Effect of different antioxidants and free radical scavengers on aflatoxin production.
Different antioxidants and free radical scavengers on aflatoxin production are analysed. The different compounds at different concentration were used: buthylated hydroxyanisole (BHA), buthylated hydroxytoluene (BHT), α-tocopherol (vitamin E), ascorbic acid (vitamin C), reduced glutathione, cysteine, cysteamine. The above compounds were tested in culture ofAspergillus parasiticus supplemented with carbon tetrachloride, a potent stimulating agent of aflatoxin biosynthesis.Cysteamine and BHA highly inhibited the aflatoxin production induced by carbon tetrachloride, the inhibition decreased by lowering the concentration.On the contrary, vitamin E, vitamin C, reduced glutathione and cysteine further enhanced the carbon tetrachloride stimulating effect. The addition of the above compounds did not significantly affect the growth of the fungal mycelia.


An infant with streptococcal uvulitis presenting with airway obstruction.
We report a case of 7-month-old infant girl with severe uvulitis with airway obstruction. Her uvula was erythematous and markedly swollen. Stridor and retraction were noted. The symptoms were resolved after treatment with ampicillin, and a throat swab isolated Group A streptococcus. It is extremely rare in children for uvulitis to cause respiratory distress from airway obstruction. However, in infants with narrow airways, physicians should consider the risk of progression to respiratory distress.


Changes in walking velocity and stride parameters with age in children with Charcot-Marie-Tooth disease.
The purpose of this study is to assess how Charcot-Marie-Tooth disease, a group of inherited peripheral neuropathies that result in distal weakness, affects walking velocity over time in comparison to age-matched controls. Comprehensive gait analysis of 57 children (mean age 12.0, SD 3.7 years) compared to 76 age-matched controls (mean age 10.1, SD 3.4 years) demonstrated slower walking velocity (p<0.001) due to both shorter stride length (p<0.001) and diminished cadence (p=0.01). There was higher walking velocity (p<0.001), stride length (p=0.002) and cadence (p<0.001) in patients with dorsiflexor strength ≥3 and higher walking velocity (p=0.001) and cadence (p=0.03) in patients plantar flexor strength ≥4. Analysis of Charcot-Marie-Tooth type 1 and type 2 subgroups showed that walking velocity increased significantly with age in controls (p=0.001) but did not increase in children with either subtype (p>0.54). Stride length increased significantly with age in all groups (p<0.001) but at a slower rate in type 1 and 2 compared to controls. These differences contributed to increasing deficits in walking velocity and stride length with age in type 1 and 2 in comparison to controls, with deficits appearing earlier in type 2. Since the slower walking velocity in children with Charcot-Marie-Tooth disease is primarily due to short stride length, treatments that enable improved stride length, such as plantar flexor strengthening and bracing, may improve walking velocity and associated gait function.


"Magnetic" termite mound surfaces are oriented to suit wind and shade conditions.
The termites Amitermes meridionalis and A. laurensis construct remarkable meridional or "magnetic" mounds in northern Australia. These mounds vary geographically in mean orientation in a manner that suggests such variation is an adaptive response to local environmental conditions. Theoretical modelling of solar irradiance and mound rotation experiments show that maintenance of an eastern face temperature plateau during the dry season is the most likely physical basis for the mound orientation response. Subsequent heat transfer analysis shows that habitat wind speed and shading conditions also affect face temperature gradients such as the rate of eastern face temperature change. It is then demonstrated that the geographic variation in mean mound orientation follows the geographic variation in long-term wind speed and shading conditions across northern Australia such that an eastern face temperature plateau is maintained in all locations.


An fMRI investigation of the cognitive reappraisal of negative memories.
Episodic memory retrieval can be influenced by individuals' current goals, including those that are emotional in nature. Participants underwent an fMRI scan while reappraising, or changing the way they thought about aversive images they had previously encoded, to down-regulate (i.e., decrease), up-regulate (i.e., increase), or maintain the emotional intensity associated with their recall. A conjunction analysis between down- and up-regulation during the entire 12-s recall period revealed that both commonly activated reappraisal-related regions, particularly in the lateral and medial prefrontal cortex (PFC). However, when we analyzed a reappraisal instruction phase prior to recall and then divided the recall phase into the time when individuals were first searching for their memories and later elaborating on their details, we found that down- and up-regulation engaged greater neural activity at different time points. Up-regulation engaged greater PFC activity than down-regulation or maintenance during the reappraisal instruction phase. In contrast, down-regulation engaged greater lateral PFC activity as images were being searched for and retrieved. Maintaining the emotional intensity associated with the aversive images engaged similar regions to a greater extent than either reappraisal condition as participants elaborated on the details of the images they were holding in mind. Our findings suggest that down- and up-regulation engage similar neural regions during memory retrieval, but differ in the timing of this engagement.


Utility of transesophageal echocardiography in the examination of adult patients with patent ductus arteriosus.
Thirteen patients with clinical suspicion of patent ductus arteriosus were evaluated by transthoracic and transesophageal echocardiographic studies. Findings were corroborated during corrective surgery in 8 patients and by cardiac catheterization in 5. Transthoracic echocardiography confirmed the diagnosis in 7 patients; in 2 of the patients endarteritis of the pulmonary artery was demonstrated, and in one infective vegetations in aortic and mitral valves. With transesophageal echocardiography, patent ductus arteriosus was established in all 8 patients and endarteritis of the pulmonary artery was shown in 3, including 1 not discovered by transthoracic technique. In 1 of these patients, vegetations were also found on the pulmonic valve. Both techniques demonstrated significant pulmonary hypertension in 5 cases; contrast studies showed the venoarterial shunt between the pulmonary artery and the aorta with particular clarity in transesophageal images. On the basis of these findings it may be concluded that transesophageal echocardiography complements the information provided by transthoracic recordings in adult patients with patent ductus arteriosus, especially when it is associated with pulmonary hypertension or pulmonary endarteritis.


Assessment of Nutritional and Inflammatory Status to Determine the Prevalence of Malnutrition in Patients Undergoing Surgery for Colorectal Carcinoma.
Colorectal Cancer is the fourth most frequent cause of cancer death worldwide and its incidence increases from 50 years of age. It is often associated with protein-caloric malnutrition and 20% of cancer deaths occur due to this event. The aim of this study was to assess the prevalence of malnutrition and inflammatory status in 78 patients undergoing surgery for colorectal carcinoma. Nutritional Status was assessed by Mini Nutritional Assessment (MNA). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA, while albumin, C-reactive protein (CRP) and transferrin (TRF) were tested using an immunometric assay. The mean MNA score in colorectal patients was 20.4±8.4, while 23/78 patients (29.4%) were well nourished, 36/78 (46.1%) were at risk of malnutrition and 19/78 (24.3%) were malnourished, reporting in the previous six months from the date of diagnosis a significant weight loss (>10 kg), muscle mass loss and severe reduction of food intake due to loss of appetite and altered taste perception. The serum means of IL-6, TNF-α and CRP, were significantly higher in colorectal patients compared to the control group (p<0.001, p<0.0001, p<0.0001, respectively) while lower TRF, albumin and HCT serum levels in cancer patients vs. healthy subjects (p<0.0001; p<0.0001 and p<0.0001) were found. more than 50% of colorectal cancer patients were malnourished or at risk of malnutrition and reported an imbalance between nutritional and inflammatory status. They, therefore, require a nutritional intervention before treatment in order to have a more effective response and improve quality of life.


An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons.
Olfactory sensory neurons expressing a given odorant receptor project to two topographically fixed glomeruli in the olfactory bulb. We have examined the contribution of different cell types in the olfactory bulb to the establishment of this topographic map. Mice with a homozygous deficiency in Tbr-1 lack most projection neurons, whereas mice with a homozygous deficiency in Dlx-1 and Dlx-2 lack most GABAergic interneurons. Mice bearing a P2-IRES-tau-lacZ allele and deficient in either Tbr-1 or Dlx-1/Dlx-2 reveal the convergence of axons to one medial and one lateral site at positions analogous to those observed in wild-type mice. These observations suggest that the establishment of a topographic map is not dependent upon cues provided by, or synapse formation with, the major neuronal cell types in the olfactory bulb.


Acute exposure of zebrafish (Danio rerio) larvae to environmental concentrations of selected antidepressants: Bioaccumulation, physiological and histological changes.
Antidepressants have been detected in surface waters worldwide at ng-μg/L concentration. These compounds can exert adverse effects on fish even at low levels. But, all previous analyses have concentrated on adult fish. The aim of the study was to assess the effect of environmental concentrations of sertraline, paroxetine, fluoxetine and mianserin, and their mixtures on such unusual endpoints as physiological and histological changes of zebrafish (Danio rerio) larvae. We also determined the bioconcentration of the pharmaceuticals. Fish Embryo Toxicity test was used to analyze the influence on developmental progression. Histological sections were stained with hematoxylin and eosin. Proliferating cells in liver were determined immunohistochemically by detection of Proliferating Cell Nuclear Antigens. The bioconcentration factor was measured by liquid chromatography coupled to mass spectrometry. Pharmaceuticals were used at low, medium and high concentrations in mixtures and at medium concentration as single compound. Exposure to the analyzed pharmaceuticals increased the rate of abnormal embryo and larvae development, accelerated the hatching time and affected the total hatching rate. Three-times lower proliferation of hepatocytes was observed in larvae exposed to paroxetine, mianserin, sertraline and the mixture of the pharmaceuticals at the highest concentrations. The highest bioaccumulation factor (BCF) was obtained for sertraline. The BCF of the analyzed compounds was higher if the organisms were exposed to the mixtures than to single pharmaceuticals. To conclude, the exposure of zebrafish larvae to selected antidepressants and their mixtures may cause disturbances in the organogenesis of fish even at environmental concentrations.


Deacylation of Echinocandin B by Streptomyces species: a novel method for the production of Echinocandin B nucleus.
Anidulafungin, a new class of antifungal agent used for the treatment of chronic fungal infections, is derived from Echinocandin B nucleus, an intermediate metabolite of Echinocandin B produced by Aspergillus nidulans. The enzyme acylase plays a key role in the bioconversion of Echinocandin B to Echinocandin B nucleus. In the present study, a rapid screening method was used to select an actinomycete capable of producing Echinocandin B acylase. Out of 140 actinomycetes screened for the production of acylase by preliminary qualitative plate assay, 53 were selected. The selected isolates were subjected to quantitative assay under submerged fermentation for the bioconversion of Echinocandin B to Echinocandin B nucleus. Among 53 strains of actinomycetes, two strains (BICC-8848 and BICC-8547) exhibited higher degree of acylase activity. Various physico-chemical parameters were optimised for maximum bioconversion of ECB to ECB nucleus. It was found that the conditions viz. pH 7.0, temperature 26 °C and substrate concentration of about 4 g/L supported higher degree of bioconversion. It was also observed that, as the medium volume increased to 500 mL, the conversion rate was also increased by more than two-folds.


Grading of gliomas using transfer learning on MRI images.
Despite the critical role of Magnetic Resonance Imaging (MRI) in the diagnosis of brain tumours, there are still many pitfalls in the exact grading of them, in particular, gliomas. In this regard, it was aimed to examine the potential of Transfer Learning (TL) and Machine Learning (ML) algorithms in the accurate grading of gliomas on MRI images. Dataset has included four types of axial MRI images of glioma brain tumours with grades I-IV: T1-weighted, T2-weighted, FLAIR, and T1-weighted Contrast-Enhanced (T1-CE). Images were resized, normalized, and randomly split into training, validation, and test sets. ImageNet pre-trained Convolutional Neural Networks (CNNs) were utilized for feature extraction and classification, using Adam and SGD optimizers. Logistic Regression (LR) and Support Vector Machine (SVM) methods were also implemented for classification instead of Fully Connected (FC) layers taking advantage of features extracted by each CNN. Evaluation metrics were computed to find the model with the best performance, and the highest overall accuracy of 99.38% was achieved for the model containing an SVM classifier and features extracted by pre-trained VGG-16. It was demonstrated that developing Computer-aided Diagnosis (CAD) systems using pre-trained CNNs and classification algorithms is a functional approach to automatically specify the grade of glioma brain tumours in MRI images. Using these models is an excellent alternative to invasive methods and helps doctors diagnose more accurately before treatment.


Perinatal mortality rate and adverse perinatal outcomes presumably attributable to placental dysfunction in (near) term gestation: A nationwide 5-year cohort study.
Placental dysfunction can lead to perinatal hypoxic events including stillbirth. Unless there is overt severe fetal growth restriction, placental dysfunction is frequently not identified in (near) term pregnancy, particularly because fetal size is not necessarily small. This study aimed to evaluate, among (near) term births, the burden of hypoxia-related adverse perinatal outcomes reflected in an association with birth weight centiles as a proxy for placental function. A nationwide 5-year cohort of the Dutch national birth registry (PeriNed) including 684,938 singleton pregnancies between 36+0 and 41+6 weeks of gestation. Diabetes, congenital anomalies, chromosomal abnormalities and non-cephalic presentations at delivery were excluded. The main outcome was antenatal mortality rate according to birthweight centiles and gestational age. Secondary outcomes included perinatal hypoxia-related outcomes, including perinatal death and neonatal morbidity, analyzed according to birthweight centiles. Between 2015 and 2019, 1,074 perinatal deaths (0.16%) occurred in the study population (n = 684,938), of which 727 (0.10%) antenatally. Of all antenatal- and perinatal deaths, 29.4% and 27.9% occurred in birthweights below the 10th centile. The incidence of perinatal hypoxia-related outcomes was highest in fetuses with lowest birthweight centiles (18.0%), falling gradually up to the 50th and 90th centile where the lowest rates of hypoxia-related outcomes (5.4%) were observed. Perinatal hypoxia-related events have the highest incidence in the lowest birthweight centiles but are identifiable throughout the entire spectrum. In fact, the majority of the adverse outcome burden in absolute numbers occurs in the group with a birthweight above the 10th centile. We hypothesize that in most cases these events are attributable to reduced placental function. Additional diagnostic modalities that indicate placental dysfunction at (near) term gestation throughout all birth weight centiles are eagerly wanted.


Nitrato(5,10,15,20-tetra-phenyl-porphinato)manganese(III)-benzene-n-hexa-ne (2/1/1).
The crystal structure of solvated [Mn(TPP)(NO3)] (TPP = 5,10,15,20-tetra-phenyl-porphyrinato, C44H28N4), [Mn(C44H28N4O3)(NO3)]·0.5C6H14·0.5C6H6, has been determined in the space group Pccn. The MnIII atom has a distorted square-pyramidal environment, being coordinated by four pyrrole N atoms of the porphyrin ligand in the basal plane and an O atom of the nitrato ligand in the apical site. The MnIII atom is displaced out of the porphyrin plane by 0.22 (4) Å with the average Mn-Np distance being 2.011 (6) Å (where Np is a porphyrin N atom). The Mn-O bond length is 2.1246 (18) Å. Two kinds of inter-molecular C-H⋯O hydrogen bonds exist in the crystal structure, with the apical nitrato ligands inter-acting with solvent mol-ecules and adjacent mol-ecules, respectively.


Transcriptome dissection of candidate genes associated with lentil seed quality traits.
Lentils provide a rich plant-based protein source and staple food in many parts of the world. Despite numerous nutritional benefits, lentil seeds also possess undesirable elements, such as anti-nutritional factors. Understanding the genetic networks of seed metabolism is of great importance for improving the seed nutritional profile. We applied RNA sequencing analysis to survey the transcriptome of developing lentil seeds and compared this with that of the pod shells and leaves. In total, we identified 2622 genes differentially expressed among the tissues examined. Genes preferentially expressed in seeds were enriched in the Gene Ontology (GO) terms associated with development, nitrogen and carbon (N/C) metabolism and lipid synthesis. We further categorized seed preferentially expressed genes based on their involvement in storage protein production, starch accumulation, lipid and suberin metabolism, phytate, saponin and phenylpropanoid biosynthesis. The availability of transcript profile datasets on lentil seed metabolism and a roadmap of candidate genes presented here will be of great value for breeding strategies towards further improvement of lentil seed quality traits.


[Application of dental chairside evidence-based medicine for the treatment temporomandibular osteoarthritis].
To obtain an evidence-based treatment for an adolescent patient with temporomandibular osteoarthritis. The detailed history of an adolescent patient with temporomandibular osteoarthritis was analysed. Clinical Evidence (to Dec 2010), National Guideline Clearinghouse (2000-Dec 2010), Cochrane Library (Issue 4, 2010), MEDLINE(OVID, 1950-Dec 2010) and China Biology Medicine Database (1978-Dec 2010) were searched to obtain evidence such as clinical guidelines, systematic reviews and randomized controlled trials related to surgery or conservative treatment to temporomandibular osteoarthritis to find a personal treatment strategy for the patient. Five articles were finally included, i.e. 1 clinical guideline, 3 systematic reviews and 1 randomized controlled trials. These evidence showed that: Conservative treatment like intra-articular injection instead of surgery should be adopted for adolescent patient; hyaluronate is the drug with sufficient evidence in supporting its use in treating temporomandibular disorders; inferior temporomandibular joint cavity injection or both upper and lower cavity injection has better effect than that of superior cavity injection only; and there was some evidence to support the use of glucosamine to treat temporomandibular disorders. Considering the situation of the case and the clinical evidence, an individual treatment plan of hyaluronate injection into the upper and lower cavity and glucosamine take orally was established. A long-term follow-up of 6 months showed a good treatment outcome. Through the evidence-based methods and the use of clinical evidence, an individual treatment plan could be established for each patient with temporomandibular disorders, and this will provide strong supporting to the treatment of temporomandibular disorders. Up to now, it is clear that hyaluronate injection into the upper and lower cavity with glucosamine administration is effective in treating temporomandibular osteoarthritis.


Review article: bile acid therapy.
Over the past 3 years there has been a renewed interest in bile acid therapy not only because of the promising results obtained by combining this therapy with extracorporeal shock-wave lithotripsy for rapid gallstone dissolution, but also because of its novel use as a treatment for primary biliary cirrhosis. This article reviews the use of bile acids for both these indications.


Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer.
Elevated levels of interleukin-6 (IL-6) are associated with metastasis and poor prognosis in various malignancies. Since the IL-6 soluble receptor (IL-6sR) potentiates the systemic effects of IL-6, each may independently impact the disease process. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder. The study group consisted of 51 patients who underwent radical cystectomy for transitional cell carcinoma and 44 men without cancer. Preoperative plasma levels of IL-6 and IL6sR were measured by enzyme-linked immunosorbent assay and correlated with pathological features and clinical outcome. IL-6 levels were higher in patients with bladder cancer than in healthy controls (p <0.001). In bladder cancer cases elevated levels of IL-6 and IL-6sR were associated with adverse pathological features, including muscle invasion, lymphovascular invasion and lymph node metastases (p <0.05). High levels of IL-6sR were also associated with pathological tumor grade (p = 0.036). In separate multivariate models that included clinical stage and grade IL-6 and IL-6sR levels were independent predictors of lymphovascular invasion, metastases to lymph nodes, disease recurrence and disease specific survival (p <0.05). In a preoperative Cox proportional hazards model IL-6 (p = 0.050) and IL-6sR (p = 0.035) predicted disease specific survival. We found that plasma IL-6 levels were higher in patients with bladder cancer than in healthy controls. Levels of IL-6 and IL-6sR were associated with cancer stage and metastases, and were strong independent predictors of disease recurrence and disease specific survival.


Acid phosphatases activity in cheese and starters.
The acid phosphatase activity levels in a number of Greek cheeses and in Cheddar cheeses were found to be unaffected by storage for up to 18 months and 12 months respectively. In Cheddar cheese, starter organisms made an insignificant contribution to this activity. Studies of acid phosphatase prepared from Streptococcus cremoris-lactis NCDO 762 starter cultures showed that the enzyme was of high molecular weight and largely particle-bound. The pH of optimum activity was 5-2 and the enzyme was inhibited by F-minus,Al-3+, a number of heavy metals, oxidizing agents and sulphydryl-modifying reagents. Kinetic measurements at pH 5-2 gave a Km value for p-nitrophenyl phosphate of 1-2 mM. Orthophosphate, pyrophosphate and isoelectrically precipitated casein behaved as competitive inhibitors to the hydrolysis of p-nitrophenyl phosphate with Ki values of 1-2 mM, 1-0 mM, 1-0 MM and 1-1 mM respectively. In spite of this binding to the enzyme, casein provided a very poor substrate for the starter acid phosphatase. The properties of acid phosphatase present in Cheddar cheese made with Str. cremoris NCDO 924 starter were consistent with the enzyme being exclusively of milk origin and small differences between this and the acid phosphatase previously isolated from bovine milk were attributable to the binding of peptides produced during the cheese maturation to the enzyme molecules. It was concluded that in cheese, phosphatase action was due largely to the enzyme of milk origin, with that provided by the starter being of minor importance.


A NO-releasing derivative of acetaminophen spares the liver by acting at several checkpoints in the Fas pathway.
NCX-701 is a nitric oxide (NO)-releasing acetaminophen (APAP) derivative. In the present study we demonstrated that NCX-701 is as effective as APAP in controlling body temperature in a rat model of endotoxin-induced fever. Liver toxicity is a major complication of APAP overdosing. To investigate whether NCX-701 is hepatotoxic, BALB/C mice were injected with 100 - 500 mg kg(-1) APAP or NCX-701 alone or in combination (i.e. 500 mg kg(-1) of both compounds). Our results demonstrated that although APAP caused a dose-dependent liver injury, NCX-701 was completely devoid of liver toxicity. At the dose of 500 mg kg(-1) APAP caused an approximately 40 fold increase of AST plasma levels and extensive centrilobular necrosis. APAP and NCX-701 share the same metabolic pathway as demonstrated by the time-course of APAP-glucuronide concentrations in plasma and liver. NCX-701 was safe in mice with pre-existing chronic liver disease. Indeed, while C57BL6 transgenic mice expressing the hepatitis B virus (HBV) at the age of 8 months were significantly more susceptible to liver damage induced by APAP (500 mg kg(-1)) than their congenic littermates, treating HBV-transgenic mice with NCX-701, 500 mg kg(-1), caused no damage. Co-administration of NCX-701 at the dose 500 mg kg(-1) to mice treated with APAP, 500 mg kg(-1), completely protected against liver damage induced by APAP. APAP, but not NCX-701, upregulated liver Fas and Fas Ligand mRNA expression in vivo. Incubating mouse hepatocytes with APAP, but not with NCX-701, increased cell surface Fas expression and sensitized hepatocytes to death induced by challenge with a Fas-agonistic antibody. Collectively, these observations suggest that APAP toxicity is Fas mediated and that NCX-701 spares the liver by acting at several checkpoints in the Fas pathway.


Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization.
Dendritic cells (DCs) express several receptors for the Fc portion of immunoglobulin (Ig)G (FcgammaR), which mediate internalization of antigen-IgG complexes (immune complexes, ICs) and promote efficient major histocompatibility complex (MHC) class II-restricted antigen presentation. We now show that FcgammaRs have two additional specific attributes in murine DCs: the induction of DC maturation and the promotion of efficient MHC class I-restricted presentation of peptides from exogenous, IgG-complexed antigens. Both FcgammaR functions require the FcgammaR-associated gamma chain. FcgammaR-mediated MHC class I-restricted antigen presentation is extremely sensitive and specific to immature DCs. It requires proteasomal degradation and is dependent on functional peptide transporter associated with antigen processing, TAP1-TAP2. By promoting DC maturation and presentation on both MHC class I and II molecules, ICs should efficiently sensitize DCs for priming of both CD4(+) helper and CD8(+) cytotoxic T lymphocytes in vivo.


Do endotoxins devoid of 3-deoxy-D-manno-2-octulosonic acid exist?
After treatment with aqueous, 50% hydrofluoric acid, a well-known dephosphorylating agent, the presence of 3-deoxy-D-manno-2-octulosonic acid (KDO), an essential and characteristic constituent of endotoxins, can be readily demonstrated in reportedly KDO-deficient bacterial lipopolysaccharides.


Reliability, sensitivity and validity of behavioral indices of neurotoxicity.
Adequate sensitivity, reliability, and validity are features of scientific testing in all fields. Accordingly, these have been central concerns in the development of behavioral methods for assessing neurotoxicity. Advances during the last 10 years have established behavioral tests that show high degrees of sensitivity and reliability both within and across laboratories. This was demonstrated in the recently completed National Center for Toxicological Research (NCTR) Collaborative Behavioral Teratology Study and other collaborative studies. Validity of behavioral testing has been based on: (a) the use of known neurotoxins; (b) comparison of agents causing behavioral dysfunction in humans; and (c) theoretical considerations of domain of central nervous system (CNS) function to be evaluated. These approaches have worked well, however, the neurochemical/neuropathologic to behavior correlations have been effective only under circumstances where a neurotoxic compound, as recognized by an identifiable neurobiologic signature, has been available. Behavioral methods are important in neurotoxicity evaluations because they provide an assessment of overall CNS functional integrity, whereas other methods in the neurosciences are directed towards specific subsystems. This presentation discusses the validity of measurements in: (1) behavioral testing; (2) neuropathologic evaluations; (3) neurochemical tests; and (4) electrophysiological techniques for detecting neurotoxicity.


Health-related quality of life of mothers of children with leukemia in Japan.
The study compared the health-related quality of life (HRQOL) of Japanese mothers of children with leukemia to that of mothers of children without leukemia. We used the Medical Outcomes Study 36-item Short-Form (SF-36) to measure the HRQOL of 97 mothers of children (average age 6.2, range 0-14) with leukemia diagnosed between 1999 and 2000, and compared their scores to those of 240 mothers of children without leukemia matched to the children with leukemia. Of the eight unadjusted domain scores of the SF-36, five were significantly low among mothers of children with leukemia compared to mothers of children without leukemia: 'role-physical functioning' (RP), 'general health perception' (GH), 'vitality' (VT), 'social functioning' (SF) and 'mental health' (MH). Their SF-36 domain scores, when adjusted for demographic and clinical factors were also significantly low in RP, GH, VT, SF, RE and MH. The MH and SF scores in mothers of children with leukemia requiring hospital care were, respectively, approximately 20 points (1 standard deviation (SD), p < 0.0001) and 30 points (1.5 SD, p < 0.0001) lower than that of mothers of children without leukemia. Mothers of children with leukemia requiring hospital care have poor HRQOL, particularly with regard to mental health and social functioning, and are at a greater risk for depression. These results suggest that the current system for treating leukemic diseases of children in Japan should also include close monitoring of mothers' mental health, and provision of appropriate treatment and psycho-social support.


Nitazoxanide treatment for giardiasis and cryptosporidiosis in children.
To review the pharmacology, pharmacokinetics, adverse effects, drug interactions, dosing recommendations, and clinical efficacy of nitazoxanide, a new antiprotozoal/anthelmintic/antibacterial agent. A MEDLINE search (1966-February 2004) of both human and animal research data published in the English language was conducted. All primary and review articles pertaining to the MEDLINE search were reviewed for inclusion. Emphasis was placed on randomized, double-blind, placebo-controlled trials. Nitazoxanide is approved for the treatment of giardiasis and cryptosporidiosis (first drug approved for the latter indication) in immune-competent children <12 years of age. Most studies in immune-competent patients have reported clinical and parasitologic response rates close to 80% and 70%, respectively, for both indications. Response rates have been lower in immune-compromised patients. Nitazoxanide should be available for patients unable to tolerate or adhere to first-line therapy employed for these intestinal protozoa.


Independent Predictors of Major Adverse Cardiovascular Events at 3 Years after Aortoiliac Stent Implantation.
To identify the risk factors for major adverse cardiovascular events (MACEs) in real-world practice for symptomatic peripheral artery disease in Japan. Data on Japanese patients (N = 880) from the Observational Prospective Multicenter Registry Study on Outcomes of Peripheral Arterial Disease Patients Treated by Angioplasty Therapy for Aortoiliac Artery who underwent de novo aortoiliac stent placement. The 3-year risk of incident MACEs was investigated. The median age of the patients was 72.6 years (range, 34-97 years), and 83.1% of the patients were men. The patients had the following conditions: smoking (35.6%), hypertension (94.1%), dyslipidemia (81.7%), diabetes (48.0%), renal failure on dialysis (12.6%), myocardial infarction (12.7%), stroke (15.8%), and chronic limb-threatening ischemia (7.1%). Femoropopliteal lesions were present in 38.8% of the limbs with aortoiliac lesions. The 3-year rate of freedom from MACEs was 89.1%. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, were independently associated with the risk of incident MACEs. When the study population was stratified according to these risk factors, the rate of MACEs was highest in patients with at least 3 risk factors (32.9% at 3 years). The 3-year rate of freedom from MACEs was reported. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, are independent risk factors for MACEs after aortoiliac stent placement.


The altered pharmacokinetics and pharmacodynamics of drugs commonly used in critically ill patients.
The critically ill patient occupies an increasing amount of time and bed space in modern hospital practice, and also commands increasing expenditure. Drug therapy in these patients has, in the past, been based on data derived from healthy volunteers, fit anaesthetised patients undergoing minor operative procedures, or patients with single organ failure. Alterations in pharmacokinetics and pharmacodynamics have not been studied in depth in critically ill patients who often have multisystem failure. This paper reviews the currently available information on drugs in common usage in these patients. The studies that have been performed have usually shown delayed drug clearance, altered volumes of distribution and prolonged elimination half-lives. The sedative and analgesic drugs, in particular, have shown marked accumulation which may confuse the clinical picture, and prolonged periods of assisted ventilation may be required until the drugs are eliminated.


Corneal endothelial morphologic assessment in pediatric cataract surgery with intraocular lens implantation: a comparison of preoperative and early postoperative specular microscopy.
To observe longitudinal changes in the corneal endothelium after pediatric cataract surgery with intraocular lens implantation. Prospective, longitudinal study. settings: Iladevi Cataract and IOL Research Centre, Ahmedabad, India. study population: This study included 100 pediatric eyes undergoing cataract surgery with intraocular lens implantation. Posterior capsule management was based on the status of the posterior capsule. Two-port anterior limbal vitrectomy was carried out after posterior capsule plaque peeling. observation procedures: Corneal endothelial morphologic features: endothelial cell density (cell/mm(2)), coefficient of variation, percentage of hexagonality, and central corneal thickness were assessed. main outcome measures: To evaluate whether there is a difference in endothelial cell morphologic features before surgery and 3 months after surgery and also whether pediatric cataract surgery with and without anterior vitrectomy has any impact on the endothelial cell morphologic features. A comparison of preoperative and postoperative specular microscopy is given here: endothelial cell density, 3225.1 ± 346.8 cells/mm(2) versus 3057.7 ± 330.1 cells/mm(2) (P < .001); coefficient of variation, 27.5 ± 10.6 versus 37.7 ± 16.3 (P < .001); percentage of hexagonality, 58.1 ± 15.3 versus 48.6 ± 13.4 (P < .001); and central corneal thickness, 529 ± 30 μm versus 527 ± 34 μm (P = .64). There was 5.1% decrease in mean endothelial cell loss at 3 months after surgery. No statistically significant difference was noted in the percentage decrease in mean endothelial cell density between eyes undergoing cataract surgery with intact posterior capsules, eyes undergoing manual posterior capsulorrhexis without anterior limbal vitrectomy, and eyes undergoing anterior limbal vitrectomy (P = .543). Endothelial cell loss with currently practiced techniques of pediatric cataract surgery is within acceptable limits by adhering to the principles of close chamber technique.


Distinct volume distribution of viable and non-viable hybridoma cells: A flow cytometric study.
Light scattering properties of hybridoma cells were examined with flow cytometry. Viable and dead cells form two distinct populations. The distribution of the two populations changes during a batch culture. the concentration of dead cells measured by flow cytometry correlates well to that measured by hemacytometer. The distribution based on small-angle light scattering is similar to the distribution based on volume as measured by Elzone particle counter. It thus appears that viable cells form the population with a larger mean cell volume. The results also indicate that the volume of viable cells decreases during the cultivation while that of dead cells remains relatively constant.


[Applications of RHD zygosity test through polymerase chain reaction for prediction of fetus Rh D-positive phenotype].
To explore a molecular method for the determination of RHD zygosity. Two pairs of primers were designed specific for downstream rhesus box and hybrid rhesus box according to the sequences in GenBank. Together with a pair of internal control primer, a dual-tube polymerase chain reaction (PCR) method was established for determination of the RHD zygosity. Thirty RhD-positive, D-negative and weak D phenotype samples were evaluated by taking a recent restriction fragment length polymorphism (RFLP) method as reference. The results of the dual-tube PCR and RFLP are identical in 29 samples, which are also in concordance with the Rh phenotype, respectively. In one weak D sample, however, both methods tested as RHD(-)/RHD(-), which showed that there was one RHD(-) haplotype in this individual, but a false negative result in testing downstream rhesus box. The dual-tube PCR is a less-labored method for RHD zygosity detection. It can be used clinically in prenatal test to determine RHD zygosity of pregnant women's partner for prediction of fetus RhD phenotype.


SUMO modification in apoptosis.
Apoptosis and clearance of dead cells is highly evolutionarily conserved from nematode to humans, which is crucial to the growth and development of multicellular organism. Fail to remove apoptotic cells often lead to homeostasis imbalance, fatal autoimmune diseases, and neurodegenerative diseases. Small ubiquitin-related modifiers (SUMOs) modification is a post-translational modification of ubiquitin proteins mediated by the sentrin-specific proteases (SENPs) family. SUMO modification is widely involved in many cellular biological process, and abnormal SUMO modification is also closely related to many major human diseases. Recent researches have revealed that SUMO modification event occurs during apoptosis and clearance of apoptotic cells, and plays an important role in the regulation of apoptotic signaling pathways. This review summarizes some recent progress in the revelation of regulatory mechanisms of these pathways and provides some potential researching hotpots of the SUMO modification regulation to apoptosis.


Efficacy and safety of purified botulinum toxin type A (Dysport) for the treatment of benign essential blepharospasm: a randomized, placebo-controlled, phase II trial.
The majority of studies on the effects of botulinum toxin in blepharospasm patients have been small or unblinded. Our large-scale, multicenter, randomized clinical trial on the efficacy and safety of botulinum toxin (Dysport; 40, 80, and 120 units/eye) versus placebo in bilateral benign essential blepharospasm (BEB) supported the high efficacy and good safety profile of Dysport, with improvement in functional impairment, reduced frequency and intensity of facial spasms, and fewer withdrawals through lack of efficacy in the active treatment group compared with controls. The best balance of sustained efficacy and favorable safety profile was provided by 80 units of Dysport/eye in this study.


Perinatal methylmercury exposure perturbs the expression of Plp1 and Cnp splice variants in cerebellum of rat pups.
Early life exposure to environmental chemicals can interfere with myelin formation in the developing brain, leading to neurological disorders. The Proteolipid Protein 1 (Plp1), Myelin Basic Protein (Mbp) and 2',3'-Cyclic Nucleotide 3'Phosphodiesterase (Cnp) genes expressed in oligodendrocytes and involved in myelination processes can be useful biomarkers of potential developmental neurotoxicity. In an earlier study, we concluded that the reduction in the expression levels of Mbp splice variants in juvenile rat cerebellum following perinatal methylmercury (MeHg) exposure were compatible with an overall reduction of mature oligodendrocytes population. This observation prompted us to analyze the expression of Plp1 and Cnp in developing rat cerebellum to further confirm and investigate the toxic effects of MeHg on vulnerable oligodendrocytes. Splice variants of Plp1 in human and of Cnp in mouse are curated in NCBI RefSeq database, but not for rat. Lack of annotation of splice variants can pose significant challenge for the reliable quantification of gene expression levels in toxicological studies. Therefore, we applied a "comparative sequence analysis" approach, relying on annotated splice variants in human/mouse and on evolutionary conservation of intron-exon structures, to identify additional splice variants of Plp1 and Cnp in rat. Then, we confirmed their identity by nucleotide sequencing and characterized their temporal expression patterns during brain development by RT-PCR. The measurement of total transcripts and individual splice variants of Plp1 and Cnp in the cerebellum of MeHg-exposed rat pups revealed a relatively similar level of reduction in their expression levels. This study further confirms that perinatal exposure to MeHg can impact oligodendrocytes in pups. Based on these observations, we conclude that monitoring the expression of these oligodendrocyte-enriched genes can be useful to identify toxic chemicals affecting myelination.


Mands for Information Using "How" Under EO-Absent and EO-Present Conditions.
The present study replicates and extends previous research on teaching "How?" mands for information to children with autism. The experimental preparation involved mand training in the context of completing preferred activities and included training and testing under conditions when the establishing operation (EO) was present and absent. Results show that two children with autism acquired mands for information using How? only in situations where information was valuable (i.e., the EO was present); they then consistently made use of the information provided in activity completion. Generalization to novel, untaught situations was assessed.


Re-exposure of chitosan by an inhalable microsphere providing the re-education of TAMs for lung cancer treatment with assistant from sustained H2S generation.
The re-education of tumor-associated macrophages (TAMs) is an effective strategy to inhibit the growth and metastasis of lung cancer. We have reported that chitosan could re-educate the TAMs and then inhibit cancer metastasis; however, the re-exposure of chitosan from the chemical corona on their surface is critical for this effect. In this study, a strategy was proposed to re-expose the chitosan from chemical corona, and a sustained H2S generation was applied to enhance the immunotherapy of chitosan. To achieve this objective, an inhalable microsphere (namely F/Fm) was designed, which could be degraded by the matrix metalloproteinase in lung cancer, releasing two kinds of nanoparticles; in an external magnetic field, these nanoparticles can aggregate with each other, and β-cyclodextrin on the surface of one nanoparticle can be hydrolyzed by amylase on the surface of another nanoparticle, leading to the re-exposure of chitosan in the inner layer of β-cyclodextrin and the release of diallyl trisulfide for H2S generation. In vitro, the expression of CD86 and secretion of TNF-α by TAMs was increased by F/Fm, proving the re-education of TAMs, and the apoptosis of A549 cells was promoted with the migration and invasion being inhibited. In the Lewis lung carcinoma-bearing mouse, the F/Fm re-educated the TAMs and provided a sustained generation of H2S in the region of lung cancer, effectively inhibiting the growth and metastasis of lung cancer cells. This work provides a new strategy for the treatment of lung cancer in combination of re-education of TAMs by chitosan and the adjuvant chemotherapy by H2S.


Proteomic responses in the human dopaminergic LUHMES cell line to imidacloprid and its metabolites imidacloprid-olefin and desnitro-imidacloprid.
Neonicotinoids (neonics) are amongst the most commonly used class of pesticides globally. In the United States, imidacloprid (IMI) is extensively used for agriculture and in other common applications such as house-hold pest control. Regular exposure to IMI, and several of its known metabolites including IMI-olefin and desnitro-imidacloprid (DN-IMI), has been shown to be harmful to many organisms including mammals, birds, and fish. Studies show that neonics bind human nicotinicacetylcholine receptors (nAChRs) and cause cellular toxicity. In the dopaminergic Lund human mesencephalic (LUHMES) cell line, IMI and other neonics (10-100 μM) have been recently shown to activate intracellular calcium signaling through nAChRs. Thus, we examined proteomic responses of LUHMES cells to a 48-h treatment with 50 μM IMI, IMI-olefin, or DN-IMI. Our findings show differential effects of these neonics on cellular protein expression. Bioinformatic analysis of significantly altered proteins indicates an effect of IMI, IMI-olefin, and DN-IMI on protein synthesis and ribosomal function. These findings suggest a role for protein synthesis and transcriptional regulation in neonic-mediated dopaminergic neurotoxicity.


TGFβ-1 and TGFBR2 polymorphisms, cooking oil fume exposure and risk of lung adenocarcinoma in Chinese nonsmoking females: a case control study.
Transforming growth factor-β (TGF-β) plays an important role in regulating cellular functions, and many studies have demonstrated important roles for TGF-β in various cancers. Single nucleotide polymorphisms (SNPs) of TGF-β may influence lung carcinogenesis. The aim of this study was to test whether TGF-β1 C509T and TGF-β receptor II (TGFBR2) G-875A polymorphisms were associated with lung adenocarcinoma in nonsmoking females. A hospital-based case-control study was performed in Chinese nonsmoking females. Genotyping was performed using TaqMan SNP genotyping assay, and demographic data and environmental exposure were collected by trained interviewers after informed consents were obtained. A total of 272 (95.4%) cases and 313 (99.4%) controls were successfully genotyped, and the results showed that the polymorphic allele frequencies of C509T and G875A were similar among lung adenocarcinoma patients and controls (P=0.589 and 0.643, respectively). However, when the data were stratified for cooking oil fume exposure, the TT genotype of the TGFB1 C509T polymorphism showed a significantly decreased risk for lung adenocarcinoma compared with the CC genotype (adjusted OR=0.362, 95% CI=0.149-0.878, P=0.025). TGF-β1 gene C509T polymorphism might be associated with decreased risk of lung adenocarcinoma in Chinese females exposed to cooking oil fumes, but no association was observed TGFBR2 gene G875A polymorphism.


Loa loa in a Sri Lankan expatriate from Nigeria.
A worm was extracted from the subconjunctival space of the left eye in a 14-year old Sri Lankan girl, who returned to Sri Lanka in 1983 after spending six years in Nigeria. It was identified as a male Loa loa. A history of evanescent (Calabar) swellings was obtained. She also had significant eosinophilia. Microfilariae were not detected in the blood. This is the first case of Loa loa infection reported from Sri Lanka.


Effects of high voltage nanosecond pulsed plasma and micro DBD plasma on seed germination, growth development and physiological activities in spinach.
In this study, we analyzed seed germination, seedling growth, and physiological aspects after treatment with high voltage nanosecond pulsed plasma and micro DBD plasma in spinach (Spinacia oleracea L.), a green leafy vegetable known to have low germination rate. Both germination and dry weight of seedlings increased after high voltage pulse shots were applied to spinach seeds. However seeds treated with many shots (10 shots) showed a decrease in germination rate and seedling growth. Seeds treated with air DBD plasma exhibited slightly higher germination and subsequent seedling growth than those treated with N2 plasma. Seed surface was degenerated after treated with high voltage pulsed plasma and micro DBD plasma but no significant difference in the degree of degeneration was observed among micro DBD plasma treatment time. Level of GA3 hormone and mRNA expression of an amylolytic enzyme-related gene in seeds were elevated 1 day after treatment with high voltage pulsed plasma. The relative amount of chlorophyll and total polyphenols in spinach seedlings grown from seeds treated with air DBD plasma was increased in 30 s, 1 min, and 3 min treatments. Taken together, our results suggest a possibility that plasma can enhance seed germination by triggering biochemical processes in seeds.


One-year outcomes after direct transcatheter aortic valve implantation with a self-expanding bioprosthesis. A two-center international experience.
Balloon aortic valvuloplasty (BAV) is considered to be an essential part of the transcatheter aortic valve implantation (TAVI) procedure and is being performed routinely. At present there is insufficient long-term data as to the benefits of routine BAV prior to TAVI. The aim of this study was to evaluate the safety of direct TAVI and the mortality rate at 1-year in patients undergoing TAVI with or without BAV with a self-expanding bioprosthesis. Between January 2008 and September 2013 consecutive patients undergoing TAVI with the Medtronic CoreValve in two experienced centers in Athens, Greece and in Siegburg, Germany were studied. All data were prospectively collected and retrospectively analyzed. Primary endpoint was mortality at 1 year. Procedural data and clinical data (bleeding, vascular complications and echocardiographic parameters) were analyzed. A total of 210 patients undergoing TAVI were evaluated (non-direct=120 patients, direct=90 patients). All-cause mortality at 30 days and at 1 year was similar in both groups (4% in non-direct versus 2% in direct, p=0.6 and 15% in non-direct versus 11% in direct, p=0.5, respectively). Device success rate was similar in both groups (77% in non-direct versus 83% in direct, p=0.2). Major vascular complications were comparable for both groups (5% in non-direct versus 3% in direct, p=0.5). The direct group had less moderate/severe paravalvular leakage than the non-direct group after the device implantation (7% versus 33%, p<0.01). Performing direct TAVI with the self-expanding bioprosthesis is safe and feasible showing similar mortality rates compared to patients undergoing non-direct TAVI at 30 days and at 1-year.


Tissue and subcellular distributions of cholecalciferol 25-hydroxylase: cytochrome P-450D25-linked monooxygenase system.
Cholecalciferol (vitamin D3) 25-hydroxylase activity and its tissue and subcellular distributions were studied using rabbit, rat, bovine, chick, duck, guinea-pig and yellowtail. Vitamin D3 25-hydroxylase was found not only rabbit and bovine livers, kidneys and intestines, but also in lungs, pituitary glands, adrenocortices, ovaries, adipose tissues, blood vessels, brains and testes. Subcellular fractions of rabbit livers were examined for the presence of this activity and it was detected in the nuclear membranes, smooth and rough endoplasmic reticula, Golgi membranes and mitochondrial membranes. The activity in microsomes was induced by sodium phenobarbital, but not by beta-naphthoflavone and 3-methylcholanthrene, and was inhibited by isocyanide and metyrapone as inhibitor of cytochrome P-450.


RFID system for newborn identity reconfirmation in hospital: exposure assessment of a realistic newborn model and effects of the change of the dielectric properties with age.
This paper addresses the exposure assessment of RFID devices for newborn identity reconfirmation. To that purpose, a realistic newborn model ("Baby") is used to evaluate by a computational approach the levels of exposure due to these devices. Considering the average technical specifications currently in use, the exposure matrix in Baby shows that the systems comply with the ICNIRP exposure guidelines. As second aim, the effects of the change of the tissue dielectric properties with age on the so called "exposure matrix" (set of induced magnetic and electric field together with the derived values of SAR) is addressed. Specifically, three different approaches proposed in literature for the age variation of the dielectric properties at 13.56 MHz (the working frequency of the RFID systems for these applications) have been implemented using the Baby geometrical model. The related exposure matrices were then compared with the results obtained using the adult properties. No clear trend can be identified on the exposure matrices obtained varying the dielectric properties at 13.56 MHz, although the results could suggest a trend toward the underestimation of the exposure using adult properties.


Two new lanostane triterpenoids from Poria cocos.
Two new lanostane triterpenoids, 29-hydroxypolyporenic acid C (4) and 25-hydroxypachymic acid (5), together with three known compounds, ergosta-7,22-dien-3beta-ol (1), polyporenic acid C (2) and pachymic acid (3), were isolated from the 95% ethanolic extract of the sclerotium of Poria cocos (Schw.) Wolf. Their structures were determined by extensive spectroscopic analyses, including IR, UV, ESITOF-MS, HRESI-MS, 1D and 2D NMR data (1H NMR, 13C NMR, 1H-1H COSY, NOESY, HSQC and HMBC).


Anti-C1s monoclonal antibody BIVV009 in late antibody-mediated kidney allograft rejection-results from a first-in-patient phase 1 trial.
The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of 4 weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years posttransplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA). During 7 weeks follow-up, no severe adverse events were reported, and BIVV009 profoundly inhibited overall and DSA-triggered CP activation in serum. Five of 8 C4d-positive recipients turned C4d-negative in 5-week follow-up biopsies, while another 2 recipients showed a substantial decrease in C4d scores. There was, however, no change in microcirculation inflammation, gene expression patterns, DSA levels, or kidney function. In conclusion, we demonstrate that BIVV009 effectively blocks alloantibody-triggered CP activation, even though short-course treatment had no effect on indices of activity in late ABMR. This initial trial provides a valuable basis for future studies designed to clarify the therapeutic value of CP blockade in transplantation. ClinicalTrials.gov NCT#02502903.


Clinical and Endoscopic Characteristics Associated With Post-Endoscopy Upper Gastrointestinal Cancers: A Systematic Review and Meta-analysis.
Ten percent of patients with an upper gastrointestinal cancer will have received an esophagogastroduodenoscopy (EGD) within 3 years before diagnosis, termed post-endoscopy upper gastrointestinal cancers (PEUGIC). We aimed to determine the characteristics of PEUGIC, and compare these with detected cancers. We searched MEDLINE and Embase from inception for studies comparing the characteristics of PEUGIC and detected upper gastrointestinal cancers, and reported findings at the initial "cancer-negative" endoscopy. We synthesized results using random effects meta-analysis. This review is registered on PROSPERO, CRD42019125780. A total of 2696 citations were screened and 25 studies were included, comprising 81,184 UGI cancers, of which 7926 were considered PEUGIC. For PEUGIC assessed within 6 to 36 months of a "cancer-negative" EGD, the mean interval was approximately 17 months. Patients with PEUGIC were less likely to present with dysphagia (odds ratio [OR] 0.37) and weight loss (OR 0.58) and were more likely to present with gastroesophageal reflux (OR 2.64) than detected cancers. PEUGICs were more common in women in Western populations (OR 1.30). PEUGICs were typically smaller at diagnosis and associated with less advanced disease staging compared with detected cancers (OR 2.87 for stage 1 vs 2-4). Most EGDs (>75%) were abnormal preceding diagnosis of PEUGIC. There is a substantial delay in the diagnosis of PEUGIC. They are less likely to present with alarm symptoms than detected cancers. PEUGICs are overall less advanced at diagnosis. Most patients with PEUGIC have abnormalities reported at the preceding "cancer-negative" EGD. The epidemiology of PEUGIC may inform preventive strategy.


Event-related potentials elicited in mothers by their own and unfamiliar infants' faces with crying and smiling expression.
Crying by an infant signals an urgent desire for care and protection. Because of the special relationship between a mother and her infant and the signal value of her crying, it is plausible to suggest that the maternal brain efficiently processes crying by infants. In the present study, we examined this hypothesis by measuring event-related potentials in mothers while they observed crying or smiling by their own or unfamiliar infants embedded within a train of neutral expressions. We found that the amplitude of the face-specific N170 component was enlarged for crying regardless of familiarity. The P300 component, which reflects a later cognitive evaluation stage of stimulus processing, was decomposed into functionally distinct components by temporal principal component analysis. The amplitude of the third temporal factor, which corresponds to the earliest portion of the P300, was larger when a mother observed her own infant crying than for the other conditions. Moreover, onset latency of P300 was shortest when mothers observed their own infant crying. These results indicate that mothers process their own infant's crying more efficiently than smiling by their own infant or crying by an unfamiliar infant.


[Muscle activity and heart rate during rhythmical work using a hand ergometer. II. Heart rate, mechanical and bioelectrical activity of muscles during work with different loads and in relation to endurance].
The study has been made to analyse changes in heart rate, in mechanical and bioelectrical muscle activity during thythmical handgrip contractions. Loads of 20% to 100% of the maximal voluntary contraction (MVC) were applied. The working frequency was 30 cpm. With loads of 40%--100% of the maximal voluntary contraction (MVC) the following characteristic changes were obtained: Both the plane of the mechanogram and the duration of the mechanogram increased permanently. The heart rate rose to the end of the experiment and so did the EMGs of the flexor, the extensor, the brachioradial muscle and the muscle of the thenar. The rate of the rise (%/s) of all physiological functions was greatest during maximal load test and decreased with decreasing contraction strength. The endurance as a function of the force showed a parabolic curve. The physical endurance capacity of this rhythmical hand work is between 20% and 40% MVC.


Robotic surgical education: a systematic approach to training urology residents to perform robotic-assisted laparoscopic radical prostatectomy.
Robotic-assisted surgery using the da Vinci Surgical System is gaining popularity among urologists. However, training residents to use this system presents new challenges for surgical educators. We describe a method for training residents to perform robotic-assisted radical prostatectomy. Residents first received da Vinci certification training followed by table-side assistance with a second attending urologist present to provide real-time instruction. After demonstrating proficiency with assistance, residents performed segments of robotic prostatectomies as the console surgeon. The procedure was divided into five steps: (a) bladder take-down, (b) endopelvic fascia and dorsal venous complex, (c) bladder neck and posterior dissection, (d) neurovascular bundles, and (e) urethral anastomosis. Performance was rated using an analog scale (0, very poor to 5, outstanding). The resident was allowed to proceed to the next step once proficiency (score greater than 3 of 5) had been demonstrated on three separate occasions. In addition, each procedure was digitally recorded and reviewed with the attending physician after the operation. Two chief residents underwent this training regimen. All 83 cases with surgical console involvement during a 7-month period were reviewed. The combined residents' mean operative time in minutes and overall performance (score 0 of 5 to 5 of 5) for each step were recorded. Using logistic regression analysis, a statistically significant trend was seen, with faster operative times and greater analog scores over time for both residents (P <0.005). A systematic approach can be used to safely and effectively train urology residents to perform robotic radical prostatectomy using the da Vinci robotic system.


The oncogenic role of NF1 in gallbladder cancer through regulation of YAP1 stability by direct interaction with YAP1.
Gallbladder cancer (GBC) is the most prevalent and invasive biliary tract malignancy. As a GTPase-activating protein, Neurofibromin 1 (NF1) is a tumor suppressor that negatively regulates the RAS signaling pathway, and its abnormality leads to neurofibromatosis type 1 (NF-1) disease. However, the role of NF1 playing in GBC and the underlying molecular mechanism has not been defined yet. A combination of NOZ and EH-GB1 cell lines as well as nude mice, were utilized in this study. mRNA expression and protein levels of NF1 and YAP1 were evaluated by quantitative real-time PCR (qRT-PCR), western blot (WB), and immunohistochemistry (IHC). In vitro and in vivo assays were performed to explore the biological effects of NF1 in NOZ and EH-GB1 cells via siRNA or lv-shRNA mediated knockdown. Direct interaction between NF1 and YAP1 was detected by confocal microscopy and co-immunoprecipitation (Co-IP), and further confirmed by GST pull-down assay and isothermal titration calorimetry assay (ITC). The stability of proteins was measured by western blot (WB) in the presence of cycloheximide. This study showed that a higher level of NF1 and YAP1 was found in GBC samples than in normal tissues and associated with worse prognoses. The NF1 knockdown impaired the proliferation and migration of NOZ in vivo and in vitro by downregulating YAP1 expression. Moreover, NF1 co-localized with YAP1 in NOZ and EH-GB1 cells, and the WW domains of YAP1 specifically recognized the PPQY motif of NF1. The structural modeling also indicated the hydrophobic interactions between YAP1 and NF1. On the other hand, YAP1 knockdown also impaired the proliferation of NOZ in vitro, phenocopying the effects of NF1 knockdown. Overexpression of YAP1 can partially rescue the impaired proliferation in NF1 stably knockdown cells. In mechanism, NF1 interacted with YAP1 and increased the stability of YAP1 by preventing ubiquitination. Our findings discovered a novel oncogenic function of NF1 by directly interacting with YAP1 protein and stabilizing YAP1 to protect it from proteasome degradation in NOZ cells. NF1 may serve as a potential therapeutic target in GBC.


[Pemphigoid mimicking epidermolysis bullosa acquisita].
Subepidermal autoimmune bullous dermatoses form a clinical entity for which there is not always an individualized clinical and pathological description. A patient presented with bullous skin disease of atypical nature. There was an almost total desepidermization of the legs, vast areas of erosion on the trunk and arms with a Nikolski sign in an area of healthy skin, buccal involvement, multiple milium cysts and ungueal dystrophies with nail loss. This clinical presentation in this patient suggested acquired bullous epidermolysis. However, according to the recently defined clinical criteria for pemphigoid, the probability of correct diagnosis of pemphigoid was greater than 95 p. 100 since nearly three fourths of the major criteria were present. This diagnosis was confirmed by reference techniques (electron microscopy, indirect electron immunomicroscopy and immunoblotting). Thus, bullous autoimmune diseases of the dermoepidermal junction can be reliably differentiated on the bases of the clinical features, together with direct and indirect immunofluorescence on salt-split skin.


Relationships between type 2 diabetes, cell dysfunction, and redox signaling: A meta-analysis of single-cell gene expression of human pancreatic α- and β-cells.
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and failure of β-cells to meet the metabolic demand for insulin. Recent advances in single-cell RNA sequencing (sc-RNA-Seq) have allowed for in-depth studies to further understand the underlying cellular mechanisms of T2DM. In β-cells, redox signaling is critical for insulin production. A meta-analysis of human pancreas islet sc-RNA-Seq data was conducted to evaluate how T2DM may modify the transcriptomes of α- and β-cells. Annotated sc-RNA-Seq data from six studies of human pancreatic islets from metabolically healthy and donors with T2DM were collected. α- and β-cells, subpopulations of proliferating α-cells, immature, and senescent β-cells were identified based on expression levels of key marker genes. Each dataset was analyzed individually before combining, using weighted comparisons. Pathways of significant genes and individual redox-related gene expression were then evaluated to further understand the role that redox signaling may play in T2DM-induced β-cell dysfunction. α- and β-cells from T2DM donors modified genes involved in energy metabolism, immune response, autophagy, and cellular stress. α- and β-cells also had an increased nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated antioxidant response in T2DM donors. The proportion of immature and senescent β-cells increased in T2DM donors, and in immature and senescent β-cells, genes regulated by NFE2L2 were further upregulated. These findings suggest that NFE2L2 plays a role in β-cell maturation and dysfunction. Redox singling maybe a key pathway for β-cell restoration and T2DM therapeutics.


Partial thickness cornea tissue from small incision lenticule extraction: A novel patch graft in glaucoma drainage implant surgery.
The aim of the present study was to observe the feasibility and effect of cornea slice acquired from femtosecond laser surgery, small incision lenticule extraction (SMILE) as patch graft for the prevention of drainage tube exposure and to compare with the sclera. The research is a prospective comparative randomized study. Patients who received Ahmed glaucoma valve implantation surgery from August 2015 to January 2017 at the Xiamen Eye Center were randomly divided into 2 groups. Group A (corneal group) included 131 cases (135 eyes), receiving the 3 layers of allogeneic cornea slices as graft. Group B (scleral group) included 124 cases (127 eyes), using the sclera as allograft. The appearance, graft, conjunctiva melting, and tube exposure were the primary observation points. After followed up for 6 to 20 months, a thinner appearance was seen in 3 eyes (2.2%) in the corneal graft group and 7 eyes (5.5%) in the scleral group. Conjunctiva melted and drainage tube exposed in 0 eyes (0%) in the corneal graft group and 2 eyes (1.6%) in the scleral group. One eye needed repair surgery. There was no statistical difference between the 2 groups (P > .05). After surgery, the intraocular pressure was reduced significantly in both groups (P < .05). The white sclera slice could be seen under the conjunctiva, thereby affecting the cosmetic appearance. The cornea slice acquired from SMILE surgery can effectively prevent drainage tube exposure. Moreover, it is easy to acquire, safe, and cheaper, giving the patient a better cosmetic appearance.


In situ cross-linked matrix tablets for sustained salbutamol sulfate release - formulation development by statistical optimization.
The use of natural polymers in designing of matrix tablets for sustained-release drug delivery systems has received much attention. The study involves the development and optimization of in situ cross-linked matrix tablets for sustained salbutamol sulfate release. In situ cross-linked matrix tablets of salbutamol sulfate were prepared by direct compression and optimized by response surface methodology based on 32 factorial design. The influence on sodium alginate and a calcium salt (calcium carbonate) amounts in salbutamol sulfate matrix tablets on the properties like drug release and hardness of salbutamol sulfate sustained release matrix tablets were analyzed by response surface plots and corresponding contour plots. Drug contents, weight variations, hardness, and in vitro drug release with release kinetic analysis of these newly developed matrix tablets were also investigated. All these in situ cross-linked salbutamol sulfate matrix tablets showed satisfactory drug contents, weight variations, hardness and prolonged sustained release of salbutamol sulfate over 6 h. The developed salbutamol sulfate matrix tablets might be beneficial over the conventional tablets to decrease the dosing frequency and enhanced patient compliance.


[History of acute kidney injury, the early development of hemodialysis in France].
From the end of the 19th century to the 1950s, from mechanisms of disease and pathology to the first success of hemodialysis, the author depicts the history of acute kidney injury. These remarkable improvements of modern medicine led concurrently to the spread of hemodialysis for the replacement of end-stage renal disease.


Temporal keratoconus in a pediatric patient.
To report a pediatric patient with bilateral temporal keratoconus. A 14-year-old male presented with a two-year history of progressively worsening visual acuity in both eyes and suspicion for undiagnosed amblyopia in the right eye. Retinoscopy revealed a scissoring reflex in both eyes and corneal topography demonstrated high keratometry values (Kmax 57.9 D and 46.1 D in the right and left eyes, respectively), with relative temporal steepening approximately coinciding with the thinnest pachymetry in both eyes. Corneal cross-linking was recommended. Keratoconus can present as a temporal variant with relative temporal steepening and thinning. It is important to maintain a high index of suspicion for keratoconus in pediatric patients with sub-normal visual acuities. Prompt assessment and diagnosis may prevent progression of keratoconus and development of amblyopia.


Distribution of B streptococcal type antigens among streptococci of serological groups B, G and L.
Serotyping of streptococci of serological group B isolated from humans revealed mainly the type patterns Ia/c and III/R. The protein antigen c components were c alpha beta, c alpha and less frequently, c beta. Extracts of two group B streptococcal cultures reacted with specific antiserum against type candidate 7271. Bovine group B streptococci mainly expressed the type antigens IV/X and NT/X. Protein antigen c occurred as c alpha beta, c alpha and less frequently as c beta component. Among the non group B streptococcal cultures used in this study, only those of serological groups G and L reacted with specific antisera against protein antigens R and X.


The stimulation of phosphorylation of intracellular proteins in GH3 rat pituitary tumour cells by phorbol esters of distinct biological activity.
Using a pituitary tumour cell line (GH3), we have studied the phosphorylation of intracellular proteins induced by phorbol esters of diverse biological activity. All the active phorbol esters, including the weakly tumour-promoting but non-platelet aggregatory compound DOPPA, stimulated the phosphorylation of a cytosolic 80 kDa protein. A protein of this molecular mass has been suggested to be a marker of PKC activity. In contrast, only TPA and the non-tumour promoting but highly active phorbol ester SAP A stimulated the phosphorylation of a 130 kDa membrane protein. The results suggest that these phorbol esters activate PKC, but induce the differential phosphorylation of a variety of intracellular proteins.


Pulmonary venous obstruction after total cavopulmonary connection in heterotaxy.
Pulmonary venous obstruction is a rare complication after total cavopulmonary connection by intraatrial grafting. We experienced this complication in two patients. In one of them, a large prosthesis produced inflow obstruction of the dominant ventricle and was successfully replaced with a smaller tube. In the other patient, the intraatrial tube had become severely adherent to the common pulmonary venous orifice and was removed entirely. Conversion to an extracardiac Fontan circulation was later successfully established.


Incorporation of [1-(13)C]1-deoxy-D-xylulose into isoprenoids of the liverwort Conocephalum conicum.
The incorporation of (13)C labeled 1-deoxy-D-xylulose into the monoterpene bornyl acetate, the sesquiterpene cubebanol, and the diterpene phytol has been studied in axenic cultures of the liverwort Conocephalum conicum. Quantitative (13)C NMR spectroscopic analysis of the labeling patterns of the sesquiterpene indicated a possible degradation of 1-deoxy-D-xylulose to acetate and subsequent incorporation via the mevalonic acid pathway. In bornyl acetate, the labeling occurred only in the acetate moiety whereas the isoprene units remained unlabelled. The isoprene units of the diterpene phytol showed incorporation of intact deoxy-D-xylulose. These results indicate the involvement of both IPP biosynthetic pathways and two independently operating compartments/cell types with MEP pathway machinery. One MEP compartment is presumably the plastid where phytol is formed; the second, involved in the build-up of the isoprene part of bornyl acetate, might be located in the oil cells. The acetylation of borneol to bornyl acetate in turn occurs in a cellular compartment that is not involved in the build-up of the isoprene units of borneol.


Disentangling Medicinal and Recreational cannabis Use Among People Living with HIV: An Ecological Momentary Assessment Study.
This study examined the feasibility of using ecological momentary assessment (EMA) to disentangle medicinal cannabis use (MCU) from recreational cannabis use (RCU) among people living HIV (PLWH). Over a 14-day period, PLWH (N = 29) who engaged in both MCU and RCU completed a smartphone-based survey before and after every cannabis use event assessing general motivation for cannabis use (MCU-only, RCU-only, or mixed MCU/RCU), cannabis use behavior, and several antecedents and outcomes of cannabis use. A total of 739 pre-cannabis surveys were completed; 590 (80%) of the prompted post-cannabis surveys were completed. Motives for cannabis use were reported as MCU-only on 24%, RCU-only on 30%, and mixed MCU/RCU on 46% of pre-cannabis surveys. Mixed effects models examined within-person differences across MCU-only, RCU-only, and mixed MCU/RCU events. Results showed that relative to RCU-only events, MCU-only events were more likely to involve symptom management and drug substitution motives, physical and sleep-related symptoms, solitary cannabis use, and use of cannabis oils and sprays; MCU-only events were less likely to involve relaxation, happiness, and wellness motives, cannabis flower use, and positive cannabis consequences. Differences between mixed MCU/RCU and RCU-only events were similar, except that mixed MCU/RCU events were additionally associated with stress reduction motives and symptoms of anxiety and depression. Findings support the feasibility of partially disentangling MCU and RCU behavior among PLWH who engage in concurrent MCU and RCU. This study highlights the need for more EMA studies isolating MCU from RCU to inform ongoing changes to cannabis policies.


Abscisic acid-induced apoplastic H2O2 accumulation up-regulates the activities of chloroplastic and cytosolic antioxidant enzymes in maize leaves.
The histochemical and cytochemical localization of abscisic acid (ABA)-induced H(2)O(2) production in leaves of maize (Zea mays L.) plants were examined, using 3,3-diaminobenzidine (DAB) and CeCl(3) staining, respectively, and the relationship between ABA-induced H(2)O(2) production and ABA-induced subcellular activities of antioxidant enzymes was studied. H(2)O(2) generated in response to ABA treatment was detected within 0.5 h in major veins of the leaves and maximized at about 2-4 h. In mesophyll and bundle sheath cells, ABA-induced H(2)O(2) accumulation was observed only in apoplast, and the greatest accumulation occurred in the walls of mesophyll cells facing large intercellular spaces. Meanwhile, ABA treatment led to a significant increase in the activities of the leaf chloroplastic and cytosolic antioxidant enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione reductase (GR), and pretreatment with the NADPH oxidase inhibitor diphenyleneiodonium (DPI), the O (2) (-) scavenger Tiron and the H(2)O(2) scavenger dimethylthiourea (DMTU) almost completely arrested the increase in the activities of these antioxidant enzymes. Our results indicate that the accumulation of apoplastic H(2)O(2) is involved in the induction of the chloroplastic and cytosolic antioxidant enzymes. Moreover, an oxidative stress induced by paraquat (PQ), which generates O (2) (-) and then H(2)O(2) in chloroplasts, also up-regulated the activities of the chloroplastic and cytosolic antioxidant enzymes, and the up-regulation was blocked by the pretreatment with Tiron and DMTU. These data suggest that H(2)O(2) produced at a specific cellular site could coordinate the activities of antioxidant enzymes in different subcellular compartments.


Cross-linking and postfunctionalization of polymer films by utilizing the orthogonal reactivity of 7,7,8,8-tetracyanoquinodimethane.
Cross-linked polymer films are prepared by the alternating copolymerization of 4-chloromethylstyrene and 7,7,8,8-tetracyanoquinodimethane comonomers, which is followed by the postfunctional surface modification with donor-acceptor chromophores or redox active components using click chemistry reactions.


The current status of the inflatable penile prosthesis in the management of impotence: Mayo Clinic experience updated.
During the last 2 years the inflatable penile prosthesis has been implanted at the Mayo Clinic in 63 organically impotent male subjects. Over-all functional success is between 90 and 95 per cent. Experience indicates that 25 per cent of the patients require a second surgical procedure to correct a mechanical problem. Further experience with the technique and improvement in the product design have significantly decreased the number of mechanical problems encountered. Patient partner acceptance of this device continues to be excellent.


Effect of LuxS/AI-2-mediated quorum sensing system on bacteriocin production of Lactobacillus plantarum NMD-17.
Lactobacillus plantarum NMD-17 separated from koumiss could produce a bacteriocin named plantaricin MX against Gram-positive bacteria and Gram-negative bacteria. The bacteriocin synthesis of L. plantarum NMD-17 was remarkably induced in co-cultivation with Lactobacillus reuteri NMD-86 as the increase of cell numbers and AI-2 activity, and the expressions of luxS encoding signal AI-2 synthetase, plnB encoding histidine protein kinase, plnD encoding response regulator, and plnE and plnF encoding structural genes of bacteriocin were significantly upregulated in co-cultivation, showing that the bacteriocin synthesis of L. plantarum NMD-17 in co-cultivation may be regulated by LuxS/AI-2-mediated quorum sensing system. In order to further demonstrate the role of LuxS/AI-2-mediated quorum sensing system in the bacteriocin synthesis of L. plantarum NMD-17, plasmids pUC18 and pMD18-T simple were used as the skeleton to construct the suicide plasmids pUC18-UF-tet-DF and pMD18-T simple-plnB-tet-plnD for luxS and plnB-plnD gene deletion, respectively. luxS and plnB-plnD gene knockout mutants were successfully obtained by homologous recombination. luxS gene knockout mutant lost its AI-2 synthesis ability, suggesting that LuxS protein encoded by luxS gene is key enzyme for AI-2 synthesis. plnB-plnD gene knockout mutant lost the ability to synthesize bacteriocin against Salmonella typhimurium ATCC14028, indicating that plnB-plnD gene was a necessary gene for bacteriocin synthesis of L. plantarum NMD-17. Bacteriocin synthesis, cell numbers, and AI-2 activity of luxS or plnB-plnD gene knockout mutants in co-cultivation with L. reuteri NMD-86 were obviously lower than those of wild-type strain in co-cultivation at 6-9 h (P < 0.01). The results showed that LuxS/AI-2-mediated quorum sensing system played an important role in the bacteriocin synthesis of L. plantarum NMD-17 in co-cultivation.


Estrogen protects neuronal cells from the cytotoxicity induced by acetylcholinesterase-amyloid complexes.
The senile plaques present in Alzheimer's disease (AD) are composed of a core of amyloid beta-peptide (Abeta) plus several proteins including acetylcholinesterase (AChE). Recently we found that AChE forms complexes with the Abeta peptide in vitro and that these are more cytotoxic than Abeta fibrils alone. Considering that estrogen has been reported to act as a protective agent against Abeta-induced cytotoxicity, the effect of 17beta-estradiol was studied in rat pheochromocytoma (PC12) and mouse neuroblastoma (Neuro 2a) cells exposed to either Abeta alone or AChE-Abeta complexes. Estrogen showed a powerful protective effect in response to the challenge of AChE-Abeta complexes as well as with Abeta fibrils. This was also the case for other cytotoxic agents such as glutamate and H2O2. Our results suggest a common mechanism for cellular protection by estrogen against the toxicity of both Abeta fibrils and AChE-Abeta complexes, likely avoiding the free radical apoptotic pathway.


Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN.
The final step in the biosynthesis of nicotinamide-adenine dinucleotide, a major coenzyme in cellular redox reactions and involved in intracellular signaling, is catalyzed by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT). The X-ray structure of human NMNAT in complex with nicotinamide mononucleotide was solved by the single-wavelength anomalous dispersion method at a resolution of 2.9 A. Human NMNAT is a symmetric hexamer whose subunit is formed by a large six-stranded parallel beta-sheet with helices on both sides. Human NMNAT displays a different oligomerization compared to the archaeal enzyme. The protein-nicotinamide mononucleotide interaction pattern provides insight into ligand binding in the human enzyme.


In-capillary formation of polymer/surfactant complexes-assisted reversed-migration micellar electrokinetic chromatography for facile analysis of neutral steroids.
In this study we developed a novel approach, using in-capillary formation of polymer/surfactant complexes (IPSC)-assisted reversed-migration MEKC (RM-MEKC), for the analysis of neutral steroids. This process involved two sequential events: in-capillary polymer/surfactant complexes formation during sample preconcentration, followed by IPSC separation. The procedure began with a polymer-filled capillary. Initially, on-line preconcentration of the sample was performed at the sample plug. Meanwhile, free surfactants migrated to interact with polymers, forming polymer-surfactant complexes. Analytes were then kinetically partitioned between the mixed phases (micelles and polymer-SDS complexes). Sodium dodecyl sulfate (SDS) and poly(N-isopropylacrylamide) (PNIPAAm) were employed as pseudo-stationary phases (PSPs). This system allowed the successful separation of five steroids (testosterone, hydrocortisone 21-acetate, dexamethasone, prednisolone, hydrocortisone) in acetate buffer and the determination of urinary free hydrocortisone; it also exhibited excellent performance for sample on-line concentration. The limit of detection for hydrocortisone was 20.98 ng/mL (R(2)=0.9995). The polymer size, concentrations, end-group charges, and SDS concentrations were evaluated. This IPSC/RM-MEKC system, which can be adopted in commercial CE instruments, is easy to operate, suitable for combination with several sample preconcentration options, sensitive, robust, and environmentally sustainable. We suspect that such systems might have potential applications in clinical analyses and in microanalytical devices.


Carapanolides T-X from Carapa guianensis (Andiroba) Seeds.
Two new mexicanolide-type limonoids, carapanolides T-U (1-2), and three new phragmalin-type limonoids, carapanolides V-X (3-5), were isolated from the seeds of Carapa guianensis (andiroba). Their structures were determined on the basis of 1D- and 2D-NMR spectroscopy.


Childhood systemic lupus erythematosus in songklanagarind hospital: a potential unique subgroup.
Twenty systemic lupus erythematosus patients under the age of 16 who had attended the Pediatric Department of Songklanagarind Hospital in the period 1985-1991 were reviewed retrospectively. The most common complaints were fever, alopecia, malar rash and oedema. The girl/boy ratio was 2.3/1. There were many unusual presentations such as Stevens-Johnson syndrome, psoriasis, rheumatoid nodules, papillitis and pseudotumor cerebri. Nephritis, haematological disorder and CNS involvement were found in 80, 50 and 35% respectively. All cases were positive for ANA. Sixty-five percent of cases had complications and mostly more than one. Common complications were infection, renal complication and side effects of chemotherapy. Five patients died because of renal failure, severe infections, cerebral infarction or GI bleeding.


An Increase in Peroxiredoxin 6 Expression Induces Neurotoxic A1 Astrocytes in the Lumbar Spinal Cord of Amyotrophic Lateral Sclerosis Mice Model.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with selective degeneration of motor neurons. It has been reported that an increase in the levels of inflammatory cytokines and glial cells such as reactive astrocytes is closely involved in the pathological progression of ALS. Recently, the levels of neuropathic cytotoxic (A1) astrocytes among reactive astrocytes have reportedly increased in the central nervous system of ALS mice, which induce motor neuron degeneration through the production of inflammatory cytokines and secretion of neuropathic factors. Hence, elucidating the induction mechanism of A1 astrocytes in ALS is important to understand the mechanism of disease progression in ALS. In this study, we observed that the expression of peroxiredoxin 6 (PRDX6), a member of the peroxiredoxin family, was markedly upregulated in astrocytes of the lumbar spinal cord of SOD1G93A mice model for ALS. Additionally, when PRDX6 was transiently transfected into the mouse astrocyte cell line C8-D1A and human astrocytoma cell line U-251 MG, the mRNA expression of complement C3 (a marker for A1 astrocyte phenotype) and inflammatory cytokines was increased. Furthermore, the mRNA expression of C3 and inflammatory cytokine was increased in C8-D1A and U-251 MG cells stably expressing PRDX6, and the increased mRNA expression was significantly suppressed by MJ33 (lithium[1-hexadecoxy-3-(2,2,2-trifluoroethoxy) propan-2-yl] methyl phosphate), an inhibitor of the phospholipase A2 activity of PRDX6. Our results suggest that the expression of PRDX6 in astrocytes plays an important role in the induction of A1 astrocytes and expression of inflammatory cytokines in the ALS mice model.


Morganelliasis pneumonia in a captive jaguar.
Suppurative bronchopneumonia was discovered in a 6-yr-old male jaguar (Panthera onca onca) that died after a 1 wk history of anorexia, depression, and respiratory difficulty. Morganella morganii was isolated as a pure culture from the lung, spleen, and heart blood. This is the first record of M. morganii induced pneumonia in a jaguar.


TAPPred prediction of TAP-binding peptides in antigens.
The transporter associated with antigen processing (TAP) plays a crucial role in the transport of the peptide fragments of the proteolysed antigenic or self-altered proteins to the endoplasmic reticulum where the association between these peptides and the major histocompatibility complex (MHC) class I molecules takes place. Therefore, prediction of TAP-binding peptides is highly helpful in identifying the MHC class I-restricted T-cell epitopes and hence in the subunit vaccine designing. In this chapter, we describe a support vector machine (SVM)-based method TAPPred that allows users to predict TAP-binding affinity of peptides over web. The server allows user to predict TAP binders using a simple SVM model or cascade SVM model. The server also allows user to customize the display/output. It is freely available for academicians and noncommercial organization at the address http://www.imtech.res.in/raghava/tappred.


Dose-response effect of a recreational team handball-based exercise programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males - a randomised controlled trial.
This study aimed at examining the dose-response of a recreational team handball (TH) exercise-based programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males without TH experience. Fifty-four inactive middle-aged-to-elderly men (67.5 ± 4.2 years; stature 168.8 ± 6.2 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups performing 1 (TH1, n = 13), 2 (TH2, n = 15), or 3 (TH3, n = 12) 60-min weekly recreational TH-based training sessions, for 16 weeks, and a control group (CG, n = 14). A time x group interaction was observed for VO2peak, aerobic performance, fasting plasma insulin and body and fat mass (p ≤ 0.043) with TH3 showing the greatest overall effects. Post-intervention differences were observed in aerobic performance (TH3>CG, TH1 and TH2; TH2>CG), body mass (TH3>CG and TH1), fat mass (TH3>CG), VO2peak (TH3>CG) and plasma insulin (TH3>CG) (p ≤ 0.040). In conclusion, recreational TH performed for 60-min thrice and twice per week results in improved aerobic performance for middle-aged-to-elderly men. Moreover, it was observed that three weekly sessions were more effective in providing overall cardiometabolic benefits compared to training with a lower weekly frequency. ClinicalTrials.gov ID: NCT05295511.Trial registration: ClinicalTrials.gov identifier: NCT05295511.Highlights: We observed high intensities and fun levels during recreational TH, organised as formal and small-sided games, for middle-aged-to-elderly men during a 16-week period, independently of the number of weekly training sessions.Marked positive effects on aerobic performance and cardiometabolic health were observed in the intervention group that performed 3 weekly sessions.The study results indicate that recreational TH training with low frequency and volume results in some beneficial effects on cardiometabolic fitness and health for middle-aged-to-elderly men, but future studies with more participants or longer intervention periods are warranted to explore this possibility.


Subjective expectations regarding longevity and future health: a cross-sectional survey among patients with Crohn's disease.
The aim was to explore the subjective health expectations (sHE) of patients with Crohn's disease (CD) for both the near future and the elderly. A cross-sectional survey was performed in four gastroenterology centres in Hungary. Consecutive outpatients with CD with age ≥ 18 were recruited. Socio-demographic and disease characteristics were recorded and the Crohn's Disease Activity Index (CDAI), Perianal Disease Activity Index, Patients' Global Assessment (PGA) and current pain visual analogue scale (VAS) were assessed. Subjective life expectancy (sLE) was explored and compared to statistical life expectancy. Current health and sHE for 1 year ahead and for ages 60/70/80/90 were assessed using the descriptive system of the EQ-5D-3L. In all, 206 patients (54.9% men) with a mean age of 34.7 (SD 10.5 years) and disease duration of 10.5 (SD 6.3) years were studied. The CDAI score was 110.5 (SD 77.0) and 66% were treated by biologic drugs. Mean current EQ-5D-3L score was 0.80 (SD 0.17) and patients expected a 0.05 (SD 0.15) improvement within a year (P < 0.05). For ages 60/70/80/90, a mean EQ-5D-3L score of 0.59, 0.38, 0.10 and -0.12 respectively was provisioned. Age, current health status, sLE, PGA and pain VAS showed significant correlation with both 1-year and older age sHE (P < 0.05). Long-term sHE and sLE were negatively affected by the presence of extraintestinal manifestations but not by previous CD-related surgery. Patients with CD expect severe deterioration in health in later life. Given that unrealistic sHE may affect patients' current quality of life and health behaviour, we encourage physicians to explore and consider CD patients' sHE in clinical care.


Mycotoxins and fungi accompanying wheat head fusariosis in Poland.
The occurrence of wheat head fusariosis in various regions of Poland was observed in 1985 and 1986. The incidence of fusariosis was usually low - about 0,01% - only on South - East in some localities reached 5 - 20%. The most important species isolated from infected heads were :Fusarium culmorum F.grami nearurn,F.ni vale andF.avenaceum, in addition to whichF.crookwel1ense,F.eqiseti,F.subqluti nans andF.tricinctum (sensu Nelson et al.1983) were observed. Deoxynivalenol was present in 100% examined kernels subsamples at level 5-18 mg/kg and 3-acetyl deoxyn i val enol in 70% at level 1-3 mg/kg. The mycotoxins amount in chaff was 1,4 to 2,6 and 1,4 to 11 times higher (DON and 3AcD0N resp.) than in kernels.


Factors affecting the quality of life in drug-resistant epilepsy patients.
Epilepsy patients whose seizures cannot be controlled by treatment have a lower quality of life (QoL). The aim of the present study was to compare the potential factors affecting the QoL in patients who were seizure-free with medication or who had drug-resistant epilepsy. The study included 46 drug-resistant and 42 seizure-free epilepsy patients. The demographic and clinical features of the patients were investigated for their effects on patient QoL. The QoL was assessed by the QoL in Epilepsy Inventory-89 and depression was detected by the Beck Depression Inventory. The QoL was significantly lower in the drug-resistant patients than in the seizure-free epilepsy patients (p < 0.001). Depression, lower education level, and unemployment were associated with lower QoL scores (p < 0.001, p < 0.01, p < 0.001, respectively). After adjusting for lower education level and unemployment, depression remained as an independent factor affecting QoL (p < 0.05). In addition to their efforts to control and stop seizures, clinicians should remain aware of depression and treat it effectively to improve the QoL of drug-resistant epilepsy patients.


[Sensory-motor intermittent claudication syndrome of the cauda equina. Etiopathogenetic study of 25 cases].
The twenty-five patients with the intermittent claudication syndrome of th cauda equina included 19 men and 6 women aged from 23 to 70 years. The results of operation were very good in 16 cases, with improvement in 6 others and failure in 3 cases. There are various mechanisms which can cause the stenosis. The authors stress the importance of congenital vertebral abnormalities and the presence of apophyseal appendices which, at the present time, have not been considered responsible.