Reoxidation of the class I disulfides of the rat adipocyte insulin receptor is dependent upon the presence of insulin: the class I disulfide of the insulin receptor is extracellular.
Elements of the quaternary structure of the native and dithiothreitol- (DTT) reduced rat adipocyte insulin receptor have been elucidated by vectorial probing and subunit cross-linking. The charged reducing agents glutathione and beta-mercaptoethylamine were used to reduce the class I disulfides of the receptor in intact adipocytes, demonstrating the extracellular location of the disulfide directly. This interpretation was confirmed by use of DTT as a reducing agent and the nonpermeant sulfhydryl blocking reagent Thiolyte MQ to prevent the reoxidation of the class I sulfhydryl groups which occurred when they were not blocked. It was found that the above reoxidation of the receptor is dependent on the concentration of insulin in the nanomolar range, not occurring measurably at 4 degrees C in its absence. Cross-linking studies with ethylene glycol bis(succinimidyl succinate) demonstrated that the alpha subunits could not be cross-linked to each other after reduction of the class I disulfides, suggesting that the interaction between the receptor heterodimers may be due primarily to the disulfide bonds.


Gallstones in Patients with Chronic Liver Diseases.
With prevalence of 10-20% in adults in developed countries, gallstone disease (GSD) is one of the most prevalent and costly gastrointestinal tract disorders in the world. In addition to gallstone disease, chronic liver disease (CLD) is also an important global public health problem. The reported frequency of gallstone in chronic liver disease tends to be higher. The prevalence of gallstone disease might be related to age, gender, etiology, and severity of liver disease in patients with chronic liver disease. In this review, the aim was to identify the epidemiology, mechanisms, and treatment strategies of gallstone disease in chronic liver disease patients.


Arthritis in patients with antimitochondrial antibodies.
We describe the clinical and radiographic findings in 15 women with antimitochondrial antibodies (AMA) without clinical liver disease. Arthralgias appeared in their third or fourth decade and typically involved the small joints of the hands with periarticular swelling and cortical erosions. Few hand nodes, deformation, or sclerodactyly. Four had histologic primary biliary cirrhosis (PBC). The association between arthritis and PBC is discussed. The arthritis and PBC may be two manifestations of some general underlying disease process, AMA being a marker. Patients with atypical arthralgias affecting the hands should have the AMA test performed in view of the possibility that this affection might accompany or progress to PBC.


Ferroptosis, a New Insight Into Acute Lung Injury.
Acute lung injury (ALI), a common and critical illness with high morbidity and mortality, is caused by multiple causes. It has been confirmed that oxidative stress plays an important role in the development of ALI. Ferroptosis, a newly discovered programmed cell death in 2012, is characterized by iron-dependent lipid peroxidation and involved in many diseases. To date, compelling evidence reveals the emerging role of ferroptosis in the pathophysiological process of ALI. Here, we review the role of ferroptosis in the pathogenesis of ALI and its therapeutic potential in ALI.


Resveratrol, 4' Acetoxy Resveratrol, R-equol, Racemic Equol or S-equol as Cosmeceuticals to Improve Dermal Health.
Phytochemicals are botanical compounds used in dermatology applications as cosmeceuticals to improve skin health. Resveratrol and equol are two of the best-known polyphenolic or phytoestrogens having similar chemical structures and some overlapping biological functions to 17β-estradiol. Human skin gene expression was reviewed for 28 different biomarkers when resveratrol, 4' acetoxy resveratrol (4AR), R-equol, racemic equol or S-equol were tested. Sirtuin 1 activator (SIRT 1) was stimulated by resveratrol and 4AR only. Resveratrol, R-equol and racemic equol were effective on the aging biomarkers proliferating cell nuclear factor (PCNA), nerve growth factor (NGF), 5α-reductase and the calcium binding proteins S100 A8 and A9. Racemic equol and 4AR displayed among the highest levels for the collagens, elastin and tissue inhibitor of the matrix metalloproteinase 1 (TIMP 1). S-equol displayed the lowest level of effectiveness compared to the other compounds. The 4AR analog was more effective compared to resveratrol by 1.6-fold. R-equol and racemic equol were almost equal in potency displaying greater inhibition vs. resveratrol or its 4' analog for the matrix metalloproteinases (MMPs), but among the inflammatory biomarkers, resveratrol, 4AR, R-equol and racemic equol displayed high inhibition. Thus, these cosmeceuticals display promise to improve dermal health; however, further study is warranted to understand how phytochemicals protect/enhance the skin.


[Social determinants of health and disability: updating the model for determination].
Social determinants of health (SDH) are conditions in which people live. These conditions impact their lives, health status and social inclusion level. In line with the conceptual and comprehensive progression of disability, it is important to update SDH due to their broad implications in implementing health interventions in society. This proposal supports incorporating disability in the model as a structural determinant, as it would lead to the same social inclusion/exclusion of people described in other structural SDH. This proposal encourages giving importance to designing and implementing public policies to improve societal conditions and contribute to social equity. This will be an act of reparation, justice and fulfilment with the Convention on the Rights of Persons with Disabilities.


Effects of outdoor housing on self-injurious and stereotypic behavior in adult male rhesus macaques (Macaca mulatta).
We examined the effects of outdoor housing on self-injurious and stereotypic behavior in adult male rhesus macaques with a history of self-wounding that were previously singly housed indoors for at least 4 y prior to the study. Baseline behavioral observations were collected over 2.5 mo. In phase 1, animals were relocated outdoors in 1 of 2 experimental conditions, group-housed (n = 8) or single-housed (n = 5), for 6 wk. In phase 2, group-housed animals were observed outdoors for an additional 6 wk. Behavioral observations were done using focal sampling techniques. In phase 1, rates of self-biting and self-directed stereotypies and time spent displaying idiosyncratic self-directed stereotypies decreased significantly when group- and single-housed animals were housed outdoors. Rates of yawning and scratching were significantly decreased for group- and single-housed animals and, for group-housed animals, self-grooming decreased with outdoor housing. In phase 2, rates of self-biting, time engaging in idiosyncratic self-directed stereotypies, and yawning remained significantly lower during weeks 7 through 12 (outdoor housing) compared with those under indoor housing. Rates of scratching and time spent self-grooming decreased significantly during the first 6 wk but then returned to baseline levels. Our findings suggest that self-biting and self-directed stereotypic behavior in rhesus macaques with a history of self-injurious behavior is significantly reduced by outdoor housing regardless of whether animals are socially or individually housed.


Hemoglobin and Endotoxin Levels Predict Sarcopenia Occurrence in Patients with Alcoholic Cirrhosis.
Alcohol is a major risk factor of liver cirrhosis (LC). This study aimed to elucidate a surrogate marker of sarcopenia in patients with LC of different etiology. Out of 775 patients with LC, 451 were assessed for handgrip strength and skeletal muscle mass (by computed tomography). They were then divided into two groups: alcoholic cirrhosis (AC; n = 149) and nonalcoholic cirrhosis (NAC; n = 302). Endotoxin activity (EA) levels were measured with an EA assay. Group AC showed significantly higher platelet counts (p = 0.027) and lower blood urea nitrogen levels and fibrosis-4 index than group NAC (p = 0.0020 and p = 0.038, respectively). The risk factors of sarcopenia were age ≥ 65 years, female sex, CP-C LC, Hb levels < 12 g/dL, and EA level > 0.4 in all patients with LC; hemoglobin (Hb) levels < 12 g/dL and EA level > 0.4 in group AC; and age ≥ 65 years, CP-C LC, and Hb levels < 12 g/dL in group NAC. The prediction accuracy of Hb for sarcopenia in group AC, group NAC, and all patients was 83.6%, 75.9%, and 78.1% (sensitivity: 92.0%, 69.0%, and 80.2%; specificity: 66.4%, 71.0%, and 64.0%), respectively. Although not significant, the predictive performance was better when using the combination of Hb and EA measurements than when using Hb alone in group AC but was comparable in all patients. Hb levels can predict sarcopenia in patients with LC, but in those with AC, the combination of Hb and EA improves the prediction performance.


A Correlational Study of Acute Stress and Resilience Among Hospitalized Burn Victims Following the Taiwan Formosa Fun Coast Explosion.
Although the survival rate of burn patients in the Formosa Fun Coast Explosion disaster increased significantly, for patients facing long-term rehabilitation, there remained great stress. Therefore, the aim of this study was to explore the predictors of resilience among burn patients in this major disaster. We conducted a cross-sectional, descriptive study in a medical center in northern Taiwan, with a total of 30 burn patients enrolled. Patients' demographics were collected, and the Resilience Scale and Perceived Stress Scale were administered. Multivariate statistical analysis by stepwise and linear regression was used to test these predictors of resilience. The results showed that perceived stress was the key predictor of resilience in the stepwise regression analysis and by adjusting variables including stress level, gender, and education level. These results indicate that the stress level of burn patients should be determined first to provide more targeted methods for reducing stress and improving resilience.


Estimating mutual information.
We present two classes of improved estimators for mutual information M(X,Y), from samples of random points distributed according to some joint probability density mu(x,y). In contrast to conventional estimators based on binnings, they are based on entropy estimates from k -nearest neighbor distances. This means that they are data efficient (with k=1 we resolve structures down to the smallest possible scales), adaptive (the resolution is higher where data are more numerous), and have minimal bias. Indeed, the bias of the underlying entropy estimates is mainly due to nonuniformity of the density at the smallest resolved scale, giving typically systematic errors which scale as functions of k/N for N points. Numerically, we find that both families become exact for independent distributions, i.e. the estimator M(X,Y) vanishes (up to statistical fluctuations) if mu(x,y)=mu(x)mu(y). This holds for all tested marginal distributions and for all dimensions of x and y. In addition, we give estimators for redundancies between more than two random variables. We compare our algorithms in detail with existing algorithms. Finally, we demonstrate the usefulness of our estimators for assessing the actual independence of components obtained from independent component analysis (ICA), for improving ICA, and for estimating the reliability of blind source separation.


[Periodic disease and periarteritis nodosa in the same patient: coincidence?].
Familial Mediterranean fever (FMF) chiefly affects patients of Arabic, Jewish, Armenian or Turkish origin and takes the form of recurrent episodes of peritonitis, arthritis or pleurisy. Periarteritis nodosa (PAN) is a vasculitis affecting elderly people and manifested by a general deterioration, unexplained fever and peripheral neuropathy or muscular weakness. We describe a patient presenting both diseases. Ours is the seventh reported case associating these two affections. This association was suspected by SACHS and co-workers who discovered an increased frequency of PAN in patients with FMF compared to the expected rate for the whole population (7). These observations warrant a search for PAN in young patients affected by FMF and showing signs of vasculitis.


[A case of microscopic polyarteritis nodosa accompanied by peripheral neuropathy].
We reported a 64-year-old woman with subacute sensorimotor polyneuropathy accompanied by marked inflammatory reactions and rapidly progressive glomerulonephritis. Polyneuropathy was followed in 3 months by a rapidly progressive renal dysfunction. Sural nerve biopsy revealed marked loss of myelinated fibers and myelin ovoid formation with vasculitis of the small-sized arteries and arterioles. Renal biopsy showed segmental necrotizing glomerulitis. These pathological findings were distinct from those of polyarteritis nodosa and led to a diagnosis of microscopic polyarteritis nodosa (MPN). Oral administration of prednisolone with an additional immunosuppressant was effective not only in alleviating the polyneuropathy, but also in preventing the deterioration of renal function. This is the first report that clearly describes the peripheral neuropathy in MPN.


Chemistry: a bridge to discovery.
American Chemical Society Regional Meetings are a convenient and economical route for students, faculty and industry representatives to come together and communicate scientific findings and ideas. This year the 47th American Chemical Society Midwest Regional Meeting was held in Omaha (NE, USA) and included a special symposium on 'New frontiers in bioanalysis'.


Primary Lung Adenocarcinoma With ALK Gene Rearrangement Mostly Occupied by the Signet-Ring Cell Carcinoma Component: A Case Report.
Primary lung carcinoma tumors possessing a signet-ring cell carcinoma (SRCC) component at varying proportions are rare, while those primarily composed of an SRCC component are much rarer. Reported here is a case of primary lung adenocarcinoma primarily composed of an SRCC component with a scant acinar component that developed in an 81-year-old male. Approximately 95% of the adenocarcinoma was occupied by an SRCC component that was shown to be diastase-resistant based on positive periodic acid-Schiff staining. Immunostaining for ALK and fluorescence in situ hybridization analysis (break-apart assay) showed the presence of an ALK gene rearrangement. Findings in this case indicated a primary lung adenocarcinoma with ALK gene rearrangement, in which an SRCC component accounted for approximately 95% of the tumor.


[On the use of an anabolic hormone in the acute myocardial infarction. Experimental trial on 486 patients (author's transl)].
An anabolic hormone, methandrostenolone, was shown to be able to decrease significantly the cicatrization-time on animals with induced sperimental acute myocardial infarction (AMI). A controlled clinical trial was performed on group of 246 patients affected by AMI, giving them methandrostenolone at dose of 25 mg im.m. per day, for the first ten days from the beginning of symptoms. An omogeneous group of 240 patients with AMI was used as control. The mortality rate resulted 13,4% in the treated group 18,7% in the control's. 10 patients in the treated group (4,2%) died of cardiac failure versus 17 (7,1%) in the control group, 9 (3,7%) of cardiac rupture in the former versus 6 (2,4%) in the latter. As far as these differences are concerned statistical significance was not reached. A larger number of patients would be requested.


Gastrointestinal Colonization with Vancomycin-Resistant Enterococci In Hospitalized and Outpatients.
The incidence of infection and intestinal colonization with vancomycin resistant enterococci (VRE) is increasing in many countries in the last decade. Concerning the difficult antimicrobial treatment of infections caused by VRE, decreasing the incidence and prevalence of these infections is an important factor in VRE-induced morbidity and mortality control. To determine the prevalence of gastrointestinal colonization with vancomycin resistant enterococci in hospitalized and outpatients, and to determine the genetic base of the vancomycin resistance in VRE isolates. Seven hundred and eighty stool specimens were investigated for the gastrointestinal carriage of vancomycin-resistant enterococci (VRE). Susceptibility to vancomycin was tested in all isolates by disk-diffusion test and E-test (AB Biodisk, Sweden). Determined vancomycin resistant enterococci were than tested for detection of vanA, vanB and vanC genes by PCR. Vancomycin resistant strains of enterococci were isolated from 46 (16.1 %) of the 285 hospitalized patients and 5 (7.7 %) of the 65 patients living in the community (p < 0.05). The most of the highly resistant enterococci strains to vancomycin (95.2 %), were identified as E. faecium. Minimal inhibitory concentrations (MICs) to vancomycin in all 39 vanA genotypes of E. faecium and two vanA genotypes of E. fecalis were > 256 μg/ml. Three vanB genotypes of E. faecium and one vanB genotype of E. faecalis had MICs of 32 μg/ml. All six vanC genotypes of E. gallinarum had MICs of 8 μg/ml. All vanA genotypes of VRE were highly resistant to vancomycin, with MICs above 256 μg/ml. Three vanB genotypes of VR E. faecium and one VR E. fecalis were resistant, with MICs 32 μg/ml. vanC genotypes of VR E. gallinarum were intermediate resistant to vancomycin with MICs of 8 μg/ml. The prevalence of vancomycin resistant enterococci in Republic of Macedonia was 2-fold higher in hospitalized than in outpatients. VanA genotype was dominant in isolates of E. faecium and it was highly associated with the MIC values above the 256 μg/ml. Since most of the enterococcal infections are endogenous, there is a need for screening the colonization of patient's intestinal flora with VRE at the hospital entry. Identification and genotyping of faecal enterococci, together with their susceptibility testing to vancomycin, could be useful marker for the infection control.


GYKI-12743 a new postsynaptic vascular alpha-adrenoceptor antagonist.
Using the pithed rat preparation it has been proven that GYKI-12743 exerted its alpha-adrenergic blocking action only at the postsynaptic vascular level in the cardiovascular system. This new molecule failed to antagonize the presynaptic alpha 2-adrenoceptors of the cardiac sympathetic nerve endings. Thereby it was possible to demonstrate the first vasoselective postsynaptic adrenoceptor antagonist which potentially might be interesting in the cardiovascular therapy.


The effects of statins in patients with advanced-stage cancers - a systematic review and meta-analysis.
Statin therapy has been shown to reduce mortality in a wide range of cancer types and overall stages. Still, there is uncertainty about its efficacy in increasing survival among advanced cancer patients. We conducted a meta-analysis with data from all studies that compared the hazard ratio of overall survival, cancer-specific survival, and progression-free survival in patients with advanced-stage cancer who receive statin therapy. Studies were selected from the PubMed, Embase, and Web of Science databases from their inception to December 31, 2022. Cancer types are limited to those rarely screened during the annual examination and more likely to develop into advanced stages, such as lung, pancreatic and ovarian cancers. This resulted in 27 studies eligible for meta-analysis. Statin therapy was associated with a 26% decreased risk of overall survival (HR, 0.74; 95% CI, 0.67, 0.81), 26% decreased risk of cancer-specific survival (HR, 0.74; 95% CI, 0.61-0.88), and 24% decreased risk of progression-free survival (HR, 0.76; 95% CI, 0.65-0.87) for advanced-stage cancer patients. The associations were not attenuated or reinforced by study design, study regions, cancer types, or other medical care. Concomitant use of other anticancer medications did not result in confounding effects. Statin therapy produces significant benefits on overall survival and cancer-specific survival. Although the benefits might be lower than the approved immunotherapy medications, its cost-effectiveness could lead to dramatic health consequences. Concomitant use of statin drugs as cancer treatments is highly recommended in future clinical trials.


Bacterial and archaeal spatial distribution and its environmental drivers in an extremely haloalkaline soil at the landscape scale.
A great number of studies have shown that the distribution of microorganisms in the soil is not random, but that their abundance changes along environmental gradients (spatial patterns). The present study examined the spatial variability of the physicochemical characteristics of an extreme alkaline saline soil and how they controlled the archaeal and bacterial communities so as to determine the main spatial community drivers. The archaeal and bacterial community structure, and soil characteristics were determined at 13 points along a 211 m transect in the former lake Texcoco. Geostatistical techniques were used to describe spatial patterns of the microbial community and soil characteristics and determine soil properties that defined the prokaryotic community structure. A high variability in electrolytic conductivity (EC) and water content (WC) was found. Euryarchaeota dominated Archaea, except when the EC was low. Proteobacteria, Bacteroidetes and Actinobacteria were the dominant bacterial phyla independent of large variations in certain soil characteristics. Multivariate analysis showed that soil WC affected the archaeal community structure and a geostatistical analysis found that variation in the relative abundance of Euryarchaeota was controlled by EC. The bacterial alpha diversity was less controlled by soil characteristics at the scale of this study than the archaeal alpha diversity. Results indicated that WC and EC played a major role in driving the microbial communities distribution and scale and sampling strategies were important to define spatial patterns.


Application of a locus-specific DNA hybridization probe in the analysis of the slow-feathering endogenous virus complex of chickens.
To investigate further the sex-linked, slow-feathering (SF) locus, a DNA hybridization probe that flanks the integration site of endogenous virus ev21 was used to probe Southern blots from a variety of commercial SF White Leghorn (WL), broiler, and endangered lines. After HaeIII digestion of DNA from SF WL, the 5' and 3' provirus-cell junction fragments were seen in addition to a 2.5-kb fragment of cell sequences that was homologous with the viral integration region. The latter polymorphism, which appeared to represent sequences duplicated after integration of EV21, was designated unoccupied repeat URa. Among SF broiler crosses, the same provirus-cell junction fragments were found but the pristine region that represented the 1.6-kb proviral URb was also found. Only URb was found among rapid-feathering (RF) chickens, regardless of breed. Although there was marked (greater than 95%), agreement between the presence of ev21-cell; junction fragments and the SF phenotype among both WL and broilers, Southern blots of DNA from a few commercial SF broiler chickens lacked ev21 junction fragments but some RF revertants harbored ev21 junction fragments. These anomalies suggest that ev21 may not be the sole determinant of the SF phenotype.


Electric field effects on Guinea pig serum: the role of free radicals.
The present study was carried out to investigate the potential effects of ELF (extremely low frequency) electric field exposure on generating free radicals in guinea pigs. For this purpose, we determined thiobarbituric acid reactive substances (TBARS) levels, one of the byproducts of lipid peroxidation, the changes of the activities of superoxide dismutase (SOD), as an antioxidant enzyme, and gamma-Glutamyl transferase (GGT) as the key enzyme in GSH metabolism. Moreover, in order to investigate electric field effects on functions of organs, we measured the alanine aminotransferase (ALT) activity, alkaline phosphatase (ALP) activity, lactate dehydrogenase (LDH) activity, total cholesterol (TC), LDL cholesterol, HDL cholesterol, VLDL cholesterol, triglycerides (TG), urea, uric acid, creatin, glucose, and blood-urea nitrogen (BUN) in serum of guinea pigs exposed to different intensities and directions electric fields. In this study we have found that vertical and horizontal application of ELF electric fields in the range of 1.35, 1.5, and 1.8 kV/m increased TBARS and SOD levels as compared to the controls (p < 0.05) and to applied electric fields of 0.3, 0.6, 0.8, and 1 kV/m. On the other hand, other serum levels of some biochemical parameters that were also investigated did not undergo statistically significant changes (p > 0.05).


[Research progress on chemical constituents and quality control of Tripterygium wilfordii preparations].
Tripterygium wilfordii preparations,with various biological activities such as immunosuppressive,anti-inflammatory and anti-cancer effects,are widely used in the treatment of autoimmune diseases such as rheumatoid arthritis,lupus erythematosus,and nephrotic syndrome. They have definite therapeutic effect,but often cause serious adverse reactions and result in damages to liver,kidney,blood,reproduction,and other systems due to their complex compositions,great toxicity,and narrow margin between the toxic and therapeutic dosages. At present,T. wilfordii preparations produced by different manufacturers exhibit large variations in clinical efficacy and side effects in account of their different chemical compositions and quality fluctuation due to differences in raw materials and production process. However,the existing quality standards are controversial in terms of index components and content limit,which cannot be effectively used for the overall quality control of the preparations. In this paper,the research progress on chemical constituents,quality standard and quality control methods of four T. wilfordii preparations including Tripterygium Tablets,Tripterygium Zongtie Tablets,Tripterygium Shuangceng Tablets and Tripterygium Glycosides Tablets was reviewed,in order to provide ideas and reference for the quality improvement of this type of preparations.


Phosphor/sulphur ratio: an indicator of malignant uterus change.
The purpose of the present study was to establish a correlation between gynaecological diseases (myoma, adenocarcinoma) and phosphor/sulphur (P/S) ratios of different regions of the uterus. Routine histological specimens were reexamined with the intention to select representative regions of the uteruses for element analysis. Conventional hematoxylin-eosin-stained sections were used to identify histological alterations by light microscopy. Scanning electron microscopic (SEM) and energy-dispersive spectroscopic (EDS) investigations were carried out to analyze the morphology and the related element composition of the samples. The results of the nonparametric statistical test (Wilcoxon rank-sum test) indicate that the P/S ratios were significantly higher in adenocarcinoma (0.8891 +/- 0.0757) than in myoma (0.4713 +/- 0.0306). P/S ratios of different pathologic regions of uteruses seem worth examining in a larger study population. Combination of routine histological examinations with element analysis of specimens may have useful applications in patients who have undergone radiation therapy and may identify a pattern for local recurrence at certain sites.


Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction.
Nm23-H1 is one of the most interesting candidate genes for a relevant role in Neuroblastoma pathogenesis. H-Prune is the most characterized Nm23-H1 binding partner, and its overexpression has been shown in different human cancers. Our study focuses on the role of the Nm23-H1/h-Prune protein complex in Neuroblastoma. Using NMR spectroscopy, we performed a conformational analysis of the h-Prune C-terminal to identify the amino acids involved in the interaction with Nm23-H1. We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation. Meta-analysis performed on three Neuroblastoma cohorts showed Nm23-H1 as the gene highly associated to Neuroblastoma aggressiveness. We also identified two other proteins (PTPRA and TRIM22) with expression levels significantly affected by CPP. These data suggest a new avenue for potential clinical application of CPP in Neuroblastoma treatment.


Concomitant application of sprint and high-intensity interval training on maximal oxygen uptake and work output in well-trained cyclists.
In this study, we compared the effects of two different training modalities on maximal oxygen uptake and work output. Participants included 26 well-trained mountain bike cyclists were divided into two groups. The first group trained using a conventional endurance protocol at steady-state (moderate) intensity and variable-intensity (high-moderate-low) free of maximal efforts. The second group combined endurance training with a sprint and high-intensity interval training protocol, which, respectively, were based on 30 s maximal repetitions and 4 min high intensity repetitions. Training duration was 8 weeks. A graded exercise test was administered pre- and post-training. Work output, oxygen uptake, minute pulmonary ventilation, heart rate and stroke volume were determined during the test. While work output significantly increased post-training in both groups (P < 0.05), the interval training group showed a greater magnitude of change (from 284.4 ± 91.9 to 314.2 ± 95.1 kJ) than the endurance training group (from 271.8 ± 73.3 to 283.4 ± 72.3 kJ). Significant increases in maximal oxygen uptake (from 57.9 ± 6.8 to 66.6 ± 5.3 ml kg(-1) min(-1)), maximal pulmonary ventilation and stroke volume were observed only in the interval training group. An exercise protocol involving endurance and sprint and high-intensity interval training was found to induce positive effects on maximal oxygen uptake in a group of well-trained cyclists with several years athletic experience.


Biological characteristics and conjugated antigens of ClfA A-FnBPA and CP5 in Staphylococcus aureus.
To obtain immunogenic conjugate antigens, adipic acid dihydrazide (ADH), as a bridge, and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimidehydrochloride (EDAC), as a coupling agent, were used to conjugate the purified fusion protein, clumping factor A-fibronectin binding protein ClfA A-FnBPA, and type 5 capsular polysaccharide (CP5). The conjugates were mixed with an adjuvant, and mice were immunized 3 times and challenged with Staphylococcus aureus 1 week later. Antibody titers were determined by indirect enzyme-linked immunosorbent assay (ELISA). At 14 days after the first immunization, antibodies against the purified protein and conjugate were detected; after 28 days, antibody levels increased; and a week after the third immunization, antibody levels continued to increase. However, the conjugate antibody titers were higher than those of the purified protein during the study, and no IgG antibodies against purified CP5 were detected during the entire experiment. The protection rate increased to 90% in the conjugate group, indicating that the conjugate imparts a relatively higher protective efficacy than the purified protein and purified CP5.


Inhibition of PAF-induced histamine secretion and bronchoconstriction by WEB 2086.
Platelet activating factor (PAF) stimulates histamine secretion from rabbit mixed leukocytes in a concentration-dependent fashion (EC50 10 ng/ml). The PAF (10 ng/ml)-induced histamine secretion was inhibited by WEB 2086 (IC50 = 20 nM). Furthermore, PAF (10 ng/kg, i.v.)-induced bronchoconstriction in guinea pig was also inhibited by WEB 2086 (ID50 = 5.3 micrograms/kg, i.v., 5 minutes). These data showed the existence of PAF-receptors on rabbit basophils and in guinea pig airways which are highly sensitive to blockade by WEB 2086.


Anti-plasmodial activity of Norcaesalpin D and extracts of four medicinal plants used traditionally for treatment of malaria.
Malaria is an old life-threatening parasitic disease that is still affecting many people, mainly children living in sub-Saharan Africa. Availability of effective antimalarial drugs played a significant role in the treatment and control of malaria. However, recent information on the emergence of P. falciparum parasites resistant to one of the artemisinin-based combination therapies suggests the need for discovery of new drug molecules. Therefore, this study aimed to evaluate the antiplasmodial activity of extracts, fractions and isolated compound from medicinal plants traditionally used in the treatment of malaria in Tanzania. Dry powdered plant materials were extracted by cold macerations using different solvents. Norcaesalpin D was isolated by column chromatography from dichloromethane root extract of Caesalpinia bonducella and its structure was assigned based on the spectral data. Crude extracts, fractions and isolated compound were evaluated for antiplasmodial activity against chloroquine-sensitive P. falciparum (3D7), chloroquine-resistant P. falciparum (Dd2, K1) and artemisinin-resistant P. falciparum (IPC 5202 Battambang, IPC 4912 Mondolkiri) strains using the parasite lactate dehydrogenase assay. The results indicated that extracts of Erythrina schliebenii, Holarrhena pubescens, Dissotis melleri and C. bonducella exhibited antiplasmodial activity against Dd2 parasites. Ethanolic root extract of E. schliebenii had an IC50 of 1.87 μg/mL while methanolic and ethanolic root extracts of H. pubescens exhibited an IC50 = 2.05 μg/mL and IC50 = 2.43 μg/mL, respectively. Fractions from H. pubescens and C. bonducella roots were found to be highly active against K1, Dd2 and artemisinin-resistant parasites. Norcaesalpin D from C. bonducella root extract was active with IC50 of 0.98, 1.85 and 2.13 μg/mL against 3D7, Dd2 and IPC 4912-Mondolkiri parasites, respectively. Antiplasmodial activity of norcaesalpin D and extracts of E. schliebenii, H. pubescens, D. melleri and C. bonducella reported in this study requires further attention for the discovery of antimalarial lead compounds for future drug development.


Rigid objects that appear to bend.
Simple rigid objects are presented that appear to bend when viewed from certain angles. These illusions illustrate that perspective information is used by the stereo system, that projective distortions can override rigidity constraints in motion perception, and that touch only corrects the illusion for a local region.


Medical education and communication companies: an updated in-depth profile.
The integrity of medical education and communication companies (MECCs) and their role in continuing medical education (CME) are frequently challenged, perhaps because of a lack of published information characterizing these providers. Published in 1998, a survey of MECCs began the identification and description of these organizations so that meaningful conclusions could be drawn about their role in CME. The present study enhances the profile created by that original survey. A 21-item questionnaire was mailed to 182 companies identified from 3 commercially available lists. Forty-six (25.2%) companies responded. Surveys revealed that 25 (54%) of the respondent companies have 1 to 25 employees, 66.6% have separate CME divisions, 64.4% are accredited to provide CME, 77.7% have at least 1 licensed health care professional on staff, and 33.2% of their leaders hold a doctoral degree and 28.8% hold professional licensure, whereas 88.6% have advisory boards, 93.1% of which review each CME activity. MECCs comprise a diverse group differing in size and accreditation status. They contribute to the CME community by providing a variety of services, with highly trained staff. Future studies of CME providers should continue to expand the base of knowledge regarding these organizations, resulting in better understanding among all types of providers, opportunities for collaboration, and, ultimately, education that improves patient care.


Conditional cold avoidance drives between-population variation in germination behaviour in Calluna vulgaris.
Across their range, widely distributed species are exposed to a variety of climatic and other environmental conditions, and accordingly may display variation in life history strategies. For seed germination in cold climates, two contrasting responses to variation in winter temperature have been documented: first, an increased ability to germinate at low temperatures (cold tolerance) as winter temperatures decrease, and secondly a reduced ability to germinate at low temperatures (cold avoidance) that concentrates germination towards the warmer parts of the season. Germination responses were tested for Calluna vulgaris, the dominant species of European heathlands, from ten populations collected along broad-scale bioclimatic gradients (latitude, altitude) in Norway, covering a substantial fraction of the species' climatic range. Incubation treatments varied from 10 to 25 °C, and germination performance across populations was analysed in relation to temperature conditions at the seed collection locations. Seeds from all populations germinated rapidly and to high final percentages under the warmer incubation temperatures. Under low incubation temperatures, cold-climate populations had significantly lower germination rates and percentages than warm-climate populations. While germination rates and percentages also increased with seed mass, seed mass did not vary along the climatic gradients, and therefore did not explain the variation in germination responses. Variation in germination responses among Calluna populations was consistent with increased temperature requirements for germination towards colder climates, indicating a cold-avoidance germination strategy conditional on the temperature at the seeds' origin. Along a gradient of increasing temperatures this suggests a shift in selection pressures on germination from climatic adversity (i.e. low temperatures and potential frost risk in early or late season) to competitive performance and better exploitation of the entire growing season.


Mechanism of insulin aggregation and stabilization in agitated aqueous solutions.
Undesirable aggregation of aqueous insulin solutions remains a serious obstacle in the development of alternative methods of diabetes therapy. We investigated the fundamental nature of the aggregation mechanism and proposed stabilization strategies based on a mathematical model for the reaction scheme. Insulin aggregation kinetics in the presence of solid-liquid and air-liquid interfaces were monitored using UV spectroscopy and quasielastic light scattering (QELS). Experimental observations were consistent with our model of monomer denaturation at hydrophobic surfaces followed by the formation of stable intermediate species which facilitated subsequent macroaggregation. The model was used to predict qualitative trends in insulin aggregation behavior, to propose stabilization strategies, and to elucidate mechanisms of stabilization. In the absence of additives, insulin solutions aggregated completely (more than 95% of the soluble protein lost) within 24 h; with sugar-based nonionic detergents, no detectable loss occurred for more than 6 weeks.


A case of growing teratoma syndrome.
Residual masses are a common finding after chemotherapy for metastases from nonseminomatous germ cell tumours of the testes. The prognosis of these patients with resected teratoma following successful cisplatin-based combination chemotherapy generally has been assumed to be good. Herein we reported an unusual teratoma case named "growing teratoma syndrome' by Logothetis et al. This patient was treated with multiple operations.


Micro- and nano-indentation of a hydroxyapatite-carbon nanotube composite.
The mechanical properties of pure synthetic hydroxyapatite and hydroxyapatite-carbon nanotube composites were examined. Vickers microhardness and nanoindentation using a Berkovich tipped indenter were used to determine the hardness, fracture toughness and Young's modulus of the pure hydroxyapatite matrix and the composite materials. Microscopy showed that for the composites produced the carbon nanotubes were present as discrete clumps. These clumps induced a detrimental effect on the hardness of the materials, while the fracture toughness values were not affected. This would be undesirable in terms of using the material for biomedical implant applications. It should be noted that the carbon nanotubes used contained free graphite. As the properties of the composite materials studied were not greatly improved over the matrix, it is speculated that if the graphite phase were removed from the reagent, this could in-turn enhance the properties of the material.


Completeness and data validity in the Danish Achilles tendon Database.
Acute Achilles tendon rupture is a severe injury causing functional deficits and sick leave. Data from the Danish Achilles tendon Database (DADB) can help us monitor and optimise treatment. The aim of this study was to investigate the completeness and data validity in the DADB. The study was performed as a registry study comparing data in the DADB with data from patient records. Data were collected from three of 11 hospitals registered in the DADB. The study was conducted from 1 January to 31 December 2016. A completeness of 80% was considered satisfactory, and a parameter was valid if there was agreement between the DADB and the patient record in 80% of the cases. Overall, completeness was 77% (155/201); for the non-operated patients 81% (150/185) and the operated patients 31% (5/16). The seven investigated parameters all showed a validity of 83-100%. This study documented a satisfactory completeness of data on the non-operated patients registered in the DADB and an unsatisfactory completeness of data on operated patients. All investigated parameters were valid. These results suggest that data in the DADB on non-operated patients can contribute to research within the field. Due to a limited sample on operated patients, conclusions should be made with caution. The logistics concerning data collection among operated patients warrants optimisation. not relevant. The study was approved by the Danish Data Protection Agency and the Danish Patient Safety Authority.


Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity.
Acetaminophen (APAP) hepatotoxicity because of overdose is the most frequent cause of acute liver failure in the western world. Metabolic activation of APAP and protein adduct formation, mitochondrial dysfunction, oxidant stress, peroxynitrite formation and nuclear DNA fragmentation are critical intracellular events in hepatocytes. However, the early cell necrosis causes the release of a number of mediators such as high-mobility group box 1 protein, DNA fragments, heat shock proteins (HSPs) and others (collectively named damage-associated molecular patterns), which can be recognized by toll-like receptors on macrophages, and leads to their activation with cytokine and chemokine formation. Although pro-inflammatory mediators recruit inflammatory cells (neutrophils, monocytes) into the liver, neither the infiltrating cells nor the activated resident macrophages cause any direct cytotoxicity. In contrast, pro- and anti-inflammatory cytokines and chemokines can directly promote intracellular injury mechanisms by inducing nitric oxide synthase or inhibit cell death mechanisms by the expression of acute-phase proteins (HSPs, heme oxygenase-1) and promote hepatocyte proliferation. In addition, the newly recruited macrophages (M2) and potentially neutrophils are involved in the removal of necrotic cell debris in preparation for tissue repair and resolution of the inflammatory response. Thus, as discussed in detail in this review, the preponderance of experimental evidence suggests that the extensive sterile inflammatory response during APAP hepatotoxicity is predominantly beneficial by limiting the formation and the impact of pro-inflammatory mediators and by promoting tissue repair.


Chromosome variation in Peromyscus: a new mechanism.
Differences in total chromosome lengths between two karyotypically divergent groups of Peromyscus maniculatus are taken as evidence for an deletion mechanism of chromosomal variation in the species. The differences may be due in part to variation in the amount of constitutive heterochromatin in the two karyotypes.


Current status of the oak gallwasp (Hymenoptera: Cynipidae: Cynipini) fauna of the Eastern Palaearctic and Oriental Regions.
Cynipid gallwasps comprise 1364 species worldwide, predominantly in temperate regions of the Holarctic. The vast majority of recorded species are from the Nearctic and the Western Palaearctic, both of which are long-standing centers of research on the taxonomy and biology of this group. In contrast, the Eastern Palaearctic and the Oriental Region faunas are much less studied, but potentially extremely rich. Previously recorded species richness of cynipid groups in the Eastern Palaearctic and Oriental regions probably represents a significant underestimate. This is particularly marked for gallwasps associated with oaks (tribe Cynipini), as has been shown by recent works, which describe many new species galling oaks in the subgenera Quercus and Cyclobalanopsis and plants of the other Fagaceae genera (Castanopsis, Lithocarpus and Castanea). In the present paper, we summarise the current knowledge of oak gallwasps in the regions that extend from Pakistan, through Nepal and China to Japan and south to Indonesia, and list a total of 97 species of Cynipini from the area.


Different responses of macrophages in retinal ganglion cell survival after acute ocular hypertension in rats with different autoimmune backgrounds.
Recently macrophages were shown to play a protective role in retinal ganglion cells (RGCs) after optic nerve (ON) injury. In the present study, we investigated how macrophages responded after acute intraocular pressure (IOP) elevation in experimental autoimmune encephalomyelitis (EAE)-resistant Fischer 344 (F344) and Sprague Dawley (SD) rats and EAE-vulnerable Lewis rats. Acute IOP elevation was performed at 110mmHg for 2h to mimic acute glaucoma. Phagocytic cells in the eye were removed by intravitreal application of clodronate liposomes whereas macrophage activation was achieved by intravitreal injection of zymosan, a yeast wall preparation. Fluorescence dye, FluoroGold, was applied behind the eyeballs to retrogradely label surviving RGCs 40h before animal sacrifice. Macrophages in the retina were identified by ED1 immunostaining. Loss of 25% RGCs in F344 but over 90% in Lewis rats was seen 2 weeks after acute IOP elevation. Significant increase in the number of macrophages in the retina was seen to accompany the great RGC loss in Lewis rats; removal of these macrophages reduced the extent of RGC loss, suggesting the involvement of macrophages in RGC death in Lewis strain. Low numbers of macrophages were seen in F344 retinas after acute IOP elevation, and removal of macrophages did not show clear effect on RGC viability. Whereas macrophage activation by zymosan protected RGCs after ON axotomy in F344 rats, the same macrophage activation became detrimental to RGCs after acute IOP elevation. The extent of RGC loss 3 weeks after acute IOP elevation or after macrophage activation by zymosan in EAE-resistant SD rats was similar to that in F344 rats. We thus demonstrate that macrophages in rats with different autoimmune backgrounds react differently to acute IOP elevation and differentially modulate RGC loss, a phenomenon contrary to the protective action in RGCs after ON axotomy. These data suggest that autoimmune background plays a role in modulating vulnerability of RGCs to acute IOP elevation.


Dichlorido{N-[2-(diphenylphosphanyl)benzylidene]-2-methylaniline}palladium(II) acetonitrile monosolvate.
The title imino-phosphine compound, [PdCl2(C26H22NP)]·CH3CN, was prepared by reaction of N-[2-(diphenylphosphanyl)benzylidene]-2-methylaniline with dichlorido(cycloocta-1,5-diene)palladium(II) in dry CH2Cl2. The Pd(II) cation is coordinated by the P and N atoms of the bidentate chelating ligand and by two chloride anions, generating a distorted square-planar coordination geometry. There is a detectable trans influence for the chloride ligands. The methyl group present in this structure has an influence on the crystal packing.


Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?
Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed.


In situ chlorhexidine substantivity on saliva and plaque-like biofilm: influence of circadian rhythm.
The aim of the present study is to assess in situ substantivity of a single mouthrinse with 0.2% chlorhexidine (CHX) on saliva and on undisturbed de novo plaque-like biofilm (PL-biofilm), differentiating between two times of application: 1) CHX mouthrinse in the morning; and 2) CHX mouthrinse at night. The study participants were 10 healthy volunteers who wore an individualized splint with glass disks for 48 hours to boost the growth of PL-biofilm. Saliva samples were collected, and two disks were removed from each volunteer's splint at 8, 10, and 12 hours after performing a mouthrinse with 0.2% CHX at 7:00 am (M-0.2% CHX-diurnal) and 1:00 am (M-0.2% CHX-nocturnal). The saliva and plaque samples were analyzed by epifluorescence and confocal laser scanning microscopy, respectively, using a green fluorescent nucleic acid stain/propidium iodide staining. With M-0.2% CHX-diurnal, the frequency of vital bacteria in saliva was significantly higher than in the PL-biofilm at 8, 10, and 12 hours after mouthrinse. After M-0.2% CHX-nocturnal, the frequency of vital bacteria in saliva was significantly lower than in the PL-biofilm at 8 hours and higher than in the PL-biofilm at 12 hours after mouthrinse. These results support the more active physiologic dynamics of the salivary flora and the possible reservoir function associated with the structure of undisturbed de novo PL-biofilm.


Patient, clinician, and population perspectives on determining the clinical significance of quality-of-life scores.
Despite the success of screening and treatment of major cancers in the United States, cancer remains a chronic condition dominated by symptoms and treatment-related adverse effects. Because of these often taxing symptoms and adverse effects, numerous studies have been conducted to document the effects of cancer diagnosis and treatment on the quality of life (QOL) of patients. But there has been limited investigation of the clinical significance of QOL scores. This article examines the clinical significance of QOL scores from 3 key perspectives: patients, clinicians, and the general population. The patient's perspective includes an evaluation of the size of difference in scores that individual patients can detect and regard as important. The clinician perspective relies on whether the clinician believes the patient's condition has stayed the same vs whether changes have occurred (decline or improvement). The population perspective represents a democratic process in which the input or votes of a community of people are used to determine if health state A is clinically significantly different from health state B. While many clinicians and researchers advocate for QOL to be defined from the patient's perspective, the reality is that QOL is often defined by clinicians in terms of observable events. Even when measures are used in which the patient identifies how his or her life has been affected, it is often the clinician who interprets the clinical importance of this information. The clinician's perspective has value in framing an experience within the context of what is usual for a group of individuals, and the population perspective provides inputs as to how society may use limited resources. However, we conclude that a more prominent role for the patient's QOL perspective is needed.


Identification of potential biomarkers of lung adenocarcinoma brain metastases via microarray analysis of cDNA expression profiles.
Brain metastases originating from lung adenocarcinoma (LAD) occur frequently. The aim of the current study was to assess potential biomarkers for the prognosis of lung adenocarcinoma brain metastasis (LAD-BM) through the analysis of gene expression microarrays. The current study downloaded two gene expression datasets, GSE14108 and GSE10245, from the Gene Expression Omnibus database. From GSE14108 and GSE10245, 19 LAD-BM samples and 40 primary LAD samples were selected for analysis. To identify the differentially expressed genes (DEGs), the current study compared the two sample groups, using the limma R package. Subsequently, pathway enrichment analysis was conducted using the Cluster Profiler R package, and the construction of the protein-protein interaction (PPI) network was executed utilizing the Search Tool for the Retrieval of Interacting Genes database. The microRNA-target network was built using the TargetScore R package. Then, these networks were established and visualized using Cytoscape software. An array of 463 DEGs was identified in the LAD-BM samples, including 256 upregulated and 207 downregulated genes. Based on functional term enrichment analysis using the Gene Ontology database and signaling pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes database, it was identified that the overlapping DEGs were primarily involved in chemokine-associated signal transduction, which may mediate lung cancer cell metastasis to the brain. Chemokine ligand 2, lysozyme, matrix metalloproteinase-2 (MMP-2), lysyl oxidase (LOX) and granzyme B were identified as potential biomarkers according to a topological analysis of the PPI networks. Two notable nodes, MMP-2 and LOX, appeared in the PPI network and were key points in the microRNA-target network, as they were regulated by hsa-let-7d. Many DEGs and microRNAs were regarded as prognostic biomarkers for lung adenocarcinoma metastasis in the current study. These DEGs were primarily associated with chemokine-mediated signaling pathways. In addition, MMP-2 and LOX were predicted to be targets of hsa-let-7d.


Monoclonal antibodies to polioviruses. Production of specific monoclonal antibodies to the Sabin vaccine strains.
Murine lymphocyte hybridomas which produce neutralizing or non-neutralizing monoclonal antibodies to different type 1, 2 or 3 poliovirus strains were isolated. The majority of these monoclonal antibodies reacted with antigenic determinants present on different poliovirus strains of the same type. However, hybridomas producing monoclonal antibodies specific for each of the three Sabin vaccine strains were also generated.


Can recent insights into cardiac development improve our understanding of congenitally malformed hearts?
Congenital cardiac malformations account for one-quarter of all human congenital abnormalities. They are caused by environmental and genetic factors. Despite increasing efforts in fundamental research, as yet, the morphogenesis of only a limited number of malformations has been elucidated. Over the last decades, new genetic modifications have made it possible to manipulate the mammalian embryo. Evidence provided using these transgenic techniques has, over the past decade, necessitated re-evaluation of several developmental processes, important in the understanding of normal as opposed to abnormal cardiac development. In this review, we discuss current understanding of the patterning of the initial heart tube, new insights into formation of the atrial and ventricular chambers, and novel information on the origin of the cells that are added to the heart after formation of the initial tube. All of these advances modify our appreciation of malformations involving the venous and arterial poles. As we demonstrate, this new information sheds light not only on normal cardiac development, but also explains the structure of several previously controversial lesions seen in malformed human hearts.


Metabolomics for Age Discrimination of Ginseng Using a Multiplex Approach to HR-MAS NMR Spectroscopy, UPLC-QTOF/MS, and GC × GC-TOF/MS.
(1) Background: The ability to determine the age of ginseng is very important because the price of ginseng depends on the cultivation period. Since morphological observation is subjective, a new scientific and systematic method for determining the age of ginseng is required. (2) Methods: Three techniques were used for a metabolomics approach. High-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy was used to analyze powdered ginseng samples without extraction. Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and gas chromatography quadrupole time-of-fight mass spectrometry (GC-TOF/MS) were used to analyze the extracts of 4-, 5-, and 6-year-old ginseng. (3) Results: A metabolomics approach has the potential to discriminate the age of ginseng. Among the primary metabolites detected from NMR spectroscopy, the levels of fumarate and choline showed moderate prediction with an area under the curve (AUC) value of more than 0.7. As a result of UPLC-QTOF/MS-based profiling, 61 metabolites referring to the VIP (variable importance in the projection) score contributed to discriminating the age of ginseng. The results of GC×GC-TOF/MS showed clear discrimination of 4-, 5-, and 6-year-old ginseng using orthogonal partial least-squares discriminant analysis (OPLS-DA) to 100% of the discrimination rate. The results of receiver operating characteristic (ROC) analysis, 16 metabolites between 4- and 5-year-old ginseng, and 18 metabolites between 5- and 6-year-old ginseng contributed to age discrimination in all regions. (4) Conclusions: These results showed that metabolic profiling and multivariate statistical analyses can distinguish the age of ginseng. Especially, it is meaningful that ginseng samples from different areas had the same metabolites for age discrimination. In future studies, it will be necessary to identify the unknown variables and to collaboratively study with other fields the biochemistry of aging in ginseng.


Teriparatide as a systemic treatment for lower extremity nonunion fractures: a case series.
To investigate the effect of teriparatide (parathyroid hormone [1-34]) on the healing of long bone nonunion fractures. We performed a retrospective chart review of patients with fracture nonunion, aged 10 to 99 years who were treated with teriparatide at the Children's Hospital of Philadelphia or the Hospital of the University of Pennsylvania between November 2002 and January 2013. The primary endpoints were radiographic evidence of callus formation and fracture union, ability to bear weight without affected limb limp, and normal range of motion and strength. Six patients aged 19 to 64 years with tibial or femoral fractures that had not healed for 3 to 36 months were treated with teriparatide 20 μg/day. Accelerated healing of fracture nonunion was confirmed in 5 of 6 patients with time to complete union of 3 to 9 months. The shortest time to recovery was observed in younger patients without comorbidities. Treatment was well tolerated. Teriparatide is a promising treatment for nonunion fractures, but its response depends on associated comorbidities. The potential benefit of teriparatide as an adjunct to treat nonunion justifies randomized placebo-controlled trials to determine its efficacy and safety in broader populations.


Silencing of Eps8 blocks migration and invasion in human glioblastoma cell lines.
Glioblastoma multiforme (GBM) is the most malignant human primary brain tumor, and its infiltrative nature represents the leading cause for the failure of therapies and tumor recurrences. It is therefore crucial the knowledge of the molecular mechanisms underlying GBM invasion to identify novel therapeutic targets to limit motility. In this study, we evaluated the role of Epidermal growth factor receptor Pathway Substrate 8 (Eps8), a crucial regulator of the actin cytoskeleton dynamics accompanying cell motility and invasion, in GBM migration and invasiveness. We found that silencing of the protein by small interfering RNAs (siRNAs) abrogated the migratory and invasive capacity of three different human GBM cell lines both in 2-dimensional (2-D) and 3-dimensional (3-D) in vitro assays. The inhibitory effect on invasion was maintained independently by the migration mode utilized by the cells in our 3-D model, and was accompanied by an impaired formation of actin-based cytoskeletal protrusive structures. Our data propose Eps8 as a key molecule involved in the control of the intrinsic invasive behavior of GBM cells, and suggest that this protein might represent a useful target for the design of new drugs for the treatment of these tumors.


Proficiency testing of creatine kinase and creatine kinase-2: the experience of the Ontario Laboratory Proficiency Testing Program.
The Ontario Laboratory Proficiency Testing Program has regularly monitored the analytical performance of total creatine kinase (CK) (approximately 230 participants) and CK isoenzyme-2 (CK-MB) (approximately 160 participants) throughout the entire province. Consistently, a wide dispersion of results has been observed not only between different analyzer systems but also among identical analyzers. Accordingly, the results of the last three proficiency surveys for these analytes were examined statistically to establish both the extent of these variations and the range of values reported for the male upper reference ranges. The results of many of the analyzer systems were significantly different from each other, as were many of the reference ranges. This unsatisfactory situation may only be remedied by the use of reference materials as shown by others. The consequences of these findings also effect the reliability of epidemiological surveys such as the WHO MONICA Project (Circulation 1994;90:583-612), which monitors deaths due to heart disease and includes cardiac enzyme results in its criteria.


Lifetime cocaine use and cardiovascular characteristics among young adults: the CARDIA study.
Cocaine is a central nervous system stimulant associated with cardiovascular disease risk factors, morbidity, and mortality. Despite these demonstrated relationships, it has been difficult to assess the long-term cardiovascular consequences of cocaine use. The Coronary Artery Risk Development in Young Adults study provides an opportunity to evaluate the association of lifetime cocaine use with cardiovascular disease risk factors in a randomly sampled biethnic cohort of men and women of varied socioeconomic status, aged 20 to 32 in 1987. More extensive cocaine use experience was associated with being White, older, and less educated, regardless of sex. Higher levels of licit and illicit substance use behavior were reported by those reporting more extensive cocaine experience; however, most cardiovascular disease risk factors such as systolic and diastolic blood pressure, heart rate, hypertension, physical activity, and anthropometric measurements were not related to lifetime cocaine experience. In this age group, the detrimental cardiovascular effects of cocaine may be limited to acute effects. Further studies are needed to determine whether continued exposure is related to cardiovascular disease risk factors later in life.


Alcohol-ingestive habits. The role of flavor and effect.
We propose that alcohol is a food and that drinking alcohol is fundamentally a feeding habit. Many feeding habits are acquired by Pavlovian conditioning in which the flavor of food [conditioned stimulus (CS)] is adjusted by the aftereffects of the ingested meal [unconditioned stimulus (US)]. Thus, repletion of nutritive deficits or recuperation from illness enhances flavor palatability, whereas toxicosis or nausea reduces it. After reviewing the major functional and neurophysiological features of this homeostatic conditioning process, we relate them to the flavor (CS) and effect (US) of alcohol. We present evidence suggesting that the caloric effects of low-dose alcoholic drinks may help to establish and maintain alcohol habits through conditioned palatability changes. Included is a general treatment of the antagonistic interactions between such homeostatic conditioning and the behavioral mechanisms used to defend again peripheral insults such as electric shock. In closing, we discuss the implications for modifying alcoholic habits.


Halovulum marinum sp. nov., isolated from deep-sea water of the Indian Ocean, and emended description of the genus Halovulum.
A novel Gram-stain-negative, aerobic, motile by peritrichous flagella, oval to rod-shaped bacterium, designated strain 2CG4T, was isolated from a deep-sea water sample collected from the Northwest Indian Ocean. The results of phylogenetic analysis of both 16S rRNA gene and RpoC protein sequences indicated that this strain was affiliated with the genus Halovulum in the Amaricoccus clade of the family Rhodobacteraceae of the class Alphaproteobacteria, sharing 95.3 % similarity at the 16S rRNA gene sequence level with the type strain of Halovulum dunhuangense YYQ-30T, the only species in the genus Halovulum. The predominant fatty acids (>10 %) of 2CG4T were summed feature 8 (C18 : 1ω7c and/ or C18 : 1ω6c; 61.1 %) and cyclo-C19 : 0ω8c (15.6 %). The polar lipids of 2CG4T were phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and sulfoquinovosyldiacylglycerol. The only isoprenoid quinone of 2CG4T was ubiquinone-10. The DNA G+C content of 2CG4T was determined to be 69.4 %. The central gene pufLM for the photosynthetic reaction was not detected. No growth occurred for 2CG4T in the absence of NaCl. On the basis of these data, it is concluded that the 2CG4T represents a novel species of the genus Halovulum, for which the name Halovulum marinum sp. nov. is proposed. The type strain is 2CG4T (=CGMCC 1.16468T=JCM 32611T).


Sero-prevalence and epidemiology of peste des petits ruminants in Libya.
We conducted a cross-sectional study during 2013 to quantify the serological prevalence of peste des petits ruminants (PPR) infection and to investigate host factors associated with PPR infection in small ruminants in Libya. A two-stage sampling design was carried out. A total number of 148 flocks owning at least 100 heads each were randomly selected. Sixteen to forty-eight samples were collected from each selected flock. A total number of 3,508 serum samples from unvaccinated animals were collected and analysed at IZSLER Brescia, Italy, by using competitive ELISA, IDvet innovative diagnostics (IDvet 310, France). The overall serological prevalence among SR was 33% (95% CI: 31.4-34.5). Significant differences between the prevalence in the geographical branches were observed. The lowest prevalence level was observed in Zawiyah branch (16.1%), whereas the highest value was obtained for the Sabha branch (56.8%). Considering the age, a serological prevalence of 24.7%, 31.5% and 42.1% was observed in SR <1 year, between 1 and 2 years and more than 2 years, respectively. Statistically significant differences (p < .001) in the sero-prevalence levels were also observed between the age groups. Our findings suggest that the southern part of Libya could be more exposed to the infections coming from the neighbouring countries and this should be better investigated to correctly identify wherever specific entry points can be considered at higher risk than others. The results also confirmed the endemic status of PPR in Libya, with a constant exposure to the infection of the animals during their life. In the framework of the global strategy for control and eradication of PPR, our results, even if obtained by a preliminary study, can contribute to the assessment of the epidemiological situation of PPR in Libya as required by the Stage 1 of the plan.


MdSWEET23, a sucrose transporter from apple (Malus × domestica Borkh.), influences sugar metabolism and enhances cold tolerance in tomato.
Photosynthetic products in most fleshy fruits are unloaded via the apoplasmic pathway. Sugar transporters play an important role in the apoplasmic unloading pathway and are involved in sugar transport for fruit development. The MdSWEET23, cloned from ''Hanfu'' apple (Malus × domestica Borkh.) fruits, belongs to Clade III of the SWEET family. Subcellular localization revealed that MdSWEET23 is localized on the plasma membrane. β-glucuronidase activity assays showed that MdSWEET23 was primarily expressed in the sepal and carpel vascular bundle of apple fruits. Heterologous expression assays in yeast showed that MdSWEET23 functions in sucrose transport. The overexpression of MdSWEET23 in the ''Orin" calli increased the soluble sugar content. The silencing of MdSWEET23 significantly reduced the contents of sucrose and sorbitol in apple fruits. Ectopic overexpression of MdSWEET23 in tomato altered sugar metabolism and distribution in leaves and fruits, causing a reduction in photosynthetic rates and plant height, enhanced cold stress tolerance, and increased the content of sucrose, fructose, and glucose in breaking color fruits, but did not increase sugar sink potency of tomato fruits.


Correlation between the sulfamethoxazole-trimethoprim resistance of Shigella flexneri and the sul genes.
The aim of this study was to discuss the correlation between the sulfamethoxazole-trimethoprim resistance of Shigella flexneri (S. flexneri) and the antibiotic resistance genes sul1, sul2, and sul3 and SXT element.From May 2013 to October 2018, 102 isolates of S. flexneri were collected from the clinical samples in Jinan. The Kirby-Bauer (K-B) test was employed to determine the antibiotic susceptibility of the S. flexneri isolates. The antibiotic resistance rate was analyzed with the WHONET5.4 software. The isolates were subject to the PCR amplification of the sul genes (sul1, sul2, and sul3) and the SXT element. On the basis of the sequencing results, the correlation between the sulfamethoxazole-trimethoprim resistance of the S. flexneri isolates and the sul genes was analyzed.The antibiotic resistance rates of the 102 S. flexneri isolates to ampicillin, streptomycin, chloramphenicol, tetracycline, and sulfamethoxazole-trimethoprim were 90.2%, 90.2%, 88.2%, 88.2%, and 62.7%, respectively. The antibiotic resistance rates of these isolates to cefotaxime, ceftazidime, and ciprofloxacin varied between 20% and 35%. However, these isolates were 100% susceptible to cefoxitin. Positive fragments were amplified from 59.8% (61/102) of the 102 S. flexneri isolates, the sizes of the sul1 and sul2 genes being 338 bp and 286 bp, respectively. The sequence alignment revealed the presence of the sul1 and sul2 genes encoding for dihydrofolate synthase. The carrying rate of the sul1 gene was 13.7% (14/102), and that of the sul2 gene was 48.0% (49/102). No target gene fragments were amplified from the 3 isolates resistant to sulfamethoxazole-trimethoprim. The sul3 gene and SXT element were not amplified from any of the isolates. The testing and statistical analysis showed that the resistance of the S. flexneri isolates to sulfamethoxazole-trimethoprim correlated to the sul1 and sul2 genes.The acquired antibiotic resistance genes sul1 and sul2 were closely associated with the resistance of the 102 S. flexneri isolates to sulfamethoxazole-trimethoprim.


Listening to hypochondriasis and hearing health anxiety.
Although hypochondriasis is categorized as a somatoform disorder in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition--Text Revision (DSM-IV-TR) due to excessive focus on bodily symptoms for at least 6 months, a contemporary conceptualization suggests that hypochondriasis represents an intense form of health anxiety. This article discusses the clinical presentation of hypochondriasis, etiological underpinnings and multiple maintaining factors, including physiological, cognitive and behavioral components. A cognitive-behavioral model of hypochondriasis as health anxiety and the empirically supported treatment based on the model are articulated. Future directions and informational resources are provided for both clinicians and patients.


Nitric oxide inhibition causes an exaggerated pressor response in Yucatan miniature swine.
The involvement to nitric oxide (NO) in cardiovascular and renal function was evaluated in 12 anesthetized Yucatan miniature swine. The effect of NO blockade on blood pressure was measured in six additional conscious swine. In the anesthetized swine, mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR), and urinary excretion of water, sodium, and potassium were measured after systemic inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME), and were compared with values for a control period. After NO synthesis blockade, MAP increased by 63 +/- 5 mm Hg, a far greater increase than those observed in rats, dogs, domestic swine, or humans. The changes in GFR, urine flow rate (UFR), and sodium excretion (UNaV) were time-dependent. The GFR decreased to 50 +/- 6% of control values immediately after L-NAME administration, but returned to control values within 1 h. Significant increases in UFR and UNaV were observed only during the third experimental period, 40 to 60 min after drug infusion. In the conscious swine, L-NAME administration increased MAP by 24 +/- 4 mm Hg. Administration of the sympatholytic hexamethonium bromide fully reversed the increase of MAP in anesthetized and conscious swine. These findings indicate that NO has an important role in the maintenance of cardiovascular and renal function in Yucatan miniature swine. The exaggerated pressor response to NO blockade in miniature swine appears to involve the sympathetic nervous system.


Cassia tora Seed Extract and Its Active Compound Aurantio-obtusin Inhibit Allergic Responses in IgE-Mediated Mast Cells and Anaphylactic Models.
Cassia tora seed is widely used due to its various biological properties including anticancer, antidiabetic, and anti-inflammatory effects. However, there has been no report of the effects of C. tora seed extract (CTE) on immunoglobulin E (IgE)-mediated allergic responses. In this research, we demonstrated the effects of CTE and its active compound aurantio-obtusin on IgE-sensitized allergic reactions in mast cells and passive cutaneous anaphylaxis (PCA). CTE and aurantio-obtusin suppressed degranulation, histamine production, and reactive oxygen species generation and inhibited the production and mRNA expression of tumor necrosis factor-α and interleukin-4. CTE and aurantio-obtusin also suppressed the prostaglandin E2 production and expression of cyclooxygenase 2. Furthermore, CTE and aurantio-obtusin suppressed IgE-mediated FcεRI signaling such as phosphorylation of Syk, protein kinase Cμ, phospholipase Cγ, and extracellular signal-regulated kinases. CTE and aurantio-obtusin blocked mast cell-dependent PCA in IgE-mediated mice. These results suggest that CTE and aurantio-obtusin are a beneficial treatment for allergy-related diseases.


Dynamic Covalent Chemistry Enables Reconfigurable All-Polysaccharide Nanogels.
Dynamic covalent bonds are established upon molecular recognition of sugar derivatives by boronic acid molecules. These reversible links can be used in a cross-linking method to fabricate polymer-based responsive nanosystems. Herein, the design of the first dynamic nanogels made entirely of polysaccharides (PS) is reported. Based on PS chains alternately modified with phenyl boronic acid groups and sugar moieties, these colloids self-assemble in physiological conditions and combine the biocompatible nature of their PS backbone with the reconfiguration capacities of their cross-linking chemistry. These dynamic nanogels are easily prepared, stable for a long time, pH responsive, and efficiently internalized by cancer cells.


CRISPR/Cas9-Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development.
The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them.


Modulated drug release from the stem-and-loop structured oligodeoxynucleotide upon UV-A irradiation in the presence of target DNA.
o-Nitrobenzyl photochemistry as induced by UV-A irradiation was applied to a photoactivated drug releasing system based on a molecular beacon strategy. A stem-and-loop structured oligodeoxynucleotide (ODN) possessing a photoreactive o-nitrobenzyl chromophore at the 3'-end and 1-aminonaphthalene quencher at the 5'-end underwent conformational change into a conventional double strand structure by hybridization with a specified target DNA. The intrinsic stem-and-loop structure suppressed photoactivated release of benzoic acid as a phantom drug from the o-nitrobenzyl chromophore because of intramolecular quenching by the 1-aminonaphthalene unit in close proximity to the chromophore. Formation of the double strand structure in the presence of perfectly matched target DNA minimized occurrence of intramolecular quenching and thereby enhanced the photoactivated drug release.


Open reduction and internal fixation of intra-articular calcaneal fractures in children.
Calcaneal fractures are rare injuries in children and adolescents, and fractures with displaced intra-articular fracture patterns are even more rare. The purpose of this study was to report 9 intra-articular calcaneal fractures in 8 children (mean age, 12.6 years; range,10-15 years) treated with open reduction and internal fixation (ORIF) and to examine cases reported in the literature to better define the classification characteristics and operational outcomes of this uncommon fracture. Preoperative radiographs and computed tomography scans were used to evaluate and classify the fractures. Clinical and radiographic examinations were performed at postoperative follow-up, and functional outcome was assessed with the modified American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score. Mean follow-up was 47 months (range, 21-72 months). Mean time to union was 9.2 weeks (range, 8-12 weeks). Mean modified AOFAS score was 65.2 points (range, 53-68 points). One foot experienced a minor complication.After a systematic review of the literature, 4 studies with a total of 35 patients (37 fractures) were included. All fractures were caused by high-energy injuries. Based on the Essex-Lopresti classification, 40.5% (15/37) were tongue-type fractures and 59.5% (22/37) were joint depression-type fractures. Based on the Sanders classification, 62.2% (23/37) of fractures were 2 parts, 32.4% (12/37) were 3 parts, and 5.4% (2/37) showed comminution. No significant difference was found in classification information between children and adults. The authors concluded that the characteristics of intra-articular calcaneal fractures in children are similar to those in adults, and operative treatment of these fractures yields good results with few complications.


Uptake of human papillomavirus vaccination and its associated factors among adolescents in Gambella town, Southwest, Ethiopia: a community-based cross-sectional study.
To assess the uptake of human papillomavirus (HPV) vaccination and its associated factors among adolescents in Gambella town, Southwest Ethiopia. A community-based cross-sectional study. Gambella town, Southwest Ethiopia. A total of 882 adolescents were included between May and July 2022. Uptake of HPV vaccination. A cluster sampling technique was used to select study participants. An interviewer-administered and pretested questionnaire was used to collect the data. The collected data were entered into Epi-data V.4.6 and exported to STATA V.16 for cleaning, coding and analysis. A binary logistic regression model was used to test the association between independent and dependent variables. Variables with a p<0.05 in the multivariable logistic regression were considered statistically significant factors for the uptake of HPV vaccination. A total of 825 adolescents participated in this study. Among participants, 48% (95% CI 44.6% to 51.4%) have been vaccinated for HPV. Ever heard of the HPV vaccine (AOR 2.5, 95% CI 1.23 to 5.08), good knowledge of HPV infection (AOR 3.62, 95% CI 2.17 to 6.02), good knowledge of the HPV vaccine (AOR 5.54, 95% CI 3.28 to 9.36) and attitude towards the HPV vaccine (AOR 2.74, 95% CI 1.88 to 3.98) were significantly associated HPV vaccination. In the current study, the uptake of HPV vaccination was found to be low. The finding highlights the importance of promoting community health education about HPV infection and vaccines and providing behaviour change education, which plays a substantial role in promoting the uptake of HPV vaccination.


Impact of Age, Gender, post infection and post vaccination status on antibody response in COVID 19 patients.
To evaluate severe acute respiratory syndrome coronavirus-2 spike protein antibodies against coronavirus disease-2019 in post-infection and post-vaccinated individuals. The cross-sectional study was conducted from June, 1 to July 31, 2021 at the Rehman Medical Institute, Peshawar, Pakistan, and comprised subjects of either gender in whom immunogenicity was checked 35 days post-vaccination and 90 days post-infection. Correlation with age and gender was checked. Specimens were collected and investigated for severe acute respiratory syndrome coronavirus-2 spike protein antibodies by consuming electro-chemiluminescence immunoassay. Data was analysed using SPSS 23. Of the total 256 patients enrolled, 70(27.34%) were included; 49(69%) males and 21(29.6%) females. The overall mean age was 44±7.75 years. Among 30(42.8%) patients with positive polymerase chain reaction test, the mean time between the positive test and antibody screening was 90±30 days. Among the 40(57.2%) vaccinated individuals, the time between vaccination and antibody screening was 35±9.74 days. Overall, 68(97%) patients revealed robust positive findings to severe acute respiratory syndrome coronavirus-2 spike proteins antibodies >50IU/mL. Male subjects had significantly higher immunogenic response compared to females (p=0.001), and immunogenicity decreased with advancing age (p<0.001). Also, post-vaccinated patients' antibody response was significant compared to post-infection patients' response (p=0.001). Majority of the patients had significantly higher antibody titers against severe acute respiratory syndrome coronavirus-2 post-infection and post-vaccination. Males and younger individuals developed a significant humoral immunity compared to females and the elderly.


Management of children with primitive neuroectodermal tumors of the posterior fossa/medulloblastoma.
Primitive neuroectodermal tumors of the posterior fossa/medulloblastoma (PNET-MB) are the most common malignant primary central nervous system tumors of childhood. Current approaches to therapy for children with PNET-MB are illustrative of both the advances which have been made in management of childhood brain tumors and the areas where increased understanding is needed. With the optimal use of surgery and radiotherapy, the majority of children with PNET-MB can be expected to be alive and free of disease 5 years after diagnosis. Based on various factors, including the age of patient, the extent of the disease at the time of diagnosis and histological parameters, it is possible to stratify patients with PNET-MB into 'risk' groups. It is unclear whether preoperative or postoperative factors are most predictive of outcome. Patients with factors predictive of a higher likelihood of disease relapse seem to benefit from treatment with chemotherapy. The amount of radiotherapy and the type and amount of chemotherapy which is most efficacious in controlling the disease has yet to be determined. Children surviving PNET-MB are at high risk for endocrinologic and neuropsychologic sequelae. Multiple prospective treatment protocols are now underway, attempting to determine which therapy is best at controlling disease without causing severe long-term damage. A multidisciplinary approach is needed for the treatment of children with PNET-MB.


Application of Perovskite Nanocrystals as Fluorescent Probes in the Detection of Agriculture- and Food-Related Hazardous Substances.
Halide perovskite nanocrystals (PNCs) are a new kind of luminescent material for fluorescent probes. Compared with traditional nanosized luminescent materials, PNCs have better optical properties, such as high fluorescence quantum yield, tunable band gap, low size dependence, narrow emission bandwidth, and so on. Therefore, they have broad application prospects as fluorescent probes in the detection of agriculture- and food-related hazardous substances. In this paper, the structure and basic properties of PNCs are briefly described. The water stabilization methods, such as polymer surface coating, ion doping, surface passivation, etc.; are summarized. The recent advances of PNCs such as fluorescent probes for detecting hazardous substances in the field of agricultural and food are reviewed, and the detection effect and mechanism are discussed and analyzed. Finally, the problems and solutions faced by PNCs as fluorescent probes in agriculture and food were summarized and prospected. It is expected to provide a reference for further application of PNCs as fluorescent probes in agriculture and food.


The Nitrogen Stress-Repressed sRNA NsrR1 Regulates Expression of all1871, a Gene Required for Diazotrophic Growth in Nostoc sp. PCC 7120.
Small regulatory RNAs (sRNAs) are post-transcriptional regulators of bacterial gene expression. In cyanobacteria, the responses to nitrogen availability, that are mostly controlled at the transcriptional level by NtcA, involve also at least two small RNAs, namely NsiR4 (nitrogen stress-induced RNA 4) and NsrR1 (nitrogen stress-repressed RNA 1). Prediction of possible mRNA targets regulated by NsrR1 in Nostoc sp. PCC 7120 allowed, in addition to previously described nblA, the identification of all1871, a nitrogen-regulated gene encoding a protein of unknown function that we describe here as required for growth at the expense of atmospheric nitrogen (N2). We show that transcription of all1871 is induced upon nitrogen step-down independently of NtcA. All1871 accumulation is repressed by NsrR1 and its expression is stronger in heterocysts, specialized cells devoted to N2 fixation. We demonstrate specific interaction between NsrR1 and the 5' untranslated region (UTR) of the all1871 mRNA, that leads to decreased expression of all1871. Because transcription of NsrR1 is partially repressed by NtcA, post-transcriptional regulation by NsrR1 would constitute an indirect way of NtcA-mediated regulation of all1871.


Effects of anesthetics on the renal sympathetic response to anaphylactic hypotension in rats.
The autonomic nervous system plays an important role in rat anaphylactic hypotension. It is well known that sympathetic nerve activity and cardiovascular function are affected by anesthetics. However, the effects of different types of anesthesia on the efferent renal sympathetic nerve activity (RSNA) during anaphylactic hypotension remain unknown. Therefore, we determined the renal sympathetic responses to anaphylactic hypotension in anesthetized and conscious rats and the roles of baroreceptors in these responses. Sprague-Dawley rats were randomly allocated to anesthetic groups that were given pentobarbital, urethane, or ketamine-xylazine and to a conscious group. The rats were sensitized using subcutaneously injected ovalbumin. The systemic arterial pressure (SAP), RSNA and heart rate (HR) were measured. The effects of sinoaortic baroreceptor denervation on RSNA during anaphylaxis were determined in pentobarbital-anesthetized and conscious rats. In all of the sensitized rats, the RSNA increased and SAP decreased after antigen injection. At the early phase within 35 min of the antigen injection, the antigen-induced sympathoexcitation in the conscious rats was significantly greater than that in the anesthetized rats. Anaphylactic hypotension was attenuated in the conscious rats compared to the anesthetized rats. The anesthetic-induced suppression of SAP and RSNA was greater in the order ketamine-xylazine >urethane = pentobarbital. Indeed, in the rats treated with ketamine-xylazine, RSNA did not increase until 40 min, and SAP remained at low levels after the antigen injection. The baroreceptor reflex, as evaluated by increases in RSNA and HR in response to the decrease in SAP induced by sodium nitroprusside (SNP), was suppressed in the anesthetized rats compared with the conscious rats. Consistent with this finding, baroreceptor denervation attenuated the excitatory responses of RSNA to anaphylaxis in the conscious rats but not in the pentobarbital-anesthetized rats. RSNA was increased markedly in conscious rats during anaphylactic hypotension. Anesthetics attenuated this antigen-induced renal sympathoexcitation through the suppression of baroreceptor function.


Characterization of cDNA clones for human myeloperoxidase: predicted amino acid sequence and evidence for multiple mRNA species.
Myeloperoxidase is a component of the microbicidal network of polymorphonuclear leukocytes. The enzyme is a tetramer consisting of two heavy and two light subunits. A large proportion of humans demonstrate genetic deficiencies in the production of myeloperoxidase. As a first step in analyzing these deficiencies in more detail, we have isolated cDNA clones for myeloperoxidase from an expression library of the HL-60 human promyelocytic leukemia cell line. Two overlapping plasmids (pMP02 and pMP062) were identified as myeloperoxidase cDNA clones based on the detection with myeloperoxidase antiserum of 70 kDa protein expressed in pMP02-containing bacteria and a 75 kDa polypeptide produced by hybridization selection and translation using pMP062 and HL-60 RNA. Formal identification of the clones was made by matching the predicted amino acid sequences with the amino terminal sequences of the heavy and light subunits. Both subunits are encoded by one mRNA in the following order: pre-pro-sequences--light subunit--heavy subunit. The molecular weight of the predicted primary translation product is 83.7 kDa. Northern blots reveal two size classes of hybridizing RNAs (approximately 3.0-3.3 and 3.5-4.0 kilobases) whose expression is restricted to cells of the granulocytic lineage and parallels the changes in enzymatic activity observed during differentiation.


Parental views of the development of children in a rural South African community.
The purpose of this study is to describe how parents/guardians, reported on the development of their children, their perceptions of social support, satisfaction, and their level of depression. This is an aspect of a larger study conducted to create a database that will help to examine and describe the health and developmental status of children and their families. The results suggested that the parent's satisfaction had a direct correlation with the social support that they received from their families and the community. The study also revealed that the level of depression of the parents was directly associated with their degree of satisfaction.


CB694, a novel antimitotic with antitumor activities.
During the course of a mechanism-based screening program aimed at identifying new antimitotic agents, a novel microtubule depolymerizing piperazine derivative, 1-(5-chloro-2-methoxybenzoyl)-4-(3-chlorophenyl) piperazine, was identified. The compound, designated CB694, caused inhibition of proliferation of a wide range of cancer cell lines, with an average IC50 of 85 nM. A multidrug-resistant cell line was sensitive to inhibition by CB694, suggesting that this compound is a poor substrate for transport by P-glycoprotein. CB694 caused formation of abnormal mitotic structures in HeLa cells. Specifically, CB694 caused a concentration-dependent increase in bipolar spindles with lagging chromosomes and, with slightly higher concentrations, formation of multipolar mitotic spindles. These mitotic abnormalities occurred at concentrations that did not cause significant changes in the appearance or quantity of interphase microtubules. Coincident with the formation of abnormal mitotic spindles, CB694 caused G2/M arrest. CB694 inhibited the assembly of purified tubulin with an IC50 of 2.3 microM. Colchicine binding was strongly inhibited by CB694, suggesting that it binds to tubulin at the colchicine site. Bcl-2 phosphorylation and activation of ERK and JNK and caspase 3-dependent cleavage of PARP were observed in MDA-MB-435 cells treated with CB694. CB694 caused phosphorylation of Aurora A within 8 hr of treatment, and increases in Aurora A protein levels were coincident with mitotic accumulation. The efficacy of CB694 against a syngeneic murine transplantable solid tumor, Mammary 16/C, was also evaluated. CB694 was well tolerated and showed antitumor activity.


Trends in private insurance, Medicaid/State Children's Health Insurance Program, and the Healthcare Safety Net: implications for vulnerable populations and health disparities.
This chapter examines trends in private and public health coverage, as well as implications for vulnerable populations and health disparities. We find that there has been erosion in employment-based health benefits. Both the percentage of employers offering coverage and the percentage of workers with coverage declined in recent years. Those with coverage face eroding benefits and increased cost sharing. Within the public sector, Medicaid enrollment has decreased, with benefits increasingly restricted. Although State Children's Health Insurance Program (SCHIP) enrollment has increased among low-income children, the future of SCHIP remains uncertain. Meeting the healthcare needs of Americans and reducing health disparities requires both the provision of health coverage to all and sufficient comprehensiveness of benefits within private and public programs to meet enrollees' healthcare needs. Our findings suggest that we have a long way to go in reaching these goals.


Quantification of protease, amylase and lipase in the gut of Schizodactylus monstrosus during the postembryonic developmental stage. Effect of starvation, stress and topical application of juvenile hormone analogue.
A quantitative picture is presented on the activities and distribution of three major digestive enzymes in the postembryonic and adult stages of Schizodactylus monstrosus. The activity of enzymes in adult insects of both sexes has also been studied under starvation stress and after the topical application of juvenile hormone analogue. Results show that amylase activity was much higher in the early stages of development while in later stages protease and lipase activity was more significant. Protease activity was highest in the adult male, while the activity of all the enzymes reached its maximum in pregnant females. Starvation stress in adult individuals led to a slight decline of enzyme activity which was insignificant statistically. Topical application of JHa in high doses caused a steady increase in the activity of all the enzymes of which the increase of protease was statistically significant. The probable reasons for the quantitative variation have been discussed.