochemical studies to determine whether putative domains apparent in the Elk-1 protein of a primitive hemichordate were functionally orthologous to those of human Elk-1. Our findings imply the existence of primordial Elk-1 proteins in primitive deuterostomes that could operate as mitogen-responsive ETS transcription factors but not as TCFs. The role of TCF was acquired later, but presumably prior to the whole genome duplications in the basal vertebrate lineage. Thus its evolutionary origins link Elk-1 to the appearance of mesoderm.


[DNA-bound proteins mediate attachment to the nuclear skeleton of transcriptionally active DNA fraction].
The proteins tightly bound to DNA are non-randomly distributed along the DNA chain and are concentrated within the transcriptionally active areas. The distribution of tightly bound proteins along the DNA reflects the type of cell differentiation and does not depend directly on transcription. In functionally active nuclei, the DNA-tightly bound proteins complexes are fixed at the nuclear matrix which is therefore associated with the whole transcriptionally active DNA fraction.


Cocaine- and amphetamine-regulated transcript peptide-immunoreactivity in adrenergic C1 neurons projecting to the intermediolateral cell column of the rat.
Cocaine- and amphetamine-regulated transcript (CART) peptide-immunoreactivity was detected in neurons of the rostral ventrolateral medulla (RVLM), but few in the caudal ventrolateral medulla (CVLM). Double-labeling the medullary sections with sheep polyclonal phenylethanolamine N-methyltransferase-antiserum (PNMT) or monoclonal tyrosine hydroxylase-antibody and rabbit polyclonal CART peptide-antiserum revealed that nearly all adrenergic cells in the C1 area were CART peptide-positive and vice versa; tyrosine hydroxylase-positive cells in the A1 area were not. In the thoracolumbar spinal cord, neurons in the intermediolateral cell column (IML) and other sympathetic autonomic nuclei were CART peptide-positive; some of these were contacted by immunoreactive fibers arising from the lateral funiculus. By immuno-electron microscopy, axon terminals containing closely packed agranular CART peptide-immunoreactive vesicles appeared to make synaptic contacts with immunoreactive dendrites and soma in the IML, albeit the incidence of such contacts was low. Microinjection of the retrograde tracer Fluorogold into the lateral horn area of the T1-T3 spinal segments labeled a population of neurons in the C1 area, many of which were also CART peptide-positive. The results indicate that CART peptide-immunoreactivity is expressed in C1 adrenergic neurons, some of which project to the thoracolumbar spinal cord. The presence of this novel peptide in C1 adrenergic neurons underscores the multiplicity of putative transmitters that may be involved in signaling between putative cardiovascular neurons in the medulla oblongata and sympathetic preganglionic neurons (SPNs) in the spinal cord.


Are there meaningful differences in blood pressure control with current antihypertensive agents?
Hypertension is a major risk factor for cardiovascular disease, and small reductions in blood pressure can have a substantial impact on outcome. Effective control of hypertension per se is important in reducing morbidity and mortality, but there is growing evidence that the class of drug used in treatment may affect patient outcomes. The Heart Outcomes Prevention Evaluation (HOPE) trial provided evidence that angiotensin converting enzyme inhibitors (ACEI), agents that inhibit the renin-angiotensin system (RAS), are particularly effective in reducing the risk of cardiovascular events in a wide range of patients. These beneficial effects of ACEI may be independent of antihypertensive effect. Angiotensin receptor blockers (ARB) are the newest class of antihypertensive drug to enter clinical use. By blocking the angiotensin II type 1 receptor, ARB achieve more complete blockade of the RAS than ACEI. The ARB also have a substantially better side effect profile than ACEI, and early evidence suggests that ARB are beneficial in combating hypertension-related target organ damage. These favorable characteristics suggest that ARB should be considered as first-line treatment for hypertension. Based on comparative antihypertensive efficacy, olmesartan, a new ARB, may represent a significant addition to this drug class.


Effects of protein kinase inhibitors on growth factor-stimulated DNA synthesis in cultured rat vascular smooth muscle cells.
The effects of H-7 and ML-9, inhibitors of protein kinase C and myosin light-chain kinase, respectively, on DNA synthesis stimulated by platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) were studied in cultured rat vascular smooth muscle cells (VSMC). H-7 and ML-9 significantly inhibited PDGF-stimulated DNA synthesis in lower concentrations, while both compounds were only effective in inhibiting EGF-induced DNA synthesis in higher concentrations. These data suggest that protein kinase C and myosin light-chain kinase activated by PDGF play a more important role in cell proliferation of VSMC than EGF.


"Heavy fluorous" cyclopentadienes and cyclopentadienyl complexes with three to five ponytails: facile syntheses from polybromocyclopentadienyl complexes, phase properties, and electronic effects.
The reactions between [(eta5-C5H(5-x)Br(x))M(CO)3] (M = Re, Mn; x = 1, 3, 4, 5) and [IZn[(CH2)(n)R(f8)]] (n = 2, 3; R(f8) = (CF2)7CF3) in the presence of [Cl2PdL2] catalysts give the title complexes [[eta5-C5H(5-x)[(CH2)(n)R(f8)]x]M(CO)3]. In the case of x = 5, the major product is actually [[eta5-C5H[(CH2)(n)R(f8)]4]M(CO)3], in which one of the bromides has been substituted by hydride. Minor amounts of multiple hydride substitution products are formed, all of them readily separable on fluorous silica gel. Irradiation of the manganese complexes in CF3C6H5/MeOH/ether gives uncoordinated cyclopentadienes, which can be deprotonated and reattached to other metals. Partition coefficients have been measured (CF3C6F11/toluene): complexes with three or more ponytails are highly fluorophilic, with values of > 99.8: < 0.2. The IR [symbol: see text]CO bands have been used to probe the inductive effects of the ponytails at the metal centers.


Novel use of XSTAT 30 for mitigation of lethal non-compressible torso hemorrhage in swine.
Management of Non-Compressible Torso Hemorrhage (NCTH) consists primarily of aortic occlusion which has significant adverse outcomes, including ischemia-reperfusion injury, in prolonged field care paradigms. One promising avenue for treatment is through use of RevMedx XSTAT 30™ (an FDA approved sponge-based dressing utilized for extremity wounds). We hypothesized that XSTAT 30™ would effectively mitigate NCTH during a prolonged pre-hospital period with correctable metabolic and physiologic derangements. Twenty-four male swine (53±2kg) were anesthetized, underwent line placement, and splenectomy. Animals then underwent laparoscopic transection of 70% of the left lobe of the liver with hemorrhage for a period of 10min. They were randomized into three groups: No intevention (CON), XSTAT 30™-Free Pellets (FP), and XSTAT 30™-Bagged Pellets (BP). Animals were observed for a pre-hospital period of 180min. At 180min, animals underwent damage control surgery (DCS), balanced blood product resuscitation and removal of pellets followed by an ICU period of 5 hours. Postoperative fluoroscopy was performed to identify remaining pellets or bags. Baseline physiologic and injury characteristics were similar. Survival rates were significantly higher in FP and BP (p<0.01) vs CON. DCS was significantly longer in FP in comparison to BP (p = 0.001). Two animals in the FP group had pellets discovered on fluoroscopy following DCS. There was no significant difference in blood product or pressor requirements between groups. End-ICU lactates trended to baseline in both FP and BP groups. While these results are promising, further study will be required to better understand the role for XSTAT in the management of NCTH.


Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08.
Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease. We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial. A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors. The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA. Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p=0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death. Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit. We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit.


Application of a europium complex, Eu(AA)3phen (AA=acrylic acid, phen=1,10-phenanthroline) as a spectroscopic probe and cleaving reagent of DNA.
A complex Eu(AA)3phen was synthesized and characterized by elemental analysis, IR spectroscopy and (1)H NMR. Interaction between Eu(AA)3phen and DNA was studied by UV/visible absorption spectroscopy, fluorescence spectrophotometer, circular-dichroism (CD) spectra and gel-electrophoresis measurements. Absorption spectral indicated that Eu(AA)3phen binding to DNA was an electrostatic mode, which was authenticated by the effect of ionic strength, thermal denaturation and fluorescence quenching experiments. The intrinsic binding constant Kb of Eu(AA)3phen was calculated to be 1.6×10(4) L mol(-1).


Prospective analysis of islet cell antibodies in children with type 1 (insulin-dependent) diabetes.
The prevalence of islet cell antibodies in children with Type 1 (insulin-dependent) diabetes was determined in a cohort of 678 children. The natural course of islet cell antibodies was followed in 375 children at 1 year, 252 and 135 children after 2 and 3 years respectively. Islet cell antibodies were determined by indirect immunofluorescence on cryostat sections of human pancreas. At diagnosis of diabetes 85% of the children had detectable islet cell antibodies (mean titre 10.4). After 3 years 62% of the children were still islet cell antibody positive (mean titre 2.9) indicating a greater persistence of islet cell antibodies than described in earlier studies. In this large cohort a significant correlation between islet cell antibody prevalence or persistence and sex, age or HLA-DR type was not observed except for a faster loss of islet cell antibodies in very young boys and in patients lacking HLA-DR types 3 and 4. Complement fixing islet cell antibodies correlated with high titre islet cell antibodies. Greater persistence of islet cell antibodies was seen for cases with high antibody titre and in children with diagnosis of diabetes during the first half of the year.


Vulvodynia: Definition, Prevalence, Impact, and Pathophysiological Factors.
Vulvodynia constitutes a highly prevalent form of chronic genital pain in women, and current information regarding its definition, prevalence, impact, and pathophysiologic factors involved is needed. To update the scientific evidence published in 2010 from the Third International Consultation of Sexual Medicine pertaining to the definition, prevalence, impact, and pathophysiologic factors of women's sexual pain. An expert committee, as part of the Fourth International Consultation of Sexual Medicine, comprised of researchers and clinicians from biological and social science disciplines, reviewed the scientific evidence on the definition, prevalence, impact, and pathophysiologic factors related to chronic genital pain. A review of the definition, prevalence, impact, and pathophysiological factors involved in vulvodynia. Vulvodynia is a prevalent and highly impactful genital pain condition. Numerous factors have been implicated in its development and maintenance. What is becoming increasingly apparent is that it likely represents the end point of different factors that can differ from patient to patient. Longitudinal research is needed to shed light on risk factors involved in the expression of vulvodynia, as well as in potential subgroups of affected patients, in order to develop an empirically supported treatment algorithm.


Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters.
The advent of the human-induced pluripotent stem cell (hiPSC) technology has transformed biomedical research, providing new tools for human disease modeling, drug development, and regenerative medicine. To fulfill its unique potential in the cardiovascular field, efficient methods should be developed for high-resolution, large-scale, long-term, and serial functional cellular phenotyping of hiPSC-derived cardiomyocytes (hiPSC-CMs). To achieve this goal, we combined the hiPSC technology with genetically encoded voltage (ArcLight) and calcium (GCaMP5G) fluorescent indicators. Expression of ArcLight and GCaMP5G in hiPSC-CMs permitted to reliably follow changes in transmembrane potential and intracellular calcium levels, respectively. This allowed monitoring short- and long-term changes in action-potential and calcium-handling properties and the development of arrhythmias in response to several pharmaceutical agents and in hiPSC-CMs derived from patients with different inherited arrhythmogenic syndromes. Combining genetically encoded fluorescent reporters with hiPSC-CMs may bring a unique value to the study of inherited disorders, developmental biology, and drug development and testing.


[Incidence of sarcoidosis in Guadeloupe. A 13-year retrospective study: 1997-2009].
Sarcoidosis is a systemic granulomatosis of unknown origin with a high incidence in the Afro-American population. There is no epidemiologic data regarding Afro-Caribbean population. The aim of our study was to evaluate the incidence and epidemiologic data of the disease, on the island of Guadeloupe, (French West Indies; 402 500 inhabitants, 90% Afro-Caribbean people) during the 13-years period between 1/01/1997 and 31/12/2009. We performed a retrospective study including exclusively patients with a diagnosis of sarcoidosis confirmed by histological examination of the involved tissues. One hundred and thirteen patients were enrolled in the study. One hundred and eleven patients (98%) were black Caribbean of African European descent. Eighteen patients (16%) were more than 65 years old. The crude annual incidence over the study period was 2.9 cases per 100,000 inhabitants (IC 95%: [2,4-3,4]). The main localization of the disease was the chest (89%). Radiographic stages were distributed as following: I (31%), II (39%), III (15%), IV (2%). Our study showed a low incidence rate of sarcoidosis on the island of Guadeloupe over the study period with a high rate of old patients.


Parent and teacher report of social skills in children with autism spectrum disorders.
The purpose of this study was to examine the agreement between parent and teacher perceptions of specific social behaviors in children with autism spectrum disorders (ASD). Informant ratings were generated concerning 45 children with ASD between the ages of 5 and 14 years who were enrolled in social skills groups at 2 Midwestern outpatient autism treatment centers. Moderate agreement was observed between parents and teachers for the overall social skills rating scores (r = 0.34; p < 0.05), but there was little agreement on specific social items. Distinct patterns of skill profiles emerged. Parents consistently provided relatively higher ratings on items that pertained to initiating interactions. Teachers, on the other hand, consistently provided higher ratings on items related to responding to and maintaining interactions. Parents and teachers agreed most often on items of affective understanding and perspective taking. These findings suggest that specific social behaviors may be context dependent, indicating the need for a multi-informant approach to provide a more complete profile of a child's social abilities, which is necessary for generating a more effective treatment plan.


Pilot study on the use of acoustic radiation force impulse imaging in the staging of cystic fibrosis associated liver disease.
Acoustic radiation force impulse (ARFI) is a novel technique for the measurement of hepatic stiffness, which could be valuable in clinical follow-up of patients affected by cystic fibrosis liver disease (CFLD). Seventy-five patients with suspected CFLD (35 males) underwent clinical and ultrasonographic evaluations, liver and pulmonary function tests, ARFI investigation, and upper gastrointestinal endoscopy. Ten ARFI measurements were taken at the deep right hepatic lobe to compute median values of Shear Wave Velocity (SWV) for each individual. SWV increased progressively from 1.02m/s (95%, Confidence Interval, CI, 0.92-1.126) in patients with no evidence of CFLD at ultrasonography (N=16), to 1.12 (95%CI 1.049-1.19) in patients with CFLD and no signs of portal hypertension (PHT, N=23), and to 1.25 (95%CI 1.14-1.358) in those with CFLD and signs of PHT (N=28). SWV was 1.63 (95%CI 1.26-1.99) in patients with oesophageal varices (N=8) (p<0.0001). ARFI may represent an easy, fast and non-invasive tool for the clinical follow-up of patients with cystic fibrosis associated liver disease.


Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers.
There is controversy concerning the prognosis of breast cancers arising in women carrying loss of function mutations in the breast cancer susceptibility genes BRCA1 and BRCA2. This study was carried out to assess the likely hormone dependence of this group of tumours in comparison with an age and grade matched group of control sporadic tumours. We used quantitative immunohistochemical analysis for the oestrogen receptor (ER), progesterone receptor (PgR), cyclin D1 and pS2 on sections of primary tumours and ductal carcinoma in situ (DCIS). Expression of PgR (P < 0.05) and cyclin D1 (P < 0.01) was low in the BRCA1- and BRCA2-associated cancers compared with sporadic cases. The low frequency of expression of ER (9/40), PgR (2/40) cyclin D1 (5/36) and pS2 (5/36) in the familial tumours indicates that the majority of such tumours will be oestrogen insensitive and unlikely to respond to hormonal manipulation even at the in situ stage in their evolution. The low level of PgR (2/40 cases) suggests that there may be some abnormality of transactivating function of the ER in these tumours.


Alpha coherence predicts accuracy during a visuomotor tracking task.
It has been shown that synchrony of neuronal oscillations plays a critical role in effective communication between functionally distinct brain areas involving motor-sensory integration. However, the patterns of cortico-cortical coupling and their relation to behavioural success are widely unknown. Here, we analysed changes in cortico-cortical coherence during an unimanual visuomotor task and their correlation with performance. A 28-channel-EEG was attained in 27 healthy subjects during the tracking of an irregularly fluctuating target on a screen by manipulating a force sensor with the right index finger and thumb. For oscillatory power in the alpha (8-12 Hz) and the lower beta-band (beta1, 13-20 Hz), we found a decrease in central and occipital areas during performance. Interregional coherence between contralateral frontal and central areas was enhanced in the alpha band. In beta1, we observed a marked increase of coherence in centroparietal regions of both hemispheres extending to occipital and frontal regions in beta2 (21-30 Hz). Most prominently, correlation analysis between alpha coherence and performance accuracy indicated that higher occipitocentral (i.e. visuomotor) coherence is associated with better visuomotor performance whereas high tracking error is associated with enhanced frontocentral coupling, suggesting additional activation of a frontoparietal control network. These results provide further evidence that coherent brain oscillations in alpha and beta bands significantly contribute to effective functional integration of visual and motor areas.


Lanosterol metabolic product(s) is involved in primordial folliculogenesis and establishment of primordial follicle pool in mouse fetal ovary.
The primordial follicles present in neonatal ovary represent the fecundity of a female throughout her reproductive life. Germ cell meiosis and apoptosis are two important events during primordial folliculogenesis. In this study, through focusing on the cytochrome P450 lanosterol 14 alphademethylase (CYP51) and its lanosterol metabolic product(s), we explored the possible regulatory mechanism of the initiation of germ cell meiosis and primordial follicle formation. The expression of CYP51 could be detected in both oocytes and granulosa cells during primordial folliculogenesis by immunochemistry. RS21745, which leads to the reduction of lanosterol metabolic product(s) level, inhibited the primordial follicle formation in a dose-dependent manner, and thus postpone the establishment of the primordial follicle pool when the mouse fetal ovaries were cultured in serum-free medium. In contrast, the number of primordial follicle increased significantly with the accumulation of the lanosterol metabolic products caused by 0.025, 0.0625, and 0.125 microM AY9944-A-7 supplements. AY9944-A-7 also up-regulated the expression of meiotic diplotene stage marker gene msy2 and primordial follicle formation regulatory gene fig-alpha. Furthermore, AY9944-A-7 decreased the expression of apoptosis gene bax and significantly prevented oocyte apoptosis from 15.37 +/- 1.97% to 3.68 +/- 0.27% (P < 0.01) in neonatal ovary in vitro. In conclusion, our results indicate that lanosterol metabolic product(s) is involved in the primordial folliculogenesis by regulating the oocyte meiosis and apoptosis.


Resveratrol vs. calorie restriction: data from rodents to humans.
Calorie restriction extends lifespan and confers metabolic benefits similar to the effect of lifestyle interventions. Poor compliance to long-term dietary restriction, however, hinders the success of this approach. Evidence is now persuasive for a role of resveratrol supplementation (a polyphenol in red grapes) as potential alternative to calorie restriction. This review summarizes the latest literature on the effects and the molecular mechanisms by which calorie restriction and resveratrol confer health benefits. Resveratrol activates SIRT1 and the associated improvement in energy utilization and insulin sensitivity closely resembles the benefits of calorie restriction. Current data largely support resveratrol as a potential calorie restriction mimetic to improve metabolic and probably functional health. Future studies which characterize the bioavailability and efficacy of resveratrol supplementation are critical to provide evidence for its long-term health benefits.


Exuberant squamous metaplasia of the gastric mucosa in a patient with gastric adenocarcinoma.
The presence of squamous epithelium in the stomach is only occasionally encountered and is associated with prolonged mucosal injury. Squamous metaplasia in patients with cancer is relatively rare and only four cases have been reported in the stomach, all of which have been associated with squamous cell carcinomas. We present the first case of exuberant squamous metaplasia in a patient with gastric adenocarcinoma of the cardia. A 56-year-old woman presented with epigastric pain and weight loss. Endoscopy showed an irregular depressed hyperemic lesion covered with a whitish plaque on the cardia. A total gastrectomy was performed and the tumor in the subcardia was found to extend up to the proximal stomach with diffuse squamous metaplasia in the surface of the tumor and proximal gastric mucosa in contiguity with the esophageal squamous epithelium. It is believed that the squamous extension from the esophagus to the proximal stomach and the gastric adenocarcinoma occurred at the same time. Synchronous squamous metaplasia and underlying adenocarcinoma in the stomach is extremely rare. Recognition of this entity would be beneficial for clinicians to avoid unnecessary treatment. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1035146445160150 .


[Quality testing and quality classification standard establishment of Trollius chinensis seeds].
To study quality test, and establish quality classification standard of Trollius chinensis. Seed purity, weight per 1 000 seeds, seed moisture content, seed viability and their exterior parameters of the seed samples from different producing areas were measured, K cluster analysis was applied for the data analysis. Quality of T. chinensis seeds from different producing areas was analyzed, and the primary T. chinensis seed quality classification standard was established.


Single-stage perineal urethroplasty for continence in female epispadias: a preliminary report.
To evaluate the results of single-stage new technique of perineal urethroplasty with double breasting of the urethra and bladder neck and sphincteroplasty in female patients with epispadias. We have treated 4 patients with severe female epispadias (male/female ratio 6:1) since 1991. They presented at the age of 3, 11, 12, and 23 years. Perineal urethroplasty with double breasting, sphincteroplasty, and genitoplasty was done in 3 cases. Cohen's cross-trigonal reimplantation with bladder neck reconstruction was done in the fourth patient who had an ectopic ureter, but the patient required perineal urethroplasty and genitoplasty because of partial incontinence. The urethral plate and bladder neck was mobilized from the surrounding tissue to the bladder neck. A urethral mucosal strip of about 5 to 10 mm was denuded from the bladder neck to the end of urethral plate on one lateral edge, and the urethral plate and urethral mucosa was tubularized over a 12F catheter. Urethroplasty was done with double breasting of the urethral muscle margins starting from inside the bladder neck downward to the neomeatus with corporoplasty, sphincteroplasty, and genital reconstruction. Of the 4 patients, 3 were fully continent during the day with a dry interval of 4 to 5 hours. One of the 3 patients was partially continent and had nocturnal enuresis, which responded to anticholinergic. The fourth patient with bladder neck reconstruction was partially incontinent initially but became continent after perineal urethroplasty. Our technique of one-stage perineal urethroplasty increases the urethral and bladder neck resistance, as well as the bladder capacity, all factors important for continence. This is a simple and effective method for the development of both continence and cosmesis in female epispadias repair.


Model referenced method of evoked potential analysis.
We have described a method for identifying component wave forms of evoked potentials by reference to a model of the dynamic behavior of neuronal systems. The method parsimoniously reproduces measured data and provides a means for utilizing a priori information from sets of experimental data to discriminate between experimental variables. The method appears successful in quantifying the physiologic variability in the amplitude, shape and latency of EP component wave forms.


Behavioral change in a cancer patient following intrathecal beta-endorphin administration.
A patient with a disseminated malignancy received 3 mg of synthetic beta-endorphin administered intrathecally by lumbar puncture. A marked behavioral syndrome characterized by confusion, hypomanic/manic behavior, and psychosis followed drug administration and persisted for more than 2 days.


Validation of the Khorana Venous Thromboembolism Risk Score in Japanese Cancer Patients.
Although the Khorana venous thromboembolism (VTE) risk score (KRS) is well recognized as a simple VTE risk assessment method in patients with cancer, whether it is suitable for Asian populations is unclear. This study validated KRS for the prediction of VTE and investigated the value of the KRS in predicting mortality in Japanese patients with cancer. A body mass index value of 25 kg/m2 or more was defined as obesity according to World Health Organization consensus. A total of 27,687 patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups by the KRS. The primary and secondary endpoints were VTE and all-cause mortality, respectively. The prevalence of VTE was 1.7%, 7.3%, and 11.0% for low-, intermediate-, and high-score patients, respectively. Receiver operating characteristic (ROC) analysis showed that the KRS significantly predicted VTE (area under the curve, 0.679; 95% confidence interval [CI] 0.666-0.692; P < 0.001). The cutoff value for the KRS was 1.0. Logistic regression analysis demonstrated that the KRS was an independent predictor of VTE (odds ratio 1.766; 95% CI 1.673-1.865; P < 0.01). The cutoff value of the KRS for all-cause mortality determined by ROC analysis was 2.0. Kaplan-Meier analysis demonstrated a significantly higher incidence of mortality in the KRS ≥2 group than in the KRS 0-1 group (log-rank: P < 0.01). The KRS was useful in Japanese patients with cancer and might be a potentially useful marker for the prediction of mortality. Establishing optimal scores for Japanese subjects is mandatory because of its low diagnostic ability. (KUMAMON Cancer registry; UMIN000047554).


Prognostic significance of the immune checkpoint HLA-G/ILT-4 in the survival of patients with gastric cancer.
Human leukocyte antigen-G (HLA-G) and its receptors, including immunoglobulin-like transcripts (ILT)-2 and ILT-4, are closely associated with cancer development and clinical outcomes of patients. However, the clinical significance of HLA-G and ILT-2/-4 in gastric cancer (GC) is limited. In this study, the percentage of HLA-G-, ILT-2 and ILT-4 positive tumor cells in 127 GC lesion suspensions of tumor cells gated for epithelialcelladhesionmolecule(EpCAM) was determined using multicolor flow cytometry and their clinical significance was evaluated. Our data showed that the median percentages of HLA-G-, ILT-2, and ILT-4 expressing GC cells were 18.0%, 67.80%, and 1.42%, respectively, and co-expression of HLA-G/ILT-2, HLA-G/ILT-4, and ILT-2/ILT-4 was 16.9%, 1.42%, and 1.70%, respectively. Kaplan-Meier survival results revealed that besides post-operation N status (p = 0.006), M status (p = 0.001), and AJCC clinical stage (p < 0.001), only high percentage of ILT-4+ GC cells was a significant factor for worse survival of patients with GC (overall survival [OS]: 42.9 months vs. 84.5 months; p = 0.031). However, among female patients with GC (n = 31), high percentage of either HLA-G+ (OS: 18.5 months vs. 89.3 months; p = 0.001) or ILT-4+ (OS: 17.9 months vs. 85.8 months; p = 0.002) GC cells was markedly associated with a poor prognosis. Our findings revealed that among HLA-G, ILT-2, and ILT-4, only a high percentage of ILT-4+ GC cells was significantly related to poor prognosis in the entire cohort of patients with GC. However, high percentage of HLA-G+ and ILT-4+ GC cells is associated with poor clinical outcome among female patients with GC.


Extending the limits of complex learning in organic amnesia: computer training in a vocational domain.
This study explored the limits of learning that could be achieved by an amnesic patient in a complex real-world domain. Using a cuing procedure known as the method of vanishing cues, a severely amnesic encephalitic patient was taught over 250 discrete pieces of new information concerning the rules and procedures for performing a task involving data entry into a computer. Subsequently, she was able to use this acquired knowledge to perform the task accurately and efficiently in the workplace. These results suggest that amnesic patients' preserved learning abilities can be extended well beyond what has been reported previously.


Hydrochemical and isotopic investigation of atmospheric precipitation in Beijing, China.
Precipitation water samples were collected at an urban site in Beijing in a hydrological cycle (July 2008-July 2009), and analyzed for TDS, total alkalinity, total hardness, free CO₂, soluble SiO₂, bromide, sulfide, phosphate, major ions (K(+), Na(+), Ca(2+), Mg(2+), NH₄(+), HCO₃(-), Cl(-), SO₄(2-), NO₃(-)), trace elements (CO₃(2-), Mn, Sr(2+), Fe(2+), Fe(3+), Al, F(-), NO₂(-)), stable isotopes ((2)H and (18)O), and radioactive isotope ((3)H). In addition, available published hydrochemical and isotopic data of precipitation of Beijing in the past were also collected and conjointly analyzed. Most of the parameters of samples tested varied considerably in the hydrological cycle. In general, HCO₃(-) and SO₄(2-), and Ca(2+) and NH₄(+) are the dominant anions and cations, respectively. Using Na(+) as an indicator of marine origin, and Al for the terrestrial inputs, the proportions of major elements from sea salt and terrestrial sources were estimated by using the combination of statistical analysis methods and analogy method. More than 70.1% of Cl(-), 98.1% of Ca(2+), and 93.6% of K(+) were non-sea-salt origin, while more than 98.4% of Na(+) was from marine sources. The LMWL (Local Meteoric Water Line) was obtained with an equation of δ(2)H=7.0181δ(18)O+3.5231 (‰, R(2)=0.86, n=36), which was similar to GMWL (Global Meteoric Water Line). δ(2)H, δ(18)O and Δ-excess changed radically with month and season, but had no apparent seasonal effect, precipitation amount effect, and temperature effect. The annual mean values of Δ-excess for 1979 (16.5‰) and 1980 (16.3‰) were much bigger than that for 2007 (7.2‰), 2008 (2.1‰) and 2009 (4.5‰). The composition of (2)H and (18)O was probably intrinsically determined by the sources of water vapor and the physical and chemical processes occurred along the migration paths of water vapor from sources to the aimed precipitation area. Temporal change of (3)H was only influenced by the nuclear testing in the early 1960s worldwide and the natural yield of (3)H in the upper atmosphere intrinsically. (3)H had nearly approached to the natural levels, which would bring difficulty if not invalidation to groundwater dating using (3)H technique.


Oxidant/antioxidant status in cases of snake bite.
Snake bites are an important cause of mortality and morbidity worldwide, especially in rural areas. The aim of this study was to investigate serum paraoxonase (PON), arylesterase (ARLY), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity and lipid hydroperoxide (LOOH) and total sulfhydryl group (-SH) levels in patients with snake venom poisoning. The study included 49 patients with snake bite envenomation (Group 1) and 39 healthy volunteers as the control group (Group 2). Plasma PON, ARLY, Cp, and MPO activity and LOOH and -SH levels were measured. Laboratory measurements of 20 patients with snake bite envenomation (Group 3) were performed again after treatment. PON and ARLY activity and -SH levels were significantly decreased in Group 1 compared with those in Group 2. Cp and MPO activity and LOOH levels were significantly elevated in Group 1 compared with those in Group 2. PON and ARLY activity were significantly elevated in Group 3 compared with those in Group 1. Cp and MPO activity and LOOH levels were significantly decreased in Group 3 compared with those in Group 1. Patients with snake bite envenomation had increased oxidants (MPO and LOOH) and decreased antioxidants (PON, ARLY, and -SH). Results obtained in this study demonstrate that snake bites are associated with a shift to oxidative status. Therapy with antioxidants can lead to an increase in the antioxidant defense system, and thus improvements in clinical symptoms.


Clinical significance of serum mitochondrial DNA in lung cancer.
The aim of the study was to investigate the clinical significance of serum mitochondrial DNA (mtDNA) in lung cancer. Serum mtDNA from 65 lung cancer patients, 20 patients with benign lung diseases and 55 healthy individuals was quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). Data were analyzed using statistical software SPSS 13.0. Serum mtDNA levels in lung cancer patients were significantly higher, compared to those in patients with benign lung diseases and healthy individuals (u=108, p=0.000; u=293, p=0.000), and closely associated with TNM stage (p=0.01). The use of serum mtDNA facilitated detection of lung cancer at a cutoff value of 0.74×10⁴ copies/μL with a sensitivity of 86.2% and specificity of 80.7%. However, serum mtDNA levels were not associated with patient age, gender, histological type, and lymph node metastasis (p>0.05). Quantification of serum mtDNA using FQ-PCR potentially serves as a novel complementary tool to improve the clinical screening and detection of lung cancer.


Sessile Droplet Freezing on Hydrophobic Structured Surfaces under Cold Ambient Conditions.
There have been conflicting reports as to whether surface wettability is effective in the freezing delay enhancement of attached water droplets. It is an important problem in the development of anti-icing surfaces needed for applications, such as aircraft wings and infrastructures. Here, we prepared precooled ambient conditions and surfaces which included smooth, microstructured, and two nanostructured surfaces with hydrophobic coatings to create an environment closer to the actual environment and to avoid frost formation, which enhances wetting transition and nucleation. Static and dynamic wetting characteristics of each surface were investigated as the fundamental properties and the freezing behavior of precooled water droplets were observed. A distinct elongation of the freezing delay time was observed for droplets on nanostructured surfaces which have static contact angles >150°, in contrast to those on smooth and microstructured surfaces. However, the difference in droplet adhesion induced by nanostructures showed a negligible impact on freezing delay. These results indicated that the reduction of the actual contact area between the solid and liquid phases restricted ice nucleus formation.


Comparison between codes MCNPX and Gate/Geant4 in volume fraction studies.
Knowing the volume fraction in a multiphase flow is of fundamental importance in predicting the performance of many systems and processes, it has been possible to model an experimental apparatus for volume fraction studies using Monte Carlo codes. Artificial neural networks have been applied for the recognition of the pulse height distributions in order to obtain the prediction of the volume fractions of the flow. In this sense, some researchers are unsure of which Monte Carlo code to use for volume fractions studies in two-phase flows. This work aims to model a biphasic flow (water and air) experiment in a stratified regime in two Monte Carlo-based codes (MCNP-X and Gate/Geant4), and to verify which one has the greatest benefits for researchers, focusing on volume fractions studies.


[Knowledge and attitudes of workers from a public emergency service about the adoption of standard precautions].
The aims of the study were to evaluate the adoption of the precaution measures, assessing knowledge and attitude of multiprofessional team. This is a transversal study, accomplished in an Emergency Medical Service of Minas Gerais. Univariate and multivariate analysis were used. The results showed that nurses and drivers had the highest and lowest level of knowledge regarding the standard precautions, respectively. The possibility of non-adoption of the precautionary measures was 3.76 (95% CI: 1.48 to 9.53) times higher among professionals aged over 31 years and 6.7 (95% CI: 1.81 to 24,75) times greater among workers in crowded unit of basic support. The conclusion is that is essential to implement strategies in order to improve the professional's knowledge related to infection control and safety recommendations.


Emotional freedom techniques for treating post traumatic stress disorder: an updated systematic review and meta-analysis.
Clinical Emotional Freedom Techniques (EFT) is a psychophysiological intervention that includes cognitive and somatic elements, utilizing techniques from both Cognitive Behavioral Therapy (CBT) and Prolonged Exposure therapy (PE). Because only a single meta-analysis existed examining EFT for PTSD, this systematic review and meta-analysis represents an update. Ten databases were searched for quantitative reviews and randomised clinical trials, and six met inclusion criteria. Study quality and effect size were evaluated and the results demonstrated that treatment with Clinical EFT, when compared to wait list, usual care, or no treatment controls, resulted in significant and large effect sizes, ranging from 1.38 to 2.51. When compared to active controls, effect sizes ranged from -0.15 to 0.79, producing treatment results similar to other evidence-based therapies. Limitations are presented and considerations for further research are proposed.


Neural generators of N18 and P14 far-field somatosensory evoked potentials studied in patients with lesion of thalamus or thalamo-cortical radiations.
Somatosensory evoked potentials (SEPs) to electrical stimulation of the right or left median nerve were studied in 4 patients with hemianesthesia and a severe thalamic or suprathalamic vascular lesion on one side. The SEPs were recorded with a non-cephalic reference. The normal side of each patient served as his or her own control. The lesion consistently abolished the parietal N20-P27-P45 and the prerolandic P22-N30 SEP components. It did not significantly affect the P9-P11-P14 positive far fields, nor the widespread bilateral N18 SEP component. This allowed N18 features to be studied without interference from cortical components. It is proposed that N18 reflects several deeply located generators in brain stem and/or thalamus whereas N20 represents the earliest cortical response of the contralateral post-central receiving areas.


Targeting the hedgehog signaling pathway to improve tendon-to-bone integration.
While the role of hedgehog (Hh) signaling in promoting zonal fibrocartilage production during development is well-established, whether this pathway can be leveraged to improve tendon-to-bone repair in adults is unknown. Our objective was to genetically and pharmacologically stimulate the Hh pathway in cells that give rise to zonal fibrocartilaginous attachments to promote tendon-to-bone integration. Hh signaling was stimulated genetically via constitutive Smo (SmoM2 construct) activation of bone marrow stromal cells or pharmacologically via systemic agonist delivery to mice following anterior cruciate ligament reconstruction (ACLR). To assess tunnel integration, we measured mineralized fibrocartilage (MFC) formation in these mice 28 days post-surgery and performed tunnel pullout testing. Hh pathway-related genes increased in cells forming the zonal attachments in wild-type mice. Both genetic and pharmacologic stimulation of the Hh pathway increased MFC formation and integration strength 28 days post-surgery. We next conducted studies to define the role of Hh in specific stages of the tunnel integration process. We found Hh agonist treatment increased the proliferation of the progenitor pool in the first week post-surgery. Additionally, genetic stimulation led to continued MFC production in the later stages of the integration process. These results indicate that Hh signaling plays an important biphasic role in cell proliferation and differentiation towards fibrochondrocytes following ACLR. This study reveals a biphasic role for Hh signaling during the tendon-to-bone integration process after ACLR. In addition, the Hh pathway is a promising therapeutic target to improve tendon-to-bone repair outcomes.


Free-standing graphene by scanning transmission electron microscopy.
Free-standing graphene sheets have been imaged by scanning transmission electron microscopy (STEM). We show that the discrete numbers of graphene layers enable an accurate calibration of STEM intensity to be performed over an extended thickness and with single atomic layer sensitivity. We have applied this calibration to carbon nanoparticles with complex structures. This leads to the direct and accurate measurement of the electron mean free path. Here, we demonstrate potentials using graphene sheets as a novel mass standard in STEM-based mass spectrometry.


Risk factors for injury associated with low, moderate, and high mileage road marching in a U.S. Army infantry brigade.
Road marching is an important physical training activity that prepares soldiers for a common occupational task. Continued exploration of risk factors for road marching-related injuries is needed. This analysis has assessed the association between modifiable characteristics of physical training and injury risk. Injuries in the previous 6 months were captured by survey from 831 U.S. Army infantry soldiers. Road marching-related injuries were reported as those attributed to road marching on foot for specified distances while carrying equipment. Frequencies, means, and relative risk ratios (RR) for road marching-related injury with 95% confidence intervals (CI) were calculated. Adjusted odds ratios (OR) and 95% CI were calculated for leading risk factors using multivariable logistic regression. Retrospective cohort study. Half (50%) of reported injuries were attributed to road marching or running. When miles of exposure were considered, injury risk during road marching was higher than during running (RRroad marching/running=1.8, 95% CI: 1.38-2.37). A higher product of road marching distance and weight worn (pound-miles per month) resulted in greater injury risk (RR≥1473 pound-miles/<1472=1.92, 95% CI: 1.17-2.41). Road marching-related injuries were associated with carrying a load >25% of one's body weight (OR>25%/1-20%=2.09, 95% CI: 1.08-4.05), having high occupational lifting demands (OR50-100+lbs/25-50lbs=3.43, 95% CI: 1.50-7.85), road marching ≥5 times per month (OR≥5 times/4 times=2.11, 95% CI: 1.14-3.91), and running <4 miles per week during personal physical training (OR0/≥10 miles/week=3.56, 95% CI: 1.49-8.54, OR1-4/≥10 miles/week=4.14, 95% CI: 1.85-9.25). Ideally, attempts should be made to decrease the percentage of body weight carried to reduce road marching-related injuries. Since this is not always operationally feasible, reducing the cumulative overloading from both physical training and occupational tasks may help prevent injury.


The increase of yellow skin colour beyond that of serum bilirubin: a proposed indicator of risk for bilirubin encephalopathy in the newborn.
Forty-seven newborn infants with 1 min Apgar score < 7 were studied. On the third postnatal day the following measurements were made: yellow skin colour, serum bilirubin concentration, reserve albumin concentration and plasma pH. Given the bilirubin concentration and the regression curve between the yellow skin colour and the bilirubin concentration, delta-TcB was calculated as the difference between measured yellow skin colour and the expected yellow skin colour. There was a negative correlation between delta-TcB and Apgar score (P = 0.003), pH (P = 0.026) and reserve albumin concentration (P = 0.045). Fourteen of the included newborns had central nervous system symptoms in the days just following birth. A tendency towards higher delta-TcB was noted in this group (P = 0.08). The results suggest that further study of delta-TcB determination as a tool in the assessment of the icteric newborn infant is justified.


Prospective analysis of carotid arterial wall structure in pediatric renal transplants with ambulatory normotension and in treated hypertensive recipients.
Increased carotid IMT was found to be associated with cardiovascular risk factors. As pediatric renal transplants are at high risk for cardiovascular disease, we examined whether there is a relationship between BP and IMT in normotensive and in treated hypertensive recipients after transplantation. Thirty-one recipients aged 10 +/- 3.5 yr (16 M, 15 F) underwent repeated carotid ultrasound examinations 5.4 +/- 3.2 yr after transplantation with a 4.1 +/- 1 yr interval and were followed with annual ambulatory BP monitoring. Baseline IMT was significantly higher in transplants compared with controls. When recipients were again investigated, follow-up IMT measurements were similar compared with measurements obtained at baseline. The analysis of variance showed that baseline IMT both in recipients with strict normotension, i.e., ambulatory normotension without antihypertensive therapy at baseline and throughout the study period (n = 9), and in recipients with treated hypertension or newly diagnosed hypertension (n = 22) was significantly higher than in healthy controls (n = 21). Baseline IMT did not differ between these subgroups of recipients. Similarly, pairwise comparisons showed that baseline and follow-up IMT within each subgroup of recipients were not significantly different. Overall and regardless of time-point, no significant associations were found between systolic and diastolic 24-h BP, daytime BP, night-time BP, ambulatory BP standard deviation scores, BP loads and IMT. Our results suggest that increased IMT in pediatric renal transplants does not seem to be related to BP but more likely to other factor(s) not investigated in this study.


Endogenous pain control mechanisms: review and hypothesis.
The anatomy, physiology, and pharmacology of an intrinsic neural network that monitors and modulates the activity of pain-transmitting neurons is reviewed. This system can be activated by opiate administration or by electrical stimulation of discrete brainstem sites. Evidence is presented that its pain-suppressing action is mediated in part by endogenous opiatelike compounds (endorphins). This pain suppression system is organized at three levels of the neuraxis: midbrain, medulla, and spinal cord. Activation of neurons in the midbrain periaqueductal gray matter (by electrical stimulation, opiates, and possibly psychological factors) excites neurons of the rostral medulla, some of which contain serotonin. The medullary neurons, in turn, project to and specifically inhibit the firing of trigeminal and spinal pain-transmission neurons. As part of a negative feedback loop, the output of the pain transmission neurons, i.e., pain itself, is an important factor in activating the pain-suppression system. A neural model which incorporates the experimental findings is proposed, and the clinical implications of the model are discussed.


BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumor heterogeneity and concordance with paired primary tumor.
BAP1 and PBRM1 are frequently mutated in primary clear cell renal cell carcinoma (ccRCC) tumors; however, the frequency and clinical relevance of these mutations in metastatic ccRCC tumors is unknown. Additionally, while intra-tumor heterogeneity has been shown to be common in primary ccRCC, little is known regarding heterogeneity in metastatic ccRCC tumors. We analyzed BAP1 and PBRM1 loss of protein expression in patient-matched primary and metastatic tumors from 97 patients. Expression was determined using a validated immunohistochemistry assay, which has been shown to be correlated with mutation status. Of the 97 patients evaluated, 20 and 57% showed loss of BAP1 and PBRM1 in their primary tumors, respectively. Comparing expression across patient-matched primary-metastatic tumor pairs, 98 and 90% had concordant BAP1 and PBRM1 expression, respectively. Both patients who demonstrated discordant BAP1 expression showed loss of BAP1 expression during progression to metastatic ccRCC. Similarly, seven of the ten patients that demonstrated discordant PBRM1 expression showed loss of PBRM1 expression during progression to metastatic ccRCC. We evaluated intra-metastatic tumor heterogeneity using 12 patients who had multiple blocks available from the same tumor with representative pathology; 100 and 92% showed concordant BAP1 and PBRM1 expression, respectively. Amongst 32 patients who had serial metastatic tumors available, both BAP1 and PBRM1 had 97% concordant expression. We observed minimal intra- and inter- tumor heterogeneity in metastatic ccRCC tumors. Patients with discordant BAP1 or PBRM1 expression across their matched primary and metastatic tumors usually showed loss of expression during progression to metastatic ccRCC.


AP-1 and Mitf interact with NFATc1 to stimulate cathepsin K promoter activity in osteoclast precursors.
Cathepsin K (CTSK) is a secreted protease that plays an essential role in osteoclastic bone resorption and osteoporotic bone loss. We have previously shown that activator protein 1 (AP-1) stimulates CTSK promoter activity and that proximal nuclear factor of activated T cells cytoplasmic 1 (NFATc1)-binding sites play a major role in the stimulation of CTSK gene expression by receptor activator of NFκB ligand (RANKL). In the present study, we have extended these observations and further dissected the effects of transcription factors involved in the regulation of CTSK gene expression. Our aim was to investigate the cooperative interplay among transcription factors AP-1, microphthalmia-associated transcription factor (Mitf), and NFATc1, and the consequent regulatory effects on CTSK transcription. Experiments were carried out in RAW 264.7 cells, which can be readily differentiated to osteoclasts upon RANKL stimulation. Our data show that AP-1, Mitf, and NFATc1 are capable of independently stimulating CTSK promoter activity. A combination of any two factors further enhances CTSK promoter activity, with the combination of AP-1 (c-fos/c-jun) and NFATc1 inducing the largest increase. We further identify a synergistic effect when all three factors cooperate intimately at the proximal promoter region, yielding maximal transcriptional upregulation of the CTSK promoter. RANKL induces temporal localization of AP-1 and NFATc1 to the CTSK promoter. These results suggest that the interaction of multiple transcription factors mediate a maximal response to RANKL-induced CTSK gene expression.


Congenital Hypotonia: Cracking a SAGA of consanguineous kindred harboring four genetic variants.
We aimed to determine the molecular and biochemical basis of an extended highly consanguineous family with multiple children presenting severe congenital hypotonia. Clinical investigations, homozygosity mapping, linkage analyses and whole exome sequencing, were performed. mRNA and protein levels were determined. Population screening was followed. We have identified a novel nonsense variant in NGLY1 in two affected siblings, and compound heterozygosity for three novel RYR1 variants in two affected sisters from another nuclear family within the broad pedigree. Population screening revealed a high prevalence of carriers for both diseases. The genetic variants were proven to be pathogenic, as demonstrated by western blot analyses. Revealing the genetic diagnosis enabled us to provide credible genetic counselling and pre-natal diagnosis to the extended family and genetic screening for this high-risk population. Whole exome/genome sequencing should be the first tier tool for accurate determination of the genetic basis of congenital hypotonia. Two different genetic disorders within a large consanguineous pedigree should be always considered.


Fatal neonatal toxoplasmosis in a bobcat (Lynx rufus).
Toxoplasma gondii was found in tissues of a captive 1-week-old bobcat (Lynx rufus) that died of myocarditis, hepatitis and encephalitis. Although infection is common in wild Felidae, clinical toxoplasmosis is rarely seen. In this case, the infection was apparently congenitally acquired.


Retraction Note to: A novel self-nanoemulsifying drug delivery system for curcumin used in the treatment of wound healing and inflammation.
[This retracts the article DOI: 10.1007/s13205-019-1885-3.].


Predispersal seed predation in Bartsia alpina.
A northern Swedish population of Bartsia alpina, an arctic-alpine perennial herb, was found to suffer high levels of predispersal seed predation by larvae of two insect species, both specialists on rhinanthoid Scrophulariaceae hosts. The primary predator is Aethes deutschiana (Lepidoptera-Tortricidae), the host of which was previously unknown. The other predator is Gimnomera dorsata (Diptera-Scatophagidae), which is basically a Pedicularis specialist. Both predators are attacked by larvae of Scambus brevicorais (Hymenoptera-Parasitica-Ichneumonidae). Total predation pressure was more or less constant during 1985-1987, but in 1988 the level was doubled, the possible reasons of which are discussed. Large inflorescences of B. alpina suffer significantly higher predation pressures than small ones. It is shown that predation is most intense in the middle of the inflorescences. The same floral nodes are known to produce more selfed seeds than distal and basal nodes. Seed predation in B. alpina thus results in an increased proportion of outcrossed seeds entering the seed pool. Selection pressures on host plant and predator fauna are discussed.


Cerebral blood flow in schizophrenia.
The regional cerebral blood flow of 27 young (mean age 24 years) schizophrenic patients was measured using the intravenous 133Xe method. The results were compared with those obtained from a group of age- and sex-matched control subjects. The main findings of the study were as follows: (a) the gray matter mean values of cerebral blood flow for both hemispheres were slightly but significantly lower in the schizophrenic group, and the statistical variance was significantly greater in the patients than in the control group; (b) the mean value for each hemisphere was found to be significantly lower for the right hemisphere; (c) the physiological hyperfrontal patterns of cerebral blood flow were identical in patients and controls; (d) visual hallucinations were associated with a reduction of regional cerebral blood flow in the temporo-occipital regions; and (e) antipsychotic medication did not appear to influence gray matter cerebral blood flow.


Impact of Collateral Circulation on Futile Endovascular Thrombectomy in Acute Anterior Circulation Ischemic Stroke.
Collateral circulation is associated with the differential treatment effect of endovascular thrombectomy (EVT) in acute ischemic stroke. We aimed to verify the ability of the collateral map to predict futile EVT in patients with acute anterior circulation ischemic stroke. This secondary analysis of a prospective observational study included data from participants underwent EVT for acute ischemic stroke due to occlusion of the internal carotid artery and/or the middle cerebral artery within 8 hours of symptom onset. Multiple logistic regression analyses were conducted to identify independent predictors of futile recanalization (modified Rankin scale score at 90 days of 4-6 despite of successful reperfusion). In a total of 214 participants, older age (OR, 2.40; 95% CI: 1.56, 3.67; P <.001), higher baseline NIHSS scores (OR, 1.12; 95% CI: 1.04, 1.21; P =.004), very poor collateral perfusion grade (OR, 35.09; 95% CI: 3.50, 351.33; P =.002), longer door-to-groin puncture time (OR, 1.08; 95% CI: 1.02, 1.14; P=.009), and failed reperfusion (OR, 3.73; 95% CI: 1.30, 10.76; P =.015) were associated with unfavorable functional outcomes. In 184 participants who achieved successful reperfusion, older age (OR, 2.30; 95% CI: 1.44, 3.67; P <.001), higher baseline NIHSS scores (OR, 1.12; 95% CI: 1.03, 1.22; P =.006), very poor collateral perfusion grade (OR, 4.96; 95% CI: 1.42, 17.37; P =.012), and longer door-to-reperfusion time (OR, 1.09; 95% CI: 1.03, 1.15; P =.003) were associated with unfavorable functional outcomes. The assessment of collateral perfusion status using the collateral map can predict futile EVT, which may help select ineligible patients for EVT, thereby potentially reducing the rate of futile EVT.


Spectroelectrochemistry of tris(bipyridyl)silicon(IV): ligand localized reductions with potential electrochromic applications.
Tris(bipyridyl)silicon(iv) was electrochemically reduced in acetonitrile to obtain the UV-vis spectra of its reduced species. Three stable, reversible reduced states (3+, 2+, and 1+) were observed with distinct isosbestic points for each of the redox reactions. The fully oxidized state (4+) is colorless, while the reduced states were green. The absorbance spectra for the three reduced states are consistent with ligand localized reductions. Potential advantages of using these complexes in electrochromic applications are discussed.


Longitudinal changes in family outcomes of very low birth weight.
Although children with very low birth weight (VLBW, <1500 g) are at high risk for developmental impairments, we know little about the long-term effects of VLBW on families. This study examined long-term family outcomes and their stability over time. Participants were the families of 64 children with <750 g birth weight, 54 with 750-1499 g birth weight, and 66 term-born controls. Family burden and parental distress were assessed annually as part of longitudinal follow-up of the children from mean ages 11-14 years. Family burden and parental distress were higher in the <750 g group than in the term-born group, but differences varied with the child's age and family environment. The findings document long-term effects of VLBW on families that are moderated by the degree of low birth weight, child's age, and family environment.


[Evaluating the first German diagnosis-related groups (G-DRG) in cardiological patients: problems in the correct medical and economic grouping].
About three years ago, the German Government initiated a complete change in the reimbursement system for costs of the in-hospital treatment of patients. A commission of representatives from every component of the German health system decided to adapt the Australian refined Diagnosis Related Groups (AR-DRG system). The AR-DRG system was selected as it would fit best to the German system and because of its high flexibility and preciseness reflecting severity of diseases and treatments. In October 2002, the first German Diagnosis Related Groups (G-DRGs) were calculated from the data of about 116 hospitals. These data now allow first analyses in how far a correct and precise grouping of patients in specific hospital settings is indeed performed and corresponds to the actual costs. Thus, we thoroughly calculated all costs for material and personnel during the in-hospital stay for each patient discharged during the first 4 months of 2002 from our cardiological department. After performing the grouping procedure for each patient, we analyzed in how far inhomogeneous patient distribution in the DRGs occurred and which impact this had on costs and potential reimbursements. Several different problems were identified which should be outlined in this work regarding three G-DRGs: costs of patients who received an implantable cardioverter defibrillator (F01Z) were markedly influenced by multimorbidity and additional expensive interventions which were not reflected by this G-DRG. Use of numerous catheters and expensive drugs represented a major factor for costs in patients with coronary angioplasty in acute myocardial infarction (F10Z) but seemed to be not sufficiently included in the cost weight. A specific area of patient management in our department is high frequency ablation of tachyarrhythmias which is included in other percutaneous interventions (F19Z). Complex procedures such as ablation of ventricular tachycardia or new innovative procedures as ablation of atrial fibrillation were associated with high costs leading to inadequate reimbursement. Furthermore, problems in the associated codes for diseases and procedures became apparent. Opportunities for future optimization such as specific new DRGs, splitting of DRGs, or the impact of changes in reimbursement for high-outliers were discussed.


Isosteres of natural phosphates. 5. The preparation of phosphotidycholine, phosphotidylethanolamine and phosphotidylglycerol.
Isosteric phosphonate analogues of phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol have been prepared in which the normal oxygen atom of the phosphate ester linkage in the glycerol backbone of the molecule has been replaced by a methylene group. These have been prepared by the coupling of the previously reported phosphotidic acid (isosteric analogue of phosphatidic acid) with the appropriate protected hydroxyl compound mediated by trichloroacetonitrile. In all cases, racemic materials have been isolated: for the analogue of phosphatidylglycerol, a mixture of two enantiomeric pairs is isolated.


Body mass, temperature, and depth shape the maximum intrinsic rate of population increase in sharks and rays.
An important challenge in ecology is to understand variation in species' maximum intrinsic rate of population increase, r max , not least because r max underpins our understanding of the limits of fishing, recovery potential, and ultimately extinction risk. Across many vertebrate species, terrestrial and aquatic, body mass and environmental temperature are important correlates of r max . In sharks and rays, specifically, r max is known to be lower in larger species, but also in deep sea ones. We use an information-theoretic approach that accounts for phylogenetic relatedness to evaluate the relative importance of body mass, temperature, and depth on r max . We show that both temperature and depth have separate effects on shark and ray r max estimates, such that species living in deeper waters have lower r max . Furthermore, temperature also correlates with changes in the mass scaling coefficient, suggesting that as body size increases, decreases in r max are much steeper for species in warmer waters. These findings suggest that there are (as-yet understood) depth-related processes that limit the maximum rate at which populations can grow in deep-sea sharks and rays. While the deep ocean is associated with colder temperatures, other factors that are independent of temperature, such as food availability and physiological constraints, may influence the low r max observed in deep-sea sharks and rays. Our study lays the foundation for predicting the intrinsic limit of fishing, recovery potential, and extinction risk species based on easily accessible environmental information such as temperature and depth, particularly for data-poor species.


Survey of patient perceptions towards short-term mobile medical aid for those living in a medically underserved area of Swaziland.
An increasing number of short-term medical missions (STMMs) are being dispatched to provide humanitarian healthcare; however, extensive investigations on how recipient patients perceive STMMs are lacking. The current study evaluated the perceptions of patients toward medical services provided by a Taiwanese STMM in a resource-poor area of Swaziland. A structured questionnaire survey was completed by patients who had received medical services from the medical mission of Taipei Medical University in Swaziland in July 2014. In total, 349 questionnaires were valid for the analysis. More respondents were female than male (69.6% vs 30.4%). The most common chief complaint was musculoskeletal problems (45.8%), followed by respiratory symptoms (35.0%). Most of the patients stated that their overall experience with the medical services was excellent (91.4%). Universal patients would like to see the service provided in the future (99.7%). Nearly 90% of the patients were aware of how to take care of the medical problem they were diagnosed with. A majority of the patients comprehended what their medical providers said. Only a few patients did not understand what physicians said (5.2%). Medical services provided by the STMM were helpful in resolving patients' problems. The data have crucial implications for evaluating overseas mobile medical aid from the viewpoint of patients.


Primary mediastinal tumors in children.
From 1950-1986, a total of 159 children (age 1 day-16 years) were treated for primary mediastinal tumors at our hospital. There were 77 malignant and 82 benign tumors. Tracheal compression causing respiratory distress was a significant symptom in 45.3% (24/53) of the children under 2 years of age. The diagnosis was based on the chest X-ray and the findings at surgery. Malignant lymphoma was usually diagnosed by cervical lymph node biopsy (23/39) but the treatment protocol was non-surgical. Non-lymphatic malignant tumors were completely or partially excised in 59.0% (23/39) of the cases. There was no early or late mortality in patients with benign tumors. At follow-up (0.5-24 years; mean 6.0 years), 62.3% (48/77) of the patients with malignant tumors were alive and symptom free. About half of the mediastinal tumors in children are malignant. Mediastinal tumors in small children can cause severe respiratory symptoms demanding urgent treatment. The treatment of choice is surgery (except in lymphomas) and the results are good even in malignant tumors.


Self-attributed body-shadows modulate tactile attention.
Our body-shadows are special stimuli in the visual world. They often have anatomical resemblance with our own body-parts and move as our body moves, with spatio-temporal correlation. Here, we show that self-attributed body-shadows cue attention to the body-part they refer to, rather than the location they occupy. Using speeded spatial discrimination for tactile or visual targets at the hands, or for visual targets delivered near the hand-shadows, we demonstrate that mere viewing of task-irrelevant shadows can selectively facilitate tactile discrimination at the body-part casting the shadow (Experiment 1). In addition, such facilitation only develops through time for cast-shadows that have no resemblance with the body-part, but move in spatio-temporal correlation with it (Experiment 2). Conversely, facilitation fades away rapidly for shadow-like images that resemble the stimulated body-part, but are in fact static pictures (Experiment 3). Thus, recognising oneself as the owner of a shadow affects distribution of tactile attention.


Genetic characterization of Sabin types 1 and 3 poliovaccine virus following serial passage in the human intestinal tract.
Poliovirus isolates types 1 and 3 were obtained from five and seven successive passages respectively, in infants who had been fed monovalent OPV in two separate clinical trials conducted in 1960. The purpose of these trials was to answer the question how much the vaccine virus would revert to its original neurovirulent phenotype following multiplication in the intestinal tract. Human passages were performed either by contact exposure or by feeding the excreted virus while the infants were maintained in isolation. Several virus isolates were obtained at each passage level. Infants participating in both studies showed no symptoms of disease. Antigenic studies (McBride, van Wezel) and protein analysis (PAGE) of the isolates, reported earlier from this laboratory, had shown that the isolates remained vaccine-like, although isolates from the later passages revealed some differences. Monkey neurovirulence test results showed that for both types 1 and 3 viruses the loss of attenuation of the vaccine strain upon passage was gradual, although the loss was faster for type 3. Examination of the oligonucleotide maps demonstrated that the oligonucleotide configuration of the isolates remained the same as for the vaccine strain but there was an increase of individual spot differences with increasing passage. The nucleotide sequence analysis of selected regions of the virus genomes revealed that there was no change from a G to A in nucleotide 480 of type 1 isolates; however, nucleotide 476 changed from a U to an A in type 1 passages 3, 4 and 5. Conversely, for type 3 the change of nucleotide 472 from a U to a C changed at the early first passage (4 days following administration of OPV), and remained a C in the six following passages; type 3 nucleotide 2034 did not change in the first passage from a U to a C, but it became a C in all further passages tested. The nucleotide changes mentioned for both virus types remained stable in successive passages. However, there was another nucleotide change for type 3 from a U to a C at position 1973 only for passages 5 and 6 which reverted to a U for passages 7L and 7LL. Study of selected human passage virus strains could further contribute to the identification of the critical nucleotides that are responsible for the attenuation of these two polio types of vaccine viruses.


Genetic Variations in FSH Action Affect Sex Hormone Levels and Breast Tissue Size in Infant Girls: A Pilot Study.
Single nucleotide polymorphisms altering FSH action (FSHB -211G>T, FSHR -29G>A, and FSHR 2039A>G) are associated with peripubertal and adult levels of reproductive hormones and age at pubertal onset in girls. To investigate whether genetic polymorphisms altering FSH action affect serum levels of female reproductive hormones and breast development as early as during minipuberty. Longitudinal study. Population-based cohort study. A total of 402 healthy girls at 3 months of age. Analyses of single nucleotide polymorphisms by PCR using Kompetitive Allele Specific PCR genotyping assays; identification of glandular breast tissue by palpation and measurement of the diameter. Serum levels of anti-Müllerian hormone, FSH, LH, estradiol, inhibin B, and sex hormone-binding globulin were assessed by immunoassays. FSHR -29G>A was associated with both FSH and anti-Müllerian hormone levels with an A allele effect size of -0.8 IU/L (P = .005) and 1.4 nmol/L (P = .003), respectively. FSHR 2039A>G correlated with breast tissue size with a negative additive effect of minor alleles (P = .021), whereas the effect on estradiol levels was only present in homozygotes. FSHB -211T carriers had smaller breast tissue size than girls who without a minor allele; GT+TT 10.5 (confidence interval 9.4-11.5) mm vs GG 12.1 (confidence interval 11.4-12.8) mm, P = .014. Our study indicates that 3 genetic polymorphisms altering FSH action, especially FSHR -29G>A and FSHR 2039A>G, affect female hormone profile and glandular breast tissue development already during minipuberty. Thus, genetic variations of FSH signaling appear to determine the individual set point of the hypothalamic-pituitary-gonadal axis already early in life.


A pre-test post-test study of a brief educational intervention demonstrates improved knowledge of potential acute myocardial infarction symptoms and appropriate responses in cardiac rehabilitation patients.
Patient delay in recognizing and responding to potential acute myocardial infarction (AMI) symptoms is an international issue. Cardiac rehabilitation provides an ideal opportunity to deliver an intervention. This study examines an individual educational intervention on knowledge of heart attack warning signs and specific chest pain action plans for people with coronary heart disease. Cardiac rehabilitation participants at five hospitals were assessed at program entry and tailored education was provided using the Heart Foundation of Australia's Heart Attack Warning Signs campaign educational tool. Participants (n=137) were reassessed at program conclusion (six to eight weeks). Study participants had a mean age of 64.48 years (SD 12.22), were predominantly male (78%) and most commonly presented with a current referral diagnosis of a percutaneous coronary intervention (PCI) (80%) and/or AMI (60%). There were statistically significant improvements in the reporting of 11 of the 14 warning signs of heart attack, with patients reporting 2.56 more warning signs on average at outcome (p<.0001). Patients reported more heart attack warning signs if they had completed high school education (β=1.14) or had better knowledge before the intervention (β=.57). There were statistically significant improvements in reporting of all appropriate actions in response to potential AMI symptoms, with patients reporting an average of 1.3 more actions at outcome (p<.001), with no change in the median time they would tolerate symptoms (p=.16). A brief education session using a single standardised tool and adapted to a patient assessment is effective in improving knowledge of potential AMI symptoms and appropriate responses in cardiac rehabilitation up to two months following.