Ambient ionization source based on a dielectric barrier discharge for direct testing of pharmaceuticals using ion mobility spectrometry.

The instrument is based on a miniature plasma source mounted at an oblique angle close to the injection gate of the ion mobility spectrometer. The plasma torch consists of two 5 mm wide external cylindrical electrodes, 10 mm apart, which are placed coaxially around a fused silica tube (1.5 mm i.d. and 3.0 mm o.d.). A small helium plasma is created by applying a alternating voltage of 8 kV at 28 kHz and employed for the direct desorption and ionization of solid or liquid samples, which are placed on an electrically isolated support. The separation section of the ion mobility spectrometer has a drift tube of 10 cm length and an applied high voltage of 4 kV. The instrument was built in-house at low cost and can easily be duplicated. Its usefulness was demonstrated by the rapid identification of five different pharmaceutical drugs, namely acetaminophen, loratadine, norfloxacin, tadalafil, thiamine as well as caffeine in ground coffee beans.

Contactless conductivity sensor employing moist paper as absorbent for in-situ detection of generated carbon dioxide gas.

This work presents an unconventional use of capacitively coupled contactless conductivity detector (C4D) for detection of gas absorption by moist paper with potential application for chemical analysis. To be suitable for measuring conductivity of moist paper absorbent, the C4D sensor was therefore designed in planar configuration. A layer of dry filter paper, only 20 mm × 25 mm in size, was placed on the C4D sensor and the device installed inside a specifically designed vaporization chamber. A vial (16 mm i.d., 8 mm high) containing a 150-µL solution of sodium bicarbonate was placed alongside. The filter paper was loaded with 110 µL of deionized water through an injection hole in the cover lid. A 100-µL aliquot of 2 M hydrochloric acid solution was directly dispensed into the vial through a second hole in the lid to generate CO2 gas from the bicarbonate solution. It was observed that the C4D sensor gave real-time response that corresponded to the absorption of the gas and subsequent production of H+ and HCO3- in the moist paper. The monitored signal reached a constant value at 160 s after the addition of the acid. Chemistry of the absorption process and equivalent circuit for the C4D are proposed. Direct measurement of cement powder was chosen to demonstrate the potential use of this device for quantifying the CaCO3 content of the cement. The calibration curve for 0.5-3 mg CaCO3 was linear for signals recorded at 160 s: Vdc = (0.172 ± 0.005) · (mg CaCO3) + (0.016 ± 0.009), with coefficient of determination of 0.9965. Linear calibrations were also observed when the signals were monitored at various time less than 160 s. The limit of quantitation (3 SD of intercept/slope) was 0.17 mg CaCO3. The method provided acceptable precision with %RSD of 4.6 (2 mg CaCO3, n = 10).

[Aspects of nutrition therapy of an infant with central nervous system tumour]. / A táplálásterápia alkalmazásának szempontjai egy központi idegrendszeri daganatos csecsemõ ellátása során.

The atypical teratoid/rhabdoid tumour (ATRT) is a rare type of central nervous system tumour appearing usually under 2 years of age. The survival of patients is insufficient despite the combined treatment (neurosurgical removal, intensive chemo- and radiotherapy). ATRT recurs one year after completion of treatment in 60% of cases. Maintaining appropriate nutritional status during treatment is of great importance in this young age group. Nutritional treatment of patients with ATRT is especially difficult due to young age and possible neurological sequelae. A successful case of a three-month-old female infant is presented, with special emphasis on the importance of feeding therapy.

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

Rapid separation of fatty acids using a poly(vinyl alcohol) coated capillary in nonaqueous capillary electrophoresis with contactless conductivity detection.

The determination of fatty acids by nonaqueous CZE with capacitively coupled contactless conductivity detection was investigated. A new deoxycholate-based BGE, which had previously been found to give significantly improved baseline stability in the determination of lipophilic organic ammonium ions, was found to be similarly beneficial for the determination of the anions. The use of a PVA-coated capillary was required for suppression of the EOF and to obtain well reproducible results. The complete separation of 12 fatty acids could be achieved with 10 mM DOC in methanol within 6 min under optimized conditions. The PVA-coated capillary demonstrated outstanding stability over 300 runs with no sign of depletion of the PVA layer. Method validation showed a good linearity range from 0.75 to 25 µM with correlation coefficients between 0.9949 and 0.9979. The LOD was determined as 0.5 µM for all fatty acids. The developed approach was successfully demonstrated for the separation of free fatty acids in commercial and home-made edible oil.

Effective induction of cells expressing GABAergic neuronal markers from mouse embryonic stem cell.

Successful derivations of specific neuronal and glial cells from embryonic stem cells have enormous potential for cell therapies and regenerative medicine. However, the low efficiency, the complexity of induction method, and the need for purification represent obstacles that make their application impractical. In this study, we found that PDGFRα(+) cells derived from mouse embryonic stem cells (mESC) can serve as a useful source from which to induce cells that express γ-aminobutyric-acid (GABA)-releasing (GABAergic) neuronal markers. PDGFRα(+) cells were induced from mESC on collagen IV-coated plates in mesenchymal stem cell (MSC) culture medium with limited exposure to retinoic acid, sorted by fluorescence-activated cell sorter and maintained in MSC culture medium containing Y-27632, a Rho-associated kinase inhibitor. We found that supplementation of vascular endothelial growth factor, fibroblast growth factor-basic, and sodium azide (NaN3) to MSC culture medium effectively differentiated PDGFRα(+) cells into cells that express GABAergic neuronal markers, such as Pax2, Dlx2, GAD67 NCAM, and tubulin-ßIII, while markers for oligodendrocyte (Sox2) and astrocyte (Glast) were suppressed. Immunostaining for GABA showed the majority (86 ± 5%) of the induced cells were GABA-positive. We also found that the PDGFRα(+) cells retained such differentiation potential even after more than ten passages and cryopreservation. In summary, this study presents a simple and highly efficient method of inducing cells that express GABAergic neuronal markers from mESC. Together with its ease of maintenance in vitro, PDGFRα(+) cells derived from mESC may serve as a useful source for such purpose.

Conferring flame retardancy on cotton using novel halogen-free flame retardant bifunctional monomers: synthesis, characterizations and applications.

Two novel halogen-free phosphorous-nitrogen flame retardant bifunctional monomers were synthesized and characterized using attenuated total reflectance/Fourier transform-infrared (ATR/FT-IR) and electrospray ionization mass spectrometry ((+)ESI-MS). The monomers were applied separately and graft polymerized on cotton in the presence of the thermal initiator K(2)S(2)O(8). The performance of each monomer was evaluated using thermal gravimetric analysis (TGA), grafting efficiency, and vertical flame test. It was shown that the performance of N,N-dimethyl di(acryloyloxyethyl)phosphoramide (DMDAEP) (monomer 2) as flame retardant outperformed that of ethyl di(acryloyloxyethyl)phosphorodiamidate (EDAEP) (monomer 1). The superior performance of DMDAEP was attributed to the presence of more nitrogen atoms compared to EDAEP. The increased nitrogen content in DMDAEP increased the synergistic effect of the P-N system. Cotton treated using padding methods showed more promising results than cotton treated by exhaust methods.

Anion separations with pressure-assisted capillary electrophoresis using a sequential injection analysis manifold and contactless conductivity detection.

It is demonstrated that a hydrodynamic flow superimposed on the mobility of analyte anions can be used for the optimization of analysis time in capillary zone electrophoresis. It was also possible to use the approach for counter-balancing the electroosmotic flow and this works as well as the use of surface modifiers. To avoid any band-broadening due to the bulk flow narrow capillaries of 10 µm internal diameter were employed. This was enabled by the use of capacitively coupled contactless conductivity detection, which does not suffer from the downscaling, and detection down to between 1 and 20 µM for a range of inorganic and small organic anions was found feasible. Precisely controlled hydrodynamic flow was generated with a sequential injection manifold based on a syringe pump. Sample injection was carried out with a new design relying on a simple piece of capillary tubing to achieve the appropriate back-pressure for the required split-injection procedure.

Gender differences in locomotor and stereotypic behavior associated with l-carnitine treatment in mice.

BACKGROUND: The carnitines exert neuroprotective and neuromodulatory actions, and carnitine supplementation increases locomotor activity (LMA) in experimental animals. METHODS: We measured 13 indexes of LMA and 3 indexes of stereotypic activity (STA) in adult male and female caged mice. In a randomized 4-week trial, 10 males and 10 females received 50 mg/kg body weight PO l-carnitine, and another 10 males and 10 females received placebo. RESULTS: Compared with placebo-treated females, placebo-treated males had a greater number of stereotypies (NSTs), stereotypy counts (STCs), stereotypy time (STT), and right front time (RFT), but smaller total distance traveled (TDT), margin distance (MD), number of vertical movements (NVMs), and left rear time (LRT). Compared with placebo-treated males, carnitine-treated males had greater horizontal activity (HA), movement time (MT), NVM, STT, TDT, STC, MD, LRT, and clockwise revolutions (CRs), but smaller left front time (LFT) and RFT. Compared with placebo-treated females, carnitine-treated females had greater NST, STC, STT, LFT, and RFT, but smaller NM, HA, NVM, VA, MT, anticlockwise revolutions (ACRs), CR, TDT, and MD; right rear time (RRT) remained statistically insignificant across all comparisons. CONCLUSIONS: In summary, l-carnitine caused gender differences to persist for STC, diminish for NST and STT, disappear for LRT and NVM, change in the opposite direction for TDT and MD, appear de novo for HA, VA, NM, MT, and LFT, and remain absent for RRT and ACR. Some indexes of LMA and STA are sexually dimorphic in adult mice, and l-carnitine differentially maintains, diminishes/cancels, inverts, or creates the sexual dimorphism of particular indexes.

Determination of carnitine in food and food supplements by capillary electrophoresis with contactless conductivity detection.

A CE method with capacitively coupled contactless conductivity detection was developed and tested for the quantification of carnitine in different types of foodstuffs, namely fruit juices, milk, yogurt, cheese, red meat and chicken meat. Sample preparation was minimal as chemical or enzymatic conversion of the analyte is not necessary with the non-UV-absorbing compound when conductivity detection is employed. A 500 mmol/L acetic acid solution at pH 2.6 with 0.05% Tween-20, was used as the optimized running buffer. The analysis time was approximately 4 min. Linearity was achieved for the concentration range of 5-500 micromol/L with a correlation coefficient of 0.9996. The LOD (3 signal/noise) was determined as 2.6 micromol/L. Intra- and inter-day variabilities were less than 10% for both migration time and peak area, indicating a good precision of the method.

Psychiatric and substance use disorders comorbidities in veterans with hepatitis C virus and HIV coinfection.

PURPOSE OF REVIEW: A growing number of veterans in the Veterans Health Administration are coinfected with HIV and hepatitis C virus. This review covers timely research relative to comorbid conditions that are common in this population including psychiatric diagnoses, substance use disorders and neurocognitive problems. RECENT FINDINGS: Current literature on the psychiatric, substance use disorders and cognitive problems of the coinfected population show that not only are rates of morbidity higher in the coinfected population but that this affects antiviral treatments as well. There is new evidence that brain injuries and infiltration of the virus into the central nervous system may be responsible for cognitive dysfunction. Cotesting, particularly in hepatitis C infected individuals, is not done routinely despite shared risk factors. SUMMARY: With this understanding of the comorbidities of the coinfected population, integrated healthcare models involving mental health, internal medicine, substance abuse treatment and internal medicine are crucial to work with these medically and psychologically complex patients.

Improper supplementation habits of folic acid intake by Hungarian pregnant women: improper recommendations.

BACKGROUND: Neural tube defects (NTDs) are some of the most common congenital anomalies. Proper folic acid supplementation is a dominant risk factor, which has been shown to decrease the incidence of NTDs. In Canada, the incidence of neuroblastoma has presented a considerable decrease of 60% as a result of enrichment cereal grain flours with synthetic folic acid. The aim of this study was to investigate the effect of folic acid intake by pregnant women on the incidence of NTDs and neuroblastoma. METHODS: Regular folic acid intake has been recommended to pregnant women in Hungary since the eighties of the last century by health visitors eventually raking effect as an official protocol which had been released in 1997. During 2001, 2002 and 2003, folic acid intake habits of pregnant women were evaluated by health visitors, proving to be successful in collecting data from 95.06% of the pregnant women. The incidence of NTDs has been registered by the Hungarian National Centre of Epidemiology, Department of Human Genetics and Teratology. The Pediatric Cancer Registry provided the incidence of neuroblastoma in children. RESULTS: Consistent findings revealed a regular intake of supplementary folic acid products by 68.71% of the pregnant women. Out of these, 93.13% of pregnant women who were taking folic acid, started the supplementation after their 7 weeks of pregnancies, a time designated as the completion period of the development of the neural tube. The dose of folic acid supplementation was evaluated as less than 5 mg/day in 84.75% of the pregnant women. In Hungary, the incidence of NTDs has remained constant, while the incidence of neuroblastoma has shown constant slight increase in spite of the introduction of folic acid supplementation in 1997. CONCLUSIONS: Based on our experience, folic acid supplementation was initiated after the recognition of pregnancy and its application in a dose of lower than 5 mg/day neither decreased the incidence of NTDs nor did it have an effect on the neuroblastoma incidence. It is implicated that proper folic acid supplementation, which is started from the conception, can be achieved only with the enrichment of cereal grain flours.

Capillary electrophoresis with capacitively coupled contactless conductivity detection for low molecular weight organic acids in different samples.

CE with capacitively coupled contactless conductivity detection (CE-C(4)D) was explored and validated for the identification and quantification of organic acids in various types of samples. The analyses were performed under optimized conditions, using a buffer system composed of 20 mM MES-histidine (His), pH 6.0, 0.1 mM CTAB, 0.025% HP-beta-CD, and 10% methanol. The investigation included a study of the effects of buffer pH, concentration of CTAB, type and concentration of organic additives, on the migration behavior, resolution and selectivity of the organic acids. The intra- and interday RSDs (n = 6) obtained for migration time and peak area were typically in the range of 0.12-2% and 0.5-4%, respectively. Linearity, detection limits, and repeatability were evaluated. In order to evaluate the application potential of the developed method, real samples from different sources were analyzed. The results demonstrate that CE-C(4)D is a versatile tool for analyzing organic acids in beverages, Chinese herbal medicines (CHM) and plants as it allows for their detection, identification, and quantification.

[Alternative therapy in childhood cancer]. / Alternatív terápia a gyermekonkológiában.

INTRODUCTION: In Hungary there are as many as 300 children diagnosed with malignant tumor each year. Along with the traditional treatments, alternative remedies have been increasingly applied in the past two decades despite the availability of the more complex and more effective malignant tumor treatments. AIMS: The authors attempted to find out about the applied alternative remedies for childhood cancer outside the traditional treatments, to determine how frequently they were applied and to examine what psychological factors had lead to their application. PATIENTS: Children's parents, getting active treatment and also the ones that have been rehabilitated at the II. Department of Pediatrics, Semmelweis University. RESULTS: 60 percent of the 34 children being examined were getting several kinds of therapy. The most frequently applied alternative remedies were the following: nature products, diet supplements, herbs, diet changes. The parents' choice was mainly influenced by other parents' opinions (42%), frequently appearing commercials in media (26%) and their current financial background (23%). The authors have found on the base of their research that the general aim of parents was: to help their own incapability to help (31%), to make sure about the efficiency of the treatment (45%). CONSEQUENCES: Independently of demographic or clinical facts the use of alternative remedies are excessively widespread and popular with children having tumor. Thus it is not advisable or reasonable to absolutely refuse them since they are quite widespread and people tend to strongly believe in them. As for doctors, they are to give professional advice and help with choosing the alternative remedies that are not harmful or even more, the ones that can make traditional treatments more effective.

[Folic acid supplementation for pregnant women in Hungary]. / A magyarországi várandósok folsavszedési szokásai.

INTRODUCTION: Neural tube defects are common major congenital anomalies. Folic acid supplementation has been shown to reduce the incidence of neural tube defects. In 2003, incidence of neuroblastoma has decreased with 60% in Canada as a result of enriched cereal grain flours with synthetic folic acid. The aim of this study was to investigate the effect of the practice of the folic acid intake by pregnant women (based on the Hungarian recommendation) to the incidence of neural tube defects and neuroblastoma. METHODS: The practice of folic acid supplementation was examined by questionnaires filled according to the documentation of health visitors. The data were worked up by computer. The incidence of neural tube defect was obtained from the data of the Hungarian Congenital Anomalies Registry, however, the data of National Health Insurance Company are also given. The incidence of neuroblastoma was the data of the Hungarian Pediatric Tumor Registry. Regular folic acid intake has been recommended to pregnant women in Hungary, since the eighties of the last century. An official protocol had been released by the Obstetric and Gynecologic Professional Board in 1997. In this paper, the authors report the Hungarian pregnant women's folic acid intake in years of 2001, 2002 and 2003. These years were chosen, because according to the data of the Hungarian Pediatric Cancer Registry 45% of the neuroblastoma cases are less than 1 year old, and 45% of them are 1-5 years old at the time of diagnosis. The authors succeeded to collect the data from 95% of the pregnant women during these years (271,748 women). RESULTS: Based on the statistical analysis of the collected data, 69% of the pregnant women were regularly taking folic acid products in Hungary, however, the dose of the daily intake was below 5 mg. 93% of the pregnant women started the folic acid intake after their 7th weeks of pregnancy The incidence of neural tube defects was constant, and the incidence of neuroblastoma slightly increased during the above mentioned period. CONCLUSIONS: This work highlighted that, the folic acid intake to prevent neural tube defects was started too late, because the formation of neural tube is finished on 28. day of pregnancy. 85% of the pregnant women used less amount of folic acid than 5 mg/day. The increasing number of planned pregnancies would allow to start folic acid intake earlier. However, based on international experience, the enrichment of cereal grain flours with synthetic folic acid could provide optimal results.

Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients.

PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). CONCLUSIONS: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.