Molecular dynamics simulations of hexahydro-1,3,5-trinitro-1,3,5-s-triazine (RDX) using a combined Sorescu-Rice-Thompson AMBER force field.
We present the results of molecular dynamics simulations of crystalline hexahydro-1,3,5-trinitro-1,3,5-s-triazine (RDX) using the SRT-AMBER force field (P. M. Agrawal et al., J. Phys. Chem. B 2006, 110, 5721), which combines the rigid-molecule force field developed by Sorescu-Rice-Thompson (D. C. Sorescu, B. M. Rice, and D. L. Thompson, J. Phys. Chem. B 1997, 101, 798) with the intramolecular interactions obtained from the Generalized AMBER Force Field (Wang et al., J. Comput. Chem. 2004, 25, 1157). The calculated crystal density at room conditions is about 10% lower than the measured value, while the lattice parameters and thermodynamic melting point are within about 5% at ambient pressure. The chair and inverted chair conformation, bond lengths, and bond angles of the RDX molecule are accurately predicted; however, there are some inaccuracies in the calculated orientations of the NO2 groups. The SRT-AMBER force field predicts overall reasonable results, but modifications, probably in the torsional parameters, are needed for a more accurate force field.


Survival after 100 years of age: a multivariate model of exceptional survival in Swedish centenarians.
Most survival studies of the elderly population have set their baselines for first examinations between 60 and 80 years. The rapidly increasing numbers of exceptionally old persons call for knowledge about determinants of exceptional survival. The Swedish Centenarian Study followed 100 centenarians from the age of 100 to death of the entire cohort, by age 111 years. A biomedical, psychological, and social multivariate survival analysis was performed based on factors identified as important in earlier studies of older adults. Latent Variable Partial Least Square Estimation (LVPLS) Soft Modeling was used to test the hypothesized predictions of survival in centenarians. Fewer predictors for survival were found in centenarians than were observed in studies of younger elderly persons. Survival after age 100 was dependent mainly on better baseline physical reserve, as measured by body mass index and body weight, and better baseline physical and cognitive function, as measured by activities of daily living and verbal ability/spatial orientation, respectively. Individual characteristics such as physiological reserve, present health and functional status, as well as chance appear important for centenarian survival. Hereditary factors, social relationships, marital status, and personality did not contribute to survival prediction in this exceptional age group. From a theoretical point of view, our data suggest that, in very old age, stochastic determinants may dominate over programmed factors (e.g., family longevity) in determining survival. More research is needed to assess survival factors at exceptional ages.


[Adaptation of skeletal muscle and myocardium to increased motor activity in hypo- and athyroid rats].
Changes in contractility and synthesis of protein were studied in different types of muscles of hypo- and athyroid ratts during adaptation to physical exercise. Intensity of the exercises used corresponded to metabolic power output of 70% VO2max. Thyroidectomy caused a significant decrease in Mg2+ activated actomyosin ATPase activity and in content of RNA in myocardium and in fast oxidative-glycogenolytic and glycogenolytic skeletal muscle fibers. Exercises, intensity of which corresponded to metabolic power output of 70% VO2max led to a more distinct decrease in Mg2+ activated actomyosin ATPase activity in fast glycogenolytic muscle fibers, but in fast oxidative-glycogenolytic fibers the enzymatic activity was increased up to the level comparable with that of intact animals. Rhysical working capacity of athyroid rats was lower by 40% as compared with intact trained animals. Hypothyroidism, induced by means of administration of KJ into previously trained rats, caused a decrease in physical working capacity by 25%.


Developmental functions in a chronic psychiatric population: diagnosis.
The research in psychopathology has revealed little interest in distinguishing between types of chronic mental patients. Chronics have usually been treated as a homogeneous group, and other possible subtypes have remained undefined because of the "melting-pot" effects of extensive hospitalization. Recently, there has been a renewed interest in the chronic patient, as well as in a differentiation of the largest group of such patients, the chronic schizophrenic. Ss were 129 inpatients at a state mental hospital in Maine. The present report begins the specification of a diagnostic system for chronic patients with the use of tasks that reflect developmental functions. Factor analysis of a set of developmental tasks, ranging from early reflex tests to later cognitive operations, resulted in a test battery which clearly defines specific developmental functions. Of most importance, the clusters of patients derived from these factors exhibited differential profiles indicating strengths and weaknesses on the developmental functions. The assumption of a developmental task sequence was not supported by the results, but the diagnosis of the chronic patient in terms of developmental functions appears promising.


[In search of a typology of drugs used by the aged living in the community].
The objective was to identify the determining factors of drug utilization in the elderly by using several classes of drugs. We studied drug utilization in 1373 women, aged 75 and over, selected in the EPIDOS study concerning hip fractures in the Languedoc-Roussillon region (France) and in 2525 men and women, aged 60 and over selected for the POLA study (age-related eye diseases) in the town of Sete. We defined a priori three types of drugs considering the perceived risk by the physician, and the potential demand from the patient (I - Etio-pathogenic drugs with iatrogenic risk; II - Symptomatic drugs without perceived risk; III - Psychotropic drugs). To validate this classification, we studied drug consumption by age and sex, its relationship with mortality and education level, the fact of living alone, subjective health and level of physical activity. The total drug consumption level, measured by the number of drugs taken daily, was higher in women but, at any age, men more often used type I drugs. Survival was also related to the number of type I drugs, that may be considered as an indicator of serious pathology. Inversely, no relationship was observed between survival and the number of type II drugs that grouped symptomatic or comfort drugs. Such typology can help to understand drug over-utilization in the elderly.


Enoxaparin-induced skin necrosis at injection site after total knee arthroplasty.
Enoxaparin is a widely used low-molecular-weight heparin for perioperative thromboembolic prophylaxis. Enoxaparin-induced skin necrosis in the setting of arthroplasty has been rarely reported in the literature with varying outcomes and management decisions. Our patient developed skin necrosis at his injection site and thrombocytopenia 10 days following left total knee arthroplasty surgery and after receiving subcutaneous Lovenox injections postoperatively. The patient was started on an alternative anticoagulation based on a high suspicion for heparin-induced thrombocytopenia and the wound was monitored without surgical debridement. Our case highlights the key clinical management decisions when facing this potentially life-threatening adverse reaction.


Nuclear DNA degradation in lymphocytes of patients with systemic lupus erythematosus.
The degradation of nuclear DNA in lymphocytes of patients with systemic lupus erythematosus (SLE) was analyzed. A low m.w. DNA fragment was identified in phytohemagglutinin (PHA)-stimulated lymphocytes from both healthy controls and SLE patients. The rate of appearance of low m.w. DNA was at least fourfold higher in lymphocytes from SLE patients, suggesting that DNA from SLE cells are more easily degraded than that from normal cells. PHA-stimulated lymphocytes from SLE patients were also shown to be more sensitive to UV irradiation than those of controls. These results suggest that DNA metabolism is abnormal in T cells of SLE patients.


Chemistry and containing: the analyst's use of unavoidable failures.
Certain patients overwhelm the analyst's capacity to contain both the patient and the analyst's own unbearable feelings. Though some such failures of containing may lead fairly quickly to self-correction and others to clinical impasse, our focus is on an in-between state in which the analyst's ability to tolerate his inevitable failures and gradually to (re)establish his containing capacities through difficult self-analytic work can lead to significant change that might not otherwise be possible. The authors argue that this internal psychological work on the analyst's part, which may require considerable time, effort, and suffering, is an important aspect of "good enough" containing. The unique chemistry generated between patient and analyst plays an important role in both establishing and maintaining this kind of productive analytic process.


Pictorial review of multidetector CT imaging of the preoperative evaluation of congenital heart disease.
Sequential segmental approach is an efficient method for complete evaluation of complex congenital heart diseases (CHD). Although echocardiography is the imaging technique of choice, recent advances in computed tomography and cardiac magnetic resonance have given a new dimension to the traditional diagnostic assessment of CHD. CT has advantages of fast speed, higher spatial resolution, and simultaneous lung and airway visualization. The purpose of this pictorial review is to discuss the role of CT and emphasize its protocol and the segmental approach for comprehensive assessment of CHD.


Predictive Accuracy of Surrogate Indices for Hepatic and Skeletal Muscle Insulin Sensitivity.
Surrogate indices of muscle and hepatic insulin sensitivity derived from an oral glucose tolerance test (OGTT) are frequently used in clinical studies. However, the predictive accuracy of these indices has not been validated. In this cross-sectional study, hyperinsulinemic-euglycemic glucose clamp with tritiated glucose infusion and a 75-g OGTT were performed in individuals (n = 659, aged 18 to 49 years, body mass index of 16 to 64 kg/m2) with varying degrees of glucose tolerance. A calibration model was used to assess the ability of OGTT-derived, tissue-specific surrogate indices [hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI)] to predict insulin sensitivity/resistance indices derived from the reference glucose clamp [Hepatic-IRbasal, a product of fasting plasma insulin and hepatic glucose production (HGP), Hepatic-IRclamp, reciprocal of the percent suppression of HGP during the insulin clamp corrected for plasma insulin concentration, and Muscle-ISclamp, a measure of peripheral glucose disposal]. Predictive accuracy was assessed by root mean squared error of prediction and leave-one-out, cross-validation-type square root of the mean squared error of prediction. HIRI and MISI were correlated with their respective clamp-derived indices. HIRI was negatively related to Muscle-ISclamp (r = -0.62, P < 0.0001) and MISI correlated with Hepatic-IR derived from the clamp (Hepatic-IRbasal: r = -0.48, P < 0.0001 and Hepatic-IRclamp: r = -0.41, P < 0.0001). However, the accuracy of HIRI and MISI to predict Hepatic-IR (basal or during clamp) was not significantly different. Likewise, the ability of HIRI and MISI to predict Muscle-ISclamp was also similar. Our findings indicate that the surrogate indices derived from an OGTT are accurate in predicting insulin sensitivity but are not tissue specific.


Multi-detector Computed Tomography (MDCT) Findings of Seven Cases with Spontaneous Regression of Hepatocellular Carcinoma.
To review Multi-detector CT findings of seven cases with spontaneous regression of hepatocellular carcinomas (HCC). This retrospective study included 7 patients confirmed with diagnosis of HCC. Triphasic CT scan using multi-detector CT scanner was done for all patients. They were 2 women and 5 men. 1st patient presented with metastatic HCC underwent fine needle aspiration cytology (FNAC) from vertebral metastasis. 2nd patient underwent only one session of trans-arterial chemo-lipidol. 3rd patient exposed to blunt trauma with rib fissure fracture. 4th patient presented with two HCCs underwent radio-frequency ablation of one lesion. 5th patient underwent FNAC from HCC and exposed to fracture acetabulum. 6th and 7th patients underwent FNAC from hepatic focal lesions. Complete regression of primary HCC and metastases occurred in 1st patient. 2nd patient showed partial lipidol uptakes of HCC with complete regression of HCC on follow up. Incomplete regression of HCC detected in 3rd, 6th and 7th patients. Partial regression of nonablated lesion detected in the 4th patient. Complete regression of HCC occurred on 5th patient. Spontaneous regression of HCC is an interesting phenomenon. It has been hypothesized that invasive techniques and trauma may be linked. They may initiate immunologic mechanisms that may be involved in the regression. More reports and accumulation of such cases should help to clarify the mechanisms, contribute to a further understanding of this phenomenon and may lead to a new treatment strategy for HCC.


Effects of indoor plants on office workers: a field study in multiple Dutch organizations.
In the period 2019-2020, the effect of plants in the workspace on (a) the physical indoor climate, (b) the perception of the workspace by office workers, and (c) their health, well-being and functioning was investigated in nine organizations. This paper reports the outcomes of the latter part. A conceptual model describing the short-term, medium and long-term effect of plants on people was formulated, containing 18 outcome variables. A "Before After Control Impact" quasi-experimental research design was used. A control workspace and an intervention workspace were selected in each of the organizations. A pre-measurement was conducted in both. Correlational analyses, based on the pre-measurements in all organizations and workspaces, confirmed the associations proposed by the conceptual model to a large extent. After placing plants in the intervention workspace, a maximum of two post-intervention measurements were conducted (due to COVID-19 not in all nine organizations), the last one at least 4 months after the introduction of the plants. Overall significant effects were found on complaints about dry air (fewer), the sense of privacy (higher), the attractiveness of the workspace (higher), satisfaction with the workspace (greater) and having a health-related complaint, especially when at work (fewer). The first three effects were already observed in the analyses only including the first post-measurement. The latter two effects only showed up in the analyses including two post-measurements. No direct effect of the plants could be demonstrated on the 13 other outcome variables. The observed effects mainly concern outcome variables that are positioned at the beginning of the proposed causal chain, starting with plants and ending with mental health, absenteeism and job satisfaction.


Comparisons of head direction cell activity in the postsubiculum and anterior thalamus of freely moving rats.
Single cells in the rat anterior thalamic nucleus (ATN) and postsubiculum (PoS) discharge as a function of the rat's directional heading in the horizontal plane, independent of its location. A previous study that compared cell firing during clockwise and counterclockwise head turns concluded that ATN 'head direction' (HD) cell discharge anticipates the rat's future directional heading, while PoS HD cell discharge is in register with the rat's current directional heading (Blair and Sharp [1995] J Neurosci 15:6260-6270). In the current study we extend these findings by using a different method of analysis. HD cells in the ATN and PoS were first characterized by three different measures: peak firing rate, range width, and information content. We then examined how these measures varied when cell firing was aligned with past (negative time shift) or future (positive time shift) head direction of the rat. We report that all three measures were optimized when ATN cell firing was aligned with the animal's future directional heading by about +23 msec. In contrast, PoS HD cell firing was optimized when cell firing was aligned with the rat's past head direction by about -7 msec. When the optimal value was plotted as a function of the amount of time spikes were shifted relative to head orientation, the mean ATN function was shifted to the right of the PoS function only at negative time shifts; at positive time shifts the two functions overlapped. Analysis of two recording sessions from the same cell indicated that each cell in a particular brain area is 'tuned' to a specific time shift so that all cells within a brain area are not uniformly tuned to the same time shift. Other analyses showed that the clockwise and counterclockwise tuning functions were not skewed in the direction of the head turn as postulated by Redish et al. ([1996] Network: Computation in Neural Systems 7:671-685) and Blair et al. ([1997] J Neurophysiol 17:145-159). Additional analysis on episodes when the rat happened to continually point its head in the preferred direction indicated that HD cell firing undergoes little adaptation. In the Discussion, we argue that these results are best accounted for by a motor efference copy signal operating on both types of HD cells such that the copy associated with the PoS HD cells is delayed in time by about 30 msec relative to the copy associated with ATN HD cells.


Rivalry under Pressure: The Coexistence of Ambient-Pressure Motifs and Close-Packing in Silicon Phosphorus Nitride Imide SiP2 N4 NH.
Non-metal nitrides such as BN, Si3 N4 , and P3 N5 meet numerous demands on high-performance materials, and their high-pressure polymorphs exhibit outstanding mechanical properties. Herein, we present the silicon phosphorus nitride imide SiP2 N4 NH featuring sixfold coordinated Si. Using the multi-anvil technique, SiP2 N4 NH was obtained by high-pressure high-temperature synthesis at 8 GPa and 1100 °C with in situ formed HCl acting as a mineralizer. Its structure was elucidated by a combination of single-crystal X-ray diffraction and solid-state NMR measurements. Moreover, SiP2 N4 NH was characterized by energy-dispersive X-ray spectroscopy and (temperature-dependent) powder X-ray diffraction. The highly condensed Si/P/N framework features PN4 tetrahedra as well as the rare motif of SiN6 octahedra, and is discussed in the context of ambient-pressure motifs competing with close-packing of nitride anions, representing a missing link in the high-pressure chemistry of non-metal nitrides.


Detection of placenta elasticity modulus by quantitative real-time shear wave imaging.
To explore the clinical values in detecting the placental elastic modulus using real-time quantitative shear wave elasticity imaging. A total of 30 women in the late pregnancy stage without complications and having normal, single pregnancies, as well as normal fetal growth, amniotic fluid index, and anterior placenta were selected. A real-time elasticity imaging shear wave ultrasonic diagnostic apparatus was used to randomly select regions of interest at the central and edge of the placenta. The elastography imaging mode was launched to measure the elasticity of the elastic modulus of these placental parts. A total of 15 measured values were obtained at the placental center and edge for each pregnancy case. Umbilical artery and uterine artery pulsatility index (PI) values for 18 cases were also randomly measured. The average value of 30 placental edges of the elastic modulus (n = 15) was (7.60 +/- 1.71) kPa. The average value of the 30 placental central elastic modulus (n = 15 ) was (7.84 +/- 1.68) kPa. No significant difference was observed between placenta central and edge elastic modulus. The PI mean value of umbilical artery in 18 cases was 0.94, whereas the average PI values of the uterine artery was 0.83. No linear correlation was found among the elastic modulus, the placental uterine artery PI values, and the umbilical artery PI values (p > 0.05). No difference between the placental center of normal pregnancies and the edge of the elastic modulus was detected. The elastic modulus of the placenta could be obtained in the best position. The placenta varied greatly between elastic modulus. No correlation was found between the placental elastic modulus, the uterine artery, and umbilical artery PI values. Real-time shear wave elasticity imaging technology can provide morphological evidence of placental function, which may emerge as a new clinical assessment approach.


Raised natriuretic peptides, big-endothelin-1 and improved beta-cell function in type 2 diabetic males with hyperuricaemia.
Urate, a naturally-occurring antioxidant, is a marker/factor for cardiovascular disease. Hyperuricaemia is associated with IR, MetS and endothelial dysfunction. We characterised the associations between neurohormones, uricaemia, and glucose homeostasis in type 2 diabetes mellitus (T2DM) males. Cross-sectional; 705 T2DM males divided into two groups: uric acid < 7.0 mg/dl (normouricaemic; n=476) versus uric acid >or= 7.0 mg/dl (hyperuricaemic; n=229). HOMA beta-cell function (B), insulin sensitivity (S), hyperbolic product (BxS), and (BxS) loss rate were determined alongside neurohormones (Nt-proANP, BNP, Big ET-1 and UII). Mean age and diabetes duration were not different between groups. Hyperuricaemics had more macroangiopathy, total/central adiposity, IR, hypertension, dyslipidemia and MetS prevalence. Nt-proANP and BNP levels were more than twice as high in hyperuricaemics, whereas Big ET-1 and UII were higher by 46% and 14%, respectively. HOMA (BxS) was higher in hyperuricaemics: 31 (16)% vs. 26 (18)% (p=0.0004). BxS loss rate was faster in normouricaemics: 1.36 (0.54)% vs. 1.20 (0.43)%/year(-1) (p<0.0001 ). The proportion with HbA(1C) < 7.0% was 39% (normouricaemics) vs. 49% (hyperuricaemics; p=0.0091). In T2DM males, hyperuricaemia is associated with raised neurohormones together with better beta-cell indices. Urate's dual properties may translate into beneficial (glucose homeostasis) and detrimental (raised neurohormones) effects.


Interleukin-8 binds to syndecan-2 on human endothelial cells.
Application of reverse transcription-PCR to total RNA prepared from TNF-alpha (tumour necrosis factor-alpha)-stimulated HUVECs (human umbilical vein endothelial cells) revealed that the syndecan-2 mRNA was up-regulated by this inflammatory stimulus. By immunoprecipitation using an anti-syndecan-2 antibody on TNF-alpha-stimulated HUVEC lysates, inflammation-induced interleukin-8 was found to be an interaction partner of this HS (heparan sulphate) proteoglycan, but not of any other syndecan on these cells. The glycosylated [Syn2(ect)(+HS)] and non-glycosylated [Syn2(ect)(-HS)] forms of Syn2(ect) (the syndecan-2 ectodomain) were purified from a stably transfected human cell line and from a bacterial expression system respectively. By CD spectroscopy, Syn2(ect) was found to adopt an all-beta secondary structure. The dissociation constant of Syn2(ect)(+HS) with respect to interleukin-8 binding was determined by isothermal fluorescence titrations to be 23 nM. Despite its lack of HS chains, Syn2(ect)(-HS) exhibited significant binding to the chemokine, with a K (d) of >1 microM. Thus, in addition to glycosaminoglycan binding, protein-protein contacts might also contribute to the chemokine-proteoglycan interaction.


A new submerged split-thickness skin graft technique to rebuild peri-implant keratinized soft tissue in composite flap reconstructed mandible or maxilla.
The objective of this study was to introduce our preliminary experience on a submerged split-thickness skin graft (STSG) technique combined with secondary vestibuloplasty to rebuild keratinized peri-implant soft tissue and oral vestibule for patients with large oromandibular defects reconstructed by composite flaps. Five patients were enrolled in this study. Stage 1 was submerged STSG and simultaneous implant placement. Stage 2 was the uncovering of the STSG and vestibuloplasty. The implant-borne fixed denture was inserted after this 2-stage treatment. All patients were followed for at least 12 months (average 18 months). Eighteen implants were placed. The rebuilt peri-implant keratinized soft tissue was healthy clinically. The STSG graft had firm adherence to the underlying periosteum. The vestibule had adequate depth to maintain local hygiene. All implants were osseointegrated and all implant-borne prostheses were functioning well. Submerged STSG technique combined with secondary vestibuloplasty may become a feasible and effective solution to rebuild keratinized soft tissue before dental implant restoration.


Goal disturbance changes pre/post-renal transplantation are related to changes in distress.
Renal transplantation (RTx) is considered the treatment of choice for end-stage renal disease (ESRD) given its association with lower mortality, and improved overall quality of life and psychological functioning compared to dialysis. However, much less is known about which factors underlie these psychological improvements across RTx. Goal theory suggests that experienced disturbances in important goals are related to lower psychological functioning. This study aimed to (1) identify the most disturbed and most important goals for patients before RTx, (2) to examine changes in goal disturbance and goal importance pre/post-RTx, and (3) to examine whether changes in goal disturbance are associated with changes in psychological distress over time, and whether this relationship is mediated by changes in perceived control. In this longitudinal study, 220 patients completed questionnaires before and after RTx, including questionnaires to assess goals (GOALS questionnaire), psychological distress (GHQ-12), and perceived control (Mastery scale). End-stage renal disease affected both general and disease-specific goals. Approximately 30% of the patients indicated to experience high or very high disturbance before transplantation. Goal disturbance generally decreased significantly pre- to post-RTx, whereas goal importance did not change significantly pre- to post-RTx. No mediation effect of perceived control was found. Instead, both changes in goal disturbance and perceived control showed independent effects on changes in distress. Intervention strategies targeting attainable and realistic goal setting, and perceived control in RTx recipients who do not benefit optimally from RTx, might enhance psychological functioning in this population. Statement of contribution What is already known on this subject? Kidney transplantation improves patients' psychological functioning. Experienced disturbances in important life goals are related to lower psychological functioning in chronic illness. What does this study add? Goal disturbance decreases after renal transplantation, and this is related to a decrease in distress over time. Perceived control does not mediate the relationship between goal disturbance and distress pre/post-transplantation. Changes in perceived control have an additional main effect on changes in distress.


A lidocaine-prilocaine cream for superficial skin surgery and painful lesions.
A eutectic mixture of lidocaine and prilocaine in a water emulsion cream base produces effective superficial dermal analgesia when applied under occlusive dressing for 60 minutes. On the genitals, lips and oral mucosa, the application time can be reduced. The cream was found to be an effective alternative to conventional infiltration anesthesia for dermabrasion and superficial surgical procedures. It is especially useful in children for the removal of molluscum contagiosum and prior to venepuncture. The preparation is also an effective pain reliever when used on certain ulcerations.


Evaluation of acceptor selectivity of Lactococcus lactis ssp. lactis trehalose 6-phosphate phosphorylase in the reverse phosphorolysis and synthesis of a new sugar phosphate.
Trehalose 6-phosphate phosphorylase (TrePP), a member of glycoside hydrolase family 65, catalyzes the reversible phosphorolysis of trehalose 6-phosphate (Tre6P) with inversion of the anomeric configuration to produce β-d-glucose 1-phosphate (β-Glc1P) and d-glucose 6-phosphate (Glc6P). TrePP in Lactococcus lactis ssp. lactis (LlTrePP) is, alongside the phosphotransferase system, involved in the metabolism of trehalose. In this study, recombinant LlTrePP was produced and characterized. It showed its highest reverse phosphorolytic activity at pH 4.8 and 40°C, and was stable in the pH range 5.0-8.0 and at up to 30°C. Kinetic analyses indicated that reverse phosphorolysis of Tre6P proceeded through a sequential bi bi mechanism involving the formation of a ternary complex of the enzyme, β-Glc1P, and Glc6P. Suitable acceptor substrates were Glc6P, and, at a low level, d-mannose 6-phosphate (Man6P). From β-Glc1P and Man6P, a novel sugar phosphate, α-d-Glcp-(1↔1)-α-d-Manp6P, was synthesized with 51% yield.


Isolation and characterization of an alpha 1,2-mannosidase cDNA from the lepidopteran insect cell line Sf9.
As part of our ongoing efforts to characterize the N-glycosylation pathway of lepidopteran insect cells, we have isolated an alpha 1,2-mannosidase homolog from an Sf9 cDNA library. This cDNA contains an open reading frame which encodes a 670 amino acid protein with a calculated molecular weight of 75,225 Da. This protein has two potential N-glycosylation sites, two consensus calcium binding sequences, and is predicted to be a type II integral membrane protein with a 22 amino acid transmembrane domain (residues 31-52). The amino acid sequence of this protein is 35-57% identical to Drosophila, human, murine, and yeast alpha 1,2-mannosidases. A transcript of approximately 6 kilobases was detected by Northern blot analysis of Sf9 mRNA. Genomic Southern blots probed with an intron-free fragment of the alpha 1,2-mannosidase gene indicated that there are at least two copies or cross-hybridizing variants of this gene in the Sf9 genome. In vivo expression of the cDNA using a recombinant baculovirus produced a protein that released [3H]mannose from [3H]Man9GlcNAc. This activity required calcium, but not magnesium, and was inhibited by 1-deoxymannojirimycin. These results indicate that Sf9 cells encode and express an alpha 1,2-mannosidase with properties similar to those of other eukaryotic processing alpha 1,2-mannosidases.


Scanning assay of beta-galactosidase activity.
Beta-galactosidase, encoded by the lacZ gene in E. coli, can cleave lactose and structurally related compounds to galactose and glucose or structurally related products. Its activity can be measured using an artificial substrate, o-nitrophenyl-beta-D-galactopyranoside (ONPG). Miller firstly described the standard quantitative assay of beta-galactosidase activity in the cells of bacterial cultures by disrupting the cell membrane with the permeabilization solution instead of preparing cell extracts. Therefore, beta-galactosidase became one of the most widely used reporters of gene expression in molecular biology to reflect intracellular gene expression difference. But the Miller assay procedure could not monitor the beta-galactosidase reaction in real time and its results were greatly influenced by some operations in the Miller procedure, such as permeabilization time, reaction time and concentration of the cell suspension. A scanning method based on the Miller method to determine the intracellular beta-galactosidase activity in E. coli Tuner (DE3) expressing -galactosidase in real time was developed and the permeabilization time of cells was optimized for that. The comparison of 3 assays of beta-galactosidase activity (Miller, colorimetric and scanning) was made. The results proved that scanning method for the determination of enzyme activity with using ONPG as substrate is simple, fast and reproducible.


Multiorder boundaries among discrete domains: relative fractal dimension and others.
In nature and society, most of competitions take place on the boundaries among a group of domains where different individuals or colonies share common resources; therefore, it is widely believed that domain boundaries play important roles in the evolution of many complex systems. Here, we first give a definition for multiorder boundaries among discrete domains and then propose a general method to calculate their relative fractal dimension, i.e., the ratio of the fractal dimension of the boundaries versus that of the domains themselves. Through analyzing three types of real-world discrete domains, several interesting results are revealed. For example, the limitation on the number of domains that an individual can join in may produce longer boundaries indicating more cruel competitions among the domains. Besides, the individuals with more social links are always considered more important in social networks, and it is found that these individuals as valuable resources of social domains are always centralized on the boundaries of higher order.


Triage flowchart to rule out acute coronary syndrome.
The aim of the study was to establish a triage flowchart to rule out acute coronary syndrome (ACS) among patients with chest pain (CP) arriving on an Emergency Department (ED). This prospective observational study included 1000 consecutive patients with CP arriving on an ED CP unit. Demographic and clinical characteristics along with vital signs were recorded as independent variables. After CP unit protocol completion and 1-month follow-up, patients were classified as (dependent variable) (1) true non-ACS (all noncoronary patients at the first visit that kept this condition when called 1 month later) or (2) true ACS (all the remaining patients). Relationship among variables was assessed by multiple logistic regression analysis. A triage flowchart was obtained from significant variables and applied to patients with CP who were then grouped in "triage non-ACS" and "triage ACS." Validity indexes to exclude ACS for triage flowchart were measured. Variables significantly associated with non-ACS and included in the triage flowchart were age <40 years (odds ratio 3.61, 95% CI 1.63-7.99), absence of diabetes (2.74, 1.53-4.88), no previously known coronary artery disease (5.46, 3.42-8.71), nonoppressive pain (10.63, 6.04-18.70), and nonretrosternal pain (5.16, 2.82-9.42). For the triage flowchart, both specificity and positive predictive value to rule out ACS were 100%. The triage flowchart is able to accurately identify patients with CP not having an ACS. It may help triage nurses make quick decisions on who should be immediately seen and who could safely wait when delays in medical attention are unavoidable. Prospective validation is needed.


The genetics of colorectal carcinoma.
Colorectal neoplasms begin as monoclonal cell populations, presumably arising from a single mutation or from a series of mutations in a single epithelial cell. Identification of the earliest mutation has been elusive. The resulting neoplastic clone is genetically unstable, perhaps owing to reduced methyl content of the deoxyribonucleic acid (DNA) molecules. Loss of DNA repair mechanisms may also be a factor. There are multiple genetic pathways to colorectal carcinoma (CRC). The multiplicity of mutations which are often associated with carcinogenesis suggests that the cancer cell is specifically adapted to its parasitic role. This is especially apparent when cancer cells become capable of invasion and metastasis. Early therapeutic experiments in vitro suggest that the carcinogenic process may be disrupted by correction of any one of the multiple genetic defects.


Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration.
Integrated hepadnaviral DNA in livers and tumors of chronic hepatitis B patients has been reported for many years. In this study, we investigated whether hepatitis B virus DNA integration occurs preferentially at sites of cell DNA damage. A single I-SceI homing endonuclease recognition site was introduced into the DNA of the chicken hepatoma cell line LMH by stable DNA transfection, and double-strand breaks were induced by transient expression of I-SceI after transfection of an I-SceI expression vector. Alteration of the target cleavage site by imprecise nonhomologous end joining occurred at a frequency of approximately 10(-3) per transfected cell. When replication of an avian hepadnavirus, duck hepatitis B virus, occurred at the time of double-strand break repair, we observed integration of viral DNA at the site of the break with a frequency of approximately 10(-4) per transfected cell. Integration depended on the production of viral double-stranded linear DNA and the expression of I-SceI, and integrated DNA was stable through at least 17 cell divisions. Integration appeared to occur through nonhomologous end joining between the viral linear DNA ends and the I-SceI-induced break, because small deletions or insertions were observed at the sites of end joining. The results suggest that integration of hepadnaviral DNA in infected livers occurs at sites of DNA damage and may indicate the presence of more widespread genetic changes beyond that caused by viral DNA integration itself [corrected].


Group Versus Standard Behavioral Couples' Therapy for Alcohol Use Disorder Patients: Cost-Effectiveness.
The purpose of this study was to evaluate the costs and cost-effectiveness of two treatments for 101 alcohol use disorder patients and their intimate partners--group behavioral couples' therapy plus individual-based treatment (G-BCT), or standard behavioral couples' therapy plus individual-based treatment (S-BCT). We estimated the per-patient cost of each intervention using a microcosting approach that allowed us to estimate costs of specific components in each intervention as well as the overall total costs. Using simple means analysis and multiple regression models, we estimated the incremental effectiveness of G-BCT relative to S-BCT. Immediately after treatment and 12 months after treatment, we computed incremental cost-effectiveness ratios (ICER) and cost-effectiveness acceptability curves for percentage days abstinent, adverse consequences of alcohol and drugs, and overall relationship functioning. The average per-patient cost of delivering G-BCT was $674, significantly less than the cost of S-BCT ($831). However, 12 months after treatment, S-BCT participants performed better on all outcomes compared with those in G-BCT, and the calculated ICER moving from G-BCT to S-BCT ranged from $10 to $12 across these outcomes. The current findings indicated that, except at very low willingness-to-pay values, S-BCT is a cost-effective option relative to G-BCT when considering 12-month posttreatment outcomes. As expected, G-BCT was delivered at a lower cost per patient than S-BCT; however, S-BCT performed better over time on the clinical outcomes studied. These economic findings indicate that alcohol use disorder treatment providers should seriously consider S-BCT over G-BCT when deciding what format to use in behavioral couples' therapy.


[Using Breteau Index to analyze the nature of sporadic and outbreak cases of Dengue fever].
To understand the threshold of Breteau Index (BI) on Dengue fever outbreak in Guangzhou. Dengue cases from Guangzhou during 2006 to 2012 in the National Infectious Disease Report and Management System were collected and described. Receiver-operating characteristic (ROC) curve was used to judge the threshold of BI on the outbreaks of Dengue fever. A total of 1 038 local cases were reported from 2006 to 2012 in Guangzhou city, with a total of 71 outbreaks and 259 sporadic episodes. Data from the ROC curve analysis showed that the highest Youden index that BI predicting Dengue fever outbreaks or sporadic were 6.4 and 9.5, respectively. When using BI = 6.4 in predicting the sporadic case of Dengue, sensitivity and specificity were 67.8% , 79.1% , respectively. When using BI = 9.5 in predicting the outbreaks of Dengue, sensitivity and specificity were 81.7%, 90.9%, respectively. Both BI = 5.0 and BI = 9.5 showed effects on predicting the nature of sporadic or outbreak on Dengue, suggesting that the threshold need to be monitored, according to the purpose of control and availability of manpower, in order to get better sensitivity and specificity.


Finger and Wrist Pain in Children Using Game Consoles and Laptops Younger Children and Longer Time Are Associated with Increased Pain.
Game consoles, handheld units, and laptops are commonly used by children. Students at schools in St. Louis, Missouri, were asked to complete questionnaires asking about type, duration, and pain levels in their wrists and fingers related to the devices they used. Roughly, 75% of students were found to be using one of the devices. Younger age, female gender, and longer playing duration were associated with increase wrist and finger pain. Use of gaming and laptops, especially in younger children and with longer duration of use, is associated with increased pain in fingers and wrists.


Multidisciplinary treatment of soft tissue sarcomas: An update.
Standard treatment for soft tissue sarcoma, based on complete surgical resection with or without adjuvant radiotherapy and chemotherapy, has not substantially changed during the last several decades. Nevertheless, recent advances have contributed to considerable improvement in the management of these patients; for example, new magnetic resonance imaging sequences such as diffusion-weighted imaging and magnetic resonance imaging radiomics can better assess tumor extension and even estimate its grade. Detection of circulating genetic material (liquid biopsy) and next-generation sequencing are powerful techniques for genetic analysis, which will increase our understanding of the underlying molecular mechanisms and may reveal potential therapeutic targets. The role of chemotherapy in non-metastatic disease is still controversial, and there is a need to identify patients who really benefit from this treatment. Novel chemotherapeutic regimens have entered clinical praxis and can change the outcome of patients with metastatic disease. Advances in radiotherapy have helped decrease local adverse effects and sustain good local control of the disease. The following report provides an updated view of the diagnosis, treatment, and future perspectives on the management of patients with soft tissue sarcomas.


Phenomic and genomic approaches to studying the inhibition of multiresistant Salmonella enterica by microcin J25.
In livestock production, antibiotics are used to promote animal growth, control infections and thereby increase profitability. This practice has led to the emergence of multiresistant bacteria such as Salmonella, of which some serovars are disseminated in the environment. The objective of this study is to evaluate microcin J25 as an inhibitor of Salmonella enterica serovars of various origins including human, livestock and food. Among the 116 isolates tested, 37 (31.8%) were found resistant to at least one antibiotic, and 28 were multiresistant with 19 expressing the penta-resistant phenotype ACSSuT. Microcin J25 inhibited all isolates, with minimal inhibitory concentration values ranging from 0.06 μg/ml (28.4 nM) to 400 μg/ml (189 μM). Interestingly, no cross-resistance was found between microcin J25 and antibiotics. Multiple sequence alignments of genes encoding for the different proteins involved in the recognition and transport of microcin J25 showed that only ferric-hydroxamate uptake is an essential determinant for susceptibility of S. enterica to microcin J25. Examination of Salmonella strains exposed to microcin J25 by transmission electronic microscopy showed for the first-time involvement of a pore formation mechanism. Microcin J25 was a strong inhibitor of several multiresistant isolates of Salmonella and may have a great potential as an alternative to antibiotics.


Extracellular SOD modulates canonical TNFα signaling and α5β1 integrin transactivation in vascular smooth muscle cells.
TNFα activates NADPH oxidase 1 (Nox1) in vascular smooth muscle cells (VSMCs). The extracellular superoxide anion (O2•-) produced is essential for the pro-inflammatory effects of the cytokine but the specific contributions of O2•- to signal transduction remain obscure. Extracellular superoxide dismutase (ecSOD, SOD3 gene) is a secreted protein that binds to cell surface heparin sulfate proteoglycans or to Fibulin-5 (Fib-5, FBLN5 gene), an extracellular matrix protein that also associates with elastin and integrins. ecSOD converts O2•- to hydrogen peroxide (H2O2) which prevents NO• inactivation, limits generation of hydroxyl radical (OH•), and creates high local concentrations of H2O2. We hypothesized that ecSOD modifies TNFα signaling in VSMCs. Knockdown of ecSOD (siSOD3) suppressed downstream TNFα signals including MAPK (JNK and ERK phosphorylation) and NF-κB activation (luciferase reporter and IκB phosphorylation), interleukin-6 (IL-6) secretion, iNOS and VCAM expression, and proliferation (Sulforhodamine B assay, PCNA western blot). These effects were associated with significant reductions in the expression of both Type1 and 2 TNFα receptors. Reduced Fib-5 expression (siFBLN5) similarly impaired NF-κB activation by TNFα, but potentiated FAK phosphorylation at Y925. siSOD3 also increased both resting and TNFα-induced phosphorylation of FAK and of glycogen synthase kinase-3β (GSK3β), a downstream target of integrin linked kinase (ILK). These effects were dependent upon α5β1 integrins and siSOD3 increased resting sulfenylation (oxidation) of both integrin subunits, while preventing TNFα-induced increases in sulfenylation. To determine how ecSOD modified TNFα-induced inflammation in intact blood vessels, mesenteric arteries from VSMC-specific ecSOD knockout (KO) mice were exposed to TNFα (10 ng/ml) in culture for 48 h. Relaxation to acetylcholine and sodium nitroprusside was impaired in WT but not ecSOD KO vessels. Thus, ecSOD association with Fib-5 supports pro-inflammatory TNFα signaling while tonically inhibiting α5β1 integrin activation.


Optimization of immunogold labeling TEM: an ELISA-based method for evaluation of blocking agents for quantitative detection of antigen.
We developed an ELISA-based method for rapid selection of optimal blocking agents to be used in antigen quantification by immunogold labeling electron microscopy. Casein, skim milk, BSA from two sources, acetylated BSA, fish skin gelatin, horse serum, and goat serum were tested for their ability to block nonspecific binding of antibody to recombinant Vitreoscilla hemoglobin (VHb) antigen expressed in Escherichia coli cells by ELISA and the results were confirmed by quantitative immunogold labeling transmission electron microscopy (TEM). Ability to minimize NSB was also evaluated by dot-blot and Western blotting methods. The results demonstrated that ELISA was most accurate in predicting the most efficient blocking agent for TEM. Existing methods could not provide an accurate picture of the ability of various reagents to suppress background labeling. The sensitivity of detection of antigens by immunoelectron microscopy depends on the assay procedure being optimized to obtain the highest possible signal along with as low a background (noise) as possible. Our study indicated that an ELISA-based evaluation of various blocking agents could help in the rapid selection and optimization of a suitable protocol for immunogold localization and quantification of antigens by TEM.


Genetic Testing for Sports Performance, Responses to Training and Injury Risk: Practical and Ethical Considerations.
This paper addresses practical and ethical considerations regarding genetic tests to predict performance and/or risk of exercise-related injury or illness. Various people might wish to conduct sport-related genetic tests for a variety of reasons. For example, an individual might seek personal genetic information to help guide their own sport participation. A sports coach might wish to test young athletes to aid team selection or individualize training. A physician might want to predict the risk of injury or illness in athletes and advise regarding selection or preventative measures. An insurance company might seek to estimate the risk of career-threatening injury for athletes based partly on genetic information. Whilst this information is, in part, encoded in our DNA sequence, the available tests allow generally only a poor prediction of the aforementioned variables. In other words, the current genetic tests and analysis methods are not powerful enough to inform important decisions in sport to a substantial degree. It is particularly disappointing that more than half of the commercially available genetic tests related to exercise and sport do not appear to identify publicly the genetic variants they assess, making scrutiny by academic scholars and consumers (or their representatives) impossible. There are also challenging ethical issues to consider. For example, the imposition of genetic tests on individuals (especially young people) by third parties is potentially susceptible to abuse. Scientists and practitioners should understand the limitations of the tests currently available, the ethical concerns and the importance of counselling before and after testing so that they are only used in a responsible manner.


Pharmacokinetics of lidocaine in healthy individuals pretreated with multiple doses of metoprolol.
The effect of pretreatment with multiple doses of 100 mg of metoprolol on the pharmacokinetics of lidocaine has been studied in six young healthy subjects. The lidocaine dose was 100 mg and the infusion time 12 minutes. Metoprolol had no effect on the levels or the time course of lidocaine in the plasma. The disposition characteristics of the antiarrhythmic agent were not significantly altered by metoprolol in these individuals. These results cannot be extrapolated to prolonged infusion of lidocaine in patients with myocardial infarction.


[Knockdown of indoleamine 2, 3-dioxygenase 2 (IDO2)gene inhibits tumor growth and enhances immune function in mice bearing melanoma].
Objective To study the role of indoleamine 2, 3-dioxygenase 2 (IDO2) in anti-tumor therapy and its effect on the immune response when using IDO2 as therapeutic target. Methods B16-BL6 cells were used to construct mouse xenografted melanoma model. IDO2-shRNA that contained IDO2-siRNA or control shRNA (scrambled-shRNA) was injected hydrodynamically via the tail vein to treat melanoma. The tumor size was measured by vernier caliper. Flow cytometry was performed to analyze the percentage of regulatory T cells (Tregs), T cell apoptosis rate in draining lymph nodes and the expressions of co-stimulatory molecules on splenic dendritic cells (DCs) from different treatment groups. The lactate dehydrogenase (LDH) assay was used to determine the CD8+ cytotoxic T lymphocyte (CTL) activity. The serum levels of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) were detected by ELISA. Results In the IDO2-shRNA treated group, the tumor formation time was delayed, tumor grew slowly, and excised tumor mass was significantly reduced. IDO2-shRNA treatment also decreased the percentage of Tregs and T cell apoptosis in draining lymph nodes and increased the expressions of co-stimulatory molecules CD80 and CD86 on splenic DCs. The capacity of CD8+ T cells to kill B16-BL6 cells was enhanced and the serum levels of TNF-α and IFN-γ were upregulated. Conclusion Silencing IDO2 can effectively inhibit the growth of melanoma and improve the anti-tumor immune response in vivo.


Combinatorial approaches to functional models for galactose oxidase.
The copper enzyme galactose oxidase (GOase, EC 188.8.131.52) catalyses the oxidation of D-galactose and other primary alcohols in air to the corresponding aldehydes and hydrogen peroxide. The current mechanistic hypothesis for this two-electron redox reaction involves a Cu(I)/Cu(II) couple and the reversible oxidation of a ligating phenolate (tyrosine residue of the Tyr272-Cys228 conjugate) to a phenoxyl radical. Our approaches to functional models for galactose oxidase comprise both the use of low-molecular-weight copper complexes of a Schiff-base and sulfonamide ligands, and the synthesis/screening of combinatorial libraries. With regard to the latter, we have synthesized (by the IRORI-directed synthesis approach) peptide libraries carrying either His or the redox-active amino acids Tyr, mod-Cys (a model for the Tyr272-Cys228 conjugate) or TOAC (a TEMPO-derived alpha-amino acid) at four variable positions. After incubation with copper ions, the catalytically active library members were identified by specially designed screening methods.


Advances in the diagnosis and treatment of chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, accounting for up to 25% of all newly diagnosed leukemia. Many cases of CLL have a non-aggressive course and often do not require treatment, while other cases exhibit rapid progression within several years. Recent advances in the diagnosis of CLL include the identification of several prognostic factors, such as ZAP70 expression and the absence of immunoglobulin gene rearrangements. These prognostic factors may identify subgroups of CLL patients who would benefit from earlier treatment rather than "watchful waiting." New combination treatment regimens that include nucleoside analogs (fludarabine, cladribine, and pentostatin) and monoclonal antibodies (rituximab and alemtuzumab) have resulted in improved rates of complete remissions in newly diagnosed and relapsed CLL patients; many of these are molecular complete remissions. The only known cure for CLL remains allogeneic hematopoietic cell transplantation. Newer conditioning strategies with lower, nonmyeloablative doses of chemotherapy and radiation therapy have made this option available to a broader group of patients, including older and sicker populations. These advances in prognostic factors, chemotherapy regimens, and allogeneic transplantation will likely enable increases in survival for CLL patients.


Screening of highly charged ions in an ionic liquid; when will ion pairs form?
The properties of pairs of doubly charged solute ions are studied as a function of their separation in the ionic liquid, dimethylimidazolium chloride ([dmim][Cl]). Free energy (potential of mean force) profiles show that, as for singly charged ions, there is a barrier to oppositely charged ion pairs forming a contact ion pair. However for doubly charged ions this barrier is about twice as large (45 ± 10 kJ mol-1 rather than 20 ± 5 kJ mol-1). Contact ion pairs form when the short range repulsive force balances the direct interaction plus the screening force, and hence depend on the sizes of the solute ions. In order to understand the existence of the barrier and the extent of screening, local charge density distributions and various contributions to the energetics were examined. The barrier arises when the decrease in stabilisation of individual ions by their own solvation shells is balanced by the increase in other screening effects and the direct solute-solute interaction.


Fructose containing sugars do not raise blood pressure or uric acid at normal levels of human consumption.
The impact of fructose, commonly consumed with sugars by humans, on blood pressure and uric acid has yet to be defined. A total of 267 weight-stable participants drank sugar-sweetened milk every day for 10 weeks as part of their usual, mixed-nutrient diet. Groups 1 and 2 had 9% estimated caloric intake from fructose or glucose, respectively, added to milk. Groups 3 and 4 had 18% of estimated caloric intake from high fructose corn syrup or sucrose, respectively, added to the milk. Blood pressure and uric acid were determined prior to and after the 10-week intervention. There was no effect of sugar type on either blood pressure or uric acid (interaction P>.05), and a significant time effect for blood pressure was noted (P<.05). The authors conclude that 10 weeks of consumption of fructose at the 50th percentile level, whether consumed as pure fructose or with fructose-glucose-containing sugars, does not promote hyperuricemia or increase blood pressure.


[Transcatheter arterial embolization in the hemorrhagic complications of kidney trauma].
Transcatheter arterial embolization is a nonsurgical alternative for the complications arising from biopsy, surgery and blunt or penetrating renal trauma. Fourteen transcatheter embolization procedures were performed in 13 patients for hemorrhage following biopsy of the native kidney (3 cases) biopsy of the transplanted kidney graft (3 cases), stone surgery (3 cases), blunt abdominal trauma (2 cases), a stab wound (1 case) and an A-V fistula (1 case). The bleeding was effectively controlled in all cases. Nephrectomy was required in 3 cases (21.4%) whose kidneys were not viable and cannot be ascribed to a complication of the embolization procedure. The diagnostic aspects of hemorrhage arising from renal trauma, the embolization technique and its indications are discussed. In our view, transcatheter arterial embolization is the technique of choice for the hemorrhagic complications of blunt or penetrating renal trauma or those caused by biopsy or surgery.


Blood pressure in the first year of life in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a pilot study.
Evaluation of blood pressure in the first year of life in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Twenty-four children were included. Retrospective blood pressure values, fludrocortisone dosages, and serum renin, 17-hydroxyprogesterone (17-OHP) and androstenedione levels in the first year of life were evaluated. Blood pressure values were compared to reference values. Correlations between blood pressures and serum renin levels, and the dosage of fludrocortisone were calculated. Mean peak systolic blood pressure values were generally not elevated, most values were around the 50th percentile, except incidentally higher mean peak systolic blood pressure values most below the 95th percentile. No significant correlations between blood pressure and serum renin, androstenedione and 17-OHP levels and fludrocortisone dosage were found. In this pilot study in CAH patients, blood pressure values do not seem to be elevated in the first year of life. Further investigations are necessary to evaluate blood pressure in the first year of life in CAH patients in more detail.


Production of interleukin-2 by mononuclear cells in vitro in patients with atopic dermatitis and psoriasis. Comparison with serum interleukin-2 receptor levels.
Atopic dermatitis is associated with profound immunological alterations, in particular decreased lymphoproliferative responses upon stimulation with T-cell mitogens. T-cell blastogenesis involves the production of the soluble cytokine interleukin-2 (IL-2), which in turn upregulates the expression of its own receptor. To investigate the potential role of this cytokine for the pathomechanisms present in atopic dermatitis, 24-h supernatants of PHA-stimulated peripheral blood mononuclear cells from patients with atopic dermatitis (n = 30) of a moderate to severe disease activity were tested for IL-2 activity. In addition, serum concentrations of soluble interleukin-2 receptor (IL-2R) were measured. Non-atopic healthy controls (n = 19) and patients with psoriasis (n = 20), an inflammatory skin disorder with distinct pathogenesis, served as controls. In comparison with psoriasis patients and normal controls, PHA-stimulated mononuclear cells of atopic dermatitis patients released significantly less IL-2 into supernatants. Moreover, there was an inverse correlation between IL-2 concentrations and body surface involvement or serum IgE levels. In contrast, serum IL-2R levels were significantly elevated in both atopic dermatitis and psoriasis, as compared with healthy controls. Furthermore, IL-2R levels in atopic dermatitis patients showed a significant correlation with IgE levels and body surface involvement. The data indicate that T cell activation may occur in both skin diseases. Atopic dermatitis, however, is further characterized by the decreased capacity of mononuclear cells to release IL-2 upon stimulation in vitro.


[Plasma tumor markers (calcitonin and carcinoembryonic antigen) in medullary thyroid cancers].
The authors have studied 43 patients operated on for medullary thyroïd carcinoma. Plasma calcitonin was measured regularly in all patients, while carcinoembryonic antigen assay was performed in only 30 patients. Calcitonin assay was found to be useful for preoperative diagnosis of medullary carcinoma, and the level of plasma calcitonin appeared to be roughly correlated with tumor extension. After surgery, simultaneous assay of calcitonin and carcinoembryonic antigen was performed, in order to obtain more accurate information concerning the evolution and prognosis of the disease. In most cases in which no metastatic lymph nodes had been discovered at operation, the level of the two markers rapidly fell to undetectable values. It was observed that in patients with lymph node involvement, cervico-mediastinal radiation treatment did not change the slow and progressive evolution of the disease. However, a rapid increase in titre of carcinoembryonic antigen occurred simultaneously with the discovery of metastases, even when calcitonin levels did not dramatically change.


Predictors of outcome in fulminant hepatic failure in children.
To identify the predictors of outcome in fulminant hepatic failure (FHF) in children. Prospective cohort study. 41 children with FHF were studied. Patient characteristics and findings on examination at the time of hospitalization were noted. Serum biochemistry and screening for hepatotropic viruses (A, B and C) were done in each patient. Patients were treated using a predefined protocol and followed up till death or discharge. Univariate and multivariate analysis was done to find the predictors of outcome. Hepatitis B was the commonest cause of FHF (11 children; 26.9%). Markers for hepatitis A and C viruses were present in one and two patients, respectively. Serology was negative in 27 children (65.9%), of whom two had history of ingestion of hepatotoxins (antitubercular drugs). The overall mortality was 61%. Irrespective of etiology, the following factors were associated with poor outcome on univariate analysis: presence of gastrointestinal (GI) hemorrhage, serum bilirubin more than 10 mg/dL, age 6 years or less, coma of grade 3 or more, presence of infection, prolongation of prothrombin time > 8 s over control, prothrombin concentration < 50%, hypoglycemia (blood glucose < 45 mg/dL), hyponatremia (serum sodium < 125 mEq/L) and hyperkalemia (serum potassium > 5.5 mEq/L). On multiple logistic regression analysis, presence of GI hemorrhage (p = 0.005), degree of coma (p = 0.02) and serum bilirubin level (p = 0.025) were identified as independent predictors of mortality.


Comparison of the clinical efficacy of percutaneous transforaminal endoscopic discectomy and traditional laminectomy in the treatment of recurrent lumbar disc herniation.
A few years ago, percutaneous transforaminal endoscopic discectomy (PTED) began to prevail in clinical treatment of recurrent lumbar disc herniation (RLDH), whereas traditional laminectomy (TL) was treated earlier in RLDH than PTED. This study aimed to compare the clinical efficacy of PTED and TL in the treatment of RLDH.Between November 2012 and October 2017, retrospective analysis of 48 patients with RLDH who were treated at the Cancer Hospital, Chinese Academy of Sciences, Hefei and Department of Orthopaedics, Second Affiliated Hospital of Anhui Medical University. Perioperative evaluation indicators included operation time, the intraoperative blood loss, length of incision and hospitalization time. Clinical outcomes were measured preoperatively, and at 1 days, 3 months, and 12 months postoperatively. The patients' lower limb pain was evaluated using Oswestry disability index (ODI) and visual analog scale (VAS) scores. The ODI is the most widely-used assessment method internationally for lumbar or leg pain at present. Every category comprises 6 options, with the highest score for each question being 5 points. higher scores represent more serious dysfunction. The VAS is the most commonly-used quantitative method for assessing the degree of pain in clinical practice. The measurement method is to draw a 10 cm horizontal line on a piece of paper, 1 end of which is 0, indicating no pain, which the other end is 10, which means severe pain, and the middle part indicates different degree of pain.Compared with the TL group, the operation time, postoperative bed-rest time, and hospitalization time of the PTED group were significantly shorter, and the intraoperative blood loss was also reduced. These differences were statistically significant (P < .01). There were no significant differences in VAS or ODI scores between the two groups before or after surgery (P > .05).PTED and TL have similar clinical efficacy in the treatment of RLDH, but PTED can shorten the operation time, postoperative bed-rest time and hospitalization time, and reduce intraoperative blood loss, so the PTED is a safe and effective surgical method for the treatment of RLDH than TL, but more randomized controlled trials are still required to further verify these conclusions.


Evidence-based practice: implications for the practising oncology nurse.
While the premises of EBP seem highly appropriate on the surface, disquieting questions are raised when one examines the implications for the practising oncology nurse of attempting to implement EBP. There are clinical situations for which no empirical evidence exists on which to base nursing decisions. In some cases, empirical evidence is sparse and based on a mix of small, descriptive studies. Although guidelines exist for examining purely quantitative literature and are being developed for examining purely qualitative literature, no guidelines exist for evaluating a mixture. The process of operationalizing EBP is time-consuming and requires expertise which many oncology nurses lack. Does this mean that EBP is a laudable but impossible enterprise? I don't think so. Nurses will need to incorporate the empirical literature as well as other sources of knowledge to inform their clinical decision-making. In addition, oncology nurses need to apply and adapt models, such as Howell and Pelton's (2001), to make the best use of all sources of knowledge to facilitate excellent patient care.


Investigations on the Reaction of C3 and C6 α-Dicarbonyl Compounds with Hydroxytyrosol and Related Compounds under Competitive Conditions.
α-Dicarbonyl compounds are intermediates in reactions that lead to the formation of potentially harmful advanced glycation end-products. Carbonyl-trapping capacities of antiglycative substances have been traditionally limited to C2 and C3 α-dicarbonyl structures. Glyoxal (GO)-, methylglyoxal (MGO)-, 3-deoxyglucosone (3-DG)-, 3-deoxygalactosone (3-DGal)-, 3,4-dideoxyglucoson-3-ene-, and glucosone-trapping capacities of hydroxytyrosol (HT), hydroxytyrosol acetate (HTA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in simple (phenolic/dicarbonyl) and competitive model systems (phenolic/dicarbonyl1/dicarbonyl2) were investigated. HT and HTA were more effective for MGO than 3-DG and 3-DGal. Furthermore, DOPAC exerted higher trapping capacity than HT and HTA for C3 and C6 α-dicarbonyl compounds. In the competitive systems, HT-related substances did not show preference for trapping 3-DG or 3-DGal and behaved as in the simple systems. In the presence of MGO, however, HT-related substances were more effective for trapping MGO than C6 structures. The results demonstrate the C6 α-dicarbonyl-trapping capacities of HT, HTA, and DOPAC, with DOPAC exerting the highest activity.


Computerize your infection surveillance for improved patient care--and savings.
Kadlec Medical Center, in Richland, Wash., was able to reduce its nosocomial infection rate by 13 percent and save nearly dollar 576,000 in 15 months by: Working with the infection control department. Developing the business case for infection control initiatives. Conducting a preliminary financial analysis. Sharing data throughout the hospital--not just with the infection control department. Making the adoption of a computerized infection-tracking system a priority.


Lyme Arthritis in a Military Dependent Child transferred from Japan.
Lyme arthritis is the most common manifestation of late Lyme disease in children. Lyme disease is known to be endemic to Japan, but is rarely diagnosed. We report the identification and successful treatment of an adolescent male with Lyme arthritis who recently relocated with his family from a US Military base in Japan to Virginia. This case highlights the importance of obtaining a travel history from military members and their families who frequently relocate due to military orders. Military medical providers must be aware of tropical and travel-related illnesses and infections that may have been acquired at a prior duty station.


Zinc, copper, manganese, and selenium metabolism in thyroid disease.
This study was designed to evaluate trace metal metabolism in adults with thyroid diseases. Erythrocyte zinc values were significantly lower than normal in hyperthyroidism and higher in hypothyroidism. A significantly higher than normal urinary excretion of zinc was observed in hyperthyroidism. The mean concentrations of plasma and erythrocyte copper were significantly above normal in hyperthyroidism. Plasma selenium levels were significantly lower than normal in hyperthyroidism. No statistically significant difference was found in plasma zinc, erythrocyte manganese, or urine copper values between patients with thyroid diseases and healthy controls. The erythrocyte manganese content correlated well with thyroxine and triiodothyronine levels. Plasma prealbumin and retinol-binding protein correlated well with the erythrocyte zinc content but not with plasma zinc levels. There was no correlation between erythrocyte superoxide dismutase activity and erythrocyte copper or zinc concentrations. The results of this study suggest that the metabolism of zinc, copper, manganese, and selenium is abnormal in thyroid diseases.


Attention to threat in high and low trait-anxious individuals: a study using extremely threatening pictorial cues.
Previous research suggested that individuals with high trait anxiety have difficulties disengaging their attention from threatening cues, whereas those with low trait anxiety have no such attentional bias. However, according to some cognitive models of threat-related attention, low anxious people should show the same pattern as high anxious people when the threat value is large enough. To test this hypothesis, extremely threatening pictures were used as predictive location cues in a cue-target task. Neutral pictures were included as controls. 15 High Anxious participants and 17 Low Anxious participants were selected from 213 volunteers who all were police veterans. Analysis showed that threat cues produced greater facilitation effects than neutral cues, but this was not modulated by anxiety. This suggests that both high and low anxious individuals may have difficulties disengaging their attention from threat-cued locations when the threat value is large enough.


Highly sensitive refractive index sensor based on plastic optical fiber balloon structure.
A novel, to the best of our knowledge, design of plastic optical fiber (POF) balloon-based refractive index sensor for the detection of different concentrations of sodium chloride is proposed and experimentally investigated. The experimental characterization supports the finding that the transmission loss is sensitive to the external environment's targeted refractive index changes of the analyte. The proposed sensor achieves a maximum intensity-based sensitivity of 3105 RIU-1, resolution of 3.22 ×10-7, and the figure of merit (FOM) is 326 RIU-1 from 2 to 2.5 Mol/L of the analyte with the chosen refractive index changes at 680 nm for a diameter D = 0.1 cm of the POF balloon structure. Furthermore, a high linear performance of 0.9896 is achieved with good robustness against the fabrication imperfection. The ultra-sensitiveness to the refractive index with a simple demonstration of the POF balloon-based structure has potential applications in the chemical, biological, and food safety sensing fields.


Trained men display increased basal heat shock protein content of skeletal muscle.
1) To compare the baseline levels of heat shock and antioxidant protein content in the skeletal muscle of trained and untrained humans and 2) to characterize the exercise-induced stress response of aerobically trained human skeletal muscle to an acute exercise challenge. Resting muscle biopsies were obtained from the vastus lateralis muscle of six untrained and six aerobically trained young males. To characterize the stress response of a trained population, the trained subjects also performed a 45-min nondamaging running exercise protocol at an intensity corresponding to 75% of V O2max. Muscle biopsies were obtained from the vastus lateralis muscle at 48 h and 7 d after exercise. Trained subjects displayed significantly higher (P<0.05) resting levels of heat shock protein 60 (HSP60, 25%), alphaB-crystallin (43%), and manganese superoxide (MnSOD, 45%) protein content compared with untrained subjects. Trained subjects also exhibited no significant change (P > 0.05) in resting levels of HSP70 (16%), HSC70 (13%), and total superoxide dismutase (SOD) activity (46%) compared with untrained subjects. Resting HSP27 levels were unaffected by exercise training (P > 0.05). In the trained subjects, exercise failed to induce significant increases (P>0.05)in muscle content of HSP70, HSC70, HSP60, HSP27, alphaB-crystallin, and MnSOD protein content or in the activity of SOD at any time point after exercise. This study demonstrates for the first time that trained men display a selective up-regulation of basal heat shock and antioxidant protein content and do not exhibit a stress response to customary running exercise. It is suggested that an increase in these protective systems functions to maintain homeostasis during the stress of exercise by protecting against disruptions to the cytoskeleton/contractile machinery, by maintaining redox balance, and by facilitating mitochondrial biogenesis.


Incidence of and factors associated with catheter-related bloodstream infection in patients with advanced solid tumors on home parenteral nutrition managed using a standardized catheter care protocol.
Catheter-related bloodstream infections (CRBSIs) are associated with high morbidity and mortality as well as increased medical costs. Cancer patients, who are often immunocompromised, are susceptible to CRBSI while receiving home parenteral nutrition (HPN). We evaluated the incidence of and factors associated with CRBSIs in cancer patients undergoing HPN managed using a standardized catheter care protocol. This is a retrospective cohort study of 335 cancer patients receiving HPN between January 2012 and July 2015. The primary outcome of interest was the incidence of CRBSI expressed as events per 1000 HPN days. HPN days were calculated from the start date with the home infusion provider until the discontinuation of HPN, or the removal of the venous access device (VAD), or the death of the patient. The VADs used were either peripherally inserted central catheters (PICCs) or a subcutaneous implanted port or tunneled central catheters (TCCs). Univariate Poisson regression analyses were used to determine the variables associated with CRBSIs. Of 335 patients, 193 were females and 142 were males. The most common cancer types were colorectal, pancreatic, ovarian and stomach. A total of 408 VADs in 335 patients were studied, covering a total of 29,403 HPN days. Of 408 VADs, 206 (50.5%) were ports, 191 (46.8%) were PICCs, and 7 (2.7%) were TCCs. The median duration of HPN was 54 days. A total of 16 CRBSI episodes were recorded (8 in ports, 7 in PICCs and 1 in TCCs). The median duration from the start of HPN to the development of CRBSI episodes was 43.5 days. The overall incidence of CRBSI per 1000 HPN days was 0.54 (95% confidence interval: 0.32-0.86). Upon univariate analysis, no variables were found to be statistically significantly associated with CRBSI incidence. We found a low rate of CRBSI following a standardized catheter maintenance protocol in a high-risk oncology population undergoing HPN.


What's eating you? head lice (Pediculus humanus capitis).
The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Infestation continues in epidemic proportions in children of all socioeconomic groups. Although not implicated as a disease vector, infestation can lead to considerable distress, missed days of school, and secondary infections. Pyrethroids are recommended for treatment, but resistance is common. Newer agents, including benzyl alcohol and spinosad, have been developed to address this gap in care.


Plant antimutagenic agents, 2. Flavonoids.
A number of known prenylated flavonoids were isolated from Psoralea corylifolia using an assay procedure based on inhibition of the mutagenic action of 2-aminoanthracene on Salmonella typhimurium (T-98). All of these compounds were toxic rather than antimutagenic or desmutagenic. Bakuchiol [17], a known prenylated phenolic terpene, was also isolated; its activity was not due to toxicity. Biochanin A [4], a known isoflavone, was similarly isolated from Cicer arientinum and was active and nontoxic. Some of the above flavonoids were studied for inhibition of the mutagenicity of several different mutagens with results depending upon the structure of the flavonoid and the mutagen.


Mead Johnson Critical Care Symposium for the Practising Surgeon. 5. The diagnosis and management of common soft-tissue infections.
Soft-tissue bacterial infections range from the superficial, relatively benign form, readily treated by oral administration of antibiotics, to the highly lethal variety which requires extensive surgical débridement, administration of broad-spectrum antibiotics and patient monitoring in the intensive care unit. The key to patient survival in the latter group is early diagnosis and treatment. Those at risk of serious infections include diabetic and cirrhotic patients and trauma victims who have been treated either surgically or medically. In addition to awareness of the possibility of serious infection, x-ray films of the soft tissue to show gas, aspiration of fluid collections for Gram's staining and local incision of the tissue to inspect fascia and muscle are all useful aids in diagnosis. This review attempts to classify soft-tissue infections and to recommend an approach to diagnosis and management.


The outcome of oral mucosal grafts to the orbit: a three-and-a-half-year study.
A 3 1/2 year audit of the outcome of oral mucosal grafts was conducted at the occuloplastic service of Wentworth Hospital, Durban, South Africa. We studied 17 consecutive patients with ages ranging from 2 years to 83 years; young males predominated. The causative pathologies included six gunshot wounds, three retinoblastomas, two congenital abnormalities, two childhood traumas, a chemical burn, an occular pemphigoid, a stab wound and a firework injury. We treated 14 patients for a contracted socket, and performed mucosal grafts to the globe in the other three. Prostheses were successfully fitted in 12 of the patients with a contracted socket and in one patient with microphthalmia. Of the former patients, 10 had a good result and two had a fair result. Out of the 14 patients with a contracted socket, 10 required a repeat procedure. An onlay prosthesis was used instead of an inlay prosthesis in one patient because of the child's social circumstances; one patient was lost to follow-up. During the first year of the study, a thermoplastic conformer of Stent's composition was used. This was later changed to a plug of medicated paraffin gauze, which was easier to use. A permanent prosthesis was fitted 1 week postoperatively. The crucial factor for success was that there should be no delay between removing the plug and inserting the prosthesis. A single-stage reconstruction of the orbital wall and socket using costal cartilage and temporalis fascia together with an oral mucosal graft is discussed for reconstruction following gunshot wounds or retinoblastoma enucleation and radiotherapy. Oral mucosal grafts can be used successfully to reconstruct the conjunctiva on the globe and in the fornices.


Analysis of the Revision Process by American Journal of Roentgenology Reviewers and Section Editors: Metrics of Rejected Manuscripts and Their Final Disposition.
The objective of this study was to evaluate metrics related to manuscripts rejected by AJR with and without review during 2014 and to determine their final disposition: no record of eventual publication, eventually published, published with modified authors and title, published with the same title but modified authors, and published with modified title but the same authors. A total of 1245 unsolicited manuscripts submitted from January to December 2014 were included in this retrospective analysis. Data were extracted from the AJR's manuscript submission system. Standard statistical analysis was used to assess the fate of a sample of 200 rejected manuscripts. Of the 200 manuscripts studied, 117 (59%) were published in other scientific journals (61 with revision, 56 without revision; Χ2 = 0.329, p = 0.566). Thirty-two of the 61 manuscripts (52%) rejected after peer review were later published in other journals without changes in their titles or authors, 16 (26%) with changes only in authors, 10 (16%) with changes only in their titles, and three (5%) with changes in authors and titles. Twenty-six of the 56 manuscripts (46%) rejected without peer review were published without changes in their titles or authors, 17 (30%) with changes in authors, 11 (20%) with changes only in their titles, and two (4%) with changes in both authors and titles (p = 0.686). Ten articles were published in open access journals. Of the remaining articles, those that had been reviewed were published in journals with a mean impact factor ± SD of 2.37 ± 1.30, and those that had not been reviewed were published in journals with a mean impact factor of 2.04 ± 1.06. Analysis of the 25th and 75th percentiles revealed that values were also higher for the group rejected with review (Wilcoxon rank sum test: W = 1679, p = 0.1127). Out of 61 articles rejected for publication with review, 52.5% were published with changes to their abstracts, whereas the remaining 47.5% were unchanged. This analysis found that manuscripts submitted to AJR that were rejected after review were published in journals with higher impact factors than those rejected without review. The commentaries provided by AJR reviewers and section editors appear to improve the quality of rejected manuscripts and thus contribute to the scientific community.


Genipin suppression of fibrogenic behaviors of the alpha-TN4 lens epithelial cell line.
To determine in a lens epithelial cell line, alpha-TN4, whether genipin, an intestinal metabolite component of the herbal medicine inchin-ko-to, suppresses profibrogenic myofibroblast generation and upregulation of fibrogenic cytokines and to evaluate the potential benefit of the medicine in preventing posterior capsule opacification (PCO). Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. In this study, alpha-TN4 cell proliferation, migration, and expression of alpha-smooth muscle actin (alpha-SMA), the hallmark of myofibroblast generation, were assayed with a colorimetric assay, scratch wound assay, immunohistochemistry, and Western blot analysis. Gene expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) was characterized with real-time reverse transcription-polymerase chain reaction. In addition, p38 mitogen-activated protein kinase (p 38 MAPK), extracellular signal-regulated kinase (ERK) limb, and Smad signalings were evaluated by Western blotting and immunohistochemistry. Cytotoxicity of genipin was evaluated using a commercial colorimetric assay kit for nuclear matrix protein 41/7 (NMP41/7) in culture medium. Genipin suppressed cell proliferation and migration in association with inhibition of Smad and p38 MAPK phosphorylation, although ERK signaling was enhanced. Genipin suppressed mRNA expression of TGF-beta1 and CTGF. Cytoplasmic fiber formation declined based on less intense alpha-SMA immunocytochemical staining. However, alpha-SMA protein expression was actually not altered. This negative result suggests that genipin attenuated formation of alpha-SMA-containing cytoskeleton. Treatment of the cells with genipin for 48 hours did not increase the release of NMP41/7 to the medium, indicating this compound is not cytotoxic. Because genipin suppressed alpha-TN4 lens cell fibrogenic behaviors, it may be of therapeutic value in preventing PCO.


Amyloid-β-Induced Changes in Molecular Clock Properties and Cellular Bioenergetics.
Ageing is an inevitable biological process that results in a progressive structural and functional decline, as well as biochemical alterations that altogether lead to reduced ability to adapt to environmental changes. As clock oscillations and clock-controlled rhythms are not resilient to the aging process, aging of the circadian system may also increase susceptibility to age-related pathologies such as Alzheimer's disease (AD). Besides the amyloid-beta protein (Aβ)-induced metabolic decline and neuronal toxicity in AD, numerous studies have demonstrated that the disruption of sleep and circadian rhythms is one of the common and earliest signs of the disease. In this study, we addressed the questions of whether Aβ contributes to an abnormal molecular circadian clock leading to a bioenergetic imbalance. For this purpose, we used different oscillator cellular models: human skin fibroblasts, human glioma cells, as well as mouse primary cortical and hippocampal neurons. We first evaluated the circadian period length, a molecular clock property, in the presence of different Aβ species. We report here that physiologically relevant Aβ1-42 concentrations ranging from 10 to 500 nM induced an increase of the period length in human skin fibroblasts, human A172 glioma cells as well as in mouse primary neurons whereas the reverse control peptide Aβ42-1, which is devoid of toxic action, did not influence the circadian period length within the same concentration range. To better understand the underlying mechanisms that are involved in the Aβ-related alterations of the circadian clock, we examined the cellular metabolic state in the human primary skin fibroblast model. Notably, under normal conditions, ATP levels displayed circadian oscillations, which correspond to the respective circadian pattern of mitochondrial respiration. In contrast, Aβ1-42 treatment provoked a strong dampening in the metabolic oscillations of ATP levels as well as mitochondrial respiration and in addition, induced an increased oxidized state. Overall, we gain here new insights into the deleterious cycle involved in Aβ-induced decay of the circadian rhythms leading to metabolic deficits, which may contribute to the failure in mitochondrial energy metabolism associated with the pathogenesis of AD.


Hereditary Dilated Cardiomyopathy: Recent Advances in Genetic Diagnostics.
Dilated cardiomyopathy (DCM) is the most common cause of heart failure in young adults and up to 50% of idiopathic DCM is thought to be caused by genetic mutations in candidate genes. Although a genetic diagnosis can confirm a clinical diagnosis of hereditary DCM, genetic testing has not been easily accessible due to genetic heterogeneity and complexity. Next-generation sequencing (NGS) technologies have recently been introduced, and genetic testing for multiple genes is currently available and more than 40 different genes have been associated with DCM. In Korea, the government has supported genetic diagnosis for patients with idiopathic DCM. When a targeted gene panel with NGS technology was used, the detection rate was about 40%. MYBPC3, LMNA, and MYH7 were the most frequently identified genes, and the pattern of causative genes was different from previous reports. In the analysis, a significant number of subjects (42.0%) had rare or novel unspecified variants in DCM candidate genes, which should be assessed as potential causative mutations. Developing a more comprehensive test panel with additional DCM genes and whole exome sequencing will improve the detection rate, and allow genetic testing to be an option for patients with idiopathic DCM. However, all genetic variations are not pathogenic mutations, and the majority of reported mutations in DCM are unique to a single family, which makes genetic data interpretation more difficult. Therefore, clinical features and familial history integration are needed to improve clinical decision making.


Triple-balloon pulmonary valvuloplasty: an advantageous technique for percutaneous repair of pulmonary valve stenosis in the large pediatric and adult patients.
This report describes a new valvuloplasty procedure for the treatment of pulmonary valve stenosis (PVS) and large pulmonary valve annulus (PVA) diameters using a triple-balloon valvuloplasty (TBV) technique. We sought to demonstrate the safety and efficacy of this new technique. Percutaneous balloon pulmonary valvuloplasty (BPV) is the preferred treatment for PVS. BPV in older patients with large PVA remains a challenge, even when the double-balloon valvuloplasty technique is performed. The technique was first attempted in a case where a large single balloon was unsuccessful and double-balloon valvuloplasty met with technical difficulties. Three subsequent patients underwent the procedure safely and successfully. An algorithm is presented to determine balloon size for TBV. The median PVA diameter was 23.9 mm. Balloon diameters ranged from 12 to 18 mm. The median peak right ventricular-to-pulmonary artery systolic pressure gradient was 43.5 mm Hg before valvuloplasty and was reduced to 12 mm Hg following intervention. No major complications were encountered. Percutaneous valvuloplasty using TBV can be performed safely and provides excellent clinical results. This technique offers advantages over single-balloon and double-balloon valvuloplasty techniques, especially in treatment of PVS in large pediatric or adult patients.


The establishment of rat model in myocardial ischemia with psychological stress.
Psychological stress can provoke and aggravate myocardial ischemia, and this stress can even trigger acute coronary syndromes or sudden cardiac death. Therefore, for the first time, this study aimed to investigate the method for establishing a rat model of myocardial ischemia with psychological stress and its evaluation. Forty male Wistar rats were randomly divided into the sham (S, n=10), myocardial infarct (MI, n=10), psychological stress (MODEL, n=10), and myocardial infarct with psychological stress (MI + MODEL, n=10) groups. The rat model of psychological stress was established by measuring the data from activity restriction for 6 hours and followed by tail clamp stimulation for 5 minutes every day for 14 days. The rat model of the myocardial infarct with psychological stress was established by occluding the left coronary anterior descending artery in the MODEL rats. The body weight of rats was measured daily, the behavior parameters were evaluated via open-field test and elevated plus-maze, tongue color and sublingual vein were observed, rats' acral blood flow perfusion was detected by PIM II (Perfusion Imager II), mesenteric microcirculation was measured by capillaroscopy, and hemodynamics was measured by a polygraph system. An automatic biochemical analyzer determined the content of serum cTnT (cardiac troponin T), Hcy (homocysteine), and activity of LDH (lactate dehydrogenase). Myocardial infarct size was measured with TTC (triphenyhetrazolium chloride) staining. We found that rats in the psychological stress (MODEL) group were characterized by coarse hair, dark mucosa of the lips and claw, low spirit, decreased body weight, and increased anxiety. Compared with rats in the sham group, rats in the MODEL + MI group showed decreased mesenteric blood flow, narrowed arteriole and venule diameter, reduced acral blood flow perfusion, and LV ±dp/dtmax (the maximal rate of the increased and decrease of left ventricular pressure), as well as increased serum content of cTnT, Hcy, and LDH activity. Compared with the MI group, rats in the MODEL + MI group showed deteriorated microcirculation dysfunction manifested as a dark tongue color of deep purple, prominently extended and varicose sublingual vein, and aggravated myocardial damage in the form of increased infarct size and LDH leakage. In conclusion, the rat model of myocardial ischemia with psychological stress was successfully established, and manifested as aggravating behavioral disorder, mesenteric microcirculation and left ventricular dysfunction, and myocardial damage.


Block sparsity promoting algorithm for efficient construction of cluster expansion models for multicomponent alloys.
Multicomponent alloys are gaining significance as drivers of technological breakthroughs especially in structural and energy storage materials. The vast configuration space of these materials prohibit computational modeling using first-principles based methods alone. The cluster expansion (CE) method is the most widely used tool for modeling configurational disorder in alloys. CE relies on machine learning algorithms to train Hamiltonians and uses first-principles calculated data as training sets. In this paper we present a new compressive sensing-based algorithm for the efficient construction of CE Hamiltonians of multicomponent alloys. Our algorithm constructs highly sparse and physically reasonable models from a carefully selected small training set of alloy structures. Compared to conventional fitting algorithms, the algorithm achieves more than 50% reduction in the training set size. The resultant sparse models can sample the configuration space at least 3 × faster. We demonstrate this algorithm on 4 different alloy systems, namely Ag-Au, Ag-Au-Cu, Ag-Au-Cu-Pd and (Ge,Sn)(S,Se,Te).The sparse CE models for these alloys can rapidly reproduce known ground state orderings and order-disorder transitions. Our method can truly enable high-throughput multicomponent alloy thermodynamics by reducing the cost associated with model construction and configuration sampling.


Vascular endothelial growth factor receptors: expression and function in solid tumors.
Vascular endothelial growth factor (VEGF) and its family members are important mediators of tumor angiogenesis. The multiple functions of the VEGF are mediated through complex and selective interactions between the ligands, their high-affinity tyrosine kinase receptors, and co-receptors (neuropilins). While these receptors are historically described as being exclusively expressed on endothelial cells, emerging evidence has documented expression of these receptors on a number of nonendothelial cells, including tumor cells. The VEGF receptors (VEGFR) have also been shown to be functional in a number of nonendothelial systems, where they may be targets for anti-VEGF therapy. This article will review the basic effects and interactions of the VEGFRs on endothelial cells and the evidence for their expression and function on tumor cells. The novel expression of VEGFRs on tumor cells contributes to the understanding of the complex roles of VEGF within the tumor microenvironment, potentially affecting both endothelial cells and tumor cells expressing the VEGFRs. This elucidation of VEGF activity may further refine antineoplastic regimens for solid malignancies.


[+Gz protection provided by tilt-back seat and GZ-2 anti-G suit].
To investigate the +Gz protection provided by tilt-back seat and GZ-2 anti-G suit. 6 subjects were exposed to centrifuge and onset rate is 3 G/s. First, their relaxed +Gz tolerances were determined while using tilt-back seat of 13 degrees. Secondly, it was their +Gz tolerance provided by pressurized GZ-2 anti-G suit and tilt-back seat of 13 degrees. Finally, their +Gz tolerances while using pressurized GZ-2 anti-G suit and tilt-back seat of 45 degrees were determined. The difference between the first and the third result was the +Gz protection that pressurized GZ-2 anti-G suit and tilt-back seat of 45 degrees offered. +Gz protection of pressurized GZ-2 anti-G suit and tilt-back seat of 13 degrees was 3.06 G, and +Gz protection of pressurized GZ-2 anti-G suit and tilt-back seat of 45 degrees was 4.13 G, which had an increase of 1.06 G. Tilt-back seat of 45 degrees can greatly enhance +Gz tolerances of human.


[The prognostic factors of early mortality in bone marrow transplantation in patients with chronic myeloid leukemia].
The use of bone marrow transplantation (BMT) in leukemia treatment is associated with high early morbid-mortality rates. Therefore, to identify morbid-mortality risk factors in this setting can be useful to improve therapeutic ratio. We studied 15 variables in 46 patients with chronic myeloid leukemia (CML) treated with cyclophosphamide, total body irradiation (TBI) and allogeneic BMT. A multivariant analysis with an unconditional logistic regression model was used. Variables found to be related with early mortality included general state of health and acute graft versus host disease. Patients with a Karnofsky index (KI) between 60% and 80% had a higher risk of early death than those with a KI between 90 and 100%. Patients who developed severe (grade II-IV) acute graft versus host disease (AGVHD), had a relative risk of 15.62 (IC 95%: 3.16-77.34) compared with those who do not. Time between diagnosis and BMT contributed to the creation of the mathematical model without reaching statistical significance. In this series and in the range of the parameters analysed, general state of health according to KI, and the appearance of severe AGVHD are the variables related with a higher risk of early mortality.