Identification of a plastidial phenylalanine exporter that influences flux distribution through the phenylalanine biosynthetic network.
In addition to proteins, L-phenylalanine is a versatile precursor for thousands of plant metabolites. Production of phenylalanine-derived compounds is a complex multi-compartmental process using phenylalanine synthesized predominantly in plastids as precursor. The transporter(s) exporting phenylalanine from plastids, however, remains unknown. Here, a gene encoding a Petunia hybrida plastidial cationic amino-acid transporter (PhpCAT) functioning in plastidial phenylalanine export is identified based on homology to an Escherichia coli phenylalanine transporter and co-expression with phenylalanine metabolic genes. Radiolabel transport assays show that PhpCAT exports all three aromatic amino acids. PhpCAT downregulation and overexpression result in decreased and increased levels, respectively, of phenylalanine-derived volatiles, as well as phenylalanine, tyrosine and their biosynthetic intermediates. Metabolic flux analysis reveals that flux through the plastidial phenylalanine biosynthetic pathway is reduced in PhpCAT RNAi lines, suggesting that the rate of phenylalanine export from plastids contributes to regulating flux through the aromatic amino-acid network.


Timing of postpartum long acting, reversible contraception was not associated with 12-month removal rates in a large Medicaid sample.
To determine whether the timing of placement of long acting, reversible contraception (LARC) methods postpartum (immediate postpartum (IPP) or interval (within 6 months postpartum) is associated with higher removal rates by 12 months postpartum. We conducted a retrospective cohort study using linked Medicaid claims and birth certificate data (n = 313,849) from Oregon and South Carolina from January 1, 2010 to December 31, 2018. Our primary outcome was LARC (intrauterine device (IUD) or implant) removal by 12 months postpartum. We compared crude proportions and rates of removal and used a multivariable survival analysis to compare removal over 12 months between IPP and interval LARC placement controlling for sociodemographic and clinical factors and clustered at the woman level. Our sample included 313,849 births to 247,884 women; a majority did not receive any postpartum contraception (207,058 [66.0%]). Out of the 54,018 (17.2%) of births followed by an immediate postpartum or interval LARC placement, 11.8% discontinued by 12 months. In multivariable analyses, births followed by IPP LARC were 10% more likely to experience discontinuation at any point up to 12 months compared with interval LARC (HR: 1.10, 95% CI: 1.00-1.22), but this was not statistically significant. IPP LARC devices are removed at similar rates as LARC placed within 6 months postpartum. Timing of postpartum long acting reversible contraception- interval or immediately postpartum- was not associated with 12 month removal rates.


[Non-steroidal anti-inflammatory agents for chemoprevention of colorectal polyps: a meta-analysis].
To assess whether or not non-steroidal anti-inflammatory agents (NSAIDs) might prevent colorectal polyps. A systematic review of all relevant randomized controlled trials was performed. We searched all randomized controlled trials of chemoprevention of colorectal polyps. Abstracts was included. 8 trials were assessed in the final systematic analysis. We found a sufficient evidence to support that aspirin might prevent the development of colorectal adenomas in comparing with placebo group in two trails of high quality and large sample (P = 0.003). However, there is no evidence to support that sulindac and celecoxib might cure or prevent colorectal adenomas or familial adenomatous polyposis (P > 0.05) and also no evidence to support that dosage of NSAIDs is related with the result of prevention of colorectal adenomas. It was shown that regular aspirin use for 30-60 months cannot reduce the risk of colorectal cancer (P = 0.8). No significant difference in the number of adverse events was found between patients taking NSAIDs and those given placebo (P = 0.9). Aspirin might prevent the development of colorectal adenomas, but there is no evidence to support that sulindac and celecoxib might cure or prevent colorectal adenomas or familial adenomatous polyposis and that regular aspirin use might reduce the risk of colorectal cancer.


The lowly chalazion.
Chalazia are localized cysts of chronic lipogranulomatous inflammation arising from the obstruction of sebaceous glands of the eyelid tarsal plate, including the Meibomian gland (deep chalazion) or Zeis gland (superficial chalazion). This disease entity is differentiated from the hordeolum (stye), an acute purulent localized swelling of the eyelid often associated with an eyelash follicle, Zeis gland, or Moll gland obstruction and infection. Ambiguously, the chalazion, hordeolum, and blepharitis are commonly categorized and described on a continuum in the literature. While it is one of the most common eyelid disorders across all age demographics, the chalazion remains largely understudied and pathophysiological, epidemiological, and therapeutic findings exist fragmented in the literature. We discuss current understandings of the chalazion and provide current best practice guidelines supported by clinical anecdotal evidence.


Investigation of Human Papillomavirus (HPV) and Epstein-Barr Virus (EBV) in antrochoanal polyps.
This study aimed to investigate the presence of HPV (HPV types 11 and 16) and EBV in antrochoanal polyps and to contribute to the current literature in this regard. A case-control study. A total of 100 patients (including 43 patients undergoing surgery for antrochoanal polyp, 27 patients undergoing surgery for nasal polyp, and 30 patients undergoing surgery for hypertrophic inferior turbinate) were included in this study. DNA was isolated from formalin-fixed, paraffin-embedded samples with the aid of the Bioneer's AccuPrep Genomic DNA Extraction Kit. In the obtained genomic DNAs, while the detection of HPV DNA was performed using the nested-PCR method, the detection of HPV types 11/16 and EBV DNA was performed using the RT-PCR method. The mean age of the patients with antrochoanal polyp was 26.7 ± 15.4 years (range 7-70). There were 20 (46.5%) women and 23 (53.5%) men in the antrochoanal polyp group. HPV DNA was positively detected using the nested-PCR method in 14 (32.6%) of the patients with antrochoanal polyp and in 3 (11.1%) of the patients with nasal polyp. HPV DNA was not detected in the hypertrophic inferior turbinate group (control group). There was a statistically significant difference between all groups in terms of HPV DNA positivity. In the antrochoanal polyp group, 2 patients had HPV 11 positivity and 12 patients had HPV 16 positivity. In the nasal polyp group, 1 patient had HPV 11 positivity and 2 patients had HPV 16 positivity. EBV DNA was positively detected in 16 (37.2%) of the patients with antrochoanal polyp, in 11 (40.7%) of the patients with nasal polyp and in 8 (26.7%) of the patients with hypertrophic inferior turbinate, respectively. There was no statistically significant difference between the groups in terms of EBV DNA positivity. This study demonstrates that there is a need for further studies investigating the presence of viruses in antrochoanal polyps.


First year evaluation of a private MRI facility.
To review the first years experience of the only private MRI facility in Australia. Utilisation Review. 1497 scans have been comprehensively analysed, with regard to the efficacy of the procedure in examining the brain, spinal cord, the lumbar region and the knee joint.


Self-initiating and applying episodic foresight in middle childhood.
This study provides an important extension to the growing literature on prospection in children by providing the first test of whether one's ability to engage in the functional (as opposed to the purely phenomenological) aspect of episodic foresight improves across middle childhood. Of the various forms of prospection, episodic foresight has been proposed to be one of the most flexible and functionally powerful, defined as the ability to not only imagine future events (simulative aspect) but also use those imaginings to guide behavior in the present (functional aspect). The current study tested 80 typically developing children aged 8 to 12 years using an extensive cognitive battery comprising Virtual Week Foresight, the Autobiographical Interview, and a series of crystallized and fluid intelligence measures. Whereas data indicated age-related improvements in detecting future-oriented problems and taking steps in the present in service of solving these, all children in this age bracket demonstrated a similar capacity for problem resolution (i.e., the ability to subsequently solve successfully identified problems). Results also revealed the importance of broader crystallized and fluid intelligence, but not episodic memory or episodic future thinking, in engaging in this capacity. Research is now required to understand the real-life consequences of episodic foresight during this developmental period as well as the ways in which parents and teachers can help to foster this capacity and consequently help to support children's growing desire for independence during this time.


Alcohol consumption in The Netherlands in the last decade: sharp decreases in binge drinking, especially among youngsters.
The aim of this study was to examine the development of alcohol consumption and 'binge drinking' in The Netherlands over the period 1997-2005. Data from three national population surveys commissioned by the Dutch Ministry of Health were compared. Decreases in binge drinking have appeared, especially for youngsters, which are not explained by changes in the composition of the population according to religious orientation, and for which no other explanation can be given at present. Trends in binge drinking in The Netherlands can vary over relatively short spaces of time.


Intravenous opioids for chemotherapy-induced severe mucositis pain in children: Systematic review and single-center case series of management with patient- or nurse-controlled analgesia (PCA/NCA).
Chemotherapy-induced oral mucositis can result in severe pain. Intravenous (IV) opioids are recommended, but management protocols vary. We systematically reviewed studies reporting IV opioid use for pain related to chemotherapy-induced severe oral mucositis in children and conducted a large single-center case series. Ovid MEDLINE, PubMed, and Cochrane databases were searched for studies reporting IV opioid duration and/or dose requirements for severe mucositis. Secondly, our pain service database was interrogated to describe episodes of opioid administration by patient- or nurse-controlled analgesia (PCA/NCA) for children with mucositis and cancer treatment-related pain. Seventeen studies (six randomized trials, two prospective observational, three retrospective cohort, six retrospective case series) included IV opioid in 618 patients (age 0.3-22.3 years), but reported parameters varied. Mucositis severity and chemotherapy indication influenced IV opioid requirements, with duration ranging from 3 to 68 days and variable dose trajectories (hourly morphine or equivalent 0-97 mcg/kg/h). Our 7-year series included PCA/NCA for 364 episodes of severe mucositis (302 patients; age 0.12-17.2 years). Duration ranged from 1 to 107 days and dose requirements in the first 3 days from 1 to 110 mcg/kg/h morphine. Longer PCA/NCA duration was associated with: higher initial morphine requirements (ρ = 0.46 [95% CI 0.35, 0.57]); subsequent increased pain and need for ketamine co-analgesia (118/364 episodes with opioid/ketamine 13.9 [9.8-22.2] days vs opioid alone 6.0 [3.9-10.8] days; median [IQR]); but not with age or sex. Management of severe mucositis pain can require prolonged IV opioid therapy. Individual and treatment-related variability in analgesic requirements highlight the need for regular review, titration, and management by specialist services.


Systematic review: the efficacy of nutritional interventions to counteract acute gastrointestinal toxicity during therapeutic pelvic radiotherapy.
Radiotherapy-induced damage to noncancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option for the prevention and management of symptoms. To synthesise the evidence for the use of elemental formula low- or modified-fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the gastrointestinal tract during pelvic radiotherapy. Four electronic databases were searched. Randomised controlled trials (RCT), controlled trials (CT) and case series in adult patients receiving radiotherapy for pelvic cancers employing nutritional interventions to reduce gastrointestinal toxicity were included. Methodological quality was assessed using a bespoke tool. Twenty-two original studies (2446 patients) were identified. Study quality was highly variable with only 37% scoring ≥10 points (maximum 17: bespoke scale). Few studies assessed compliance with the intervention. End-points varied and included symptom scales (IBDQ, CTC, Bristol Stool and RTOG). Evidence from RCTs was weak for elemental, low- or modified-fat, fibre and low-lactose interventions with 1/4, 3/4, 1/2, 0/1 trials respectively reporting favourable outcomes. Evidence for probiotics as prophylactic interventions was more promising (4/5 favourable), but dose, strains and methodologies varied. There is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula may be appropriate in severe toxicity. Probiotics offer promise, but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients. The methodological quality of nutritional intervention studies needs to be improved.


Accuracy of preoperative cross-sectional imaging in cervical cancer patients undergoing primary radical surgery.
We aim to describe the false negative (FN) and false positive (FP) rates of preoperative cross-sectional imaging (PCI) prior to radical surgery for cervical cancer. A retrospective cohort study of patients who underwent radical hysterectomy for early-stage cervical cancer from January 2010 until December 2017 at a single tertiary care center was performed. Patients were included if they underwent preoperative PCI and radical surgery. Patient demographics and clinicopathologic information were recorded from medical record review. Descriptive statistics were used. Overall, 106 patients met inclusion criteria. Eighty-four percent (89/106) of patients had no suspicion for metastatic disease on PCI, while 16% (17/106) had suspicion for metastatic disease. Of the 89 without suspicion for metastatic disease on PCI, 16% (14/89) had a false negative study with metastatic disease identified on final surgical pathology. False negative rates by modality were 16% (11/70) for PET/CT and 6% (2/33) for diagnostic CT. Of the 17 cases with suspicion for metastatic disease on imaging, 53% (9/17) were false positive studies with no metastatic disease identified histologically. False positive rates by modality were 7% (5/70) for PET/CT and 12% (4/33) for diagnostic CT. PCI is a tool to help identify patients who are optimal candidates for radical surgery. In this sample, the false negative rate was 16%, and false positive rate was 53% for PCI among women who underwent primary radical surgery. Further study is needed to explore preoperative testing that may more accurately identify optimal surgical candidates.


Heterodyne detected nonlinear optical imaging in a lock-in free manner.
We report a compact, cost-effective tuned amplifier for frequency-selective amplification of the modulated signal in heterodyne detected nonlinear optical microscopy. Our method improved the signal to noise ratio by an order of magnitude compared to conventional lock-in detection, as demonstrated through stimulated Raman scattering imaging of live cells and tissues at the speed of 2 μsec/pixel. Application of the tuned amplifier to transient absorption microscopy is also demonstrated. The increased signal to noise ratio allowed epi-detected in vivo imaging of myelin and blood in rat spinal cord with high spatial resolution.


Quercetin and polycystic ovary syndrome; inflammation, hormonal parameters and pregnancy outcome: A randomized clinical trial.
Women with PCOS have a reduced total antioxidant level in addition to higher oxidative stress. Quercetin is a flavonol-type antioxidant that may be found in many foods. Does quercetin affect inflammatory and hormonal factors and clinical outcomes in PCOS patients? Seventy-two women with PCOS were randomly allocated to one of two intervention groups, and each received a daily dosage of 500 mg of Quercetin for the intervention group or a placebo for the control group for a period of 40 days from the start of the menstrual cycle until the day of ovulation. Serum levels of IL-6, TNF-alpha, LH, FSH, and AMH were measured using ELISA. In addition, oocyte and embryo grade before IVF and pregnancy rate have been examined. LH levels reduce significantly in the quercetin group (4.351.62 at baseline to 3.061.43 after 3 months) (p = .029). The results indicated that Quercetin significantly decreased TNF alpha levels in comparison to the pretest (p = .008). Following capsule administration, IL-6 levels significantly decreased in the quercetin group (p = .001). Except for Δ LH, ΔIL6, and ΔFSH, there was no significant difference in any of the hormones and inflammations parameter changes. Quercetin consumption causes improvement in oocyte and embryo grade and the pregnancy rate in PCOS patients. As a result, regular consumption of Quercetin has been shown to decrease inflammatory and LH parameters, making it beneficial for the management of PCOS and related diseases.


Tetrathiafulvalene-annulated [28]hexaphyrin(184.108.40.206.1.1): a multi-electron donor system subject to conformational control.
Tetrathiafulvalenes (TTF)-annulated [28]hexaphyrin affords an electron rich flexible π-conjugated system whose limiting conformations can be controlled through choice of solvents. The conformation-dependent intramolecular charge transfer character, as well as electron reserve capability of the hexakis-TTF annulated hexaphyrin, was analyzed.


The effect of substance P and related peptides on the guinea-pig lung strip.
Substance P is present in sensory nerves in the lung and we report here its actions on the lung strip. Substance P was shown to produce rapid, small contractions of trhe lung strip at doses from 10(-9) to 10(-5) M, and there was no apparent dose-response relationship. In the presence of a mixture of three inhibitors of substance P breakdown: bacitracin, 1,4-dithio-L- threitol and ethylenediaminetetra-acetic acid all at 10(-4) M, the responses to substance P were greatly increased and dose-response curves could be established. The concentrations producing half maximal effect in the presence of these inhibitors were 6 X 10(-6) M +/- 4 X 10(-6) M. The inhibitors of substance P breakdown were found to have no effect on the histamine dose-response curve: any small shifts obtained were not significant. Chlorpheniramine 10(-6) M and 10(-5) M shifted the histamine dose-response curve to the right producing dose ratios of 100 and 900 respectively. At these doses chlorpheniramine had no effect on the dose-response curve to substance P. A dose of substance P not itself producing a response (5 X 10(-8) M) caused an increase in the size of the responses to histamine. The histamine dose-response curve was shifted to the left in the presence of substance P producing an average dose ratio of 1.4 +/- 0.2. In the presence of the peptidase inhibitors, dose-response curves have also been produced for physalaemin (10(-7) - 10(-5) M) and eledoisin (10(-7) - 10(-5) M).


The use of monoclonal antibodies in fine needle aspiration biopsy of the renal transplant.
This report deals with the clinical application of monoclonal antibody techniques to fine needle aspiration biopsy (FNAB) of the renal transplant. The technique was deemed to be quite helpful in corroborating cell type analysis made by classical cytochemistry (Giemsa staining), and determination of the nature of the lymphoid subset at play in rejection. The role of activation marker analysis and class 2 alloantigen analysis in particular for rejection was also discussed.


Quadrupolar transients, cosine correlation functions, and two-dimensional exchange spectra of non-selectively excited spin-3/2 nuclei: A (7)Li NMR study of the superionic conductor lithium indium phosphate.
Cos-cos stimulated echoes of non-selectively excited spin-3/2 nuclei were not exploited in studies of slow motional processes in solids and solid-like samples, so far. Based on a theoretical analysis of the quadrupolar transients which hitherto obviously precluded the application of such echoes, their utility is demonstrated for the example of (7)Li NMR on the polycrystalline fast ion conductor lithium indium phosphate. Quadrupolar transients can adversely affect the shape of two- and three-pulse echo spectra and strategies are successfully tested that mitigate their impact. Furthermore, by means of suitably adapted cos-cos echo sequences an effective suppression of central-line contributions to the NMR spectra is achieved. By combining cos-cos and sin-sin datasets static two-dimensional exchange spectra were recorded that display quadrupolarly modulated off-diagonal intensity indicative of ionic motion.


A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems.
Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 μg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.


Pectus carinatum: results of surgical therapy.
There are a variety of protrusion defects of the anterior chest which are collectively referred to as pectus carinatum. Over a 14-yr period, 13 patients have had surgical correction of pectus carinatum at The Johns Hopkins Hospital. Technique includes costal cartilage resection and a sternal osteotomy. There was no mortality, complications were few and results are good. Repair is recommended for patients in late adolescence due to the cosmetic nature of the procedure, the apparent lack of an associated postural deformity and the good results of operation in this age group.


Effect of pathological perinatal conditions on the maternofetal transfer of mononuclear cells.
It is known that mononuclear cells can cross the placenta in both directions: from mother to fetus and the other way. In addition, it has been shown that perinatal pathological conditions can affect the fetomaternal cell transfer. This study has focused on the question whether perinatal conditions will also support the transfer of maternal cells in the fetus. Minisatellite polymerase chain reaction (PCR) with a sensitivity of 1:100 was used to examine blood samples of 36 mother-child pairs for transplacental mononuclear cell transfer (group 1). Furthermore, 28 blood samples of mother-child pairs were examined by allele-specific PCR (sensitivity 1:1,000) for maternofetal mononuclear cell transfer; only 9 of these mother-child pairs were informative (group 2). Three cases of maternofetal and 2 additional cases of fetomaternal mononuclear cell transfer could be documented in group 1; 2 of the 9 informative samples in group 2 showed a maternofetal mononuclear cell transfer. In conclusion, 9 of 40 cases lacking maternofetal cell transfer and 4 of 5 cases with maternofetal cell transfer were high-risk deliveries (p < 0.01). The current study shows that certain ante-partum conditions like placental insufficiency or chorioamnionitis increase significantly the chance that maternal cells enter the fetus.


Sodium potassium hydrogen citrate, NaKHC6H5O7.
The crystal structure of sodium potassium hydrogen citrate has been solved and refined using laboratory X-ray powder diffraction data, and optimized using density functional theory techniques. The Na(+) cation is six-coordinate, with a bond-valence sum of 1.17. The K(+) cation is also six-coordinate, with a bond-valence sum of 1.08. The distorted [NaO6] octahedra share edges, forming chains along the a axis. The likewise distorted [KO6] octahedra share edges with the [NaO6] octahedra on either side of the chain, and share corners with other [KO6] octahedra, resulting in triple chains along the a axis. The most prominent feature of the structure is the chain along [111] of very short, very strong hydrogen bonds; the O⋯O distances are 2.414 and 2.400 Å. The Mulliken overlap populations in these hydrogen bonds are 0.138 and 0.142 e, which correspond to hydrogen-bond energies of 20.3 and 20.6 kcal mol(-1).


Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes.
Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a highly sensitive assay capable of detecting early-stage tumors. We report accurate classification of patients across all stages of renal cell carcinoma (RCC) in plasma (area under the receiver operating characteristic (AUROC) curve of 0.99) and demonstrate the validity of this assay to identify patients with RCC using urine cell-free DNA (cfDNA; AUROC of 0.86).


Common pulmonary vein atresia without anomalous pulmonary venous connection.
Common pulmonary vein atresia without pulmonary venous connection is a rare form of congenital heart disease. No communication exists between the confluence of the pulmonary veins and the heart or a major systemic vessel. A case diagnosed antemortem is presented. Correct early diagnosis is imperative as surgery may be corrective.


Comparison of dermatophyte PCR kit with conventional methods for detection of dermatophytes in skin specimens.
The laboratory diagnosis of dermatophytosis is usually based on direct microscopic examination and culturing of clinical specimens. A commercial polymerase chain reaction kit (Dermatophyte PCR) has had favorable results when used for detection of dermatophytes and identification of Trichophyton rubrum in nail specimens. This study investigated the efficacy of the Dermatophyte PCR kit for detecting dermatophytosis in 191 hair or skin specimens from patients with suspected dermatophytosis. PCR was positive for 37 % of samples, whereas 31 and 39 % of the specimens were positive by culturing and direct microscopy, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for PCR analysis were 83, 84, 71, and 91 %, respectively. The sensitivity of the PCR test was higher in specimens obtained from skin (88 %) than in those obtained from hair (58 %), while the specificity remained almost the same (84 and 86 % for skin and hair, respectively). Our results show that the Dermatophyte PCR kit is a promising diagnostic tool for detection of dermatophytosis in skin samples, providing clinicians with a rapid diagnosis.


Use of electrophoretic techniques and specific antibodies to analyse tubulin isotypes in rabbit testis and spermatozoa.
Multiple tubulin isotypes have been described in vertebrate cells and they are known to be tissue specific (Cleveland and Sullivan, 1985; Cowan and Dudley, 1983). In this study, tubulin heterogeneity has been analysed in rabbit testis and spermatozoa by isoelectric focusing, two dimensional electrophoresis and immunoblotting performed using antibodies with different specificities. These biochemical techniques evidenced a small number of tubulin isotypes expressed by immature testis and fully maturated testis and spermatozoa of rabbit, and showed that the alpha isotypes are less acidic than the beta ones and present the post-translational detyrosinated form.


Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.
In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302. Prostate-specific antigen (PSA) response was assessed. Median time to PSA progression was estimated using the Kaplan-Meier method. The PSA response rate (≥50% PSA decline, unconfirmed) was 44% and 67%, respectively. The median time to PSA progression was 3.9 mo (range 2.6-not estimable) for subsequent abiraterone acetate plus prednisone and 2.8 mo (range 1.8-not estimable) for subsequent enzalutamide. The majority of patients (68%) received intervening chemotherapy before subsequent abiraterone acetate plus prednisone or enzalutamide. While acknowledging the limitations of post hoc analyses and high censoring (>75%) in both treatment groups, these results suggest that subsequent therapy with abiraterone acetate plus prednisone or enzalutamide for patients who progressed on abiraterone acetate is associated with limited clinical benefit. This analysis showed limited clinical benefit for subsequent abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castration-resistant prostate cancer following initial treatment with abiraterone acetate plus prednisone. This analysis does not support prioritization of subsequent abiraterone acetate plus prednisone or enzalutamide following initial therapy with abiraterone acetate plus prednisone.


Knowledge of adolescents regarding sexually transmitted infections and pregnancy.
To investigate the knowledge of adolescents related to sexually transmitted infections (STIs), AIDS, and pregnancy, and understand the role of school in sex education. A qualitative descriptive study, developed through a semi-structured interview and a form for participant characterization, with 22 high school students from a public school aged 16 to 19 years. Data were submitted to content analysis. After analysis, four thematic categories were developed: sexuality and sex education; understanding of risk behaviors; knowledge of STI/AIDS; and knowledge of and practices for prevention. This study showed the need for preventive educational actions for adolescents, because the lack of information contributes to their vulnerability. The adolescents recognize the importance of sex education; therefore it is important to implement strategies to promote and protect health in the school environment to encourage and strengthen self-care in health. investigar o conhecimento de adolescentes relacionado às Infecções Sexualmente Transmissíveis (IST), AIDS e gravidez, além de conhecer a compreensão sobre o papel da escola na educação sexual. estudo qualitativo, descritivo, desenvolvido por meio de entrevista semiestruturada e formulário para caracterização dos participantes, com 22 adolescentes entre 16 e 19 anos de idade, estudantes do Ensino Médio em uma escola pública. Os dados foram submetidos à análise de conteúdo. da análise emergiram quatro categorias temáticas: Sexualidade e educação sexual; Compreensão de comportamentos de risco; Conhecimento de IST/AIDS; Conhecimento e práticas de prevenção. revelou-se a necessidade de ações educativas de prevenção para os adolescentes, pois a falta de informações contribui para a sua vulnerabilidade. Os adolescentes reconhecem a importância da educação sexual; consequentemente, é importante a implementação de estratégias de promoção e de proteção à saúde no ambiente escolar para contribuir e fortalecer o autocuidado na saúde.


Phase behaviour of transkarbam 12.
Transkarbam 12 (T12), the carbamic acid salt of omega-aminocaproic acid dodecyl ester, is a recently synthesized substance, whose high permeation enhancing activity through the human skin was found for certain drugs. In this work, the thermotropic phase behaviour of T12 has been studied by means of various techniques, namely, DSC, FTIR and FT-Raman spectroscopy, X-ray powder diffraction, and DRS. The temperature development of the X-ray reflections as well as of the conformationally sensitive Raman bands and the IR bands have been observed. At room temperature, the hydrocarbon chains of T12 exhibit a highly ordered structure, arranged in an orthorhombic perpendicular subcell. On heating, two transitions occur at 54 and at 66 degrees C. The first transition is related to the disruption of the carbamate structure and changes in the polar head group. The other transition represents the melting of hydrocarbon chains and the subsequent release of carbon dioxide. The time required for the rebinding of carbon dioxide and the reformation of the carbamate structure is dependent upon numerous factors and it was not possible to precisely determine the length of this process.


Isoniazid-induced polyneuropathy in a tuberculosis patient - implication for individual risk stratification with genotyping?
Development of polyneuropathy (PNP) under treatment for tuberculosis (TB), including isoniazid (INH), is a highly relevant adverse drug effect. The NAT2 acetylation status is a predictor of potential toxic effects of INH. The question as to whether individual risk stratification by genotyping is useful to avoid suffering of patients and to lower costs for the health care system is of considerable clinical importance. After drug treatment for TB, including INH, a 23-year-old man developed severe PNP. During the treatment, laboratory results have been indicating incipient liver and renal injury. Later, molecular genetic analyses were performed and revealed a variation in the NAT2 gene and the c1/c2 genotype of the CYP2E1 gene, both described to contribute to an elevated risk for anti-tuberculostatic-induced liver damages (ATIL). The combination of metabolizer genotypes should be taken into account as a cause for toxic effects and the development of PNP. Individual genotyping, performed before medication or at least if an elevation of liver parameters is observed, may reduce the risk of severe cases of PNP by early adjustment of treatment. Our case study indicates that evaluation of individual risk stratification with systematic pharmacogenetic genotyping of metabolizer gene combinations in the context of TB treatment should be addressed in clinical studies with larger cohorts.


Effect of Morphologically Transformed Acellular Dermal Matrix on Chronic Diabetic Wounds: An Experimental Study in a Calvarial Bone Exposure Diabetic Rat Model.
The use of acellular dermal matrix on chronic diabetic wounds in clinical practice is hindered by its high cost and difficulty in application. We aimed to acquire experimental evidence on the effect of morphologically transformed acellular dermal matrix on chronic diabetic wounds and investigate how this transformation affects the wound healing mechanism. We developed a new chronic wound model that resembles a diabetic chronic wound as it involves an open wound with partial calvarial bone exposure in diabetic rats. According to treatment materials, rats were assigned into the CONTROL, ADM, and PASTE groups. The wound healing period was subdivided into T1 and T2 (postoperative days 14 and 30, respectively). Three-staged analyses were performed using 3D camera, histological analysis, and real-time quantitative polymerase chain reaction. The morphologically transformed acellular dermal matrix showed a compatible treatment rate in the total wound and more rapidly reduced the initial bone exposure area. In the PASTE group, collagen scaffold appeared at a later period and expression levels of epidermal growth factor and epidermal growth factor receptor increased. The transformation of acellular dermal matrix into the pulverized form is thought to contribute to its non-inferior therapeutic effect compared with normal acellular dermal matrix. With respect to the mechanism, the pulverized form reduced the bone exposure area in the early stage and provided a collagen scaffold at a later period. An increase in epithelial growth factors through mechanochemical transformations along with increased contact area contribute to the enhanced healing capacity of the morphologically transformed acellular dermal matrix.


Heat-induced antigen retrieval utilizing modified Tris-EDTA buffer for reprobing of Western blots on nitrocellulose paper.
The development of heat-induced antigen retrieval technologies with Tris-EDTA buffer has dramatically improved immunostaining of specific antigens for routine immunohistochemical detection (Krenacs et al., 2010) [1]. However, little evidence exists on whether heat-Induced antigen retrieval utilizing Tris-EDTA buffer can strip western blot (WB) membranes and allow sequential reprobing. Here, we serendipitously discover that ∼95 °C Tris-EDTA buffer with 0.01% Tween 20 could repeatedly strip the Nitrocellulose membranes (NC). After electroblotting, NC blots were soaked into Tris-EDTA stripping buffer (∼95 °C, 10-25min) and we could perform at least five rounds (the following antibodies used: Vinculin, Atg7, Caspase-3, UBA5, JNK and ERK1/2) stripping in sequential chemiluminescent detections. The NC membranes also show clear western signals and background without losing transferred proteins during the reprobing process of WB. Hence, this study report additional new roles of the heat-Induced antigen retrieval Tris-EDTA buffer with 0.01% Tween 20. The method is simpler, more affordable and harmless for the nitrocellulose paper, which will be helpful for effective reprobing in western blotting applications.


Imaging Phenotypes of Breast Cancer Heterogeneity in Preoperative Breast Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Scans Predict 10-Year Recurrence.
Identifying imaging phenotypes and understanding their relationship with prognostic markers and patient outcomes can allow for a noninvasive assessment of cancer. The purpose of this study was to identify and validate intrinsic imaging phenotypes of breast cancer heterogeneity in preoperative breast dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scans and evaluate their prognostic performance in predicting 10 years recurrence. Pretreatment DCE-MRI scans of 95 women with primary invasive breast cancer with at least 10 years of follow-up from a clinical trial at our institution (2002-2006) were retrospectively analyzed. For each woman, a signal enhancement ratio (SER) map was generated for the entire segmented primary lesion volume from which 60 radiomic features of texture and morphology were extracted. Intrinsic phenotypes of tumor heterogeneity were identified via unsupervised hierarchical clustering of the extracted features. An independent sample of 163 women diagnosed with primary invasive breast cancer (2002-2006), publicly available via The Cancer Imaging Archive, was used to validate phenotype reproducibility. Three significant phenotypes of low, medium, and high heterogeneity were identified in the discovery cohort and reproduced in the validation cohort (P < 0.01). Kaplan-Meier curves showed statistically significant differences (P < 0.05) in recurrence-free survival (RFS) across phenotypes. Radiomic phenotypes demonstrated added prognostic value (c = 0.73) predicting RFS. Intrinsic imaging phenotypes of breast cancer tumor heterogeneity at primary diagnosis can predict 10-year recurrence. The independent and additional prognostic value of imaging heterogeneity phenotypes suggests that radiomic phenotypes can provide a noninvasive characterization of tumor heterogeneity to augment personalized prognosis and treatment.


The TO strains of Theiler's viruses cause "slow virus-like" infections in mice.
Intracerebral inoculation of mice with tissue culture-adapted TO strains of Theiler's mouse encephalomyelitis viruses results in a clinical disease consisting of spastic paralysis due to demyelination after a lengthy incubation period. Thus, in effect, these ordinary picornaviruses are capable of causing a slow infection in their natural host, the mouse. In addition, through the use of tissue culture-adapted virus stocks, virus content in mouse tissues now can be accurately quantified by standard plaque assay.


Perceptions of patients' and healthcare workers' experiences in cohort isolation units: a qualitative study.
Given the scarce therapeutic options for carbapenemase-producing Enterobacterales (CPE), aggressive interventions are implemented to limit its spread among hospitalized patients. One such option is contact isolation by cohorting patients in designated units. To describe the experiences in a cohort isolation unit (CIU) due to CPE from the perspectives of patients admitted to this unit and their families, and those of healthcare workers (HCWs) who served in the same unit. Qualitative study. Face-to-face, semi-structured interviews were conducted in a large tertiary hospital. Twenty-four participants were interviewed, including 15 HCWs, three patients and six family members. Data were coded using thematic analysis. The CIU provoked negative feelings such as fear, risk, loneliness, distrust and unfairness. They also created a sense of conflict with the curative assumptions of hospital care. The poor CIU infrastructure was echoed in perceptions of crowdedness in the site. Moreover, family members described HCWs' inconsistent protective behaviours that led them to a state of vigilance. The hospital infection control unit imparted and refreshed HCWs' knowledge and expected behaviours regarding the CIU. However, patients and families expressed dissatisfaction with the information, guidance and education regarding the 'why and how' of the CIU. They were not guided consistently about recommended behaviours after discharge. In retrospect, HCWs found that the CIU took a psychological, physical and professional toll. The CIU was planned as a temporary containment mechanism. It needs to develop into a permanent system, capable of addressing the various needs of all involved.


Pain relief practices of parents before presenting to pediatric emergency services.
Pain, which is a condition that is experienced very frequently by children and leads to negative consequences, is one of the most prevalent reasons for presentation to emergency services. This study was conducted to determine the pain relief practices implemented by parents for their children before presenting to pediatric emergency services. This descriptive study included the parents of 425 children who were brought to the pediatric emergency service of a state hospital in Turkey. The data were collected using a form that was developed by the researchers, and the collected data were analyzed using frequency, percentage, mean, standard deviation, and chi-squared tests. The mean age of the children brought to the emergency service was 8.16±4.03, while 50.8% were female. It was determined that 60.7% of the children presented to the emergency service with abdominal pain, 69.9% were subjected to a pain relief intervention before presenting to the emergency service, 81% were given drugs as an intervention, and alternative methods were used by the parents of 64.4%. Statistically significant relationships were found between the working statuses of mothers and fathers and their implementation of any intervention to pain and between the type of pain and the status of the parents giving drugs to their children (p < 0.05). The rates of parents who gave drugs to their children to relieve pain or applied non-pharmaceutical alternative methods were high. For the effective control and management of pain at pediatric emergency services, it may be recommended to inform parents about this issue and include them in the process.


Preparation of 32P-labeled inositides and their degradation by soluble kidney enzymes.
A method is described for the preparation of radioactive inositol lipids for studies of their enzymic degradation. Kidney cytosol fractions have been used to produce diesteratic cleavage. High voltage electrophoresis at pH 4.3 is used to separate D-myoinositol 1 : 2-cyclic phosphate and D-myoinositol 1-phosphate from hydrolysis of phosphatidylinositol. Radioactivity co-migrating with myoinositol diphosphate and triphosphate is separated by electrophoresis at pH 1.5 following enzymatic hydrolysis of phosphatidylinositol phosphate and phosphatidylinositol diphosphate. Relative activities for hydrolysis of the various inositides suggest the presence of more than one phosphodiesterase.


[André Bullinger's contributions to the management of prematurity in neonatology].
Between 30 and 50 % of very premature babies have disorders that can affect their schooling, training and future life. Their origin is often multifactorial, and environmental, socioeconomic and family factors can influence the subsequent development of these children. Among these factors, the neonatal environment, which is generally very noisy and bright, as well as the numerous tactile solicitations, have been blamed. In 1978, the kangaroo method transformed this reality by improving the parent-baby relationship and reducing neonatal mortality. Since then, a trend has developed around developmental care with the Neonatal Individualized Developmental Care Assessment Program and the approach of André Bullinger.


Octanoic Acid-An Insecticidal Metabolite of Conidiobolus coronatus (Entomopthorales) That Affects Two Majors Antifungal Protection Systems in Galleria mellonella (Lepidoptera): Cuticular Lipids and Hemocytes.
The food flavour additive octanoic acid (C8:0) is also a metabolite of the entomopathogenic fungus Conidiobolus coronatus, which efficiently infects and rapidly kills Galleria mellonella. GC-MS analysis confirmed the presence of C8:0 in insecticidal fraction FR3 extracted from C. coronatus filtrate. Topical administration of C8:0 had a dose-dependent effect on survival rates of larvae but not on pupation or adult eclosion times of the survivors. Topically applied C8:0 was more toxic to adults than larvae (LD100 for adults 18.33 ± 2.49 vs. 33.56 ± 2.57 µg/mg of body mass for larvae). The administration of C8:0 on the cuticle of larvae and adults, in amounts corresponding to their LD50 and LD100 doses, had a considerable impact on the two main defense systems engaged in protecting against pathogens, causing serious changes in the developmental-stage-specific profiles of free fatty acids (FFAs) covering the cuticle of larvae and adults and damaging larval hemocytes. In vitro cultures of G. mellonella hemocytes, either directly treated with C8:0 or taken from C8:0 treated larvae, revealed deformation of hemocytes, disordered networking, late apoptosis, and necrosis, as well as caspase 1-9 activation and elevation of 8-OHdG level. C8:0 was also confirmed to have a cytotoxic effect on the SF-9 insect cell line, as determined by WST-1 and LDH tests.


Value of new performance information in healthcare: evidence from Japan.
Mandatory measurement and disclosure of outcome measures are commonly used policy tools in healthcare. The effectiveness of such disclosures relies on the extent to which the new information produced by the mandatory system is internalized by the healthcare organization and influences its operations and decision-making processes. We use panel data from the Japanese National Hospital Organization to analyze performance improvements following regulation mandating standardized measurement and peer disclosure of patient satisfaction performance. Drawing on value of information theory, we document the absolute value and the benchmarking value of new information for future performance. Controlling for ceiling effects in the opportunities for improvement, we find that the new patient satisfaction measurement system introduced positive, significant, and persistent mean shifts in performance (absolute value of information) with larger improvements for poorly performing hospitals (benchmarking value of information). Our setting allows us to explore these effects in the absence of confounding factors such as incentive compensation or demand pressures. The largest positive effects occur in the initial period, and improvements diminish over time, especially for hospitals with poorer baseline performance. Our study provides empirical evidence that disclosure of patient satisfaction performance information has value to hospital decision makers.


Bubble hair. Case caused by an overheating hair dryer and reproducibility in normal hair with heat.
Bubble hair is an acquired hair shaft deformity characterized by bubble-like areas in the hair shaft seen with light microscopy and corresponding cavitary defects with scanning electron microscopy. Our purpose was to report the fourth case of bubble hair, to demonstrate a cause, and to determine whether the cavities contain gas or liquid. Light and scanning electron microscopy were performed. The patient's hair dryer was examined. We applied heat to normal hair of the patient and that of 16 human volunteers. Approximate temperatures for bubble formation were measured. The bubble contents were investigated by applying aqueous and nonaqueous liquids to affected hairs. No person's hair failed to develop bubbles when subjected to sufficient heat. The cause of bubble hair in the patient was an overheating hair dryer. The cavitations contained a gas. Bubble hair is a reproducible hair shaft defect caused by heat. The use of overheating hair dryers, or any other hair care equipment that overheats, should be avoided.


Vitamin D metabolism in a frugivorous nocturnal mammal, the Egyptian fruit bat (Rousettus aegyptiacus).
The nocturnal, frugivorous Egyptian fruit bat (Rousettus aegyptiacus) has no obvious access to either endogenous or dietary sources of vitamin D. We hypothesized that this species under natural conditions would be vitamin D deficient and that both serum mineral concentrations and vitamin D metabolite concentrations would be low. Both wild populations and captive populations appear to have an impoverished vitamin D status, as concentrations of the principle circulating metabolite, 25-hydroxyvitamin D [25(OH)D] are undetectable (<4 ng/mL) and those of the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D] are low. Intraperitoneal administration of labelled 25(OH)D revealed enhanced 1 alpha-hydroxylase activity confirming a natural state of vitamin D deficiency. This may account for the undetectable levels of 25(OH)D; for limited amounts of the prohormone substrate are rapidly converted to the active hormone. Both vitamin D(2) and D(3) metabolites were detected in bat serum, albeit in very small amounts, inferring that in their natural habitat fruit bats may have limited access to both exogenous dietary sources and endogenous sources. Despite the low levels of vitamin D metabolites in wild-caught and captive D-unsupplemented individuals, serum mineral concentrations were well regulated and similar to those of bats receiving D-supplements, with no pathological problems associated with vitamin D deficiency evident.


Reach of Messages in a Dental Twitter Network: Cohort Study Examining User Popularity, Communication Pattern, and Network Structure.
Increasing the reach of messages disseminated through Twitter promotes the success of Twitter-based health education campaigns. This study aimed to identify factors associated with reach in a dental Twitter network (1) initially and (2) sustainably at individual and network levels. We used instructors' and students' Twitter usernames from a Saudi dental school in 2016-2017 and applied Gephi (a social network analysis tool) and social media analytics to calculate user and network metrics. Content analysis was performed to identify users disseminating oral health information. The study outcomes were reach at baseline and sustainably over 1.5 years. The explanatory variables were indicators of popularity (number of followers, likes, tweets retweeted by others), communication pattern (number of tweets, retweets, replies, tweeting/ retweeting oral health information or not). Multiple logistic regression models were used to investigate associations. Among dental users, 31.8% had reach at baseline and 62.9% at the end of the study, reaching a total of 749,923 and dropping to 37,169 users at the end. At an individual level, reach was associated with the number of followers (baseline: odds ratio, OR=1.003, 95% CI=1.001-1.005 and sustainability: OR=1.002, 95% CI=1.0001-1.003), likes (baseline: OR=1.001, 95% CI=1.0001-1.002 and sustainability: OR=1.0031, 95% CI=1.0003-1.002), and replies (baseline: OR=1.02, 95% CI=1.005-1.04 and sustainability: OR=1.02, 95% CI=1.004-1.03). At the network level, users with the least followers, tweets, retweets, and replies had the greatest reach. Reach was reduced by time. Factors increasing reach at the user level had different impact at the network level. More than one strategy is needed to maximize reach.


Enhancing the thermal stability of lipases through mutagenesis and immobilization on zeolites.
The hydrolysis reaction of p-nitrophenyl butyrate catalyzed by lipases was followed with in situ UV/vis diode array spectrophotometry. Five enzymes - Candida antarctica lipase B and Fusarium solani pisi cutinase wild-type and three single-mutation variants - were tested as catalysts in homogeneous conditions and immobilized on zeolite NaY, on a polyacrylate support and as cross-linked aggregates. Using deconvolution techniques and kinetic modeling, the thermal stability of the different biocatalysts was compared in operational conditions and the results were supported by steady-state enzyme fluorescence measurements. We concluded that both the mutagenesis and the immobilization on zeolite NaY had a positive effect on the thermal stability of F. solani pisi cutinase.


Aerial and aquatic oxygen uptake by freely-diving snapping turtles (Chelydra serpentina).
Aerial oxygen consumption of unrestrained, freely-diving warm-and cold-acclimated snapping turtles, Chelydra serpentina, was measured at 10, 20, and 30°C. Also, simultaneous determinations of aerial and aquatic oxygen uptake by voluntarilydiving animals were made at 4 and 20°C. The standard rates of aerial oxygen consumption are equivalent in cold-and warm-acclimated animals in water and in cold-acclimated ones in air; these rates are all lower than those of warm-acclimated animals in air. Thus either cold acclimation or voluntary submergence reduces the standard metabolic rate of snapping turtles but the effects are not additive. Aquatic oxygen uptake during voluntary submergence is more important at low than at moderate temperatures and probably contributes significantly to gas exchange in these animals as they overwinter beneath the ice of ponds and streams.


Metabolomic assays of amoxicillin, cephapirin and ceftiofur in chicken muscle: application to treated chicken samples by liquid chromatography quadrupole time-of-flight mass spectrometry.
The aim of this study was to identity metabolites and transformation products (TPs) in chicken muscle from amoxicillin (AMX), cephapirin (PIR) and ceftiofur (TIO), which are antibiotics of the β-lactam family. Liquid chromatography coupled to quadrupole time-of-flight (QqTOF) mass spectrometry was utilized due to its high resolution, high mass accuracy and MS/MS capacity for elemental composition determination and structural elucidation. Amoxicilloic acid (AMA) and amoxicillin diketopiperazine (DKP) were found as transformation products from AMX. Desacetylcephapirin (DAC) was detected as a metabolite of PIR. Desfuroylceftiofur (DFC) and its conjugated compound with cysteine (DFC-S-Cys) were detected as a result of TIO in contact with chicken muscle tissue. The metabolites and transformation products were also monitored during the in vivo AMX treatment and slaughtering period. It was found that two days were enough to eliminate AMX and associated metabolites/transformation products after the end of administration.


Cortical brain responses to semantic incongruity and syntactic violation in Italian language: an event-related potential study.
The present experiment investigated cortical responses of native Italian subjects during reading of short sentences including semantic or morphosyntactic violations. Given the specificity of the Italian language in which the sequencing of words is relatively more free than in English or other languages, we investigated whether syntactic and semantic violations were able to elicit event-related potential (ERP) components similar to those found in other languages. Cortical potentials evoked by the anomalous target word were recorded at frontal, central and parietal electrodes. Results showed that, in Italian, semantic anomaly elicited a negative wave (N400) in the 400-500 ms time-window and syntactic error evoked a slower positive wave (P600) in the 500-700 ms time-window. Syntactic error also evoked a significant left anterior negativity in the 350-450 ms time-window, supporting the view that syntactic processes precedes semantic analysis. Thus, Italian language, notwithstanding its specificity, shows ERPs responses to semantic and syntactic violations, with effects, scalp distribution and latency similar to those found in German, Dutch and English. Results point to a cross-linguistic consistency of the semantic and syntactic ERP components associated with the detection of linguistic anomalies.


Clearing shrubland and extensive livestock farming: Active prevention to control wildfires in the Mediterranean mountains.
Forest fires are one of the main environmental problems in Mediterranean environments and different fire prevention policies have been applied: livestock grazing, prescribed fires and a combination of both. However, none present satisfactory results. In that context, in 1986 the Regional Government of La Rioja started the Plan for Shrub Clearing (PSC), combining shrub clearings and livestock grazing to control fires and improve the land management of abandoned mountain areas. Our study aims to analyse the effects of shrub clearings on forest fires in La Rioja and to compare the main results with those observed in Spain in the last 30 years. We apply an interdisciplinary methodology based on the analysis of the evolution of cleared areas, the evolution of wildfires in La Rioja and Spain, mapping land use and land cover changes, and quantifying the combustibility. Results obtained in La Rioja are very positive compared with the evolution of Spain, both in the reduction of the number of fires and the burned areas. Decreases in the combustible material, fuel load and biomass and in the occurrence of fires (>1 ha) were observed. In addition, clearing shrubland and extensive livestock provided other environmental benefits (i.e. mosaic landscapes, ecosystem services). Finally, this study suggested that they are good and sustainable techniques to prevent and control wildfires and they could be used as a land management strategy in other Mediterranean areas.


Cerebral metastasis without known primary tumour: a retrospective study.
A retrospective study was made of 19 patients who underwent operation for an intracerebral metastasis of an unknown primary tumour. Most patients survived for a few months only, with 2 remarkable ecceptions. In only 8 of them, the primary tumour became manifest in the further course of the illness.


Population biology of infectious diseases: Part I.
If the host population is taken to be a dynamic variable (rather than constant, as conventionally assumed), a wider understanding of the population biology of infectious diseases emerges. In this first part of a two-part article, mathematical models are developed, shown to fit data from laboratory experiments, and used to explore the evolutionary relations among transmission parameters. In the second part of the article, to be published in next week's issue, the models are extended to include indirectly transmitted infections, and the general implications for infectious diseases are considered.


The number of sentinel nodes identified as prognostic factor in oral epidermoid cancer.
In patients with oral cavity epidermoid cancer without palpable nodes, the standard cervical treatment is supraomohyoid dissection; nevertheless, lymphatic mapping with sentinel node (SN) biopsy has been useful and allows the identification of a group of patients where neck dissection may be prevented. The objective of this study was to examine which factors diagnose the possibility of metastasis in SN. A non-randomized prospective study was performed during a two year period and included patients with T1-2, N0 oral cavity cancer >4 mm thick, SN was identified by blue dye and Rhenium colloid. All patients underwent pre-operatory lymphogammagraphy and elective-selective neck dissection. Age, gender, tumor site, T, tumor thickness and number of sentinel nodes found were evaluated. In 48 patients, at least one sentinel node was found, 2 per patient on average. 10.4% showed drainage outside the supraomohyoid region, 13/48 had nodular metastasis, 4 with negative SN(8.3%). T, location, thickness and number of SN are related to non-SN metastasis. Identification of 3SN or more was related to the possibility of SN metastasis p=0 (RR 10.1, I. C. 95% 1.1 91.2). The combined technique (dye-colloid) offers a high index of success in the identification of SN in patients with oral cavity cancer, while lymphogammagraphy identifies patients with anatomically unexpected drainage. Patients with T1 less than 2cm, not located on the tongue with thickness <5 mm and more than 2 SN were less likely to have metastasis in non-sentinel nodes. The identification of at least 3 sentinel nodes decreases the possibility of identifying patients with hidden metastasis (p=0.04).


Relative effectiveness of interposed abdominal compression CPR: sensitivity analysis and recommended compression rates.
Interposed abdominal compression, IAC-CPR incorporates alternating chest and abdominal compressions to generate enhanced artificial circulation during cardiac arrest. The technique has been generally successful in improving blood flow and survival compared to standard CPR; however, some questions remain. To determine "why does IAC-CPR produce more apparent benefit in some subjects than in others?" and "what is the proper compression rate, given that there are actually two compressions (chest and abdomen) in each cycle?" Computer models provide a means to search for subtle effects in complex systems. The present study employs a validated 12-compartment mathematical model of the human circulation to explore the effects upon systemic perfusion pressure of changes in 35 different variables, including vascular resistances, vascular compliances, and rescuer technique. CPR with and without IAC was modeled. Computed results show that the effect of 100 mmHg abdominal compressions on systemic perfusion pressure is relatively constant (about 16 mmHg augmentation). However, the effect of chest compression depends strongly upon chest compression frequency and technique. When chest compression is less effective, as is often true in adults, the addition of IAC produces relatively dramatic augmentation (e.g. from 24 to 40 mmHg). When chest compression is more effective, the apparent augmentation with IAC is relatively less (e.g. from 60 to 76 mmHg). The optimal frequency for uninterrupted IAC-CPR is near 50 complete cycles/min with very little change in efficacy over 20-100 cycles/min. In theory, the modest increase in systemic perfusion pressure produced by IAC can make up in part for poor or ineffective chest compressions in CPR. IAC appears relatively less effective in circumstances when chest pump output is high.


Use of recombinant calflagin protein as a potential candidate for diagnosis of Trypanosoma evansi infection.
Serodiagnosis of surra, caused by Trypanosoma evansi, is still based on native antigens purified from bloodstream form of T. evansi grown in rodents. In order to investigate prospective diagnostic possibilities as an alternative for native antigens, we cloned, expressed 26 kDa calflagin protein containing 218 amino acids from T. evansi (Indian Strain) in Escherichia coli. The potential of recombinant calflagin (rCLF) protein as diagnostic antigen was evaluated in immunoblot and indirect ELISA using experimentally infected equine serum samples from 0 to 84 days post infection. The antibodies against T. evansi were detected with rCLF antigen in serum samples of experimentally infected equines as early as 10 days and 14 days post infection, using immunoblot and ELISA respectively. No cross-reactivity was observed with rCLF antigen in ELISA with different serum samples of equines positive for Equine herpesvirus 1, Burkholderia mallei, and Theileria equi infections. Several immunoreactive regions ranging from 10 to 28 kDa were detected using distinct T. evansi isolates (pony, cattle, donkey and camel origin) indicating presence of multiple calflagin family members in a single trypanosome. Indirect immunofluorescence antibody test with anti-CLF rabbit hyperimmune serum showed localisation of native immunogenic protein near attachment of flagellum. The rCLF protein was found to be a potential diagnostic candidate for distinguishing T. evansi positive and negative equine serum sample, suggesting that it could be used for serological surveys in animals for surra. In addition, it could be used with other potential diagnostic candidates to improve the diagnostic efficiency.


[Diagnosis of cerebral cysticercosis on Réunion Island by an immuno-enzymological method (ELISA): comparison with x-ray computed tomography].
An immunoenzymologic (Elisa) serodiagnosis of cysticercosis is evaluated in 75 encephalic cysticercosis patients whose diagnosis of the disease and its progression in assessed by tomodensitometry. A Taenia solium antigen is used. Only IgG are investigated. The sensibility of serodiagnosis is 85% and specificity 87% when there is a progression of the disease; no difference is noticed in the patients without any progression of the disease and in control normal subjects. This serodiagnosis of cysticercosis appears of value for the evaluation of the activity of the disease.


External Quality Assessment of stat test intralaboratory turnaround times. Pilot study from the Members of the Working Group for the Standardization and Promotion of Turnaround Time Control under the Auspices of the Comitato Italiano per la Standardizzazione dei Metodi Ematologici e di Laboratorio.
We describe procedures, results and prospects of a pilot program in External Quality Assessment (EQA) of the stat test intralaboratory turnaround times. Our goals are to promote quality by systematic monitoring and comparison of performances by laboratories, continuous investigation into the state of the art of the processes from receipt of sample to transmission of results and creation of a data base for standardization of measures and definition of consensus values for turnaround time. Of 30 laboratories invited to participate, 25 took part, agreeing to record times of arrival and transmission for all determinations of three analytes (blood hemoglobin, serum/plasma potassium and plasma prothrombin time) for seven consecutive days and to continue for one or more further periods of seven days as necessary if there were less than 300 determinations for each analyte. Within a preset time limit, data were sent by e-mail on an Excel file and we sent back two reports per analyte, showing: i) the graph for time vs. percentage of tests completed and several measures of turnaround time; ii) results of all laboratories in graph form, allowing each laboratory to identify only its own data. The high proportion of participating laboratories among those invited (83%) encourages us to implement the EQA program systematically, on a half-yearly basis, extending it to all laboratories wishing to participate in Italy or elsewhere in Europe.


Development of a facile fluorophosphonate-functionalised titanium surface for potential orthopaedic applications.
Aseptic loosening of total joint replacements (TJRs) continues to be the main cause of implant failures. The socioeconomic impact of surgical revisions is hugely significant; in the United Kingdom alone, it is estimated that £137 m is spent annually on revision arthroplasties. Enhancing the longevity of titanium implants will help reduce the incidence and overall cost of failed devices. In realising the development of a superior titanium technology, we exploited the natural affinity of titanium for phosphonic acids and developed a facile means of coating the metal with (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), a phosphatase-resistant analogue of lysophosphatidic acid (LPA). Importantly LPA and selected LPA analogues like FHBP synergistically cooperate with calcitriol to promote human osteoblast formation and maturation. Herein, we provide evidence that simply immersing titanium in aqueous solutions of FHBP afforded a surface that was superior to unmodified metal at enhancing osteoblast maturation. Importantly, FHBP-functionalised titanium remained stable to 2 years of ambient storage, resisted ∼35 kGy of gamma irradiation and survived implantation into a bone substitute (Sawbone™) and irrigation. The facile step we have taken to modify titanium and the robustness of the final surface finish are appealing properties that are likely to attract the attention of implant manufacturers in the future. We have generated a functionalised titanium (Ti) surface by simply immersing Ti in aqueous solutions of a bioactive lipid. As a facile procedure it will have greater appeal to implant manufacturers compared to onerous and costly developmental processes.


High-Efficient Visible-Light Photocatalysis Performance and Light-Corrosion Resistance of Ag3PO4 Constructed by double-Z System Composites.
Novel visible-light-driven Ag3PO4/AgBr/AgI photocatalysts were prepared via a simple self-assembly strategy combined with in-situ anion-exchanging process. The photocatalytic activity of Ag3PO4 was significantly improved by constructing double-Z system. Specifically, the obtained materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and UV-vis diffuse reflectance spectroscopy (DRS). Under visible light irradiation (λ > 420 nm), the Ag3PO4/AgBr/AgI photocatalysts showed much higher photocatalytic activity than bulk Ag3PO4 for the degradation of formaldehyde (HCHO), and 100% HCHO degradation could be obtained within 28 min. The degradation efficiency could be maintained in five cycles. Further electron paramagnetic resonance (ESR) tests demonstrated that both •OH and •O2- generated in the system. This study provides new insights into the fabrication of highly efficient visible-light-driven photocatalysts and facilitates their practical application in emerging environment issues.


Serum vitamin E level and functional prognosis after traumatic brain injury with intracranial injury: A multicenter prospective study.
Traumatic brain injury (TBI) is a major public health problem with high mortality and disability. Vitamin E, one of the antioxidants for treatment of TBI, has not been sufficiently evaluated for predicting prognosis of TBI. This study aimed to evaluate the prognostic value of vitamin E on functional outcomes of TBI patients with intracranial injury. A multi-center prospective cohort study was conducted in five university hospitals between 2018 and 2020. Adult TBI patients who visited the emergency department (ED) with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination were eligible. Serum vitamin E levels (mg/dL) were categorized into 4 groups: low (0.0-5.4), low-normal (5.5-10.9), high-normal (11.0-16.9), and high (17.0-). Study outcomes were set as 1- and 6-month disability (Glasgow outcome scale (GOS) 1-4). Multilevel logistic regression analysis was conducted to calculate the adjusted odds ratios (AORs) of vitamin E for related outcomes. Among 550 eligible TBI patients with intracranial injury, the median (IQR) of serum vitamin E was 10.0 (8.0-12.3) mg/dL; 204/550 (37.1%) had 1-month disability and 197/544 (36.1%) had 6-month disability of GOS 1-4. Compared with the high-normal group, the odds of 1-month disability and 6-month disability increased in the low and low-normal group (AORs (95% CIs): 3.66 (1.62-8.27) and 2.60 (1.15-5.85) for the low group and 1.63 (1.08-2.48) and 1.60 (1.04-2.43) for the low-normal group, respectively). Low serum vitamin E level was associated with poor prognosis at 1 and 6 months after TBI with intracranial injury.


The role of E2F-1 and downstream target genes in mediating ischemia/reperfusion injury in vivo.
E2Fs are a family of transcription factors that regulate proliferation, differentiation and apoptosis in many cell types. E2F-1 is the prototypical E2F and the family member that has most often been implicated in also mediating apoptosis. To better understand the role of E2F-1 in mediating cardiomyocyte injury we initially analyzed E2F family member expression after ischemia/reperfusion (I/R) in vivo or simulated ischemia in vitro. I/R injury in vivo caused a 3.4-fold increase specifically in E2F-1 protein levels. Expression of other E2F family members did not change. To establish the role of E2F-1 in I/R we examined the response of germline deleted E2F-1 mice to I/R injury. Infarct size as a percentage of the area at risk was decreased 39.8% in E2F-1(-/-) mice compared to E2F-1(+/+) controls. Interestingly, expression of classic, E2F-1 apoptotic target genes was not altered in E2F-1 null cardiomyocytes after I/R. However, upregulation of the primary member of the Forkhead family of transcription factors, FoxO-1a, was attenuated. Consistent, with a role for FoxO-1a as an important target of E2F-1 in I/R, a number of proapoptotic FoxO-1a target genes were also altered. These results suggest that E2F-1 and FoxO-1a belong to a complex transcriptional network that may modulate myocardial cell death during I/R injury.


Monitoring photographic proof of cecal intubation: A closed-loop audit of best practice colonoscopy.
Gold standard colonoscopy in the UK demands a 90% cecal intubation (CI) rate. Endoscopists must provide photographic evidence of CI, which can include images of the terminal ileum, appendix orifice, anastomosis or ileocecal valve. Whilst photographic proof of intubation should be obtained for all complete colonoscopies, this is not routinely audited. Three hundred and ninety-six complete colonoscopies were analyzed, 200 in an initial audit, and 196 in a second audit. Photos taken during colonoscopy were reviewed for evidence of successful CI, as well as whether these photographs had been marked as "proof of intubation" (POI). Results were shared at departmental governance meetings in order to assess any improvement in practice. Initial audit revealed 70% of colonoscopies had provided sufficient proof of CI but only 50% provided photographs that were described as such. Twenty percent of colonoscopies provided sufficient images, but these were not identified as POI. Thirty percent of all colonoscopies provided insufficient proof of CI. Upon repeat audit, 71% of colonoscopies met best practice standards, with the remaining 29% showing insufficient evidence of CI. In the modern era of digital technology, lack of photographic evidence should be seen as unacceptable and may raise important clinical and medicolegal concerns. We recommend that audits such as this become standard practice to ensure best practice.


Erythrocyte membrane lipids in Friedreich's ataxia.
In a study of the lipid composition of erythrocyte membranes in Friedreich's ataxia, the concentration of the major membrane components (phospholipids, cholesterol and protein) in ataxic patients, family members, and control subjects were found to be the same. The total fatty acid distribution was also normal. However, an altered distribution of phospholipid classes in erythrocytes was noted (an increase of PI + PS and a decrease of PE in Friedreich's ataxia patients).


The impact of intra- and postoperative fluid balance in pancreatic surgery - A retrospective cohort study.
The aim of this study was to evaluate the impact of perioperative fluid administration in pancreatic surgery. Patients who underwent pancreatic resections were identified from our institution's prospectively maintained database. Fluid balances were recorded intraoperatively and at 24hr postoperatively. Patients were stratified into tertiles of fluid administration (low, medium, high). Adjusted multivariable analysis was performed and outcome measures were postoperative complications. A total of 211 patients were included from 2012 to 2017. Complication rates were POPF(B/C) 19.4%, DGE(B/C) 14.7%, PPH(C) 10.0% and CDC ≥ IIIb 26.1%. In multivariable analysis, high perioperative fluid balance was an independent risk factor associated with POPF (OR = 10.5, 95%CI 2.7-40.7, p = .001), CDC (OR = 2.5, 95%CI 1.2-5.3, p < .002), DGE (OR = 2.3, 95%CI 1.0-5.2, p = .017), PPH (OR = 6.7 95%CI 2.2-20.0, p = .038) and reoperation (OR = 3.1, 95%CI 1.6-6.2, p = .006). In multivariable analysis with intraoperative and postoperative fluid balances as separate predictors, intraoperative (OR = 2,5, 95%CI 1.2-5.5, p = .04) and postoperative fluid balance (OR = 2.5, 95%CI 1.2-5.5, p = .02) were predictors of POPF. Postoperative fluid balance was the only predictor for mortality (OR = 4.5, 95%CI 1.0-18.9, p = .041) and predictor for CDC (OR = 2.0, 95%CI 1.0-4.0, p = .043) and OHS days (OR = 6.9, 95%CI 0.03-13.7, p = .038). High postoperative fluid balance in particular is associated with postoperative morbidity. Maintaining a fluid-restrictive strategy postoperatively should be recommended for patients undergoing pancreatic surgery.


PTPMT1 protects cardiomyocytes from necroptosis induced by γ-ray irradiation through alleviating mitochondria injury.
Radiation-induced heart disease (RIHD) progresses over time and may manifest decades after the initial radiation exposure, which is associated with significant morbidity and mortality. The clinical benefit of radiotherapy is always counterbalanced by an increased risk of cardiovascular events in survivors. There is an urgent need to explore the effect and the underlying mechanism of radiation-induced heart injury. Mitochondrial damage widely occurs in irradiation-induced injury, and mitochondrial dysfunction contributes to necroptosis development. Experiments were performed using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and rat H9C2 cells to investigate the effect of mitochondrial injury on necroptosis in irradiated cardiomyocytes and to further elucidate the mechanism underlying radiation-induced heart disease and discover possible preventive targets. After γ-ray irradiation, the expression levels of necroptosis markers were increased, along with higher oxidative stress and mitochondrial injury. These effects could be abated by overexpression of protein tyrosine phosphatase, mitochondrial 1 (PTPMT1). Inhibiting oxidative stress or increasing the expression of PTPMT1 could protect against radiation-induced mitochondrial injury and then decrease the necroptosis of cardiomyocytes. These results suggest that PTPMT1 may be a new target for the treatment of radiation-induced heart disease.NEW & NOTEWORTHY Effective strategies are still lacking for treating RIHD, with unclear pathological mechanisms. In cardiomyocytes model of radiation-induced injuries, we found γ-ray irradiation decreased the expression of PTPMT1, increased oxidative stress, and induced mitochondrial dysfunction and necroptosis in iPSC-CMs. ROS inhibition attenuated radiation-induced mitochondrial damage and necroptosis. PTPMT1 protected cardiomyocytes from necroptosis induced by γ-ray irradiation by alleviating mitochondrial injury. Therefore, PTPMT1 might be a potential strategy for treating RIHD.


Transplant registrants with implanted left ventricular assist devices have insufficient risk to justify elective organ procurement and transplantation network status 1A time.
The goal of this research was to identify disparities in risk within heart transplant urgency designations. Patients with left ventricular assist devices (LVADs) are given 30 days of elective status 1A time. This allowance may create competition for organs between stable LVAD-supported registrants and less stable registrants listed status 1A or 1B. The Scientific Registry of Transplant Recipients database was analyzed for all status 1A and 1B listings between 2005 and 2010. Cox models were used to estimate the relative and absolute risk of adverse events (death or delisting as too ill) during status 1A or 1B listing. Status 1A registrants supported with dual inotropes and right heart monitoring had a higher risk of adverse events compared to those supported with implanted LVADs using elective 1A time (hazard ratio: 3.2; 95% confidence interval: 1.8 to 5.7). The 30-day risk of events was 1% (95% confidence interval: 0.1% to 3%) for implanted LVADs using elective 1A time and 6% (95% confidence interval: 4% to 8%) for dual inotrope support. Registrants listed with paracorporeal ventricular assist devices had a higher risk of adverse events (hazard ratio: 9.1; p < 0.0001) compared with registrants with implanted LVADs using elective 1A time. The odds of transplant were higher for implanted LVADs (odds ratio: 1.5; p < 0.0001) compared with dual-inotrope and intra-aortic balloon pump support. The historic allowance for 30 days of elective status 1A time for implanted LVADs creates disparities in risk among status 1A registrants. The allowance of 30 days of elective status 1A time should not be allocated to stable registrants with implanted LVADs. Registrants supported with paracorporeal ventricular assist devices should be listed status 1A indefinitely.


ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia.
Interest is growing in the role of adenosine triphosphate (ATP) on P2 receptors during hypoxic/ischemic events in the brain. However, there is no direct evidence of an increase in extracellular ATP levels during cerebral ischemia in vivo. The aim of the present study was to evaluate ATP outflow from the rat striatum by the microdialysis technique associated with focal cerebral ischemia in vivo by intraluminal occlusion of the right middle cerebral artery (MCA). Between 1 and 4h after ischemia, rats showed a clear turning behavior contralateral to the ischemic side. Twenty-four hour after MCA occlusion, ischemic rats had definite neurological deficit and striatal and cortical damage. The ATP concentration (mean+/-S.E.M.) in the striatum of normoxic rats (n = 8) was 3.10+/-0.34 nM. During 220 min after MCA occlusion, the extracellular ATP levels significantly increased two-fold, being 5.90+/-0.61 nM (p < 0.01 versus normoxic level). ATP outflow showed a tendency to increase over time during the 220 min of ischemia. Since extracellular ATP is rapidly metabolized to adenosine, we also assessed ATP outflow in the presence of the ecto-5'-nucleotidase inhibitor, alpha,beta-methylene-adenosine diphosphate (AOPCP, 1 mM) directly perfused into the striatum. The ATP concentration in normoxic rats (n = 8) was increased three-fold in the presence of the ecto-5'-nucleotidase inhibitor (9.57+/-0.26 nM). During 220 min of ischemia, extracellular ATP levels significantly increased 1.3-fold in AOPCP-treated rats (12.62+/-0.65 nM, p < 0.01 versus normoxic level). The present study confirms that ATP is continuously released in the brain and demonstrates for the first time that ATP outflow increases during ischemia in vivo. These results confirm that ATP may be an important mediator in brain ischemia.


Theoretical aspects pertinent to the interpretation of concentration data.
Toxicological risk assessment requires knowledge of the kinetics of the test compound and its metabolites in the respective animal species. The toxic effects are dependent on the maximum, minimum, integral and mean systemic exposure as well as its fluctuation index at steady state. If these variables are set appropriately, defined toxicological hypotheses can be tested: the assessment of the no-effect dose level, the evaluation of the toxicological significance of high peak versus attenuated systemic exposure and the toxicological rating of species-specific metabolic pathways.


Experimental infection of Fusarium proliferatum in Oryza sativa plants; fumonisin B1 production and survival rate in grains.
Fusarium proliferatum is a plant pathogenic fungus associated with crops such as asparagus and corn, and it possesses the ability to produce a range of mycotoxins, including fumonisins. In Asia, rice (Oryza sativa) is a staple cereal and is occasionally colonized by this fungus without obvious physiological changes. F. proliferatum is closely related to Gibberella fujikuroi (anamorph F. fujikuroi) responsible for Bakanae disease in rice; however there are few reports of F. proliferatum as a rice pathogen. In this study, we examined the pathogenic potential of F. proliferatum in rice plants with respect to browning, fumonisin production, and survival rates in rice grains. Fungal inoculation was conducted by spraying a conidial suspension of F. proliferatum onto rice plants during the flowering period. Browning was found on the stalk, leaf, and ear of rice. Fumonisin B(1) was detected at levels from trace to 21 ng/g grains, using tandem mass spectrometry. Fungal recovery after 6 months indicated that F. proliferatum had high affinity to rice plants being still viable in grains. From this study, it can be concluded that F. proliferatum is a possible pathogen of rice and possesses a potential to produce fumonisin B(1) in rice grains in the field.


Cholesteryl ester and triacylglycerol fatty acids in type V hyperlipidemia.
The fatty acid compositions of plasma cholesteryl esters (CF) and triacylglycerols (TG) from seven healthy individuals and five patients with type V hyperlipoproteinemia were determined. Very low density (VLDL), low density (LDL) and high density lipoproteins (HDL) wer isolated. The lipids were extracted from the lipoproteins and the triacylglycerols and cholesteryl esters separated for analysis. The fatty acid compositions of triacylglycerols from healthy and type V individuals were very similar. The cholesteryl esters from type V patients had increased contents of palmitic and decreased amounts of linoleic and arachidonic acids as compared to the normal individuals. The fatty acid composition of the cholesteryl esters from high density lipoproteins had the greatest deviation. The fatty acid compositions of the triacylglycerols from the two groups were similar. However, the triacylglycerols in all lipoprotein fractions contained more palmitic and oleic and less linoleic and arachidonic acids than the cholesteryl esters.


Lung oxidative stress as related to exercise and altitude. Lipid peroxidation evidence in exhaled breath condensate: a possible predictor of acute mountain sickness.
Lung oxidative stress (OS) was explored in resting and in exercising subjects exposed to moderate and high altitude. Exhaled breath condensate (EBC) was collected under field conditions in male high-competition mountain bikers performing a maximal cycloergometric exercise at 670 m and at 2,160 m, as well as, in male soldiers climbing up to 6,125 m in Northern Chile. Malondialdehyde concentration [MDA] was measured by high-performance liquid chromatography in EBC and in serum samples. Hydrogen peroxide concentration [H(2)O(2)] was analysed in EBC according to the spectrophotometric FOX(2) assay. [MDA] in EBC of bikers did not change while exercising at 670 m, but increased from 30.0+/-8.0 to 50.0+/-11.0 nmol l(-1) (P<0.05) at 2,160 m. Concomitantly, [MDA] in serum and [H(2)O(2)] in EBC remained constant. On the other hand, in mountaineering soldiers, [H(2)O(2)] in EBC under resting conditions increased from 0.30+/-0.12 mumol l(-1) at 670 m to 1.14+/-0.29 mumol l(-1) immediately on return from the mountain. Three days later, [H(2)O(2)] in EBC (0.93 +/-0.23 mumol l(-1)) continued to be elevated (P<0.05). [MDA] in EBC increased from 71+/-16 nmol l(-1) at 670 m to 128+/-26 nmol l(-1) at 3,000 m (P<0.05). Changes of [H(2)O(2)] in EBC while ascending from 670 m up to 3,000 m inversely correlated with concomitant variations in HbO2 saturation (r=-0.48, P<0.05). AMS score evaluated at 5,000 m directly correlated with changes of [MDA] in EBC occurring while the subjects moved from 670 to 3,000 m (r=0.51, P<0.05). Lung OS may constitute a pathogenic factor in AMS.


Characteristics of detection thresholds and maximum comfortable loudness levels as a function of pulse rate in human cochlear implant users.
The ability of an implanted ear to integrate multiple pulses, as measured by the slopes of detection threshold level (T level) versus pulse rate functions, may reflect cochlear health in the cochlea, as suggested by previous animal studies (Kang et al., 2010; Pfingst et al., 2011). In the current study, we examined the slopes of T level versus pulse rate functions in human subjects with cochlear implants. Typically, T levels decrease as a function of pulse rate, consistent with a multipulse integration mechanism. The magnitudes of the slopes of the T level versus pulse rate functions obtained from the human subjects were comparable to those reported in the animal studies. The slopes varied across stimulation sites, but did not change systematically along the tonotopic axis. This suggests that the slopes are dependent on local conditions near the individual stimulation sites. The characteristics of these functions were also similar to those found in animals in that the slopes for higher pulse rates were steeper than those for the lower pulse rates, consistent with a combined effect of multipulse integration and cumulative partial depolarization mechanisms at rates above 1000 pps. The maximum comfortable loudness level (C level) versus pulse rate functions were also examined to determine the effect of level on the slopes. Slopes of C-level functions were shallower than those for the T-level functions and were not correlated with those of the T-level functions, so the mechanisms underlying these two functions are probably not identical. The slopes of the T- or C-level functions were not dependent on stimulus-current level. Based on these results, we suggest that slopes of T level versus pulse rate functions might be a useful measure for estimating nerve survival in the cochlea in regions close to the stimulation sites.


Iron-mediated modular decarboxylative cross-nucleophile coupling.
Carboxylic acids are valuable building blocks for pharmaceutical discovery because of their chemical stability, commercial availability, and structural diversity. Decarboxylative coupling reactions enable versatile functionalization of these feedstock chemicals, but many of the most general methods require prefunctionalization of carboxylic acids with redox-active moieties. These internal oxidants can be costly, their installation impedes rapid library synthesis, and their use results in environmentally problematic organic byproducts. We report herein a method for the direct decarboxylative cross-coupling of native carboxylic acids with nucleophilic coupling partners mediated by inexpensive, terrestrially abundant, and nontoxic Fe(III) salts. This method involves an initial photochemical decarboxylation followed by radical-polar crossover, which enables the construction of diverse carbon-carbon, carbon-oxygen, and carbon-nitrogen bonds with remarkable generality.


Differential localization and pH dependency of phosphoinositide 1,4,5-IP3, 1,3,4,5-IP4 and IP6 receptors in rat and human brains.
It is well established that the inositol lipids mediate signal transduction in several cellular populations. Many neurotransmitters, hormones and growth factors act at plasma membrane receptors to induce the hydrolysis of phosphatidylinositols and hence the generation of various inositol phosphates (IP). The best known member of this family is 1,4,5-IP3, which is associated with the release of Ca2+ from intracellular pools. It has also been proposed that two others inositides, 1,3,4,5-IP4 and IP6, may be involved in Ca2+ homeostasis. In order to study the possible relevance of these various inositides in neuronal tissues, we have localized the respective receptors in rat and human brain under both acidic and basic pH conditions. In the hippocampal formation, [3H]1,3,4,5-IP4 binding sites are concentrated in the hilus and the molecular layer while a clearly different pattern of distribution is seen for [3H]1,4,5-IP3, its highest concentration of labelling being concentrated in the oriens and radiatum laminae. This contrasting profile of distribution is also observed in other brain areas such as the caudate-putamen, the septo-hippocampal area, and the molecular and granular layers of the cerebellum. Moreover, while highest amounts of specific [3H]1,4,5-IP3 binding are obtained at pH 8.5, the opposite is found for [3H]1,3,4,5-IP4, with high binding levels seen under acidic conditions. [3H]IP6 binding sites are broadly distributed with specific labelling concentrated in areas enriched with neuronal perikarya such as the granular cell layer of the dentate gyrus, the pyramidal cell layers of the hippocampus and the granular cell layer of the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)


Monitoring testicular activity of male Eurasian (Lynx lynx) and Iberian (Lynx pardinus) lynx by fecal testosterone metabolite measurement.
The aim of the present study was to identify relevant fecal testosterone metabolites in the Eurasian lynx (Lynx lynx) using HPLC analysis and to evaluate the specificity of two testosterone immunoassays against these fecal metabolites. Finally, fecal hormone analysis was used to characterize seasonal reproductive activity of captive male Eurasian and Iberian (Lynx pardinus) lynx. Fecal samples from a male Eurasian lynx who received an i.v. injection of [3H]testosterone were subjected to HPLC analysis. All HPLC fractions were analyzed for radioactivity and androgen content by two testosterone immune assays (EIA and Testosterone-Immulite kits, DPC Biermann, Germany). Furthermore, fecal samples from four Eurasian lynx males (n=174) and three Iberian lynx (n=52) were collected throughout the year and fecal testosterone metabolites were determined with Testosterone-Immulite assay. HPLC separation of radiolabeled Eurasian lynx fecal extract indicated that the majority of testosterone metabolites are substances with a higher polarity than testosterone. Only minor proportion of radioactivity co-eluted with authentic testosterone and dihydrotestosterone. Enzymatic hydrolysis and solvolysis of the fecal extract were insufficient to liberate testosterone. After solvolysis relatively more activity was eluated the position of DHT, but the majority of metabolites remained unaffected. The EIA measured substantial amount of immunoreactivity, which corresponded with two radioactive peaks. Additionally, both immunoassays recognized two metabolites, which were only minor components according to their radioactivity. The Immulite assay was able to recognize a metabolite at the position of dihydrotestosterone. HPLC separation of Iberian lynx feces extracts revealed a similar metabolite pattern determined by EIA that were typical for Eurasian lynx fecal extracts. Simultaneous analyses of fecal samples with both testosterone assays provided comparative results for both lynx species (Eurasian lynx, r2=0.488; p<0.001; Iberian lynx, r2=0.85, p<0.0001). Thus, seasonal reproductive activity of male Eurasian lynx was demonstrated also by Immulite -assay, confirming high testosterone levels during breeding season in March/April as previously documented with EIA. Preliminary results on testosterone measurements in Iberian lynx feces confirmed the suitability of the applied Immulite test in this highly endangered species.