Adipocyte beta-adrenergic receptors. Identification and subcellular localization by (-)-[3H]dihydroalprenolol binding.
(--)-[3H]Dihydroalprenolol, a potent beta-adrenergic antagonist, was used to identify binding sites which have the characteristics of beta-adrenergic receptors in membranes from rat adipocytes. The subcellular distribution of the (--)-[3H]Dihydroalprenolol binding sites was examined. The binding sites were predominantly in the plasma membrane fraction, consistent with the proposal that the physiologically significant beta-adrenergic receptors are localized in the adipocyte plasma membrane. Binding of (--)-[3H]dihydroalprenolol to unfractionated adipose membranes was saturable with 0.24 pmol bound/mg of protein at saturation. Half-maximal saturation occurred at 15 nM providing an estimate of the equilibrium dissociation constant, KD, for the interaction of (--)-[3H]dihydroalprenolol with its adipocyte receptor. Kinetic analysis of (--)-[3H]dihydroalprenolol binding provided a value of 2.4 X 10(7) M-1 min-1 for the forward bimolecular rate constant, k1. Dissociation of (--)-[3H]dihydroalprenolol was a first order reaction with a rate constant, k2, of 2.94 X 10(-1) min-1. The ratio k2/k1 = 12 nM provides an independent measurement of the KD for the interaction of (--)-[3H]dihydroalprenolol with its receptor which is in good agreement with the values obtained by steady state analysis (12 to 15 nM). Beta-Adrenergic agonists and antagonists competed for the binding sites in unfractionated adipocyte membranes with a typical beta1-adrenergic specificity. The order of potency of agonists was (--)-isoproterenol greater than (--)-norepinephrine congruent to (--)-epinephrine. The beta-adrenergic antagonist, (--)-propranolol, potently competed for the binding sites with a KD of 17 nM. Compounds such as dihydroxyphenylaline, dihydroxymandelic acid, normetanephrine, pyrocatechol, and phentolamine which are structurally related to beta-adrenergic agents, but are devoid of beta-adrenergic physiologicl effects in adipocytes, did not compete for the binding sites. Binding was highly stereospecific, the (+) isomers of adrenergic agonists and antagonists requiring 23- to 330-fold higher concentrations to half-maximally inhibit binding than the corresponding (--) stereoisomers. (--)-[3H]Dihydroalprenolol binding was examined highly enriched plasma membrane, mitochondrial, and microsomal (endoplasmic reticulum) fractions of adipocytes. In the presence of 12 nM (--)-[3H]dihydroalprenolol, the specific activity of binding in the plasma membrane fraction was 5-fold higher than that of the mitochondrial fraction and 8-fold higher than that of the microsomal (endoplasmic reticulum) fraction. The specificity and affinity characteristics of the plasma membrane binding sites were found to be virtually identical with those of the unfractionated adipocyte membranes. The observation that (--)-[3H]dihydroalprenolol binding sites are predominantly localized in the plasma membrane fraction suggests the potential usefulness of this ligand as a marker for adipocyte plasma membranes.


Data-Driven Approach toward Long-Term Equipment Condition Assessment in Sterile Drug Product Manufacturing.
A two-stage data-driven methodology for long-term equipment condition assessment in drug product manufacturing is presented with a case study for a commercially operating aseptic filling line. The methodology leverages process monitoring data. Sensor measurements are partitioned using process information and maintenance schedules that are available on different databases. Data is processed to tackle heterogeneity in sources and formats. The data is cleaned to remove the effects of short-term variabilities and to enhance underlying long-term trends. Two approaches are presented for data analysis: first, anomaly detection using independent component analysis (ICA), where clusters of outliers are identified. The frequency and timing of such outliers yield important insights regarding maintenance schedules and actions. The second approach enables condition monitoring using principal component analysis (PCA). Long-term operational baselines are identified and shifts therein are linked with different process and equipment faults. This approach highlights the impact of equipment deterioration on shifting operational data baselines and shows the potential for the combined application of ICA and PCA for equipment condition monitoring. It can be applied within predictive maintenance applications where the installation of new specialized sensors is difficult, like in the pharmaceutical industry.


Adrenal Venous Sampling Via an Antecubital Approach in Primary Aldosteronism: A Multicenter Study.
Adrenal venous sampling (AVS) is considered as the gold standard for differentiating unilateral and bilateral forms of primary aldosteronism. Currently, almost all AVS procedures are performed via femoral vein access. The aim of this study was to evaluate the success rate and safety of AVS via an antecubital approach. In a retrospective multicenter study involving 7 Chinese medical centers, patients with primary aldosteronism underwent AVS via an antecubital approach between January 2012 and December 2018 were analyzed. Successful sampling was determined by selectivity index (cortisol in the adrenal vein/cortisol in inferior vena cava) >2. A total of 1226 participants (mean age, 47.1 years; 57.9% male) were included. The puncture site was right and left antecubital vein in 1211(98.8%), and 15(1.2%) patients. The access of 6 patients (0.5%) was changed to right femoral vein due to the failure of antecubital vein cannulation or anatomic variation of adrenal vein. The success rate of bilateral, right and left sampling was 91.5%, 94.9% and 95.1%, respectively. The success rate of bilateral, right, left sampling increased from 82.9% ,87.1% and 88.6% during the initial 70 cases (total of initial 10 cases each center) to 92.0% (P=0.012), 95.3% (P=0.008) and 95.5% (P=0.018) with subsequent cases. Adrenal vein rupture occurred in 5 patients (0.46%), with no sequelae. The multicenter study demonstrated that AVS via an antecubital approach was safe and feasible, with a high rate of successful sampling, which may be an alternative to the femoral vein access method.


Emergency Intubation outside Operating Room/Intensive Care Unit Settings: Are We Following the Recommendations for Safe Practice?
Although international guidelines have been developed for emergency tracheal intubation (ETI), there is little evidence of their applicability in developing countries. The aim of this study was done to evaluate the different methods of ETI that are practiced among anesthetist and anesthesia trainees in India outside operating room (OR)/intensive care unit (ICU) settings. This was prospective observational audit did among anesthesia personals managing ETI outside OR and ICU. The study was conducted through an online survey using electronic media. Certified anesthetists and anesthesia trainees were sent a questionnaire where they were asked to complete and submit it online. Out of 145 respondents, 52% were certified anesthetists. Availability of equipment, technical staff, and visual monitors was a big constraint. About 28% of the participants do not examine the airway before ETI, 61% of participants invariably do not perform rapid sequence induction and intubation, and 89% of the participants have only the bougie at their disposal with the availability of videolaryngoscope (10%) and Fibreoptic bronchoscopy (FOB) (6%) being scarce. About 12% of the respondents use capnography for ETI confirmation. Only 48% of the participants accompany the patient during shifting. Our survey has reported wide disparity during ETI with poor compliance to the international guidelines.


Structure and function of the pre-T cell receptor.
The pre-T cell receptor (pre-TCR) that minimally consists of the TCR beta chain and the disulfide-linked pre-T cell receptor alpha (pT alpha) chain in association with signal-transducing CD3 molecules rescues from programmed cell death cells with productive TCR beta rearrangements. The pre-TCR induces expansion and differentiation of these cells such that they become TCR alpha beta bearing CD4+8+ thymocytes, which express only a single TCR beta chain and then either die of neglect or--upon TCR-ligand interaction--undergo either positive or negative selection. The newly discovered pT alpha gene encodes a transmembrane protein that belongs to the Ig superfamily and contains a cytoplasmic tail that, however, has no essential function in signal transduction, which is mediated by CD3 molecules and most likely p56lck. Experiments in pT alpha gene-deficient mice show that the pre-TCR has a crucial role in maturation as well as allelic exclusion of alpha beta T cells but is not required for the development of gamma delta-expressing cells. The function of the pre-TCR cannot be fully assumed by an alpha beta TCR that is expressed abnormally early in T cell development.


Elevated serum ferritin level as a predictor of reduced survival in patients with sporadic amyotrophic lateral sclerosis in China: a retrospective study.
Objective: The objective of this study was to compare iron metabolic variables in the serum and cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (sALS) with those of patients with multiple system atrophy (MSA) and control subjects. We also assessed the correlations of these variables with sALS progression and severity and estimated their roles in predicting prognosis. Methods: We retrospectively collected iron metabolic parameters, including serum levels of iron, ferritin, transferrin levels and total iron binding capacity and the CSF level of ferritin, from 435 sALS patients, 176 MSA patients and 431 control subjects. Results: Serum ferritin levels were significantly higher in the sALS group compared with the MSA and control groups in both males (p = 0.001 and p < 0.0001, respectively) and females (p = 0.034 and p < 0.0001, respectively). However, serum transferrin levels were significantly lower in females of the sALS group compared with the MSA (p = 0.016) and control (p = 0.015) groups. The CSF ferritin level and the serum levels of total iron binding capacity and iron were similar among the sALS, MSA and control groups. Survival analysis demonstrated that higher serum ferritin levels were predictors of reduced survival of sALS patients. No correlations between iron metabolic variables and clinical parameters were found. Conclusion: An elevated serum ferritin level is associated with reduced survival of sALS patients. However, the levels of iron metabolic parameters were not associated with clinical deterioration or disease severity at diagnosis.


Relation between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size in patients with myocardial infarction.
We analyzed signal-averaged electrocardiograms (ECG) obtained in 50 patients with recent myocardial infarction (RMI: 25 anterior and 25 inferior) and 20 normal subjects to determine the relationship between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size. We examined (1) the root mean square voltage (RMS10-40, microV), (2) the integration (A10-40, microV.msec) at 10-msec intervals over the first 40 msec of the signal-averaged QRS complex, and (3) the intervals (T) of the magnitude of the signal-averaged ECG achieved at 10-microV intervals over the first 40 microV (T10-40, msec). The mean RMS10-40 (p < 0.01) and A10-40 (A10, p < 0.05; A20-40, p < 0.01) were significantly lower and the T10-40 (p < 0.01) was significantly longer in RMI patients than in normal subjects. The RMS10-40 (p < 0.01) and A10-40 (p < 0.05) were significantly lower and the T10-40 (T10.20, p < 0.01; T30.40, p < 0.05) was significantly longer in patients with anterior RMI patients than in patients with inferior RMI. The A30 was correlated with the ejection fraction and total creatine kinase (CK) release in all patients (r = 0.73, and -0.78, respectively, p < 0.001). These results suggest that the A30 may be an important predictor of ventricular dysfunction and infarct size in patients with RMI.


Causes of intravenous medication errors: an ethnographic study.
Intravenous (IV) medication errors are frequent events. They are associated with considerable harm, but little is known about their causes. Human error theory is increasingly used to understand adverse events in medicine, but has not yet been applied to study IV errors. Our aim was to investigate causes of errors in IV drug preparation and administration using a framework of human error theory. A trained and experienced observer accompanied nurses during IV drug rounds on 10 wards in two hospitals (one university teaching hospital and one non-teaching hospital) in the UK. Information came from observation and talking informally to staff. Human error theory was used to analyse the causes of IV error. 265 IV drug errors were identified during observation of 483 drug preparations and 447 administrations. The most common type of error was the deliberate violation of guidelines when injecting bolus doses faster than the recommended speed of 3-5 minutes. Causes included a lack of perceived risk, poor role models, and available technology. Mistakes occurred when drug preparation or administration involved uncommon procedures such as the preparation of very small volumes or the use of unusual drug vial presentations. Causes included a lack of knowledge of preparation or administration procedures and complex design of equipment. Underlying problems were the cultural context allowing unsafe drug use, the failure to teach practical aspects of drug handling, and design failures. Training needs and design issues should be addressed to reduce the rate of IV drug preparation and administration errors. This needs a coordinated approach from practitioners, regulators, and the pharmaceutical industry.


Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge.
Anti-IgE (omalizumab) inhibited early and late asthmatic reactions and infiltration of inflammatory cells in asthmatic bronchial biopsies at baseline. The effect of chronic allergen exposure on these outcomes is unknown. Repeat allergen challenge in human skin represents a suitable model to address this question. To study the effect of anti-IgE (omalizumab) on early-phase (EPR) and late-phase (LPR) skin reactions and cellular infiltration by using a repeat skin allergen challenge designed to imitate chronic allergen exposure. Twenty-four atopic allergic volunteers received omalizumab or placebo for 12 weeks. Paired intradermal challenges of allergen (30 biological units) and diluent control were administered on 9 occasions at 2-week intervals. Early-phase and late-phase skin reactions and cellular infiltration in skin biopsies (using immunohistochemistry and in situ hybridization) were measured at intervals. Compared with placebo, omalizumab-treated patients had a progressive reduction in the LPR that was significantly greater than its effect on the EPR (median, --63% vs--24% respectively; P=.009). In addition, significant reduction of the LPR was reached within 2 weeks of commencing treatment, compared with 8 weeks for the EPR. There was a priming effect of repeated allergen challenge on infiltration of eosinophil, neutrophil, T(H)2 (CD3(+)/IL-4(+)), and total FcepsilonRI(+) cells in patients on placebo that was abrogated in those receiving omalizumab. The more marked effect of omalizumab on the LPR and prevention of the repeat-dose priming effect on several inflammatory cell types support a role for anti-IgE treatment in conditions associated with chronic allergic inflammation.


Biophoton research in blood reveals its holistic properties.
Monitoring of spontaneous and luminophore amplified photon emission (PE) from non-diluted human blood under resting conditions and artificially induced immune reaction revealed that blood is a continuous source of biophotons indicating that it persists in electronically excited state. This state is pumped through generation of electron excitation produced in reactive oxygen species (ROS) reactions. Excited state of blood and of neutrophil suspensions (primary sources of ROS in blood) is an oscillatory one suggesting of interaction between individual sources of electron excitation. Excited state of blood is extremely sensitive to the tiniest fluctuations of external photonic fields but resistant to temperature variations as reflected in hysteresis of PE in response to temperature variations. These data suggest that blood is a highly cooperative non-equilibrium and non-linear system, whose components unceasingly interact in time and space. At least in part this property is provided by the ability of blood to store energy of electron excitation that is produced in course of its own normal metabolism. From a practical point of view analysis of these qualities of blood may be a basement of new approach to diagnostic procedures.


Positive control of tylosin biosynthesis: pivotal role of TylR.
Control of tylosin production in Streptomyces fradiae features interplay between a repressor, TylQ, and an activator, TylS, during regulation of tylR. The latter encodes a pathway-specific activator that controls most of the tylosin-biosynthetic (tyl) genes that are subject to regulation. This was established by targeted gene disruption applied separately to tylR and tylS together with transcript analysis involving reverse transcription polymerase chain reaction (RT-PCR). TylR controls multiple genes that encode the synthesis or addition of all three tylosin sugars, plus polyketide ring oxidation, and at least one of the polyketide synthase (PKS) megagenes, tylGI. (Expression of a few tyl genes, plus the resistance determinants tlrB and tlrD, together with some ancillary or unassigned genes, is not apparently regulated during fermentation, consistent with constitutive expression.) In contrast, the only gene known for sure to be directly controlled by TylS is tylR, and there are very few additional candidates. These include the mycinose-biosynthetic gene, tylJ, and two previously unassigned genes, ORF12* (tylU) plus ORF11* (tylV). TylS also controls the PKS genes [tylGIII-tylGIV-tylGV] although not in obligatory fashion. These genes can be transcribed (i.e. tylosin can be produced) in a tylS-KO strain by forcing overexpression of tylR using a foreign promoter. We therefore suspect that TylS might control the PKS genes indirectly, although this remains to be established unequivocally. Conceivably, the direct effects of TylS are exerted exclusively on other regulators. Tylosin production levels were elevated when tylS or (especially) tylR was overexpressed in S. fradiae wild-type and yield increments of industrial significance were generated by similar manipulation of an enhanced production strain.


Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL-286, a novel retinoic acid receptor-β agonist for treatment of spinal cord injury, in male healthy participants.
KCL-286 is an orally available agonist that activates the retinoic acid receptor (RAR) β2, a transcription factor which stimulates axonal outgrowth. The investigational medicinal product is being developed for treatment of spinal cord injury (SCI). This adaptive dose escalation study evaluated the tolerability, safety and pharmacokinetics and pharmacodynamic activity of KCL-286 in male healthy volunteers to establish dosing to be used in the SCI patient population. The design was a double blind, randomized, placebo-controlled dose escalation study in 2 parts: a single ascending dose adaptive design with a food interaction arm, and a multiple ascending dose design. RARβ2 mRNA expression was evaluated in white blood cells. At the highest single and multiple ascending doses (100 mg), no trends or clinically important differences were noted in the incidence or intensity of adverse events (AEs), serious AEs or other safety assessments with none leading to withdrawal from the study. The AEs were dry skin, rash, skin exfoliation, raised liver enzymes and eye disorders. There was an increase in mean maximum observed concentration and area under the plasma concentration-time curve up to 24 h showing a trend to subproportionality with dose. RARβ2 was upregulated by the investigational medicinal product in white blood cells. KCL-286 was well tolerated by healthy human participants following doses that exceeded potentially clinically relevant plasma exposures based on preclinical in vivo models. Target engagement shows the drug candidate activates its receptor. These findings support further development of KCL-286 as a novel oral treatment for SCI.


Antimicrobial susceptibility testing of Serpulina hyodysenteriae.
The macrobroth dilution technique was used to test the in-vitro effectiveness of 4 commonly used antimicrobial agents against 23 Australian isolates and 7 overseas strains of Serpulina hyodysenteriae. Minimum inhibitory concentrations and minimum bactericidal concentrations were determined. The growth of 90% of isolates was inhibited by dimetridazole at a concentration of 4 micrograms/mL, and by tiamulin at 8 micrograms/mL. Australian isolates resistant to both antimicrobial agents were identified. Lincomycin was less effective than these antimicrobial agents, with 90% of isolates requiring a concentration of 128 micrograms/mL for inhibition of growth, and 54% being susceptible at 64 micrograms/mL. Tylosin did not prevent the growth of the majority of S hyodysenteriae isolates tested, and 90% were resistant to concentrations of > or = 128 micrograms/mL. Resistant isolates came from different geographical areas. Resistance was not related to overall genetic background of the spirochaetes, and was not correlated with the presence of plasmids or the serogroup of the isolates.


Meningeal worm is a long-lived parasitic nematode in white-tailed deer.
A natural infection of the meningeal worm, Parelaphostrongylus tenuis, persisted for at least 3.7 yr in a white-tailed deer (Odocoileus virginianus). The deer was 5-7 yr old and was shedding dorsal-spined nematode larvae at the time of quarantine. Larvae were extracted from all fecal samples collected up to 730 days post-quarantine (dpq) and thereafter only at 862 dpq and at necropsy (1,350 dpq). Live adults of P. tenuis, one male and one female, were recovered from the cranium at necropsy. Parelaphostrongylus tenuis infections are long lived and latent periods may be extended. Our findings reaffirm the need for reliable antemortem diagnosis to identify non-patent P. tenuis infections to prevent inadvertent introduction of infected animals to non-endemic areas.


A Newly Isolated Strain Lysobacter brunescens YQ20 and Its Performance on Wool Waste Biodegradation.
Wool keratin is difficult to degrade as comparing to feathers because of its tough secondary structure. In order to develop an approach for high-value utilization of wool fiber waste by keratinolytic microorganisms, which is produced from shearing, weaving, and industrial processing of wool, screening of wool-degrading bacterium with high degradation efficiency were performed in this study. To this end, Lysobacter brunescens YQ20 was identified and characterized. The optimized conditions for wool degradation were pH 9.0 and 37°C with 20% liquid volume of Erlenmeyer flask. After fermentation, 15 essential amino acids were detected when wool fiber waste was fermented. The total amino acids produced from 1% wool per hour were 13.7 mg/L. The concentration was 8.6-fold higher than that produced by the strain Stenotrophomonas maltophilia BBE11-1, which had previously been reported to have the highest wool-degrading capacity. Our study reports the first Lysobacter strain that exhibits efficient wool degradation and yields higher concentrations of amino acids than previously reported strains. Whole-genome sequencing indicated that there were 18 keratinase-like genes in the genome of YQ20, which exhibited a long evolutionary distance from those of Bacillus. Therefore, L. brunescens YQ20 may have applications in the environmentally friendly management of wool waste as fertilizer in agriculture.


Magnesium and the lungs.
Recently, there has been considerable interest generated in the possible importance of magnesium ions (Mg2+) in the regulation of bronchial smooth muscle tone and pulmonary vascular tone. These factors have aroused interest in the possible utilization of Mg salts in the treatment of lung diseases (e.g., asthma, allergies, and pulmonary hypertension). Evidence is reviewed which indicates that Mg2+ can influence bronchial vasomotor tone, both indirectly and directly, as well as pulmonary vascular muscle contractility, mast cell granulation and neurohumoral mediator release. In addition, new experimental data suggest that Mg2+ influences a variety of lung structures and chemicals (e.g., capillary endothelial cell integrity, number of type II epithelial cells, surfactant, etc.). Surprisingly, pulmonary arterial muscle cells have a lower Mg content compared to other types of blood vessels and the myocardium, which might point to the vulnerability of the lung vasculature to lower than normal dietary intake of Mg. Several clinical reports point to the salutary actions of Mg2+ in asthma and asthma-like conditions. Very recent experimental findings in rats indicate that Mg2+ treatment can prevent development of experimental chemically induced pulmonary hypertension. Hypoxic pulmonary vasoconstriction has been reported to be attenuated by Mg2+. Although it is not clear as to whether dietary Mg2+ deficiency plays a role in development of some asthma-like conditions or pulmonary hypertension, Mg salts certainly appear to be potentially useful therapeutic avenues for these conditions and should be thoroughly investigated, both from clinical as well as experimental points of view.


Age-related changes in medial septal cholinergic and GABAergic projection neurons and hippocampal neurotransmitter receptors: relationship with memory impairment.
The hippocampus, which provides cognitive functions, has been shown to become highly vulnerable during aging. One important modulator of the hippocampal neural network is the medial septum (MS). The present study attempts to determine how age-related mnemonic dysfunction is associated with neurochemical changes in the septohippocampal (SH) system, using behavioral and immunochemical experiments performed on young-adult, middle-aged and aged rats. According to these behavioral results, the aged and around 52.8% of middle-aged rats (within the "middle-aged-impaired" sub-group) showed both impaired spatial reference memory in the Morris water maze and habituation in the open field. Immunohistochemical studies revealed a significant decrease in the number of MS choline acetyltransferase immunoreactive cells in the aged and all middle-aged rats, in comparison to the young; however the number of gamma-aminobutyric acid-ergic (GABAergic) parvalbumin immunoreactive cells was higher in middle-aged-impaired and older rats compared to young and middle-aged-unimpaired rats. Western Blot analysis moreover showed a decrease in the level of expression of cholinergic, GABAergic and glutamatergic receptors in the hippocampus of middle-aged-impaired and aged rats in contrast to middle-aged-unimpaired and young rats. The present results demonstrate for the first time that a decrease in the expression level of hippocampal receptors in naturally aged rats with impaired cognitive abilities occurs in parallel with an increase in the number of GABAergic neurons in the MS, and it highlights the particular importance of inhibitory signaling in the SH network for memory function.


Evaluating the Effect of Knowledge, Attitude, and Practice on Self-Management in Type 2 Diabetic Patients on Dialysis.
Background. Type 2 diabetes is an increasingly common condition with several preventable microvascular complications such as kidney damage. Nephropathy is expensive to manage, especially as hospital dialysis treatment. Improving patients' knowledge, attitude, and practice (KAP) toward their condition can achieve better control, delay complications, and improve their quality of life. This study evaluated the KAP and self-care behaviors of diabetic patients on dialysis and variables that affect it. Methods. This cross-sectional study was conducted at Shahid Beheshti academic hospitals of Tehran, Iran. Face-to-face interviews were held to fill five validated questionnaires: three evaluating KAP, one evaluating self-management, and one evaluating quality of life. Result. 117 diabetic patients on hemodialysis (42 females) with mean (SD) age of 68.70 ± 9.26 years were enrolled in the survey. The scores for patient's KAP, self-care, and quality of life were 59.90 ± 11.23, 44.27 ± 8.35, 45.06 ± 12.87, 46.21 ± 10.23, and 26.85 ± 13.23, respectively. There was significant negative correlation between patients' knowledge and attitude with their glycosylated hemoglobin level and their fasting blood sugar. There was significant correlation between patients' knowledge and practice with their self-care activities. Conclusion. The present study suggests that patients' KAP scores have a practical effect upon self-care behavior. This highlights the needs for effective diabetes education programs in developing countries like Iran.


Delayed Slipped Capital Femoral Epiphysis After Treatment of Femoral Neck Fracture in Children.
Slipped capital femoral epiphysis (SCFE) after the treatment of femoral neck fracture is a rare entity in children that poses important treatment challenges. We describe the presentation and management of two patients, a 12-year-old girl and a 6-year-old girl, each of whom developed SCFE at 5 months and 9 months, respectively, after operative treatment of femoral neck fracture. Five similar cases have been reported in the literature. Along with our two case studies, the average age of all seven patients was 8.9 years (range, 3.6-12 years; boys, 8.9 years; girls, 9 years). None of the children was in a high weight percentile or had any known endocrinologic disorder. Two had asymptomatic mild SCFE, whereas the others felt unexplained pain with ambulation when the slippage was brought to their attention. Although it is not possible to prove a causal relationship between the initial fracture and the subsequent SCFE, clinical factors such as implant irritation, early return to weightbearing, delayed union or nonunion, coxa vara, and avascular necrosis warrant consideration as potentially related to the subsequent slip. The onset of SCFE after surgical treatment of a femoral neck fracture may reflect inadequate treatment of the fracture. For best practice, we should perform a gentle anatomic reduction, appropriate internal fixation for femoral neck fracture in skeletally immature patients. Postoperative cast immobilization and delayed weightbearing are also important to avoid complication. It is essential for pediatric orthopaedic surgeons to be aware of this clinical scenario to allow prompt recognition and patient treatment.


Evaluating drug cost per responder and number needed to treat associated with lixisenatide on top of glargine when compared to rapid-acting insulin intensification regimens on top of glargine, in patients with type 2 diabetes in the UK, Italy, and Spain.
This study investigated the cost per responder and number needed to treat (NNT) in type 2 diabetes mellitus (T2DM) patients for lixisenatide compared to insulin intensification regimens using composite endpoints in the UK, Italy, and Spain. Efficacy and safety outcomes were obtained from GetGoal Duo-2, a 26-week phase 3 trial comparing lixisenatide vs insulin glulisine (IG) once daily (QD) and three times daily (TID). Response at week 26 was extrapolated to 52 weeks, assuming a maintained treatment effect, based on long-term evidence in other T2DM populations. Responders were defined using composite end-points, based on an HbA1c threshold and/or no weight gain and/or no hypoglycemia. The HbA1c threshold was varied in sensitivity analyses. Annual treatment costs were estimated in euros (1 GBP = 1.26 EUR), including drug acquisition and resource use costs. Cost per responder was computed by dividing annual treatment costs per patient by the proportion of responders. Lixisenatide was associated with the lowest cost per responder for all composite end-points that included a weight-related component. For the main composite end-point of HbA1c ≤7.5% AND no weight gain AND no symptomatic hypoglycemia, cost per responder results were: UK: 6,867€, 8,746€, and 12,410€; Italy: 7,057€, 9,160€, and 12,844€; Spain: 8,370€, 11,365€, and 17,038€, for lixisenatide, IG QD, and TID, respectively. The NNT analysis showed that, for every 6.85 and 5.86 patients treated with lixisenatide, there was approximately one additional responder compared to IG QD and TID, respectively. A limitation of the clinical inputs is the lack of 52-week trial data from GetGoal Duo-2, which led to the assumption of a maintained treatment effect from week 26 to 52. This analysis suggests lixisenatide is an efficient economic resource allocation in the UK, Italy, and Spain.


[Value of fractional flow reserve measurement in intracavitary therapy for patients with moderate renal artery stenosis].
To analyze the value of fractional flow reserve (FFR) measurement on endovascular therapy for patients with renal artery stenosis. Clinical data of 9 patients underwent endovascular therapy due to moderate renal artery stenosis (50%-69%) in Anzhen hospital from May to September 2013 were retrospectively analyzed. Fractional flow reserve (FFR) were measured in patients with moderate stenosis in renal artery and abnormal glomerular filtration rate (GFR) or different between renal artery angiography and ultrasound before the procedure. Endovascular therapy was not applied for patients with FFR > 0.90, and the patients were subsequently followed up clinically. Endovascular therapy was applied in patients with FFR less than 0.90 or the pressure difference between the two ends of stenosis was more than 20 mmHg (1 mmHg = 0.133 kPa). Blood pressure, ultrasound and contrast-enhanced ultrasonography data were obtained at 1 and 3 months later, respectively. There were 6 patients diagnosed as severe renal artery stenosis (≥ 70%) and the other 3 patients diagnosed as moderate renal artery stenosis by renal artery ultrasound before operation. Two patients with FFR > 0.90 were not undertaken the endovascular therapy. Seven patients with FFR < 0.90 underwent endovascular therapy. After renal artery stenting, renal stenosis was relieved immediately and the transstent blood flow was fluency in these 7 patients. There was significant difference in the FFR before and after operation (0.81 ± 0.09 vs.0.94 ± 0.03, P = 0.008). Among the patients underwent endovascular therapy, blood pressure was normal without medication in 2 patients and well controlled with 1 or 2 combined antihypertensive drugs in the rest 5 patients. In patients with moderate renal artery stenosis, fractional flow reserve measurement could be used as a useful index to guide intervention procedure and to evaluate the efficacy of endovascular therapy.


Golgi-ANAE positivity in leukemic blast cells: a possible T-suppressor cell leukemia.
Different patterns of acid alpha-naphthyl-acetate esterase (ANAE) positivity in lymphocytes have been related to distinct functional lymphocyte subpopulations. A case of T-ALL with a cytochemical and immunological phenotype consistent with a T-suppressor cell leukemia is reported. In particular a specific pattern of Golgi-ANAE positivity is probably characteristic of TG cells, which include a subset with suppressor function.


A PAR-1-dependent orientation gradient of dynamic microtubules directs posterior cargo transport in the Drosophila oocyte.
Cytoskeletal organization is central to establishing cell polarity in various cellular contexts, including during messenger ribonucleic acid sorting in Drosophila melanogaster oocytes by microtubule (MT)-dependent molecular motors. However, MT organization and dynamics remain controversial in the oocyte. In this paper, we use rapid multichannel live-cell imaging with novel image analysis, tracking, and visualization tools to characterize MT polarity and dynamics while imaging posterior cargo transport. We found that all MTs in the oocyte were highly dynamic and were organized with a biased random polarity that increased toward the posterior. This organization originated through MT nucleation at the oocyte nucleus and cortex, except at the posterior end of the oocyte, where PAR-1 suppressed nucleation. Our findings explain the biased random posterior cargo movements in the oocyte that establish the germline and posterior.


Adolescent self-selection of service formats: implications for secondary interventions targeting alcohol use.
A novel motivational enhancement based secondary alcohol intervention has been shown to increase quit attempts for youth with heavier alcohol use histories (Brown et al., 2005). In the present study, we examined rates of self-selection into the three formats of this alcohol intervention: group, individual, and website; and examined differences between intervention participants and the general school population and across the three formats. Over four years, students at four schools were surveyed (n=6000) and were provided the opportunity to participate in Project Options (PO). Youth who were selected into PO (n=1147) were younger and more likely to identify as African American or Multiple/Other ethnicity than the school populations. More teens in PO reported lifetime alcohol use (65% vs. 60%); however, the school population reported more current (past 30 day) drinking. Boys were more likely to utilize the group format and minority youth were more likely to select the individual format. Findings highlight the utility of multiple intervention formats to engage youth in early intervention for alcohol problems.


Acute and chronic thoracic aortic disease: surgical considerations.
Acute thoracic aortic aneurysm is one of the most life-threatening vascular disorders recognized to date. The majority of these aortic ruptures rapidly end in mortality, with 50% of patients suffering death before reaching the hospital. Thus, acute management through surgical intervention is often indicated, especially in cases of ascending aortic rupture. Physical examination is critical in making the diagnosis, as clinical signs and symptoms often vary depending on the location of the dissection. Clinicians should have a low threshold for including thoracic aortic dissection in their differential diagnosis, especially when a patient presents with acute onset chest or back pain. In this report, we discuss the different categories of aortic dissections and the current treatment modalities for each. These include endovascular aortic repair, which has become a viable treatment modality in certain cases of type B dissection. Offering a less invasive approach, the technique known as thoracic endovascular repair currently affords a treatment option to a patient population who would have otherwise been deemed non-surgical candidates. Hybrid thoracic endovascular aortic repair has also become a pertinent surgical technique, and successful outcomes have been demonstrated when it is employed to repair ascending aortic aneurysms. We also describe our Acute Aortic Treatment Center, a rapid multicentric triage system for the management of acute aortic pathologies, which has resulted in significant improvements in patient outcomes.


Phototoxic plant burns: report of a case and review of topical wound treatment in children.
Acute photodermatitis provoked by skin contact with giant hogweed (Heracleum mantegazzianum) and exposure to ultraviolet radiation is a rare cause of phytophotodermatitis in children. We report the case of a 10-year-old girl with extensive photodermatitis after contact with giant hogweed and prolonged exposure to sunlight. The lesions involved 10% of the body surface area, mainly the lower extremities. After initial application of topical steroids to the skin erythema, the topical approach was changed due to extensive bullae. Debridement and temporary wound closure with an adequate dressing was undertaken. This is the first case report of application of Suprathel (PolyMedics Innovations, Denkendorf, Germany) on a phytophototoxic burn-like wound with a favorable outcome.


Carbon Monoxide Production during Bio-Waste Composting under Different Temperature and Aeration Regimes.
Despite the development of biorefinery processes, the possibility of coupling the "conventional" composting process with the production of biochemicals is not taken into account. However, net carbon monoxide (CO) production has been observed during bio-waste composting. So far, O2 concentration and temperature have been identified as the main variables influencing CO formation. This study aimed to investigate CO net production during bio-waste composting under controlled laboratory conditions by varying aeration rates and temperatures. A series of composting processes was carried out in conditions ranging from mesophilic to thermophilic (T = 35, 45, 55, and 65 °C) and an aeration rate of 2.7, 3.4, 4.8, and 7.8 L·h-1. Based on the findings of this study, suggestions for the improvement of CO production throughout the composting process have been developed for the first time. The highest concentrations of CO in each thermal variant was achieved with an O2 deficit (aeration rate 2.7 L·h-1); additionally, CO levels increased with temperature, reaching ~300 ppm at 65 °C. The production of CO in mesophilic and thermophilic conditions draws attention to biological CO formation by microorganisms capable of producing the CODH enzyme. Further research on CO production efficiency in these thermal ranges is necessary with the characterization of the microbial community and analysis of the ability of the identified bacteria to produce the CODH enzyme and convert CO from CO2.


Deferiprone (DFP) Targets Cancer Stem Cell (CSC) Propagation by Inhibiting Mitochondrial Metabolism and Inducing ROS Production.
Deferiprone (DFP), also known as Ferriprox, is an FDA-approved, orally active, iron chelator that is currently used clinically for the treatment of iron-overload, especially in thalassaemia major. As iron is a critical factor in Fe-S cluster assembly that is absolutely required for the metabolic function of mitochondria, we hypothesized that DFP treatment could be used to selectively target mitochondria in cancer stem cells (CSCs). For this purpose, we used two ER(+) human breast cancer cell lines, namely MCF7 and T47D cells, as model systems. More specifically, a 3D tumorsphere assay was employed as a functional readout of CSC activity which measures anchorage-independent growth under low attachment conditions. Here, we show that DFP dose dependently inhibited the propagation of CSCs, with an IC-50 of ~100 nM for MCF7 and an IC-50 of ~0.5 to 1 μM for T47D cells, making DFP one the most potent FDA-approved drugs that we and others have thus far identified for targeting CSCs. Mechanistically, we show that high concentrations of DFP metabolically targeted both mitochondrial oxygen consumption (OCR) and glycolysis (extracellular acidification rates (ECAR)) in MCF7 and T47D cell monolayers. Most importantly, we demonstrate that DFP also induced a generalized increase in reactive oxygen species (ROS) and mitochondrial superoxide production, and its effects reverted in the presence of N-acetyl-cysteine (NAC). Therefore, we propose that DFP is a new candidate therapeutic for drug repurposing and for Phase II clinical trials aimed at eradicating CSCs.


Context-dependent dysregulation of transcription by mutant huntingtin.
Huntington disease (HD) is an adult-onset neurodegenerative disease caused by expansion of a polyglutamine (poly(Q) tract in the N-terminal region of huntingtin (htt). Although the precise mechanisms leading to neurodegeneration in HD have not been fully elucidated, transcriptional dysregulation has been implicated in disease pathogenesis. In HD, multiple N-terminal mutant htt fragments smaller than the first 500 amino acids have been found to accumulate in the nucleus and adversely affect gene transcription. It is unknown whether different htt fragments in the nucleus can differentially bind transcription factors and affect transcription. Here, we report that shorter N-terminal htt fragments, which are more prone to misfolding and aggregation, are more competent to bind Sp1 and inhibit its activity. These effects can be reversed by Hsp40, a molecular chaperone that reduces the misfolding of mutant htt. Our results provide insight into the beneficial effects of molecular chaperones and suggest that context dependent transcriptional dysregulation may contribute to differential toxicity of various N-terminal htt fragments.


[Examination of a new tube connector concerning the ventilation-leakage during intraoperative bronchoskopy and bronchal suction].
Intra-operative bronchial suction and bronchoscopy regularly diminishes ventilation pressures and volumes and causes a leakage of narcotic gases. This study was undertaken to compare the influence of a newly-developed connecting tube with check valve on these problems. Examinations were carried out in a pressure controlled test lung with ventilation pressures between 5 and 50 mbar. Usual tube connectors and newly developed connectors with check valve were examined with respect to ventilation pressures, ventilation volumes, and leakage before and after insertion of suction catheters and bronchoscopes. Using normal connectors, ventilation pressures and volumes collapsed even at lowest expiratory pressures, and significant leakage occurred. The insertion of catheters or bronchoscopes had only little beneficial effects. In contrast, the new connectors with check valve showed only small leakage, even at high ventilation pressures. The new tube connectors with check valve allow intra-operative suction and bronchoscopy under constant ventilation parameters with minor leakage of anaesthetic gas.


FTIR spectroscopic studies on aggregation process of the beta-amyloid 11-28 fragment and its variants.
Aggregation of Abeta peptides is a seminal event in Alzheimer's disease. Detailed understanding of the Abeta assembly process would facilitate the targeting and design of fibrillogenesis inhibitors. Here, conformational studies using FTIR spectroscopy are presented. As a model peptide, the 11-28 fragment of Abeta was used. This model peptide is known to contain the core region responsible for Abeta aggregation. The structural behavior of the peptide during aggregation provoked by the addition of water to Abeta(11-28) solution in hexafluoroisopropanol was compared with the properties of its variants corresponding to natural, clinically relevant mutants at positions 21-23 (A21G, E22K, E22G, E22Q and D23N). The results showed that the aggregation of the peptides proceeds via a helical intermediate, and it is possible that the formation of alpha-helical structures is preceded by creation of 3(10)-helix/3(10)-turn structures.


Occurrence, spatial distribution and risk assessment of high concern endocrine-disrupting chemicals in Jiangsu Province, China.
Endocrine-disrupting chemicals (EDCs) have attracted much concern because of the environmental and health risks they pose. Here we used liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry to quantify 10 types of EDCs at 118 sampling sites in Jiangsu Province, China, and then evaluated their respective environmental risk using a conservative risk quotient method. The results show that, in surface water, the targeted nonylphenol (NP), 4-tert-octylphenol (4-t-OP), and (2-ethylhexyl)phthalate (DEHP) were ranked highest, having mean concentrations above 300 ng/L. In comparison, both 4-t-OP and DEHP were also ranked highest, with mean concentrations above 100 ng/g, in the sediment samples. Moreover, the ∑10EDCs concentration in the Huai River Basin was similar to that in the Yangtze River Basin. Notably, Huai'an city had the maximum mean concentration for EDCs in the Huai River Basin, followed by Xuzhou city and Suqian city, while Yangzhou city ranked highest in the Yangtze River Basin. Furthermore, the corresponding risk distribution revealed that (1) NP, bisphenol A (BPA), and 4-t-OP are of medium to high risk in 70%, 100% and 95% of the surface water samples, and likewise in 45%, 88% and 100% of the sediment samples, respectively; the maximum RQ value for NP in surface water samples reached 74.9; (2) DEHP belongs to the high-risk category in all samples (100%), whose maximum RQ reached 54.7. To our best knowledge, this is the first study to report on the occurrence, spatial distribution, and risk assessment of EDCs of high concern in Jiangsu Province, China.


High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis.
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.


Associative diazotrophic bacteria in grass roots and soils from heavy metal contaminated sites.
This work aimed to evaluate density of associative diazotrophic bacteria populations in soil and grass root samples from heavy metal contaminated sites, and to characterize isolates from these populations, both, phenotypically (Zinc, Cadmium and NaCl tolerance in vitro, and protein profiles) and genotypically (16S rDNA sequencing), as compared to type strains of known diazotrophic species. Densities were evaluated by using NFb, Fam and JNFb media, commonly used for enrichment cultures of diazotrophic bacteria. Bacterial densities found in soil and grass root samples from contaminated sites were similar to those reported for agricultural soils. Azospirillum spp. isolates from contaminated sites and type strains from non-contaminated sites varied substantially in their in vitro tolerance to Zn+2 and Cd+2, being Cd+2 more toxic than Zn+2. Among the most tolerant isolates (UFLA 1S, 1R, S181, S34 and S22), some (1R, S34 and S22) were more tolerant to heavy metals than rhizobia from tropical and temperate soils. The majority of the isolates tolerant to heavy metals were also tolerant to salt stress as indicated by their ability to grow in solid medium supplemented with 30 g L(-1) NaCl. Five isolates exhibited high dissimilarity in protein profiles, and the 16S rDNA sequence analysis of two of them revealed new sequences for Azospirillum.


Spatial Distribution of Land Surface Temperatures in Kuwait: Urban Heat and Cool Islands.
The global rise of urbanization has led to the formation of surface urban heat islands and surface urban cool islands. Urban heat islands have been shown to increase thermal discomfort, which increases heat stress and heat-related diseases. In Kuwait, a hyper-arid desert climate, most of the population lives in urban and suburban areas. In this study, we characterized the spatial distribution of land surface temperatures and investigated the presence of urban heat and cool effects in Kuwait. We used historical Moderate-Resolution Imaging Spectroradiometer (MODIS) Terra satellite 8-day composite land surface temperature (LST) from 2001 to 2017. We calculated the average LSTs of the urban/suburban governorates and compared them to the average LSTs of the rural and barren lands. We repeated the analysis for daytime and nighttime LST. During the day, the temperature difference (urban/suburban minus versus governorates) was -1.1 °C (95% CI; -1.2, -1.00, p < 0.001) indicating a daytime urban cool island. At night, the temperature difference (urban/suburban versus rural governorates) became 3.6 °C (95% CI; 3.5, 3.7, p < 0.001) indicating a nighttime urban heat island. In light of rising temperatures in Kuwait, this work can inform climate change adaptation efforts in the country including urban planning policies, but also has the potential to improve temperature exposure assessment for future population health studies.


Environmental Factors and Hypertension.
Environmental factors are a major cause of poor health worldwide. The most solid evidence is for air pollution, leading to increased disability-adjusted life years. Outdoor temperature and other seasonal climate changes may also influence cardiovascular health, according to their direct modulation of air pollution. Moreover, an increasing body of evidence associates environmental exposure to noise with poor cardiovascular outcome, and in particular with hypertension. This review is aimed at reviewing current evidence about the role of these environmental factors in cardiovascular disease and specifically hypertension. In particular, the impact of air pollution, with its short-term and long-term effects, the outdoor temperature and noise pollution will be investigated. People belonging to low social classes, as well as children, women, older people and those with established cardiovascular diseases, seem to have a greater susceptibility to the effects of environmental stressors, recalling the concept of "environmental justice". The accumulating strong scientific evidence may thus support public health policies aimed at reducing social inequalities in cardiovascular health.


Whole-genome duplication as a key factor in crop domestication.
Polyploidy is commonly thought to be associated with the domestication process because of its concurrence with agriculturally favourable traits and because it is widespread among the major plant crops(1-4). Furthermore, the genetic consequences of polyploidy(5-7) might have increased the adaptive plasticity of those plants, enabling successful domestication(6-8). Nevertheless, a detailed phylogenetic analysis regarding the association of polyploidy with the domestication process, and the temporal order of these distinct events, has been lacking(3). Here, we have gathered a comprehensive data set including dozens of genera, each containing one or more major crop species and for which sufficient sequence and chromosome number data exist. Using probabilistic inference of ploidy levels conducted within a phylogenetic framework, we have examined the incidence of polyploidization events within each genus. We found that domesticated plants have gone through more polyploidy events than their wild relatives, with monocots exhibiting the most profound difference: 54% of the crops are polyploids versus 40% of the wild species. We then examined whether the preponderance of polyploidy among crop species is the result of two, non-mutually-exclusive hypotheses: (1) polyploidy followed by domestication, and (2) domestication followed by polyploidy. We found support for the first hypothesis, whereby polyploid species were more likely to be domesticated than their wild relatives, suggesting that the genetic consequences of polyploidy have conferred genetic preconditions for successful domestication on many of these plants.


OsIDD2, a zinc finger and INDETERMINATE DOMAIN protein, regulates secondary cell wall formation.
Previously, we found 123 transcription factors (TFs) as candidate regulators of secondary cell wall (SCW) formation in rice by using phylogenetic and co-expression network analyses. Among them, we examined in this work the role of OsIDD2, a zinc finger and indeterminate domain (IDD) family TF. Its overexpressors showed dwarfism, fragile leaves, and decreased lignin content, which are typical phenotypes of plants defective in SCW formation, whereas its knockout plants showed slightly increased lignin content. The RNA-seq and quantitative reverse transcription polymerase chain reaction analyses confirmed that some lignin biosynthetic genes were downregulated in the OsIDD2-overexpressing plants, and revealed the same case for other genes involved in cellulose synthesis and sucrose metabolism. The transient expression assay using rice protoplasts revealed that OsIDD2 negatively regulates the transcription of genes involved in lignin biosynthesis, cinnamyl alcohol dehydrogenase 2 and 3 (CAD2 and 3), and sucrose metabolism, sucrose synthase 5 (SUS5), whereas an AlphaScreen assay, which can detect the interaction between TFs and their target DNA sequences, directly confirmed the interaction between OsIDD2 and the target sequences located in the promoter regions of CAD2 and CAD3. Based on these observations, we conclude that OsIDD2 is negatively involved in SCW formation and other biological events by downregulating its target genes.


Some observations on the rescue of fallen women.
Citing the example of the creator of Professor Higgins of Pygmalion , as well as other celebrated figures, this paper delineates a number of biographical features common to some would-be rescuers of degraded women. Aside from demonstrating the relevance of these portraits to Freud's observations on the oedipal aspects of the subject, the author emphasizes the attempted verification of phallic attributes in the women as an additional motive in their redemption .


Comparison of automated ribosomal intergenic spacer analysis (ARISA) and denaturing gradient gel electrophoresis (DGGE) techniques for analysing the influence of diet on ruminal bacterial diversity.
The objective of this study was to compare the automated ribosomal intergenic spacer analysis (ARISA) and the denaturing gradient gel electrophoresis (DGGE) techniques for analysing the effects of diet on diversity in bacterial pellets isolated from the liquid (liquid-associated bacteria (LAB)) and solid (solid-associated bacteria (SAB)) phase of the rumen. The four experimental diets contained forage to concentrate ratios of 70:30 or 30:70 and had either alfalfa hay or grass hay as forage. Four rumen-fistulated animals (two sheep and two goats) received the diets in a Latin square design. Bacterial pellets (LAB and SAB) were isolated at 2 h post-feeding for DNA extraction and analysed by ARISA and DGGE. The number of peaks in individual samples ranged from 48 to 99 for LAB and from 41 to 95 for SAB with ARISA, and values of DGGE-bands ranged from 27 to 50 for LAB and from 18 to 45 for SAB. The LAB samples from high concentrate-fed animals tended (p < 0.10) to show greater peak numbers and Shannon index values than those isolated from high forage-fed animals with ARISA, but no differences were identified with DGGE. The SAB samples from high concentrate-fed animals had lower (p < 0.05) peak numbers and Shannon index values than those from animals fed high-forage diets with ARISA, but only a trend was noticed for these parameters with DGGE (p < 0.10). The ARISA detected that animals fed alfalfa hay diets showed lower (p < 0.05) SAB diversity than those fed grass hay diets, but no differences were observed with DGGE. No effect of forage type on LAB diversity was detected by any technique. In this study, ARISA detected some changes in ruminal bacterial communities that were not detected by DGGE, and therefore ARISA was considered more appropriate for assessing bacterial diversity of ruminal bacterial pellets. The results highlight the impact of the fingerprinting technique used to draw conclusions on dietary factors affecting bacterial diversity in ruminal bacterial pellets.


[Erythropoietin determination in clinical medicine].
Erythropoietin (EPO) is a prime stimulating factor for red cell production. EPO is a glycoprotein which has a molecular weight of 34,000, and is mainly produced by the kidney. EPO stimulates the differentiation and proliferation of erythroid progenitor cells in the bone marrow. The rate of production of EPO is regulated primarily by renal oxygen availability. Because anemia reduces renal oxygen availability, anemic stress accelerates EPO production in the kidney. Recently, EPO has mainly been determined by radioimmunoassay. Serum EPO titer is usually inversely correlated with hemoglobin concentration, as typically shown in iron deficiency anemia. Serum EPO titers in aplastic anemia are much higher than those in iron deficiency anemia relative to the hemoglobin concentration. Serum EPO titers in anemia caused by malignancies sometimes differ considerably among patients. Serum EPO in renal anemia usually show low titers irrespective of the degree of anemia. Serum EPO titers in untreated polycythemia vera are lower than those in treated polycythemia vera or secondary polycythemia. Determination of serum EPO is useful in differential diagnosis of polycythemia vera. Recombinant human EPO has been used to treat various anemias including renal anemia, refractory anemia, anemia in malignancies and secondary anemia. Determination of serum EPO titers is also valuable in many other situations of clinical medicine.


Belimumab in systemic lupus erythematosus (SLE): evidence-to-date and clinical usefulness.
Systemic lupus erythematosus (SLE) is a complex autoimmune rheumatic disease with multiple presentations, whose management presents many challenges. Many disease modifying or immunosuppressive drugs have been used with limited success, especially in patients with more severe disease activity. Belimumab is the first drug to be approved specifically for the treatment of SLE in more than 50 years. By blocking the B-cell activating factor, it interferes in B-cell differentiation and survival. Here we consider the results of the clinical trials that led to its approval, as well as the post-hoc analyses, follow-up studies and the current trials.


Screening for hepatitis B in patients with lymphoma.
Chronic hepatitis B virus (HBV) infection can be reactivated during lymphoma chemotherapy, specifically with rituximab. In 2008, the Centers for Disease Control and Prevention and, in 2010, the American Society of Clinical Oncology made recommendations that anyone who received cytotoxic or immunosuppressive therapy should be tested for serologic markers of HBV infection. In our study, we wanted to determine the screening rates for HBV infection at our institution and if simply adding a checkbox onto the rituximab order would improve HBV screening. We performed a retrospective chart review of two cohorts of lymphoma patients at Scott & White Health Clinic. Cohort 1 included patients from 1993 to 2008. Cohort 2 included patients who received rituximab after an institutionwide protocol (rituximab order checkbox) was initiated in 2011. A total of 452 patients treated for lymphoma were reviewed. Only 15 of the 404 Cohort 1 patients received HBV screening (3.7%; 95% confidence interval, 2.1%-6.1%). Screening rates were statistically higher if baseline liver laboratory values were elevated (P < 0.0001). HBV was also checked more frequently if patients' liver function tests became elevated while on chemotherapy, 85.7% (12/14). Of the 48 patients in Cohort 2, 33 patients (68.7%) received HBV screening. No patients in either cohort had a positive HBV surface antigen or developed reactivation of HBV during chemotherapy. The addition of a checkbox on the rituximab order form significantly increased our screening for HBV infection in lymphoma patients initiating chemotherapy.


[Continuity and longitudinal aspects of care in general practice in four European countries].
The objective of the study was to compare continuity and longitudinality of care in general practice in four European countries with a public salary model. Descriptive and prospective study. 63 general practitioners/family physicians working in public health centers registered all encounters (direct and indirect) over a period of one week in Spain, Finland, Portugal and Sweden. 92% of the contacts were office encounters: 75% were direct (face to face), the average number of encounters per doctor, per week was 103. The principal problem was chronic in 42% of cases and acute in 31%. The physician has previous knowledge of the principal problem in 63% of the encounters and previous knowledge of concurrent problems in 79%. In 66% of cases the doctor has previous knowledge of the patient relatives. The level of continuity and longitudinality is variable; from high to low: Portugal, Spain, Sweden and Finland. In Spain the duration of the encounter is short and repeated prescription are infrequent. In Portugal there are waitings lists which implies low accessibility for acute problems. In Finland general practitioners have no patients lists and the care is des-personalized. In Sweden there are waiting lists and high use of telephone encounters.


Transmitral endoventricular repair of left ventricular pseudoaneurysm following mitral valve replacement.
Left ventricular (LV) pseudoaneurysm is a rare but serious complication of mitral valve replacement and is usually the consequence of atrioventricular separation. Although there may be a role for nonoperative treatment in the presence of a small false aneurysm and in the absence of paravalvular leak, the presence of a large false aneurysm usually mandates surgical intervention. This may be hazardous in patients with concomitant LV dysfunction. We report a case of a patient who presented with a large LV pseudoaneurysm following numerous attempts of mitral valve replacements for a variety of reasons, including endocarditis. Some of the technical details of aneurysm repair and aspects of myocardial protection are discussed. In our patient, avoidance of cardioplegic arrest may have contributed to the successful outcome.


PPh3/I2 Promoted Synthesis of Unsymmetrical Disulfides from Sodium Sulfites and 2-Mercaptobenzo Heterocyclics.
A simple and efficient method for the synthesis of unsymmetrical disulfides is reported. Using sodium sulfites and 2-mercaptobenzo heterocyclic compounds as starting materials, the unsymmetrical sulfur-sulfur bonds could be quickly constructed in the PPh3/I2 reaction system under transition-metal-free conditions. This protocol has the advantages of mild reaction conditions, easily available starting materials, and wide substrate scope, showing potential synthetic value for the synthesis of a diversity of biologically or pharmaceutically active compounds.


SNPs of excision repair cross complementing group 5 and gastric cancer risk in Chinese populations.
We conducted a case-control study to determine the association between several potential SNPs of excision repair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphisms in combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newly diagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>T and rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detector system. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147 CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258 TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258 TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CC was associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findings suggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, but the effect needs to be further validated by larger sample size studies.


Conventional MRI features for predicting the clinical outcome of patients with invasive placenta.
We aimed to evaluate whether morphologic magnetic resonance imaging (MRI) features could help to predict the maternal outcome after uterine artery embolization (UAE)-assisted cesarean section (CS) in patients with invasive placenta previa. We retrospectively reviewed the MRI data of 40 pregnant women who have undergone UAE-assisted cesarean section due to suspected high risk of massive hemorrhage caused by invasive placenta previa. Patients were divided into two groups based on the maternal outcome (good-outcome group: minor hemorrhage and uterus preserved; poor-outcome group: significant hemorrhage or emergency hysterectomy). Morphologic MRI features were compared between the two groups. Multivariate logistic regression analysis was used to identify the most valuable variables, and predictive value of the identified risk factor was determined. Low signal intensity bands on T2-weighted imaging (P < 0.001), placenta percreta (P = 0.011), and placental cervical protrusion sign (P = 0.002) were more frequently observed in patients with poor outcome. Low signal intensity bands on T2-weighted imaging was the only significant predictor of poor maternal outcome in multivariate analysis (P = 0.020; odds ratio, 14.79), with 81.3% sensitivity and 84.3% specificity. Low signal intensity bands on T2-weighted imaging might be a predictor of poor maternal outcome after UAE-assisted cesarean section in patients with invasive placenta previa.


Effect of HDAC9 inhibition on epithelial-mesenchymal transition in CD133+ prostate cancer cell lines.
A small fraction of cancer cells known as cancer stem cells (CSCs) are considered to give rise to differentiated cancer cells and have been proposed to predict cancer recurrence and metastasis. There is further evidence that CSCs may act as metastatic precursors of epithelial-mesenchymal transition (EMT). In the present study, we investigated the key molecules involved in maintaining the stability of CSCs by inducing ectopic overexpression of CD133 to characterize EMT in human prostate cancer cell lines, including PC-3, DU145, and LnCaP cells. Additionally, we investigated whether a specific inhibitor of concomitantly expressed metastasis-related genes could alleviate EMT properties in CD133-overexpressing prostate cancer cells. Ectopic overexpression of CD133 in PC-3, DU145, and LnCaP cells led to an increase in the expression of HDAC9. Moreover, HDAC9 inhibition led to a decrease in EMT properties along with increased E-cadherin expression, a narrower wound gap distance, and enhanced cell invasiveness through the suppression of β-catenin activation and its translocation to the nucleus. Overall, these results suggest that HDAC9 inhibition plays a functional role in the modulation of EMT properties in CSC-like prostate cancer cells. Therefore, these findings could facilitate the development of therapeutic strategies for controlling prostate cancer metastasis.


Impact of Isomaltulose and Sucrose Based Breakfasts on Postprandial Substrate Oxidation and Glycemic/Insulinemic Changes in Type-2 Diabetes Mellitus Subjects.
To investigate the effect of isomaltulose (ISO) and sucrose (SUC) based breakfast on the postprandial substrate oxidation and glycemic/insulinemic changes in type 2 diabetes mellitus subjects (T2DM). This was a randomized, controlled, double blind, and crossover study performed in two to five days. About 10 to 12 hours prior to the test, the subjects were not allowed to consume food or drink other than water. On the experimental day pre- and postprandial plasma glucose, serum insulin, and substrate utilization were measured after the subjects consumed a test breakfast with ISO or SUC, followed by a standard lunch three hours later. The plasma glucose levels in subjects after consuming ISO breakfast tended to be lower than subjects consuming SUC breakfast at 30- and 60-minute, respectively. The second meal effect after standard lunch (240-minute) on insulin levels in subject consuming ISO breakfast tended to be lower than that of subjects consuming SUC breakfast. Substrate oxidation indicated that the incremental area under the fat oxidation of ISO breakfast was 20% higher comparing to SUC breakfast. Therefore, ISO based breakfast tends to provide less postprandial glucose and insulin levels than SUC based breakfast, thereby increasing postprandial fat oxidation.


Impact of an exercise and walking protocol on quality of life for elderly people with OA of the knee.
The knee is the weight-bearing joint most commonly affected by osteoarthritis (OA). The symptoms of pain, morning stiffness of short duration and physical dysfunction in the activities of daily living (ADL) can have an effect on many aspects of health, affecting quality of life. Regular and moderate physical activity adapted to individuals' life-styles and education, and joint protection strategies have been advocated as conservative management. The purpose of the present study was to assess the impact of an exercise and walking protocol on the quality of life of elderly people with knee OA. The study design was a randomized controlled clinical trial. The subjects comprised 50 elderly people, aged 65 or more, with knee OA who had been referred to the geriatric outpatient unit for rehabilitation. Changes in severity of pain and quality of life were compared between a control group (CG) and an experimental group (EG). Both groups participated in an educational session and the EG also received a 12-week exercise and walking protocol. Both groups were assessed at baseline and after three and six months by an independent observer. The Lequesne Index of Knee OA Severity (LI), the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Short-Form Health Survey (SF-36) were used as measurement instruments. In the CG, the measures of quality of life (SF-36), the HAQ and the LI between subjects did not yield statistically significant differences over the three measurement points. For the EG, there was a significant improvement in function, measured by HAQ, and decreasing OA symptom severity, measured by LI. For the SF-36 there were significant improvements in physical function, functional role limitation and pain. Comparisons between the groups showed statistically significant differences after three and six months for all measures, except for the SF-36 emotional domains. The exercise protocol and walking programme had a positive effect on the quality of life of elderly individuals with knee OA.


Transurethral En bloc Excision of Pediatric Bladder Tumor using Holmium Laser.
A 12-year-old male child, during evaluation of chronic constipation, was incidentally diagnosed to have a fronded bladder growth. Transurethral en bloc excision of the tumor was achieved using holmium laser. Histopathology confirmed it to be an inflammatory pseudotumor. This case is reported for its unusual presentation and management by holmium laser.


Analysing and correcting the differences between multi-source and multi-scale spatial remote sensing observations.
Differences exist among analysis results of agriculture monitoring and crop production based on remote sensing observations, which are obtained at different spatial scales from multiple remote sensors in same time period, and processed by same algorithms, models or methods. These differences can be mainly quantitatively described from three aspects, i.e. multiple remote sensing observations, crop parameters estimation models, and spatial scale effects of surface parameters. Our research proposed a new method to analyse and correct the differences between multi-source and multi-scale spatial remote sensing surface reflectance datasets, aiming to provide references for further studies in agricultural application with multiple remotely sensed observations from different sources. The new method was constructed on the basis of physical and mathematical properties of multi-source and multi-scale reflectance datasets. Theories of statistics were involved to extract statistical characteristics of multiple surface reflectance datasets, and further quantitatively analyse spatial variations of these characteristics at multiple spatial scales. Then, taking the surface reflectance at small spatial scale as the baseline data, theories of Gaussian distribution were selected for multiple surface reflectance datasets correction based on the above obtained physical characteristics and mathematical distribution properties, and their spatial variations. This proposed method was verified by two sets of multiple satellite images, which were obtained in two experimental fields located in Inner Mongolia and Beijing, China with different degrees of homogeneity of underlying surfaces. Experimental results indicate that differences of surface reflectance datasets at multiple spatial scales could be effectively corrected over non-homogeneous underlying surfaces, which provide database for further multi-source and multi-scale crop growth monitoring and yield prediction, and their corresponding consistency analysis evaluation.


The eel genus Macrocephenchelys (Anguilliformes: Congridae) in Taiwan, with description of a new species.
The congrid eel genus Macrocephenchelys in Taiwan is reviewed. Three species are recognized. Macrocephenchelys brachialis was originally described from Indonesia and is also known from Taiwan, Madagascar, and Vanuatu; it is common in Taiwan but known from few specimens elsewhere. Macrocephenchelys brevirostris was described from Taiwan, where it is common; its occurrence outside Taiwan is uncertain. Macrocephenchelys nigriventris sp. nov. is described here from 28 specimens collected in Taiwan. Macrocephenchelys brachialis is distinguished from the other two species by its more elongate body, more posterior dorsal-fin origin (behind tip of pectoral fin), shorter head (less than 10% total length), presence of a supratemporal pore, absence of fleshy papillae dorsally on the head, absence of sensory pits on the abdomen, and more than 170 vertebrae. Macrocephenchelys nigriventris is distinguished from M. brevirostris by the presence of a patch of black pigment around the anus and adjacent abdomen (absent in M. brevirostris), preanal length 24-28% total length (27-34% in M. nigriventris), and 128-135 vertebrae (147-154 in M. brevirostris). The only other species currently recognized is M. soela from Australia; it is distinguished from all the others by the more anterior origin of the dorsal fin, over the middle of the pectoral fin (vs. over or behind the tip of the pectoral fin).


2-year clinical performance of a fluoride-containing fissure sealant in young schoolchildren at caries risk.
To evaluate the clinical performance of Helioseal-F, a fluoride-containing fissure sealant, in school children at caries risk. A caries risk assessment based on past caries experience, saliva microbial tests, buffer capacity and frequency of sugar intake was carried out in 204 healthy children, 6-7 years of age. Children exhibiting one or more risk factors were considered at caries risk (n = 121) and their permanent molars were sealed with a fluoride-containing fissure sealant, thus forming a fissure sealant group (FSG). The remaining 83 children with low caries risk received no fissure sealants and constituted a reference group (RG). Both groups were followed for 2 years. From 15 children of both groups, unstimulated whole saliva was collected 1 month after sealant placement in order to determine fluoride levels. In another 20 children, a split-mouth study design was utilized to compare the colonization of mutans streptococci adjacent to and on F-containing sealants and conventional controls. The sealants were placed by dental hygienists according to the manufacturers' instructions. A total of 431 fissure sealants were placed at baseline. Complete retention was found in 76.6% during the study period while 22.0% were partially lost. Six sealants (1.4%) were completely lost. The enamel caries incidence was 45% lower (P < 0.05) in the permanent molars of the caries risk FSG compared with the low risk RG. There was no significant increase in saliva fluoride concentration following placement of the sealants and the proportion of mutans streptococci in relation to total viable counts was unaffected by type of material. The levels of salivary mutans streptococci were mainly unchanged in both groups during the study period, while the levels of salivary lactobacilli decreased in the FSG.


Synthesis, structure, and superconductivity in the new-structure-type compound: SrPt6P2.
A metal-rich ternary phosphide, SrPt(6)P(2), with a unique structure type was synthesized at high temperatures. Its crystal structure was determined by single-crystal X-ray diffraction [cubic space group Pa3̅; Z = 4; a = 8.474(2) Å, and V = 608.51(2) Å(3)]. The structure features a unique three-dimensional anionic (Pt(6)P(2))(2-) network of vertex-shared Pt(6)P trigonal prisms. The Sr atoms occupy a 12-coordinate (Pt) cage site and form a cubic close-packed (face-centered-cubic) arrangement, and the P atoms formally occupy tetrahedral interstices. The metallic compound becomes superconducting at 0.6 K, as evidenced by magnetic and resistivity measurements.


[Prevalence of dyslipoproteinemia in workers engaged in the production of higher fatty alcohols].
To reveal serum serum lipoprotein disorders, the authors studied serum lipids and lipoproteins compositions in 116 male workers engaged into production of higher fatty alcohols at oil-processing plant. All the cases of serum lipoprotein disorders were divided into 8 types. Secondary are the disorders of those examines (63.8%) who have chronic diseases. Six types of the disorders were identified in apparently healthy examines (36.2%).


Thyroid: an unusual hideout for sarcoidosis.
To present a case of dysphagia secondary to a progressively increasing nontoxic multinodular goiter caused by sarcoidosis. We summarize the clinical presentation and pertinent pathology in a patient with sarcoidosis involving the thyroid gland. A review of literature regarding this topic is also presented. A 54-year-old man was noted to have asymptomatic nontoxic thyromegaly. Biopsy of right thyroid nodule was benign while the biopsy from the isthmus nodule was nondiagnostic. He presented with acute onset of dysphagia two months later and the work-up for gastrointestinal causes was negative. Chest imaging showed left-sided lymphadenopathy, and biopsy of a lymph node showed sarcoidosis. Two years after the initial presentation a repeat biopsy of the isthmus nodule was again reported as nondiagnostic. Because he had persistent dysphagia, he underwent total thyroidectomy with resolution of dysphagia. Histopathological examination of the thyroid revealed non necrotizing granulomas consistent with sarcoidosis. This case brings to light this uncommon etiology of a nontoxic multinodular goiter. Involvement of the thyroid gland by sarcoidosis is very rare. It has been reported in 4.2 to 4.6% of patients with sarcoidosis. In patients with pulmonary or extrapulmonary sarcoidosis and associated thyromegaly, possible involvement of the thyroid by this process should be considered.


Relationships between Leydig cell morphometry and plasma testosterone during postnatal development of the monkey, Macaca fascicularis.
In neonates (0 to 3-4 months), the testis contained a mean number of 4.6 X 10(6) Leydig cells representing 4.2 % of its volume; Leydig cell cytoplasm contained 10.2 % of SER. In infants (up to 45 months), Leydig cells regressed but their number increased; their volume density did not change. Leydig cell cytoplasmic volume (454 microns3 ), which was about 2.5-fold less than in neonates (1 119 microns3 ) or adults (1 170 microns3 ), contained only 8.7% of SER. During meiosis stage (38-52 months). Leydig cell numbers and volume density did not vary but the cells reached a maximal size and an amount of SER comparable with that at birth was measured. When spermatogenesis was complete, the Leydig cells represented no more than 0.8% of testis volume, but their number and SER content were significantly increased. Except for a significant decrease when spermatogenesis was completed, Leydig cell lipid content did not change during development, and the volume density of mitochondria did not vary. The mean level of plasma testosterone was 2 ng/ml in neonates and 0.4 ng/ml in infants; it increased to 3 ng/ml during onset of meiosis and reached 10 ng/ml in adults. The profile of testosterone was positively and significantly correlated with the total volume and total number of Leydig cells (P less than 0.01 and P less than 0.02, respectively) and with changes in their cytoplasmic volume (P less than 0.001). Moreover, plasma testosterone levels were positively and significantly correlated with changes in Leydig cell SER content i.e. SER volume density and mean absolute volume per cell (P less than 0.001), total SER in the whole testis (P less than 0.01).


Effect and Mechanisms of Huangqi-Shanzhuyu in the Treatment of Diabetic Nephropathy based on Network Pharmacology and In Vitro Experiments.
Huangqi-Shanzhuyu (HS), a classic combination of Chinese herbal formulae, has been widely used for the treatment of diabetic nephropathy (DN). However, its pharmacological mechanism of action is still unclear. The active ingredients of HS and their potential targets were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the DN-related targets were determined from GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGkb, and Therapeutic Target Database (TTD). The Cytoscape software was used to construct a herb-disease-target network and screen core genes. STRING was employed to generate a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the mechanism of action of HS in DN. Animal experiments and molecular docking were used to verify the potential mechanism. In total, 40 active ingredients and 180 effective targets of HS in DN were identified and 1115 DN-related targets were retrieved. From the PPI network, VEGFA, AKT1, IL6, IL1B, TP53, MMP9, PTGS2, CASP3, EGF and EGFR were identified as core genes. The anti-DN mechanism mainly involved multiple signaling pathways such as AGEs-RAGE. Animal experiments and molecular docking analysis confirmed that HS downregulated the expression of IL-1 and IL-6 via kaempferol-mediated inhibition of JNK1 phosphorylation. HS exhibits a therapeutic effect in DN through its multiple ingredients that act on several targets and multiple signaling pathways, including AGEs-RAGE.


[Early professional contact supports professional development of medical students. EPC--a new course in medical education in Gothenburg].
Early professional contact (EPC) is a new course for medical students during the first two years of the medical curriculum in the Sahlgrenska Academy at Göteborg University. Small groups with four students and one tutor meet one day every month. The students participate in the clinical work together with the physician and his/her staff and practise communication with and examination of patients. In this article we describe the structure, the content, the basic knowledge and values of the course and the learning methods. We also discuss the results from a Course Experience Questionnaire and two focus groups. The students got insights into medical profession and health care and inspiration for future medical profession and confidence with patients. The physicians as tutors in clinical practice have an important role in supporting the medical students to build up their professional confidence by seeing, listening to and acknowledging them. EPC in the biomedical curriculum can help students balance and synthesize different knowledge, skills and attitudes.


Marriage problems; dealing with them in private practice.
Marriages and divorces in Los Angeles County almost equal each other. Marriage per se is not the cause of neurosis. When two neurotic persons marry, the resulting neurotic interaction too often ends in conflict, broken homes and a new generation of neurotic children. Psychotherapy must be related to the diagnosis of family psychopathology, should include all the involved members and should be directed toward the realistic goal of integrating them into family living. Of 100 cases taken from the author's experience, 64 involved married couples and the majority of these had serious interspouse conflicts. In 37 cases both spouses were treated and substantial psychotherapy was given to one or both of the partners. It included one or more modalities varying from electroshock therapy, tranquilizers, and such psychotherapy as supportive, dynamic interpretive, individual, spouses together, group and hypnotherapy. Thirteen achieved clinical recovery, nine improved, twelve were still in therapy. In three cases therapy failed.


Predication of second-order optical nonlinearity of [(Bu2t Im)AuX] (X=halogen) using time-dependent density-functional theory combined with sum-over-states method.
The dipole polarizability and second-order polarizability of recently synthesized (1,3-di-ter-butylimidazol-2-ylidine) gold complexes [(Bu2t Im)AuX] (X=halogen) were investigated by using time-dependent density-functional theory combined with sum-over-states method. We have discovered that these complexes possess remarkably larger molecular second-order polarizability compared with the organometallic and organic complexes. The value of the second-order polarizability increases in the order of F<Cl<Br<I. The analysis of the molecular orbital suggests that the charge transfer from halogen atom to the carbene ligand plays the key role in nonlinear optical response of gold complexes. The gold of these complexes is a bridge of charge transfer, unlike other organometallic complexes, the metal center may be a strong donor or acceptor. These complexes have a possibility to be excellent second-order nonlinear optical materials from the standpoint of transparency, relatively large beta values and relatively small dispersion behaviors.


Simplifying pyridoxal: practical methods for amino acid dynamic kinetic resolution.
Metal complexes of picolinaldehyde are identified as low-cost and environmentally benign catalysts, providing high reaction rates and turnovers for the racemization of amino acids. These pyridoxal surrogates demonstrate activity toward a variety of amino acid esters. Applications to chemoenzymatic dynamic kinetic resolutions provide access to amino acids in high yields and with excellent enantioselectivities, demonstrating their compatibility with protease-mediated transformations.


Antimicrobial resistance of Helicobacter pylori clinical strains in the last 10 years.
In the present work primary antimicrobial resistance was analyzed in clinical H. pylori strain isolates from adult patients from Polish Wielkopolska region within the last 10 years. Drug sensitivity was evaluated in a total of 142 H. pylori isolates, with 66 strains originating from years 1997/1998 forming group 1 and 76 strains isolated in 2007/2008 forming group 2. Sensitivity to amoxicillin, tetracycline, metronidazole and clarithromycin was determined by E-test. All strains were susceptible to amoxicillin and tetracycline. On the other hand, a high proportion of strains resistant to metronidazole was determined (36.4% in group 1 and 44.7% in group 2). In parallel, a growing tendency was discovered for resistance to clarithromycin (9.1% strains resistant in group 1 and 18.4% isolates resistant in group 2). The studies confirm the need for monitoring the drug resistance of Helicobacter pylori strains.


Genetics and ALS: Cause for Optimism.
While drug development has done little to slow the devastating symptoms of amyotrophic lateral sclerosis (ALS), there is some good news in the fact that scientists have identified some 100 related genes and believe that genetic research offers the best hope for treatments. More good news came on the heels of the Ice Bucket Challenge, which raised $220 million globally and has fueled renewed optimism and energy in the ALS community.


Production characteristics of Papaver somniferum L. cultivars of different origin and vegetation cycles.
Poppy cultivars of different origin were investigated in long-term experiments during the period 1976-1980. The production ability of plants was established with both spring and autumn sowing, using different plant spacing (20 cm X 20 cm and 50 cm X 20 cm). All important poppy-growing areas within northern and southern Europe were represented by the cultivars brought under investigation ("P-360", "Ankara", "Botosani", "Kompolti-M", "Kék Duna", "Modran", "KM-Ihar" and "Reading"). The extension of the vegetation cycle by autumn sowing and wintering had a generally favourable effect on dry matter and alkaloid production, resulting in a fivefold increase in production. In spite of high production ability, the wintering of the cold-sensitive cultivars, known as spring types, was uncertain. The shortening of the vegetation cycle (spring sowing) seemed to be unfavourable for the production of both spring and autumn cultivars. However, that disadvantage was compensated to some extent by spring cultivars having relatively lower sensitivity and higher alkaloid production levels. The weight of individual plants was much higher when cultivated in large areas. However, a higher yield could be obtained with 20cm X 20cm spacing because more plants could be harvested per square metre. On the basis of production analyses, a negative correlation was established between the total capsule mass (i.e. capsule plus seed) and the ratio of the drug-forming part. In the case of alkaloid production, a positive correlation was established between the accumulation of codeine and the intensification of over-all alkaloid formation.


Selling to the moneyed masses.
Over the past decade, the distribution of household incomes has shifted so much that a much larger proportion of consumers now earn significantly higher-than-average incomes--while still falling short of being truly rich. As a result, what used to be a no-man's-land for new product introductions has in many categories become an extremely profitable "new middle ground." How can marketers capitalize on this new territory? The key, say the authors, is to rethink the positioning and design of offerings and the ways they can be brought to market. Take, for instance, how Procter & Gamble redefined the positioning map for tooth-whitening solutions. A decade ago, dental centers were popularizing expensive bleaching techniques that put the price of a professionally brightened smile in the 400 dollars range. At the low end, consumers also had the choice of whitening toothpastes that cost anywhere from 2 dollars to 8 dollars. P&G wisely positioned itself between the two ends, successfully targeting the new mass market with its 35 dollars Whitestrips. In product categories where it's clear the middle ground has already been populated, it's important for companies to design or redesign offerings to compete. An example is the Polo shirt. How do you sell a man yet another one after he's bought every color he wants? Add some features, and call it a golf shirt. Here, marketers have introduced designs based on the concept of "occasional use" in order to stand out. Finally, companies wishing to reach the "almost rich" can change how they go to market. Perhaps no mass retailer has made a stronger bid for the mass affluent than Target Stores, which has pioneered a focus the company itself characterizes as upscale discount. The strategy has made Target an everyday shopping phenomenon among well-heeled urbanites and prosperous professionals.


Epigenetic changes in lymphocytes of solvent-exposed individuals.
We investigated global DNA methylation alterations in lymphocytes of solvent workers and chronic toxic encephalopathy (CTE) patients and explored potential gene-environment interactions for GST. POPULATION & METHODS: A cross-sectional study was set up in 41 referents, 128 solvent workers and 23 CTE patients. We found a global DNA hypermethylation in the solvent-exposed population compared with the referents (p = 0.001, r = -0.544). Global DNA methylation was negatively associated with exposure. Furthermore, GSTP1 genotypic polymorphism was found to be significantly associated (p = 0.033) with global DNA hypomethylation, which indicates a potential role for gene-environment interaction in the etiology of solvent-induced neurobehavioral disorders. This study indicates that solvent-induced DNA methylation alterations have an impact on neurotoxicity and development of CTE.