Pancreatic cancer: experience from an emerging country in North Africa.
Pancreatic cancer is a major global health problem, it's a highly aggressive and often has a poor prognosis. The aim of this work is to carry out a retrospective epidemiological study on pancreatic cancer in a university hospital in a North African country. This is a monocentric, descriptive and analytical retrospective cohort study carried out in the Gastroenterology department of the Mohammed VI University Hospital of Oujda, Morocco, between January 2018 and December 2022. Analysis were performed using IBM SPSS Version 21.0 RESULTS: During this period, 197 cases of pancreatic cancers were collected, the median age was 64.6 years, the majority of patients (90.9%) were over 50 year's old. and there was no significant difference in gender distribution. Among the patients, several risk factors were prevalent, including chronic tobacco smoking (22.8%), alcohol consumption (12.7%), diabetes (38.1%), obesity (7.6%), and a family history of pancreatic cancer (3%). The most common symptoms at presentation were abdominal pain and obstructive jaundice. Imaging revealed that the majority of cases were located in the head of the pancreas (80.7%). Only 19.8% of the cancers were diagnosed at a resectable stage and adenocarcinoma was the predominant histological type (96.4%). Patients with advanced cancer stages showed higher levels of CA 19-9 and hypoalbuminemia. Our study aligns with previous research, indicating an increased incidence of pancreatic cancer among elderly individuals, particularly those with several risk factors such as chronic tobacco smoking, alcohol consumption, diabetes. A small proportion of cancer cases are deemed resectable at the time of diagnosis.


Drinking water quality and inflammatory bowel disease: a prospective cohort study.
Environmental factors, such as drinking water and diets, play an important role in the development of inflammatory bowel disease (IBD). This study aimed to investigate the associations of metal elements and disinfectants in drinking water with the risk of inflammatory bowel disease (IBD) and to assess whether diet influences these associations. We conducted a prospective cohort study including 22,824 participants free from IBD from the Yinzhou cohort study in the 2016-2022 period with an average follow-up of 5.24 years. The metal and disinfectant concentrations were measured in local pipeline terminal tap water samples. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). During an average follow-up period of 5.24 years, 46 cases of IBD were identified. For every 1 standard deviation (SD) increase in the concentration of manganese, mercury, selenium, sulfur tetraoxide (SO4), chlorine, and nitrate nitrogen (NO3_N) were associated with a higher risk of IBD with the HRs of 1.45 (95% CI: 1.14 to 1.84), 1.51 (95% CI: 1.24-1.82), 1.29 (95% CI: 1.03-1.61), 1.52 (95% CI: 1.26-1.83), 1.26 (95% CI: 1.18-1.34), and 1.66 (95% CI: 1.32-2.09), whereas zinc and fluorine were inversely associated with IBD with the HRs of 0.42 (95% CI: 0.24 to 0.73) and 0.68 (95% CI: 0.54-0.84), respectively. Stronger associations were observed in females, higher income groups, low education groups, former drinkers, and participants who never drink tea. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of IBD. We found significant associations between exposure to metals and disinfectants and IBD. Diets regulated the associations to some extent.


Dental compensation for skeletal Class III malocclusion by isolated extraction of mandibular teeth. Part 1: Occlusal situation 12 years after completion of active treatment.
The purpose of this work was to statistically evaluate the outcomes achieved by isolated extraction of mandibular teeth (second premolars or first molars) for Class III compensation. Part A of the study dealt with the quality of outcomes at the end of active treatment, using weighted Peer Assessment Rating (PAR) scores determined on the basis of casts for 25 (14 female and 11 male) consecutive patients aged 16 ± 1.7 years at the time of debonding. These results were compared to the scores in a randomly selected control group of 25 (14 female and 11 male) patients who were 14.7 ± 1.9 years old at debonding. Part B evaluated the long-term stability of the outcomes based on 12 (all of them female) patients available for examination after a mean of 11.8 years. The mean weighted PAR scores obtained in both study parts were analyzed for statistical differences using a two-tailed paired Student's t-test at a significance level of p ≤ 0.05. Mean weighted PAR scores of 4.76 ± 3.94 and 3.92 ± 3.44 were obtained in the Class III extraction group and the control group, respectively, at the end of active treatment. This difference was not significant (p = 0.49). Among the 12 longitudinal patients, the mean score increased from 4 ± 3.46 at debonding to 6.25 ± 3.67 by the end of the 11.8-year follow-up period. This difference was significant (p = 0.0008). Treatment of Class III anomalies by isolated extraction of lower premolars or molars can yield PAR scores similar to those achieved by standard therapies. These scores, while increasing significantly, remained at a clinically acceptable level over 11.8 years. Hence this treatment modality--intended for cases that border on requiring orthognathic surgery--may also be recommended from a long-term point of view.


Ductal carcinoma in situ with microinvasion.
Ductal carcinoma in situ (DCIS) accounts for nearly 20% of new breast cancer diagnoses and ductal carcinoma in situ with microinvasion (DCIS-MI) is found in 5% to 10% of DCIS. Controversy exists regarding the appropriate local treatment as well as whether or not examination of the axilla should be performed either by sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND) or not at all. A MEDLINE search was performed using the keywords ductal carcinoma in situ and microinvasion. Recent articles pertaining to the definition and characterization of DCIS-MI as well as treatment and prognosis were analyzed. The data at this time demonstrate no survival benefit for patients undergoing mastectomy versus lumpectomy and radiation. Numerous studies demonstrate axillary lymph node involvement to be as high as 20% with DCIS-MI; therefore, we believe that axillary sampling is essential. We recommend SLNB, which is accurate, provides information necessary for staging and treatment, and is associated with less morbidity than traditional ALND.


Combining natural antimicrobials and nanotechnology for disinfecting food surfaces and control microbial biofilm formation.
The elimination of microbial surface contaminants is one of the most important steps in Good Manufacturing Practices in order to maintain food safety. This is usually achieved by detergents and chemical sanitizers, although an increased demand exists for the use of natural products for disinfection purposes. Several natural substances present antibacterial activity against the main foodborne pathogens, demonstrating great potential for use in the food industry. Some difficulties such as high volatility, residual taste and/or degradation by exposure to harsh processing conditions have been reported. Nanoparticle encapsulation appears as a strategy to protect bioactive compounds, maintaining their antimicrobial activity and providing controlled release as well. This article presents the potential of natural antimicrobials and their combination with nanotechnological strategies as an alternative for food surface disinfection and prevent microbial biofilm formation.


Ba(2+)-induced chromaffin cell death: cytoprotection by Ca(2+) channel antagonists.
Exposure of bovine adrenal medullary chromaffin cells to Ba(2+) ions (in the absence of Ca(2+) ions) caused their death, measured as lactate dehydrogenase (LDH) release. The concentration of Ba(2+) required to damage the cells by about 65% ranged between 1 and 10 mM (no Ca(2+) added); the required exposure time was rather brief (15 min-4 h). The simultaneous presence of Ca(2+), Mg(2+) or Zn(2+) together with Ba(2+) (2 mM, 4 h) afforded cyprotection (60-80%). Individual selective blockers of Ca(2+) channel subtypes afforded no protection. However, combined nifedipine (3 microM) plus omega-conotoxin MVIIC (3 microM) offered full protection. Substantial protection was also seen with the "wide-spectrum" Ca(2+) channel blockers penfluridol (0.3 microM), lubeluzole (3 microM), dotarizine (3 microM), flunarizine (3 microM), and mibefradil (3 microM). This protection was due to blockade of Ba(2+) entry through Ca(2+) channels because dotarizine (10 microM) inhibited the increase in cytosolic [Ba(2+)] seen in fura-2-loaded chromaffin cells. Once Ba(2+) accumulated in the cytosol, it was not extruded by the Na(+)/Ca(2+) exchanger, as shown by the prolonged and sustained elevation of the fura-2 signal. This contrasts with the fast dissipation of the fura-2 signal generated by [Ca(2+)](i) elevation. Thus, Ba(2+) overload can cause cell death by mechanisms similar to those reported for Ca(2+) overload and might be used as a novel and convenient tool to search for new cytoprotective compounds.


Two structural genes on different chromosomes are required for encoding the major subunit of human red cell glucose-6-phosphate dehydrogenase.
Structural analysis revealed the existence of two types of subunits in human red cell glucose-6-phosphate dehydrogenase. The two subunits have the same COOH region consisting of 479 amino acid residues, but their NH2-terminal regions are different in size and sequence. The minor subunit can be fully encoded by the X-linked G6PD cDNA, but the NH2-terminal region of the major subunit cannot. The cDNA and the gene for the NH2-terminal region of the major subunit were cloned and characterized. Southern blot hybridization indicated that the gene for the NH2-terminal region is on chromosome 6, not on the X chromosome. Northern blot hybridization demonstrated an existence of two separate mRNA components, one for the COOH-terminal region and the other for the NH2-terminal region. Two separate structural genes, the X-linked and chromosome 6-linked genes, must be coresponsible for encoding the single chain subunit. Either cross-translation of two mRNAs, or transpeptidation, or some other mechanism must be involved in the synthesis of human red cell G6PD.


Systematic review of red yeast rice compared with simvastatin in dyslipidaemia.
Red yeast rice is believed to be a useful alternative in the management of dyslipidaemia. However, the comparative effectiveness of red yeast rice and simvastatin for the management of dyslipidaemia is unknown. This review assesses the efficacy and safety of red yeast rice versus simvastatin in dyslipidaemia. Electronic databases were searched up to May 2015 without publication date and language restriction. The Cochrane Risk of Bias Assessment Tool was used to assess the quality of included trials. Changes in total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were examined. Ten randomized controlled trials involving 905 Chinese subjects with dyslipidaemia were systematically reviewed. Overall, red yeast rice and simvastatin did not show any statistically significant difference in any of the outcomes examined. A number of small trials show that red yeast rice and simvastatin produce similar lipid-lowering effects. Larger trials with increased methodological rigour and trials with clinical outcomes are necessary for more robust inferences.


Differential involvement of 5-HT(2A) receptors in the discriminative-stimulus effects of cocaine and methamphetamine.
Involvement of 5-HT(2A) receptors in the discriminative-stimulus effects of cocaine versus methamphetamine was studied in Sprague Dawley rats (n=10) trained to discriminate 10 mg/kg cocaine, i.p., from saline under a fixed-ratio 10 (FR10) schedule of food presentation. The ability of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT(2A) receptor agonist, and ketanserin, a 5-HT(2A) receptor antagonist, to either substitute for or block the discriminative-stimulus effects of cocaine, or to shift the cocaine dose-response curve, was evaluated. DOI (0.18-1.0 mg/kg) partially substituted for the training dose of 10 mg/kg cocaine, but only at doses that decreased rates of responding. At the highest dose of DOI tested (1.0 mg/kg), there was about 65% cocaine-appropriate responding. Substitution of DOI for cocaine and DOI-induced decreases in rates of responding were completely reversed by ketanserin (3.0 mg/kg). Ketanserin (3.0 mg/kg) also produced a significant shift to the right of the cocaine dose-response curve and antagonized increases in rates of responding produced by lower doses of cocaine. Ketanserin (1.0-10.0 mg/kg), however, did not block the discriminative-stimulus effects of the training dose of cocaine. When DOI (0.3 mg/kg) was co-administered with different doses of cocaine, there was a slight leftward shift in the cocaine dose-response curve, which was not significant and appeared to reflect simple additive effects of DOI and cocaine. In contrast, the same dose of DOI (0.3 mg/kg) produced a marked and highly significant shift to the left of the methamphetamine (0.18-1.0 mg/kg) dose-response curve in the same subjects and the effects of DOI and methamphetamine were clearly more than additive. The present findings provide new evidence that there is some serotonergic modulation of cocaine's discriminative-stimulus actions, which appears to involve stimulation of 5-HT(2A) receptors. However, involvement of 5-HT(2A) receptor activity in the discriminative-stimulus actions of cocaine appears to be less pronounced than in similar actions of methamphetamine.


MRI of Pediatric Foot and Ankle Conditions.
The increase in competitive sports practice among children and lack of ionizing radiation have resulted in a higher demand for MRI examinations. MRI of the children skeleton has some particularities that can lead orthopedists, pediatricians, and radiologists to diagnostic errors. The foot and ankle have several bones with abundant radiolucent and high signal intensity cartilage in several ossification centers, apophysis and physis, that can make this interpretation even harder. The present revision aims to show, how to differentiate between normal developmental findings and anatomic variants from pathologic conditions, whether mechanical, inflammatory, infectious, or neoplastic.


Platelet to lymphocyte and neutrophil to lymphocyte ratio in the first trimester of pregnancy, are they useful for predicting spontaneous miscarriage? A case-control study.
In 15% of all clinical pregnancies, a miscarriage can occur, but the exact cause of this phenomenon is not fully understood. However, it is believed that a faulty placenta, which triggers an inflammatory response in the mother's body, may be one of the causes. Medical literature has increasingly focused on 2 indicators of inflammation, the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR). Despite this, there has yet to be a study conducted that examines the rates of PLR and NLR in cases of miscarriage. This study aims to determine whether there is an increase in complete blood count inflammatory parameters such as NLR and PLR in women who experience miscarriages. This retrospective case-control study was conducted from March 2021 to March 2022, across 3 academic hospitals in Tehran, Iran. A total of 240 participants were enrolled comprising individuals with either miscarriages or normal pregnancies (n = 120/each). Data were collected from the medical records of participants aged between 18-42 yr old, with gestational age ranging from 6-13 wk. The demographic information, including age, body mass index, parity, history of abortion, number of abortions, number of living children, hematocrit and hemoglobin levels, platelet distribution width (PDW), PLR, NLR, mean platelet volume, and platelet were extracted from their records. The gestational age was also recorded. A total of 240 participants were recruited for the study. PDW, NLR, PLR, and lymphocyte values were higher in the miscarriage group compared to the healthy normal pregnant women (p < 0.001). Mean platelet volumes were found to be lower in the miscarriage group compared to the healthy normal pregnant women (p < 0.001). Although, no statistically significant difference was observed in the hemoglobin, hematocrit, platelets, and neutrophils in these 2 groups of pregnant women. The higher inflammatory markers including PDW, NLR, and PLR could potentially aid in the speculation of defective placentation as a contributing factor to the development of miscarriage. Measurement of these markers may be useful to predict pregnancy leading to miscarriage.


Describing sorption of pharmaceuticals to lake and river sediments, and sewage sludge from UNESCO Biosphere Reserve Kristianstads Vattenrike by chromatographic asymmetry factors and recovery measurements.
Over the past 30 years a vast number of studies have demonstrated the presence of pharmaceutical residues in the environment. But still knowledge is scarce regarding the interaction of these emerging pollutants with various matrices in nature. A chromatographic system with on-line detection was developed to perform a sorption study of six selected pharmaceuticals to four natural sediments and dewatered digested sewage treatment plant sludge with differing physicochemical characteristics. Sorption effects, measured as asymmetry factors and recoveries, differed pronouncedly among the pharmaceuticals and between the matrices, which could be explained by basic physicochemical properties of the investigated compounds in relation to matrix characteristics. Protonated and deprotonated molecular properties had the greatest importance for sorbate-sorbent interactions. Atenolol, with cationic properties, showed the highest degree of sorption regardless of the matrix studied. Diclofenac and furosemide, both acids, showed the least tendency towards interactions to natural matrices. Among the neutral compounds bendroflumethiazide, carbamazepine and oxazepam, weaker forces, such as van der Waals, aromatic electron donor-acceptor interactions, and hydrogen forces, seemed more important to determine sorption differences. Results revealed that sorption of pharmaceuticals on natural sediments decreased in the order: atenolol (+)>bendroflumethiazide>oxazepam>carbamazepine>diclofenac (-)>furosemide (-). The matrix content of organic matter measured as total organic carbon (TOC) clearly dictated drug sorption. Beside from studying matrix interaction, these results and the developed technique and methodology might find use in the development of new removal processes of pharmaceuticals from wastewater based on improved knowledge concerning chemical interactions to filter materials.


The therapeutic effect of Shenhua tablet against mesangial cell proliferation and renal inflammation in mesangial proliferative glomerulonephritis.
Shenhua tablet (SH), a formulation of traditional Chinese medicine, exerts renoprotective effect on chronic kidney diseases, and it has been found to restrain inflammation, but the mechanism is still unclear. Here, we explored the potential renoprotection of SH in mesangial proliferative glomerulonephritis (MsPGN) rat model induced by anti-Thy1 antibody. Administration of SH reduced urinary albumin/creatinine ratio (UACR) and significantly attenuated mesangial cell proliferation and renal inflammation. Notably, SH protected rats against renal inflammation, which was associated with decreasing macrophage infiltration and promoting macrophage anti-inflammatory activity. Network analysis combined with arrays identified the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway as the main pathways of SH could target inflammation. Furthermore, it was confirmed that mesangial cell proliferation, which response to inflammation, were alleviated by ASS1 expression enhanced after SH administration both in vivo and in vitro. Collectively, SH has the beneficial on relieving the progression of MsPGN to alleviate inflammation and mesangial proliferation by inhibiting STAT3 phosphorylation and maintains the expression level of ASS1, might be an effective strategy for treating MsPGN.


5-Hydroxyindoleacetic acid and homovanillic acid in human cerebrospinal fluid below partial and complete spinal subarachnoid block.
Concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were investigated by lumbar cerebrospinal fluid (CSF) of 21 patients with partial and total spinal subarachnoid block. HVA levels in CSF below a complete block were significantly lower and 5-HIAA levels were signigicantly higher than controls. Below a partial block, HVA levels were normal; 5-HIAA levels were higher than in patients with complete block. Possible explanations for these findings are discussed.


Paeoniflorin improves the in vitro maturation of benzo(a)pyrene treated porcine oocytes via effects on the sonic hedgehog pathway.
Benzo(a)pyrene (BaP) is a toxic substance that people are often exposed to. It has serious harmful effects on the body, and has a destructive effect on oocytes and cumulus cells. Here, we found that paeoniflorin (Pae), a traditional Chinese medicine monomer with antioxidant effects, decreased BaP-induced meiotic failure by increasing the activity of the Sonic hedgehog (SHH) signaling pathway and reducing the level of reactive oxygen species (ROS). We found that the in vitro maturation (IVM) rate was significantly increased (P < 0.05) in the 0.1 μM Pae and BaP (co-treatment) group compared with BaP group due to reduced ROS levels and increased mitochondrial membrane potential (ΔΨ) and ATP content. The mRNA expression levels of oocyte maturation and cumulus cell expansion-related genes were also significantly higher in the co-treatment group. To demonstrate the quality of oocytes, the development capacity of parthenogenetically activated (PA) and in vitro fertilization (IVF) embryos from different treatment groups oocytes were determined.The blastocyst formation rate was significantly higher in PA and IVF embryos derived from oocytes in the co-treatment group than in those derived from oocytes in the BaP group. To further confirm that the SHH signaling pathway was involved in causing these effects of Pae, we treated oocytes with Pae and BaP in the presence or absence of cyclopamine (Cy), an inhibitor of this pathway. Cy abolished the effects of Pae in BaP treated porcine oocytes. In conclusion, Pae improves the IVM capacity of BaP-treated porcine oocytes by activating the SHH signaling pathway, inhibiting ROS production, and increasing ΔΨ.


The characterization of transaldolase gene tal from Pichia stipitis and its heterologous expression in Fusarium oxysporum.
The 972 bp length of transaldolase gene tal was cloned from Pichia stipitis CICC1960, encoding a 323 amino acid protein with a calculated molecular mass of 35.36 kDa and isoelectric point of 5.20. Real time PCR analysis demonstrated that the mRNA transcript level of constitutive tal gene rise on xylose, glucose, fructose, mannose, galactose and sucrose as carbon source, respectively. Furthermore, the transcription of tal gene in P. stipitis on xylose was higher than on other carbon source, indicating that transaldolase plays a part in xylose utilization. To deeply study the tal gene biological function, it was expressed in Fusarium oxysporum CCTCC M209040. Recombinant transaldolase activity of transformant F. oxysporum M209040-Tal2 was about 0.52 U mg(-1) protein and was 1.57 times higher than that of the wild type F. oxysporum CCTCC M209040, indicating that the improvement of transaldolase activity in transformant was due to expression of the exogenous tal gene. Growth of transformant F. oxysporum M209040-Tal2 without selection pressure did not affect the level of hygromycin resistance of the transformants, suggesting that integrated tal gene was stable in mitosis. Fermentation trials of F. oxysporum M209040-Tal2 showed that the ethanol yield improved by 8.39 and 11.71% on glucose and xylose substrates, respectively, demonstrating that the expression of tal gene from P. stipitis CICC1960 in F. oxysporum CCTCC M209040 could improve ethanol production.


Monomelic Multifocal Neuropathy: An Unrecognized Electrophysiological Feature of Hereditary Neuropathy with Liability to Pressure Palsies in Childhood.
Hereditary neuropathy with liability to pressure palsies (HNPP) is well defined in adults, but its clinical and electrophysiological features in childhood have not been well characterized. We describe a case of HNPP in a child with the unique electrophysiological presentation, affecting only one upper extremity.


Association of the ephreceptor tyrosinekinase-type A2 (EPHA2) gene polymorphism rs3754334 with age-related cataract risk: a meta-analysis.
Recent clinical studies have assessed the association of various polymorphisms on the ephreceptor tyrosinekinase-type A2 (EPHA2) with the risk for age-related cataract in populations of different ethnic/racial backgrounds, but inconsistent results have been obtained. This meta-analysis aimed to identify if any polymorphism(s) might be commonly present in different ethnic/racial populations in association with the age-related cataract risk. The PubMed and Web of Science databases (up to December 1, 2012) were searched for clinical studies on the association of EPHA2 polymorphisms with the risk for age-related cataract. The polymorphisms that were assessed in all eligible studies were analyzed for their association with the risk for age-related cataract using different models. Three studies were identified, which were conducted, respectively, on white Americans in the Unites States and on Asians in Indian and China. The polymorphism, rs3754334, was the only one studied in all these three studies and was therefore the focus of this meta-analysis. No publication bias or heterogeneity was found. Our analysis results demonstrated that rs3754334 was associated with the risk of any cataracts in the recessive (OR = 1.202, 95% CI: 1.051-1.375, P = 0.007) and Codominant (OR = 1.194, 95% CI: 1.035-1.378, P = 0.015) models, but its association with cortical or nuclear phenotype of age-related cataract was not evident. Polymorphism, rs3754334, might be a variant on the EPHA2 gene that is commonly associated with the risk for age-related cataract in different ethnical and geographical populations.


Focal nodular hyperplasia on accessory lobe of the liver: preoperative diagnosis and management.
We report the case of a 13 year-old girl transferred to our department with a one month history of vomiting, weight loss, and abdominal mass that was diagnosed as Focal Nodular Hyperplasia in an accessory lobe of the liver. Accessory liver lobe is a rare congenital anomaly whose preoperative diagnosis is difficult and usually presents as an incidental finding intraoperatively. Depending on their location and size, they can present as acute abdomen or abdominopelvic mass. In the literature reviewed, we found no association of focal nodular hyperplasia and accessory liver lobe in children.


Post-treatment drinking among HIV patients: Relationship to pre-treatment marijuana and cocaine use.
For individuals with HIV, heavy drinking can pose serious threats to health. Some interventions are effective at reducing drinking in this population, but many HIV-infected heavy drinkers also use marijuana or cocaine. Although these drugs have predicted poor alcohol outcomes in other treatment studies, whether this occurs among HIV patients who drink heavily is unknown. Participants were binge-drinking HIV primary care patients (N=254) enrolled in a randomized trial of three brief drinking interventions over 60 days that varied in intensity. We investigated the relationship of baseline past-year drug use (marijuana-only, cocaine-only, both, neither) to end-of-treatment drinking quantity and frequency. We also evaluated whether the relationship between intervention type and end-of-treatment drinking varied by baseline drug use. Final models incorporated control for patients' demographic and HIV characteristics. In final models, drinking frequency at the end of treatment did not vary by baseline drug use, but drinking quantity did (X(2)[3] = 13.87, p < 0.01), with individuals using cocaine-only drinking significantly more per occasion (B = 0.32, p < 0.01). Baseline drug use also interacted with intervention condition in predicting end-of-treatment drinking quantity (X(2)[6] = 13.98, p < 0.05), but not frequency, with the largest discrepancies in end-of-treatment drinks per drinking day by intervention intensity among cocaine-only patients. In general, HIV patients using cocaine evidenced the highest levels of drinking after alcohol intervention. However, these individuals also evidenced the most pronounced differences in end-of-treatment drinking by intervention intensity. These results suggest the importance of more intensive intervention for individuals using alcohol and cocaine.


Elution of group-specific substance A from RBC of various subgroups of A and its effect on the agglutination of AX RBC.
Experiments are described which demonstrate that when the Landsteiner heat elution technique is used to prepare eluates from group A cells, some A substance as well as anti-A is released into the eluates. The concentration found is greatest from A1 RBC and least from Ax, suggesting a relationship with the number of antigen sites on RBC of the various subgroups. Further experiments have shown that the presence of this A-specific substance in eluates accounts for the well-know phenomenon that anti-A from selected group O sera, when eluted from A1 RBC, will not agglutinate Ax even though the original serum showed an appreciable titre against Ax. The presence of the eluted antigen also suggests an explanation for the behaviour of antibody recovered from the red cells of various subgroups of A towards Ax.


The surgical menopause.
Surgical menopause (iatrogenic menopause) happens when both ovaries are removed before the natural "switching off" of ovarian function; it can cause premature ovarian insufficiency where the menopause occurs in women before the age of 40. Surgical menopause is associated with a sudden reduction of ovarian sex steroid production rather than a gradual one as is the case in natural menopause. In women who have undergone bilateral salpingo-oophorectomy (BSO) before the natural age of menopause, strong consideration should be given to giving hormone replacement therapy (HRT) till the natural age of menopause at least. Sexual function and sexual desire are altered post-BSO, especially in younger women hence part of HRT prescription must include consideration of androgen too.


[Principles of treatment, coordination of medical care and patient education in fibromyalgia syndrome and chronic widespread pain].
A guideline for the treatment and diagnostic procedures for fibromyalgia syndrome (FMS) was developed in cooperation with 10 German medical and psychological associations and 2 patient self-help groups. A systematic literature search including all controlled studies evaluating physiotherapy, exercise and strength training as well as physical therapies was performed in the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-12/2006), PsychInfo (1966-12/2006) and Scopus (1980-12/2006). Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. Grading of the strengths of recommendations was done according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. Patient's information at first diagnosis of FMS is strongly recommended (grade A). Patient-centered communication is recommended (grade B). A stepwise treatment approach depending on the adapatation to restrictions in daily life and response to treatment options can be considered (grade C). The long-term treatment should be based on principles of basic psychosomatic care and shared decision making on treatment options.


Partial purification and characterization of a human lymphokine which induces antileishmanial activity in mouse macrophages.
Human blood mononuclear cells stimulated in vitro with concanavalin A secrete a lymphokine which activates mouse macrophages to kill Leishmania enriettii. Supernatants of cells cultivated for 1 day and for 2 days were analyzed for this activity after G-100 gel filtration and isoelectrofocusing. First day antileishmanial activity was found in a MW range of 23,000 with an isoelectric point of 3.6 to 4.0. Second day antileishmanial activity eluted in a peak in the MW range of 23,000 to 65,000 with an isoelectric point of 4.0 to 4.3. This activity could be completely separated from migration-inhibitory factor (MIF) after isoelectrofocusing in first day and in second day supernatants. Antileishmanial activity could be separated from interferon-gamma in first day, but not in second day supernatants.


Principles of protein architecture.
The three-dimensional structure of a protein is governed by the thermodynamical principle established experimentally by Anfinsen, Isemura, and others. The rapidity of the folding process is another important key phenomenon. With these basics in mind an island model is proposed which requires a restricted folding pathway. A physicochemical method of the prediction of alpha-helices and beta-strands is also discussed. By virtue of the long-range hydrophobic interaction and the specific interactions between hydrophobic residues which are determined by the basic idea underlying the island model, one can fold the polypeptide chain into a tertiary structure upon determination of the secondary structures. Several examples of folding are presented. In myoglobin the heme group must be considered to reach the correct final tertiary structure. In lysozyme and phospholipase, the disulfide bondings are necessary to fasten the polypeptide chain. The selection of proper cysteine pairs among other possible ones is carried out by drawing the lampshades (locus of H atom of SH) of cysteines. In flavodoxin and thioredoxin the formation of parallel beta-structure from beta-strands is considered. The formations of antiparallel beta-structure in lysozyme and phospholipase are also discussed.


Investigation of the extracts from Bidens pilosa Linn. var. radiata Sch. Bip. for antioxidant activities and cytotoxicity against human tumor cells.
The aim of this study was to evaluate antioxidant activities and cytotoxicity against human tumor cell lines of extracts from Bidens pilosa Linn. var. radiata Sch. Bip. (BP). Total phenolic and flavonoid contents of the extracts were determined by ultraviolet spectrophotometry. Furthermore, the antioxidant properties of different polarity fractions extracted from BP were evaluated using DPPH and ABTS radical scavenging test and FRAP assay. The ethyl acetate fraction (EE-BP) showed the highest antioxidant activity compared to other fractions. In addition, the anti-proliferative activities of the extracts on four human tumor cells, namely MCF-7, HepG2, MGC 803 and RKO, were investigated by MTT method. The EE-BP displayed the most remarkable anti-proliferative effect against the tumor cells, particularly RKO cell in dose- and time-dependent manner. The antioxidant activities and cytotoxicity correlated highly with the total phenolic and flavonoid contents, respectively. Furthermore, The active ingredient BP-6, namely 5,7,4'-trihydroxy-3,3'-dimethyl-flavonol, was isolated and purified with the purity above 99.00% and content of 0.15% in EE-BP detected by HPLC, which could significantly inhibit the proliferation of RKO cells with the IC(50) value of 6.66 μmol/l. In order to characterize the apoptotic RKO cells, flow cytometry and DNA fragmentation assay were performed. Apoptotic cell numbers increased in a dose-dependent manner after the treatment with different concentrations of EE-BP and BP-6 for 12 and 6 h, respectively. DNA ladders in apoptotic RKO cells could be easily visualized when exposed to 200 μg/ml of the EE-BP for 36 h. Taken together, our work indicated that BP had potentially therapeutic value against colorectal cancer.


Mechanism of L-alpha-methyldopa transport through a monolayer of polarized human intestinal epithelial cells (Caco-2).
The Caco-2 model system (Hidalgo et al., Gastroenterology, 96:736-749, 1989), which is a monolayer of polarized intestinal epithelial cells grown onto a porous polycarbonate membrane, was used to study the mechanism of transcellular transport of an antihypertensive agent, L-alpha-methyldopa (L-alpha-MD). The results showed that the transport of L-alpha-MD was pH, glucose, concentration, and temperature dependent, and it could be inhibited by metabolic inhibitors (e.g., 2,4-dinitrophenol) and by amino acids (e.g., L-phenylalanine) which have an affinity for the large neutral amino acid (LNAA) carrier. In addition, the apparent kinetic constants describing the transcellular transport of L-alpha-MD were altered depending on the time interval between feeding the cells and the transport experiments (postfeeding time, PFT). The apparent maximum carrier flux (Jmax) of L-alpha-MD was significantly increased (from 155 to 547 pmol/mg protein/min) when PFT was prolonged from 8.5 to 56 hr. These results indicated that the transcellular transport of L-alpha-MD through the polarized Caco-2 cell monolayer was carrier mediated via the LNAA carrier. The similarities in the characteristics of L-alpha-MD transport exhibited by the Caco-2 model system and other intestinal models in vitro further substantiate the usefulness of this cell culture model for studying the intestinal transport of nutrients and drugs.


Metabolic intermediates, enzymes and lysosomal activity in aortas of spontaneously hypertensive rats.
Metabolic intermediate levels, glycolytic and Krebs cycle enzyme activities and lysosomal acid hydrolase activities were measured in aortas of spontaneously hypertensive (SHR) versus normotensive (WKY) rats. In the hypertensive aortas the level of lactate, the ratio of lactate to glucose and of lactate to malate was higher in the SHR than WKY aortas. In the hypertensive aortas the obvious shift of metabolism toward higher rate of glycolysis was associated with decreased activity of malate dehydrogenase and espically of lipoamide dehydrogenase. The latter is an essential compoenent of the alpha-ketoglutarate and pyruvate dehydrogenase enzyme complexes and it appears that these complexes are among the sites of arterialmetavolism which are primarily altered by the elevated blood pressure, resulting in increased production of lactate. The activity of the marker lysosomal enzyme N-acetyl-beta-glucosaminidase was unequivocally elevated in the hypertensive aortas. The activity of beta-glucuronidase exhibited incogruous differences between the SHR and WKY aortas and the activity of aortic acid phosphatase did not differ in the two rat strains. The results are discussed in relation to arterial injury, permeability, and atherogenesis.


Common genetic background in anorexia nervosa and obsessive compulsive disorder: preliminary results from an association study.
Several lines of evidence, including psychopathological, neurobiological, pharmacological and epidemiological data, supported the association between Anorexia Nervosa (AN) and Obsessive-Compulsive Disorder (OCD). The aim of the present study is to test the hypothesis of partial common genetic background of both disease, AN and OCD. A total of 116 patients with AN, 74 patients with OCD and 91 controls participated in this study. 213 single-nucleotide polymorphisms (SNPs) in 28 candidate genes were analyzed. Five SNPs achieved 0.004 (the nominal p-value expected by chance), 3 with empirical significant p-values (rs10070190 (CDH9) p = 1 × 10(-3), rs4825476 (GRIA3) p = 4 × 10(-4), and rs1074815 (TPH2) p = 8 × 10(-4)) and 2 additional polymorphisms showing nominal significance (rs2834070 (OLIG2) p = 2 × 10(-3) and rs11783752 (SCL18A1) p = 3 × 10(-3)), were found to be related to both AN and OCD. In addition, rs3825885 (NTRK3, p = 9 × 10(-4)) was identified as an AN risk variant, and rs11179027 (TPH2, p = 2 × 10(-3)) as an OCD marker. The ROC analysis confirmed these results and showed interaction among the significant SNPs. The preliminary results we report here reveal a partial common genetic background in AN and OCD, in agreement with previous clinical findings of common symptomathology between these two diseases and open the field of possible treatments for AN. The interaction observed between the associated polymorphisms, could indicate that there is a biological interaction between the serotonin (TPH2 and SLC18A1) and glutamate (GRIA3) pathways and the factors related to neurogenesis (CDH9, OLIG2 and NTRK3) for the explanation of etiopathophysiology in both diseases. However, the results must be replicated in studies with larger cohorts in order to confirm these associations.


A multivariate data reduction system.
The problem of predictive diagnosis based on laboratory data is approached from a mathematical standpoint. A descriptive system is introduced which examines the current information about a clinical problem and identifies best predictors of the problem. Algorithms are described for the assessment of current diagnostic ability, the evaluation of new laboratory tests, and the identification of patients to study for the development of new procedures. The laboratory approach to the predictive diagnosis of iron deficiency is chosen as an example of the system.


Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis.
It's clear that environmental factors play a role in the aetiology of orofacial clefting (OFC) and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo. Periconceptional folic acid supplementation may reduce the risk of OFC. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methylenetetrahydrofolate, the predominant circulating form of folic acid. To determine the effect of MTHFR gene mutation on murine embryonic palatal mesenchymal (MEPM) cells and the interaction with folic acid supplement, we used RNAi study in the primary cultures of MEPM cells. The cells of MTHFR gene silencing grew slower and the apoptosis cell number was more than the cells of control. Supplement with 20 microg/ml folic acid was the best to preventing teratogenic effect of MTHFR gene silencing. By flow cytometry analysis of cell cycle, results were shown that the MEPM cells were retarded in G(0)/G(1) after MTHFR gene silencing. While using 20 microg/ml folic acid supplements could make cell transit the G(1)/S restriction point and the cells growth was close to normal level.


A multicentre study to introduce naltrexone for opiate dependence in Spain.
A multicentre prospective study was performed in eight centres in Spain in order to assess the usefulness of naltrexone in the treatment of opiate dependents and abusers (113 dependents and 37 abusers) non-selected in terms of social class or professional skill. The fundamental criterion for evaluation of clinical outcome was the retention rate. At 6 months this parameter was 40%, i.e. higher than any previously reported for non-selected patients. The adverse effects were mild and did not lead to therapeutic failures. Non-pharmacological factors may have contributed to the good clinical results obtained.


Non-commutability of results of highly sensitive troponin I and T immunoassays.
The measurement of cardiospecific troponins is pivotal in the diagnostic and prognostic approach of patients with suspected acute myocardial infarction (AMI). However, no information is available on the commutability of results between the novel highly-sensitive (HS) troponin T (TnT) and I (TnI) immunoassays. The study population consisted in 47 consecutive patients presenting at the emergency department (ED) of the Academic Hospital of Parma with suspected AMI. TnI was measured with the novel prototype Beckman Coulter HS-AccuTnI immunoassay on Access 2, whereas TnT was measured with the Roche HS-TnT immunoassay on Cobas. Eight out of the 47 patients (17%) were finally diagnosed as having an AMI. The overall correlation between TnT and TnI for total patient group was acceptable (r = 0.944; P < 0.01). Nevertheless, when the analysis of data was carried out in separate groups according to the final diagnosis of AMI, two different equation results were obtained, i.e., HS-TnT = HS-AccuTnI x 0.349 + 20 (r = 0.823; P < 0.01) in non-AMI patients, and HS-TnT = HS-AccuTnI x 0.134 + 67 (r = 0.972; P < 0.01) in those with AMI. This study suggests the existence of two biological relationships between Tnl and TnT in plasma, depending on the source of release from the myocardium. Moreover, the non-commutability of data between HS-TnT and HS-AccuTnI jeopardizes the clinical decision making, makes it impossible to calculate the delta or reference change value using the two biomarkers and to finally establish a reliable kinetics of troponin release from the injured myocardium.


Physical activity and nutrition among youth in rural, suburban and urban neighbourhood types.
Physical activity and nutrition are essential to healthy living and particularly important during youth, when growth and development are key. This study examined rates of physical activity (PA) and diet quality (DQ) among youth in grades 7 to 9 in Halifax, Nova Scotia, during the 2008/09 school year and tested differences among students in rural, urban and suburban neighbourhood types of high and low socio-economic status (SES). Youth in grades 7 through 9 (aged 12-16; 53% male) from six schools (N=380), stratified by neighbourhood type (urban, suburban, rural) and SES, wore accelerometers for up to 7 days (mean=4.14, standard deviation=1.49) and completed a nutritional survey. The findings suggest important differences in PA and DQ across SES and neighbourhood type. Specifically, rates of moderate to vigorous physical activity among youth from schools in lower socio-economic areas were higher in urban than in suburban or rural settings. Furthermore, DQ was better among youth in higher than in lower socio-economic urban settings. Understanding these differences in PA and DQ across rural, urban and suburban environments of high and low SES may highlight subgroups and targeted geographic areas for the design of interventions to improve rates of PA and health nutrition.


Trends in HIV prevalence among men who have sex with men in China 2003-09: a systematic review and meta-analysis.
The year-by-year trend of HIV prevalence among men who have sex with men (MSM) in China is not well documented. Published studies on HIV prevalence among MSM in China were reviewed and grouped by year, region and age group. Meta-analysis was used to summarise the estimates of national and regional HIV prevalence rates and trends among MSM from 2003 to 2009. HIV prevalence among MSM in different age groups (<25 years old v. ≥25 years old) was also calculated. Eighty-three publications were included in the meta-analysis. The pooled HIV prevalence among MSM in China increased from 0.6% (95% confidence interval (CI): 0.0-2.1%) in 2003 to 7.4% (95% CI: 5.7-9.2%) in 2009. A yearly increase of 1.1% (95% CI: 0.5-1.5%, P<0.001) in HIV prevalence was detected. The pooled regional HIV prevalence among MSM ranged from 2.3% (95% CI: 1.7-2.9%) in east China to 11.4% (95% CI: 9.2-13.6%) in south-west China. No difference was detected (χ(2)=0.5160, P=0.4726) between HIV prevalence in the <25-year-old age group (3.1%, 95% CI: 1.6-4.6%) and that in the ≥25-year-old age group (4.0%, 95% CI: 1.8-6.3%). The HIV prevalence among MSM in China is high and climbing. Effective strategies are required to prevent the epidemic from continuing to spread.


Cubic Cu2O nanoframes with a unique edge-truncated structure and a good electrocatalytic activity for immunosensor application.
In this work, an ultrasensitive sandwich-type electrochemical immunosensor was developed for the quantitative detection of prostate specific antigen (PSA). Gold nanoparticles decorated 3-aminopropyltriethoxysilane functionalized graphene sheets (Au@APTES-GS) with a large specific surface area, good biocompatibility and superior electron transfer ability were employed as the matrix. In addition, cubic Cu2O nanoframes with hollow edges were employed as the label for the first time. Scanning electron microscope (SEM) images were used to confirm the nanostructure of Au@APTES-GS and Cu2O. Using square wave voltammetry (SWV) to monitor the electrocatalytic process, the signal amplification mechanism of the matrix and the label were explored successfully. Here we find that the unique edge-truncated structure of Cu2O nanoframes can load with a larger amount of redox mediators, ferrocenecarboxylic acid (Fc-COOH), offering a higher electrochemical signal response. Apart from that, Cu2O nanoframes have a good electrocatalytic activity towards the Fc-COOH and hydrogen peroxide (H2O2), making a contribution to further enhance the sensitivity of the fabricated immunosensor. Under optimal conditions, the proposed immunosensor achieved an ultrasensitive and specific detection of PSA, and displayed acceptable reproducibility, selectivity and stability. This work may provide an effective method for the clinical monitoring of tumor markers and demonstrate the potential application promising of nanoframes in the fabrication of immunosensors.


Sodium fluoride evoked histamine release from mast cells. A study of cyclic AMP levels and effects of catecholamines.
Calcium triggers the secretion of histamine from mast cells after previous exposure to sodium fluoride. The secretory process can be divided into a fluoride-activation step and a calcium-induced secretory step. It was observed that the fluoride-activation step is accompanied by an elevation of cAMP levels within the cells. The attained high levels of cAMP persist during histamine release. It was further found that catecholamines do not markedly alter the fluoride-induced histamine release. It was also confirmed that the second, but not the first, step in sodium fluoride-induced histamine secretion is inhibited by theophylline.


Intra-arterial chemotherapy for bladder cancer.
Intra-arterial infusion chemotherapy with adriamycin (ADM) was carried out in 32 patients with bladder cancer prior to total cystectomy. An oblique incision approximately 12 cm long was made in the gluteal region to expose either the superior or inferior gluteal artery, into which a Teflon catheter was inserted and fixed. The distal end of the catheter was taken out from under the skin in the precordial region. Via this catheter, a single dose of 10 mg ADM was injected twice a week. Superior-gluteal-artery infusion chemotherapy was performed in 7 patients; the 5-year survival rate was 14.3%, which was not as high as expected. Inferior-gluteal-artery infusion chemotherapy was performed in 25 patients. Cisplatin (CDDP) was used with ADM in 8 patients. Radiation and/or hyperthermia were used in 11 patients. The 5-year survival rate in these 25 patients was 58.4%, which was considered to be satisfactory. Of these 25 patients, 5 were stage-T4 cases; for these, the treatment was ineffective, and all 5 died within 2 years. Of the 6 patients at stage T2, 1 died, as did 1 patient with carcinoma in situ (CIS). Of the 13 patients with bladder cancer at stage T3, 3 died; lymph-node metastases were found in all 3 of these cases. Of the 25 patients who received inferior-gluteal-artery infusion chemotherapy, 9 died of cancer; all 9 died within 2 years due to distant metastases. There was no evidence of recurrence in any patient who survived for 2 years or more after total cystectomy. Therefore, inferior-gluteal-artery infusion chemotherapy may be effective as a preoperative adjuvant therapy with no serious side effects.


Successful transurethral drainage of bilateral seminal vesicle abscesses.
We report the successful management of bilateral seminal vesicle abscesses with transurethral unroofing and drainage of the abscess cavities. The diagnosis was confirmed by computerized tomography. Transurethral drainage became necessary after percutaneous drainage had proved to be inadequate.


Decay of hexokinase during reticulocyte maturation: is oxidative damage a signal for destruction?
Proteolysis of hexokinase in cell-free systems prepared from rabbit reticulocytes has been shown previously to be ATP-dependent and apparently mediated by the ubiquitin system (Magnani et al. J. Biol.Chem.261, 8327-8333). We have investigated this phenomenon, but found no substantial loss of hexokinase in cell-free systems prepared from fresh lysates. Storage of lysates at -20 degrees C or addition of a free radical generating system was required to demonstrate rapid ATP-dependent decay. It appears that initial oxidative damage to hexokinase does not abolish its activity but allows it to be recognized by an ATP-dependent proteolytic system. The relevance of this mechanism to in vivo degradation of hexokinase is discussed.


Photoinactivation of photosystem II by flashing light.
Inhibition of Photosystem II (PS II) activity by single turnover visible light flashes was studied in thylakoid membranes isolated form spinach. Flash illumination results in decreased oxygen evolving activity of PS II, which effect is most pronounced when the water-oxidizing complex is in the S2 and S3 states, and increases with increasing time delay between the subsequent flashes. By applying the fluorescent spin-trap DanePy, we detected the production of singlet oxygen, whose amount was increasing with increasing flash spacing. These findings were explained in the framework of a model, which assumes that recombination of the S2QB - and S3QB - states generate the triplet state of the reaction center chlorophyll and lead to the production of singlet oxygen.


Diverse sulfate-reducing bacteria of the Desulfosarcina/Desulfococcus clade are the key alkane degraders at marine seeps.
Biogeochemical and microbiological data indicate that the anaerobic oxidation of non-methane hydrocarbons by sulfate-reducing bacteria (SRB) has an important role in carbon and sulfur cycling at marine seeps. Yet, little is known about the bacterial hydrocarbon degraders active in situ. Here, we provide the link between previous biogeochemical measurements and the cultivation of degraders by direct identification of SRB responsible for butane and dodecane degradation in complex on-site microbiota. Two contrasting seep sediments from Mediterranean Amon mud volcano and Guaymas Basin (Gulf of California) were incubated with (13)C-labeled butane or dodecane under sulfate-reducing conditions and analyzed via complementary stable isotope probing (SIP) techniques. Using DNA- and rRNA-SIP, we identified four specialized clades of alkane oxidizers within Desulfobacteraceae to be distinctively active in oxidation of short- and long-chain alkanes. All clades belong to the Desulfosarcina/Desulfococcus (DSS) clade, substantiating the crucial role of these bacteria in anaerobic hydrocarbon degradation at marine seeps. The identification of key enzymes of anaerobic alkane degradation, subsequent β-oxidation and the reverse Wood-Ljungdahl pathway for complete substrate oxidation by protein-SIP further corroborated the importance of the DSS clade and indicated that biochemical pathways, analog to those discovered in the laboratory, are of great relevance for natural settings. The high diversity within identified subclades together with their capability to initiate alkane degradation and growth within days to weeks after substrate amendment suggest an overlooked potential of marine benthic microbiota to react to natural changes in seepage, as well as to massive hydrocarbon input, for example, as encountered during anthropogenic oil spills.


Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration.
To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 μm, -146 μm, and -142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.


Multidimensional separation and analysis of alpha-1-acid glycoprotein N-glycopeptides using high-field asymmetric waveform ion mobility spectrometry (FAIMS) and nano-liquid chromatography tandem mass spectrometry.
Bottom-up nLC-MS/MS-based glycoprotein mass spectrometry workflows rely on the generation of a mixture of non-glycosylated and glycosylated peptides via proteolysis of glycoproteins. Such methods are challenged by suppression of hydrophilic glycopeptide ions by more abundant, hydrophobic, and readily ionizable non-glycosylated peptides. Commercially available high-field asymmetric waveform ion mobility spectrometry (FAIMS) devices have recently been introduced and present a potential benefit for glycoproteomic workflows by enabling orthogonal separation of non-glycosylated peptides and glycopeptides following chromatographic separation, and prior to MS/MS analysis. However, knowledge is lacking regarding optimal FAIMS conditions for glycopeptide analyses. Here, we document optimal FAIMS compensation voltages for the transmission and analysis of human alpha-1-acid glycoprotein (AGP) tryptic N-glycopeptide ions. Further, we evaluate the effect of FAIMS on AGP glycopeptide assignment confidence by comparing the number of assigned glycopeptides at different confidence levels using a standard nLC-MS/MS method or an otherwise identical method employing FAIMS. Optimized methods will potentiate glycoproteomic analyses by increasing the number of unique glycopeptide identifications and the confidence of glycopeptide assignments. Data are available via ProteomeXchange with identifier PXD036667. Analysis of alpha-1-acid glycoprotein (AGP) tryptic digests via nLC-FAIMS-MS/MS (top) led to the establishment of ideal FAIMS voltages for the analysis of AGP N-glycopeptides (bottom), suggesting that FAIMS can improve the depth of glycoproteome characterization. Pairs of CV magnitudes are shown along the x-axis.


Effects of ion concentration and natural organic matter on arsenic(V) removal by nanofiltration under different transmembrane pressures.
The removal of As(V) from synthetic water was studied using four different nanofiltration (NF) membranes (ESNA-1-K1, NF270, ESNA-1-LF, and HODRA-CORE). The influences of ion concentration, transmembrane pressure (TMP), and the presence of natural organic matter (humic acid, HA) on the arsenic removal efficiency and permeate flux were investigated. The arsenic rejection of ESNA-1-LF was higher than those of the other membranes in all experiments (> 94%), and the HODRA-CORE membrane gave the lowest removal of arsenic (< 47%). An increase in the ion concentration in the feed solution and addition of HA decreased the arsenic rejection of the HODRA-CORE membrane. However, both increasing of the ion concentration and addition of HA made the rejection increased for the other membranes (ESNA-1-K1, NF270, and ESNA-1-LF). With increasing TMP, for all four NF membranes, increases in both arsenic rejection and permeate flux were observed. The permeate fluxes of the four NF membranes decreased to some extent after addition of HA to the solutions for operating time of 6 hr.


Olaryngologic manifestations in children with chronic neutropenia.
Chronic neutropenia of childhood (CNC) is a rare disorder in which the absolute neutrophil count is below 1500/μL over an extended period of time. The objective of this study is to describe the otolaryngolgic manifestations associated with CNC to facilitate diagnosis and treatment of this condition. We performed a retrospective chart review of patients with the diagnosis of CNC between 1970 and 2005 at a tertiary pediatric hematology center. After Institutional Review Board approval, 43 patients were evaluated. The average age at hematologic diagnosis was 49 months (range: 1 month - 15 years with 35% <1 year, 44% 1-10 years, 21% >10 years). A total of 2049 encounters were analyzed from the hospital charts. Twenty four subjects (56%) presented with recurrent otitis media (ROM), sinusitis or pharyngo-tonsillitis, while 11% presented with oral mucosal lesions. After diagnosis, otolaryngologic problems persisted, including ROM (81%), viral upper respiratory tract infection (67%), oral ulcers or gingivitis (53%), tonsillitis (39%) and sinusitis (37%) and were more common than other systemic infections. Myringotomy tube placement, endoscopic sinus debridement, adeno-tonsillectomy or tracheostomy were required in 42% of patients. After G-CSF (granulocyte colony-stimulating factor) became available in the early 1990s, the infection rate markedly decreased. Five deaths occurred (12% mortality) including one due to sepsis from otolaryngologic infection. The majority of children with CNC had otolaryngologic problems at presentation and these continued after diagnosis. While managing common otolaryngologic infections in children, a high index of suspicion for chronic neutropenia is necessary. An otolaryngologist is frequently one of the first physicians to encounter children with this condition. Awareness of CNC and its management will enhance earlier diagnosis and more effective treatment for these children.


The current and emerging sources of technical lignins and their applications.
Technical lignins are bulk feedstocks. They are generated as byproducts from pulping or cellulosic ethanol production. Since lignin undergoes significant structural changes in the chemical and physical treatments, all technical lignins are unique in terms of chemical structure, molecular weight, polydispersity, and impurity profile. Kraft lignin is potentially the largest source of technical lignin as new isolation technologies have been implemented on industrial scale in recent years. Lignosulfonate has been an integral product in sulfite pulping biorefinery. It has a well-established market in construction industry. Organosolv-like lignin production is increasing as cellulosic ethanol has been promoted as the substitute of fossil fuel. It may have unique applications because it has low molecule weight and is free from sulfur. Technical lignin application is expected to expand as the characteristics are improved with fractionation or chemical modification. The application of technical lignin has been focusing on developing products equivalent to those made by petroleum chemicals. The recent development in technical lignin supply should increase its market share as additives in polyurethanes and as the substitute of phenol-formaldehyde adhesives. Quality improvement of technical lignin may also encourage the study of lignin as an alternative feedstock for carbon fiber. In addition, technical lignin depolymerization has been extensively explored to provide renewable aromatic chemicals. Starting from controlled pyrolysis and thermal liquefaction as the baseline technologies, many different chemical depolymerization have been invented with a wide range of underlying chemical principles.


Treatment of hyperhidrosis.
The patient who complains of hyperhidrosis presents the physician with a diagnostic and therapeutic challenge. Patients who present with generalized hyperhidrosis are, in general, adults whose sweating occurs both during the waking and sleeping hours. Such patients require a search for a cause that may sometimes be as simple as a drug that they are taking for some medical disorder. Occasionally a systemic illness may account for the onset of hyperhidrosis and a thorough exam and appropriate testing may be necessary to identify the cause. Most patients with primary or essential hyperhidrosis present in childhood or adolescence and have a problem localized to their hands and/or feet. They have a physiologic disorder not a psychiatric or endocrinologic disease. A number of systemic, topical, surgical, and electrical remedies are available for the treatment of hyperhidrosis. Patients with hyperhidrosis of the palm or soles deserve a trial of conservative therapy, iontophoresis in particular, before aggressive surgical techniques that carry with them the risk of lifelong troublesome side effects are offered.


A long-lasting taxonomic problem in European Sympycnus resolved, with the description of a new species and data on habitat preferences.
Type specimens of Sympycnus pulicarius, S. annulipes, S. cinerellus and S. desoutteri were examined to clear up a long-lasting taxonomic confusion. Our study revealed that they represent, together with S. pygmaeus and S. annulipes var. brunnitibialis, a single species, with S. pulicarius as the senior subjective synonym, which is redescribed in this paper. Lectotypes were designated for Dolichopus pulicarius, Porphyrops annulipes, Chrysotus cinerellus and Sympycnus desoutteri. The postpedicel in this species shows substantial variation in shape and size, but the presence of a posteroventral bristle on the mid tibia is more reliable and the particular chaetotaxy and relative lengths of the tarsomeres of the male hind tarsus are entirely consistent. Both latter features separate S. pulicarius from another species, S. septentrionalis sp. nov., that is described here. Ecological data on both species were examined. An analysis of Malaise trap and white pan trap samples collected in Belgium revealed that S. pulicarius is most common in the western part of Flanders, and most abundant in open grassy habitats. In contrast to S. pulicarius, which is widespread over Europe, S. septentrionalis sp. nov. seems confined to northern Europe, where it exhibits a similar habitat preference.


Development of a novel method for the simultaneous detection of trimethylamine N-oxide and creatinine in the saliva of patients with chronic kidney disease - Its utility in saliva as an alternative to blood.
Chronic kidney disease (CKD) is associated with increased levels of creatinine and other uremic toxins (UTs), which impaired kidneys cannot filtrate. Typically, CKD is diagnosed by calculating the estimated glomerular filtration rate using serum creatinine or cystatin C levels. In pursuit of more sensitive and reliable biomarkers of kidney dysfunction, scientific attention has turned towards other UTs, such as trimethylamine N-oxide (TMAO), successfully quantified in standard matrices, blood and urine. However, less invasive monitoring of kidney function can be performed using an alternative diagnostic biofluid, saliva, which has been shown to contain clinically relevant concentrations of renal function markers. Accurate quantitative estimation of serum biomarkers using saliva measurements can only be achieved provided that there is a tight saliva-serum correlation for the analyte of interest. Therefore, we aimed to verify the correlation between saliva and serum levels of TMAO in CKD patients using newly developed and validated quantitative liquid chromatography coupled to mass spectrometry (LC-MS) method for simultaneous detection of TMAO, and creatinine - the conventional marker of renal impairment. Secondly, we applied this method to quantify TMAO and creatinine levels in the resting saliva of CKD patients collected with a standardised method involving swab-based collectors. A good linear correlation was obtained between the concentration of creatinine in serum and resting saliva of CKD patients (r = 0.72, p = 0.029) and even better in the case of TMAO (r = 0.81, p = 0.008). The analysed validation criteria were fulfilled. No significant influence of the type of swab in the Salivette® device on creatinine and TMAO concentrations in saliva was detected. Our study indicates that saliva can be successfully used in the non-invasive monitoring of renal failure in CKD by measuring salivary TMAO concentrations.


Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy.
Biological molecular markers such as proto-oncogene erbB-2 (HER-2/neu, c-erbB-2), the CXC chemokine receptor 4 (CXCR4), estrogen receptor (ER), Proliferating Cell Nuclear Antigen (PCNA), DNA topoisomerase II (topo II), P-glycoprotein (P-gp) and glutathione S-transferase (GST) were observed for changes after administration of neochemotherapy and whether these protein expression changes were correlated with response to chemotherapy. Sixty-four patients with primary breast cancer who had undergone neo-adjuvant chemotherapy were enrolled in the present study. The expressions of C-erbB-2, CXCR4 and ER-α were measured by immunohistochemistry (IHC) on full tissue sections and on tissue microarrays (TMAs). PCNA, TopoII, P-gp and GST were measured by IHC on TMAs. On the other hand, CXCR4, C-erbB-2 and ER-α expressions were detected using western blot analysis to 16 pairs of fresh preoperative core biopsies. The final surgical specimens were obtained from patients with breast carcinoma who received neo-adjuvant chemotherapy and obtained a partial response (PR). Our data demonstrated that the levels of C-erbB-2, CXCR4 and ER-α in patients decreased after they received neo-adjuvant chemotherapy on full tissue sections and on TMAs. The PCNA level was down-regulated after receiving neo-adjuvant chemotherapy, and no significant change was observed for TopoII, P-gp and GST. The levels of C-erbB-2, CXCR4 and ER-α were also down-regulated after neo-adjuvant chemotherapy was administered, as detected by western blot. In addition, the change expressions of C-erbB-2 and CXCR4 in specimens tended to be correlated with pathological change to neo-adjuvant chemotherapy on full tissue sections and on TMAs in a Pearson chi-square analysis. As demonstrated in our study, after breast cancer patients were treated with neo-adjuvant systemic therapy, decreased expressions of C-erbB2, ER-α and CXCR4 were observed. Down-regulated expressions of c-erbB-2 and CXCR4 may be a novel mechanism of chemotherapy; the changes of these objective markers may be useful in evaluating the clinical response of neo-adjuvant chemotherapy in breast cancer.


[Vascular Calcification - Pathological Mechanism and Clinical Application - . Mechanisms of vascular calcification].
Vascular calcification is an independent risk factor for the development of cardiovascular disease and is classified into two types based on the site of calcification : intimal atherosclerotic calcification and Mönckeberg's medial calcification. Matrix vesicles released from macrophages and vascular smooth muscle cells (VSMC) during apoptosis play a pivotal role in formation of fine granular calcification, while osteogenic differentiation of VSMC contributes to progression of advanced calcification. Recent noninvasive imaging studies of atherosclerotic calcification provide robust evidence that inflammation precedes active calcification, leading to establish the inflammation-dependent calcification paradigm. On the other hand, elastin degradation by increased elastolytic activities and disturbance of regulatory systems of extracellular pyrophosphate metabolism play an important role in development of Mönckeberg's medial calcification.


Effect of Kelp Waste Extracts on the Growth and Development of Pakchoi (Brassica chinensis L.).
To explore the effects of kelp waste extracts (KWE) on the growth and development of Brassia chinensis L., germination and greenhouse experiments were carried out under different concentrations of KWE. The results showed that a higher germination percentage (95%), associated with high germination index (8.70), germination energy (71.67%) and seedling vigor index (734.67), was obtained under a lower KWE concentration (2%) compared with the control. The radicle length (4.97 cm), fresh weight (0.32 g/10 seedlings) and dry weight (0.015 g/10 seedlings) were significantly increased in the treatment of 2% KWE. KWE also could enhance the root growth, the maximum leaf length × width and the fresh weight of plants, the optimal value of which increased by 8.37 cm, 58.14 cm2 and 7.76 g under the treatment of 10% KWE compared with the control respectively. Meanwhile, the contents of vitamin C and soluble sugars in pakchoi leaf were improved by 19.6 mg/100 g and 1.44 mg/g compared with the control, and the nitrate content was decreased by 212.27 mg/kg. Briefly, KWE could markedly stimulate the pakchoi seeds germination at a lower concentration (2%) and enhance the plant growth and quality at a higher concentration (10%).


The effect of n-3 fatty acids on coronary atherosclerosis: results from SCIMO, an angiographic study, background and implications.
According to the model of "response to injury," the arterial endothelium is occasionally injured in hyperlipidemia, hypertension, diabetes mellitus and in other states known as risk factors. The ensuing inflammatory response is modulated by cytokines and growth factors, among them platelet-derived growth factor (PDGF), and monocyte chemoattractant protein-1 (MCP-1). In two independent studies, we demonstrated that mRNA levels for PDGF-A and -B and for MCP-1 are reduced after ingestion of n-3 fatty acids by human volunteers. This reduction persists after monocyte stimulation/differentiation by adherence. Moreover, the reduction is brought about only by dietary n-3 fatty acids and not by other classes of unsaturated fatty acids (n-6 or n-9). This appears to be one major mechanism of action of reduced progression/increased regression of established coronary artery disease by ingestion of 1.5 g/d n-3 fatty acids, as assessed by coronary angiography in a randomized placebo-controlled double-blind intervention study in 223 patients. The study was conducted according to "Good Clinical Practice," comprehensive rules regulating investigations with pharmaceutical compounds. Together, our investigations lend support to the importance of PDGF-A, PDGF-B, and MCP-1 in the pathogenesis of atherosclerosis, and the beneficial role of n-3 fatty acids therein.


Medroxyprogesterone acetate positively modulates specific GABAA-receptor subtypes - affecting memory and cognition.
Medroxyprogesterone acetate (MPA) is a progestin widely used in humans as hormone replacement therapy and at other indications. Many progestin metabolites, as the progesterone metabolite allopregnanolone, have GABAA-receptor modulatory effects and are known to affect memory, learning, appetite, and mood. In women, 4 years chronic treatment with MPA doubles the frequency of dementia and in rats, MPA causes cognitive impairment related to the GABAergic system. Activation of the membrane bound GABAA receptor results in a chloride ion flux that can be studied by whole-cell patch-clamp electrophysiological recordings. The purpose of this study was to clarify the modulatory effects of MPA and specific MPA metabolites, with structures like known GABAA-receptor modulators, on different GABAA-receptor subtypes. An additional aim was to verify the results as steroid effects on GABA response in single cells taken from rat hypothalamus. HEK-293 cell-lines permanently expressing the recombinant human GABAA-receptor subtype α1β2γ2L or α5β3γ2L or α2β3γ2S were created. The MPA metabolites 3α5α-MPA,3β5α-MPA and 3β5β-MPA were synthesised and purified for electrophysiological patch-clamp measurements with a Dynaflow system. The effects of MPA and tetrahydrodeoxycorticosterone were also studied. None of the studied MPA metabolites affected the responses mediated by α1β2γ2L or α5β3γ2L GABAA receptors. Contrary, MPA clearly acted both as a positive modulator and as a direct activator of the α5β3γ2L and α2β3γ2S GABAA receptors. However, in concentrations up to 10 μM, MPA was inactive at the α1β2γ2L GABAA receptor. In the patch-clamp recordings from dissociated cells of the preoptic area in rats, MPA increased the amplitude of responses to GABA. In addition, MPA alone without added GABA, evoked a current response. In conclusion, MPA acts as a positive modulator of specific GABAA receptor subtypes expressed in HEK cells and at native GABA receptors in single cells from the hypothalamic preoptic area.


Genome instability mechanisms and the structure of cancer genomes.
Genomic instability is a hallmark of cancer cells, and arises from the aberrations that these cells exhibit in the normal biological mechanisms that repair and replicate the genome, or ensure its accurate segregation during cell division. Increasingly detailed descriptions of cancer genomes have begun to emerge from next-generation sequencing (NGS), providing snapshots of their nature and heterogeneity in different cancers at different stages in their evolution. Here, we attempt to extract from these sequencing studies insights into the role of genome instability mechanisms in carcinogenesis, and to identify challenges impeding further progress.


New immunodeficiency syndromes that help us understand the IFN-mediated antiviral immune response.
Studying primary immunodeficiencies (PIDs) provides insights into human antiviral immunity in the natural infectious environment. This review describes new PIDs with genetic defects that impair innate antiviral responses. New genetic defects in the interferon (IFN) signaling pathway include IFNAR1 deficiency, which causes uncontrolled infections with measles-mumps-rubella or yellow fever vaccines, and possibly also cytomegalovirus (CMV); and IRF9 deficiency, which results in influenza virus susceptibility. Genetic defects in several pattern recognition receptors include MDA5 deficiency, which impairs viral RNA sensing and confers human rhinovirus susceptibility; RNA polymerase III haploinsufficiency, which impairs sensing of A:T-rich virus DNA and confers VZV susceptibility; and TLR3 deficiency, which causes HSV-1 encephalitis (HSE) or influenza virus pneumonitis. Defects in RNA metabolism, such as that caused by Debranching enzyme 1 deficiency, can cause virus meningoencephalitis. Finally, defects in host restriction factors for virus replication, such as in CIB1 deficiency, contribute to uncontrolled β-HPV infections. Several new PIDs highlight the role of type I/III IFN signaling pathway, virus sensors, and host virus restriction factors in human antiviral immunity.


Decoding PERG: A neuro-ophthalmic retinal ganglion cell function review.
Currently, the clinical evaluation of neuro-ophthalmologic diseases are mainly focused on identifying stages where structural or functional damage occur. Recognition of retinal ganglion cell (RGC) functional patterns as well as monitoring RGC dysfunction can be performed using steady-state pattern electroretinogram (PERG). The analysis of the amplitude and latency shift aid on providing information on early damage or monitoring of the RGC, allowing for prompt clinical intervention and management modification, potentially changing the natural history of the disease. The purpose of this article is to review the latest findings in PERG, in early manifest glaucoma, non arteritic ischemic optic neuropathy, multiple sclerosis with unilateral recovered optic neuritis and its fellow eyes. The steady-state PERG responses provide new and early specific information in neuro-ophthalmic diseases affecting the inner retina. Steady state PERG presents specific amplitude and latency outcomes based on the neuro-ophthalmic disease affecting the inner retina, allowing early recognition of changes at the level of RGC and the degree of RGC dysfunction. In addition, PERG alterations may be induced in healthy subjects as well as susceptible eyes using different stress tests such as head down tilting or water drinking tests.


Indoor and outdoor poly- and perfluoroalkyl substances (PFASs) in Korea determined by passive air sampler.
Despite concerns to their increasing contribution to ecological and human exposure, the atmospheric levels of poly- and perfluoroalkyl substances (PFASs) have been determined mainly in Europe and North America. This study presents the indoor and outdoor air concentrations of volatile PFASs [fluorotelomer alcohols (FTOHs), and perfluoroalkyl sulfonamides/sulfonamidoethanols/sulfonamide ethyl acetate (FOSAs/FOSEs/FOSEA)] for the first time in Korean cities. In contrast to the good agreement observed for indoor FTOHs levels in Korea and Europea/North America, FOSAs/FOSEs levels were 10-100-fold lower in Korean indoor air, representing a cultural difference of indoor source. Korean outdoor air contained higher PFAS levels than indoor air, and additionally showed different PFAS composition profile from indoor air. Thus, indoor air would not likely be a main contributor to atmospheric PFAS contamination in Korea, in contrast to western countries. Inhalation exposure of volatile PFASs was estimated to be a minor contributor to PFOA and PFOS exposure in Korea.


Quantitative MRI analysis of menisci using biexponential T2* fitting with a variable echo time sequence.
The goal of this study was to differentiate between normal, degenerative meniscus, and meniscal tears using monoexponentially and biexponentially calculated T2*. Meniscal disease, characterized by an altered collagen fiber matrix, might be detectable in vivo using quantitative T2* mapping. A 3D Cartesian spoiled gradient echo technique was adapted to enable the use of a variable echo time approach in combination with a highly asymmetric readout. T2* was calculated monoexponentially and biexponentially using three- and five-parametric non-linear fits, respectively. From a total of 68 evaluated menisci, 48 were normal, 12 were degenerated, and eight had tears. Mean values for the short (T2*s) and long (T2*l) T2* components were as follows: in normal menisci, 0.82 ± 0.38/15.0 ± 5.4 ms, respectively; in degenerated menisci, 1.29 ± 0.53/19.97 ± 5.59 ms, respectively; and, in meniscal tears, 2.05 ± 0.73 and 26.83 ± 7.72 ms, respectively. Biexponentially fitted T2* demonstrated a greater ability to distinguish normal and degenerated menisci using receiver operating characteristic (ROC) analysis (higher area under curve as well as higher specificity and sensitivity). This study suggests that biexponential fitting, used for T2* calculation in the menisci, provides better results compared to monoexponential fitting. Observed changes in T2* result from the matrix reorganization in degenerative processes in the menisci, which affects the collagen fiber orientation, as well as content.


Selenium in human nutrition: dietary intakes and effects of supplementation.
The dietary selenium intakes of a young couple residing in Southern California were determined to be 107 and 99 micrograms/day for the husband and the wife, respectively, on the basis of a 30 day study. For other young adult Californians, the selenium intakes were estimated from 90 to 168 micrograms/day. The highest intakes were observed in individuals subsisting on diets rich in whole wheat grain cereal products and seafoods. The selenium concentrations in whole blood of the subjects under study correlated with the dietary selenium intakes directly (P less than 0.001). The administration of 150 micrograms of selenium/day in the form of commercially available supplements increases the blood selenium concentrations. After 3 weeks of supplementation, the selenium concentrations in whole blood of our subjects reached 0.21 micrograms/ml. Prolonged supplementation at higher Se dosage levels causes further increases of the blood concentrations: Two individuals who had been ingesting 350 and 600 micrograms/day for 18 months exhibited blood selenium levels of 0.35 and 0.62 micrograms/ml. The blood selenium concentration of all subjects declined slowly after cessation of supplementation. Selenium uptake from the supplements was not affected by the joint administration of zinc supplements at 15 mg zinc/day. Glutathione peroxidase blood levels did not correlate with blood Se concentrations.


Hepatitis C virus-related acute and chronic hepatitis in hemodialysis patients.
The incidence of HCV antibodies has been evaluated in 123 chronic hemodialysis (HD) patients (Group A; 55 M and 68 F) and in 37 consecutive HD patients (group B) admitted to our hospitals for acute hepatitis. In group A, HCV antibodies were present in 27% of the patients. 20 of 36 (55%) had previously received blood transfusions. 21 patients (58%) were also positive for HBV Ab. In 8 patients, ALT were significantly increased. In group B, the diagnosis of HCV-related acute hepatitis was made in 11 patients. 8 of them had previously received blood transfusions. Seroconversion occurred 2-3 months after onset of the disease.


Kiitricha minuta n. sp., a peculiar hypotrichous ciliate (Ciliophora, Spirotrichea) from the Yellow Sea.
The morphology and infraciliature of a new ciliate, Kiitricha minuta n. sp., isolated from the Yellow Sea, were investigated using live observation and protargol impregnation. Kiitricha minuta represents a third member of the rarely known order Kiitrichida. It is unique in the subclass Hypotrichia in having many rows of small uniform cirri along the right side of the body and the dorsal kineties composed of dikinetids, most of which bear two cilia. Kiitricha minuta n. sp. is ovoid and measures about 60 x 45 microm in vivo. It has a huge buccal cavity occupying about 80% of the body length, numerous body extrusomes, one macronucleus and two micronuclei, 27-27 adoral membranelles, 9-12 frontoventral cirral rows, a submarginal row of 7-9 cirri, 6 or 7 transverse cirri, and roughly 7-9 dorsal kineties. This new species differs distinctly from its only congener Kiitricha marina by its smaller size (60 microm vs. 80-150 microm), the presence of body extrusomes (vs. absent), the different macronuclear pattern (one vs. two nodules), and the lower number of frontoventral cirral rows (9-12 vs. 21-26), which terminate at the anterior two-thirds of body (vs. extend to the posterior). The new term "submarginal cirral row" is introduced to distinguish from the marginal cirral row in typical hypotrichs sensu lato. Based on our new observations and the literature, an improved diagnosis for the genus Kiitricha is provided and its phylogenetic importance is discussed.


Pregnancy in a patient with Raynaud's disease.
We report a patient who, at the time of her third pregnancy at the age of 35, had had Raynaud's disease for 18 years. Her first pregnancy (during which she took Marcumar, an anticoagulant) ended in a miscarriage at three months gestation. The second pregnancy ended in fetal death due to placental insufficiency. The third pregnancy was also complicated by placental insufficiency which became evident during the second trimester. The patient was observed carefully and allowed to continue to 37 weeks gestation when a Caesarean section was done for late fetal heart rate decelerations during early labour of spontaneous onset. The baby had a low birth weight but developed normally. The placenta showed certain abnormalities which are described.


Influence of social stress on risk-taking behavior in adolescents.
Risk-taking behavior involves making choices with uncertain positive or negative outcomes. Evidence suggests that risk-taking behavior is influenced by emotional state. One such emotional experience is social anxiety, which has been related to both risk-avoidant and risk-seeking decision making. The present study examined a community sample of 34 adolescents grouped into low (Low SA Group) and high (High SA Group) social anxiety (SA). Both groups were compared on changes in performance on a risk taking task (Balloon Analogue Risk Task) between a social threat condition (modified Trier Social Stress Test, High Stress) and a control condition (Low Stress). These conditions were administered on different days, and the order was counterbalanced across subjects. A group×condition interaction revealed that the High SA Group showed greater risk-taking behavior when exposed to the High Stress Condition compared to the Low Stress Condition, while the Low SA Group evidenced no difference between the two conditions. Interpretations for the increased risk behavior under the condition of social stress for those high in social anxiety are discussed as well as implications for understanding the complex relationship between social anxiety and risk behavior.


Mitochondrial control region sequences from a Vietnamese population sample.
Entire mitochondrial control region data were generated for 187 individuals from Vietnam. These samples have been previously typed for 16 autosomal short-tandem repeats (STRs) [1].


Comparative transcriptome analysis of resistant and susceptible Kentucky bluegrass varieties in response to powdery mildew infection.
Poa pratensis is one of the most common cold-season turfgrasses used for urban turf building, and it is also widely used in ecological environment management worldwide. Powdery mildew is a common disease of P. pratensis. To scientifically and ecologically control lawn powdery mildew, the molecular mechanism underlying the response of P. pratensis to powdery mildew infection must better understood. To explore molecular mechanism underlying the response of P. pratensis to powdery mildew infection, this study compared physiological changes and transcriptomic level differences between the highly resistant variety 'BlackJack' and the extremely susceptible variety 'EverGlade' under powdery mildew infection conditions. We analyzed DEGs using reference canonical pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the results showed that "starch and sucrose metabolism", "photosynthesis" and "fatty acid metabolism"pathways were only enriched in 'BlackJack', and the expression of DEGs such as HXK, INV, GS, SS, AGpase and β-amylase in "starch and sucrose metabolism" pathway of 'BlackJack' were closely related to powdery mildew resistance. Meanwhile, compared with 'EverGlade', powdery mildew infection promoted synthesis of sucrose, expression of photosynthesis parameters and photosynthesis-related enzymes in leaves of 'BlackJack' and decreased accumulation of monosaccharides such as glucose and fructose. This study identified the key metabolic pathways of a P. pratensis variety with high resistance to powdery mildew infection and explored the differences in physiological characteristics and key genes related to sugar metabolism pathways under powdery mildew stress. These findings provide important insights for studying underlying molecular response mechanism.


1H-NMR relaxation studies of native and thermally denatured lysozyme solutions: an isotope dilution experiment.
1H-NMR relaxation times are reported for native and thermally denatured lysozyme aqueous solutions measured as the function of the proton mole fraction in the sample. A two-exponential character of proton longitudinal relaxation function was observed for native lysozyme solutions: the fast component was attributed to the non-exchangeable protein protons, the slow one to water protons. Purely exponential decay of longitudinal magnetization was observed for the thermally denatured samples. This has been explained in terms of a fast spin exchange model. The contributions of the protein protons to the water proton relaxation rate in native and thermally denatured samples were determined, too.


Biochar-assisted phytoextraction of arsenic in soil using Pteris vittata L.
The alkaline nature of biochar provides a potential for soil arsenic (As) mobilization and, hence, enhancing efficiency of As phytoextraction by combining with As hyperaccumulator. To testify the feasibility and potential risk of the above strategy, biochar effect on As transfer in a paddy soil and accumulation in P. vittata was investigated in a pot experiment. By leaching soil (total As concentration 141.17 mg/kg) with simulated acid rain (pH 4.2), As the concentration in leaching eluate increased proportionally with increasing biochar ratio. Coincident with elevated soil As mobility, apparent enhancement in As uptake and translocation in P. vittata was determined with 1-5% biochar amendment after 40 days of plant growth. Furthermore, diffusive gradients in thin film (DGT) technique were employed to characterize any potential risk in vertical downward migration of As at 2-mm resolution. A significantly increasing profile of DGT-As ranging from on average 20 μg/L in CK to 50-100 μg/L in 1-3% biochar treatments was recorded over 0-60 mm depth, with 25-71% lower labile As in the rhizosphere than non-rhizosphere zone with few exceptions. As compared to Chinese quality standard for groundwater (Class IV 50 μg/L), biochar ratio at ≤ 1% was suggested for local water safety while actual application should take the physicochemical characteristic of tested soil into account. Our results demonstrated the biochar-assisted P. vittata phytoremediation can serve as an emerging pathway to enhance efficiency of soil As phytoextraction. The combination of DGT techniques and greenhouse assay provided a powerful tool for evaluating the gradient distribution of heavy metal in rhizosphere and accessing corresponding ecological risk at more precise scale.


Nesfatin-1 stimulates glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide secretion from STC-1 cells in vitro.
Nesfatin-1 is an 82 amino acid peptide encoded in a secreted precursor, nucleobindin 2. It is an anorexigenic and insulinotropic peptide found abundantly in the hypothalamus, pancreas and gastric oxyntic mucosa. NUCB2 mRNA expression is 10 fold higher in the gastric mucosa than in brain, suggesting gastrointestinal tract as a main source of nesfatin-1. Meal responsive insulin secretion is regulated by incretins glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP). Since both nesfatin-1 and incretins modulate insulin secretion, we hypothesized that nesfatin-1 is present in the enteroendocrine cells, and that it regulates incretin secretion. RT-PCR analysis found NUCB2 mRNA expression, and immunofluorescence microscopy determined nesfatin-1 immunoreactivity in STC-1, an enteroendocrine cell line. NUCB2/nesfatin-1 is co-localized with GLP-1 and GIP in mouse small intestinal cells. Static incubation of STC-1 cells with nesfatin-1 upregulated preproglucagon (GLP-1 precursor) mRNA (0.01, 0.1, 1 and 10 nM) and GLP-1 secretion (0.1, 1 and 10 nM). Nesfatin-1 also enhanced GIP mRNA (0.1, 1 and 10 nM) and GIP secretion (1 and 10 nM). Together, our data support the hypothesis that nesfatin-1 is present in enteroendocrine cells and that it stimulates incretin secretion. Future studies should aim for nesfatin-1 and incretin interactions in vivo.


Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo.
Sphingosine 1-phosphate (S1P, 1) regulates vascular barrier and lymphoid development, as well as lymphocyte egress from lymphoid organs, by activating high-affinity S1P1 receptors. We used reversible chemical probes (i) to gain mechanistic insights into S1P systems organization not accessible through genetic manipulations and (ii) to investigate their potential for therapeutic modulation. Vascular (but not airway) administration of the preferred R enantiomer of an in vivo-active chiral S1P1 receptor antagonist induced loss of capillary integrity in mouse skin and lung. In contrast, the antagonist did not affect the number of constitutive blood lymphocytes. Instead, alteration of lymphocyte trafficking and phenotype required supraphysiological elevation of S1P1 tone and was reversed by the antagonist. In vivo two-photon imaging of lymph nodes confirmed requirements for obligate agonism, and the data were consistent with the presence of a stromal barrier mechanism for gating lymphocyte egress. Thus, chemical modulation reveals differences in S1P-S1P1 'set points' among tissues and highlights both mechanistic advantages (lymphocyte sequestration) and risks (pulmonary edema) of therapeutic intervention.


Intracellular calcium in cystic fibrosis heterozygotes.
Increased intracellular calcium (Ca) has been reported in several cell types in cystic fibrosis (CF). Because CF is an autosomal recessive trait examination of asymptomatic obligate carriers (HZ) of the gene is a powerful way to determine the relevance of this observation to the abnormal gene product. We report here that Ca as determined by atomic absorption spectrophotometry in cultured skin fibroblasts and circulating lymphocytes is greater in HZ than in control cells. Since an intracellular Ca increase is expressed in HZ the Ca differences in CF likely reflect action of the gene product responsible for CF and not some secondary or tertiary effect of the disease.