MSMPathfinder: Identification of Pathways in Markov State Models.
Markov state models represent a popular means to interpret biomolecular processes in terms of memoryless transitions between metastable conformational states. To gain insight into the underlying mechanism, it is instructive to determine all relevant pathways between initial and final states of the process. Currently available methods, such as Markov chain Monte Carlo and transition path theory, are convenient for identifying the most frequented pathways. They are less suited to account for the typically huge amount of pathways with low probability which, though, may dominate the cumulative flux of the reaction. On the basis of a systematic construction of all possible pathways, the here proposed method MSMPathfinder is able to characterize the multitude of unique pathways (say, up to 1010) in a complex system and to quantitatively calculate their correct weights and associated waiting times with predefined accuracy. Adopting the chiral transitions of a peptide helix and the folding of the villin headpiece as model problems, mechanisms and associated waiting times of these processes are discussed using a kinetic network representation. The analysis reveals that the waiting time distribution may yield only little insight into the diversity of pathways, because the measured folding times do typically not reflect the most probable path lengths but rather the cumulative effect of many different pathways.


Facile Synthesis of Porous ZnO Nanoparticles Efficient for Photocatalytic Degradation of Biomass-Derived Bisphenol A Under Simulated Sunlight Irradiation.
Bisphenol A (BPA) produced from biomass is a typical endocrine disrupting compound that is carcinogenic and genotoxic and can be accumulated in water due to its extensive use and difficult degradation. In this study, the porous ZnO photocatalyst with core-shell structure and large surface area was successfully developed for the efficient photocatalytic degradation of BPA. The various effects of calcination temperatures, BPA concentrations, ZnO dosages, pH and inorganic ions on the degradation performance were systemically studied. The results showed that 99% degradation of BPA was achieved in 1 h using the porous ZnO calcined at 550°C under the conditions of 30 mg/L BPA, 1 g/L ZnO, and pH of 6.5. Besides, the inhibition effects of anions for the photocatalytic removal of BPA decreased in the order of H2 PO 4 - > HCO 3 - > SO 4 2 - > Cl-, while the cations K+, Ca2+, and Na+ had little effect on the photocatalytic degradation of BPA. The results of scavenging experiments showed that h+, · O 2 - , and e- played the key role in the photocatalytic degradation process. Finally, the main pathways of BPA degradation were proposed based on ten intermediates found in the degradation process. This work may provide a good guideline to degrade various endocrine disrupting compounds in wastewater treatment.


Impact of the COVID-19 Pandemic on Emergency Department Workload and Emergency Care Workers' Psychosocial Stress in the Outbreak Area.
Background and Objectives: Due to the unexpected spread of coronavirus disease 2019 (COVID-19), there was a serious crisis of emergency medical system collapse. Healthcare workers working in the emergency department were faced with psychosocial stress and workload changes. Materials and Methods: This was a cross-sectional survey of healthcare workers in the emergency department in Daegu and Gyeongbuk, Korea, from November 16 to 25, 2020. In the survey, we assessed the general characteristics of the respondents; changes in the working conditions before and after the COVID-19 pandemic; and resulting post-traumatic stress disorder, depression and anxiety statuses using 49 questions. Results: A total of 529 responses were collected, and 520 responses were included for the final analyses. Changes in working conditions and other factors due to COVID-19 varied by emergency department level, region and disease group. Working hours, intensity, role changes, depression and anxiety scores were higher in the higher level emergency department. Isolation ward insufficiency and the risk of infection felt by healthcare workers tended to increase in the lower level emergency department. Treatment and transfer delay were higher in the fever and respiratory disease groups (M = 3.58, SD = 1.18; M = 4.08, SD = 0.95), respectively. In all the disease groups, both treatment and transfer were delayed more in Gyeongbuk than in Daegu. Conclusions: Different goals should be pursued by the levels and region of the emergency department to overcome the effects of the COVID-19 pandemic and promote optimal care.


Photophosphorylation during Chloroplast Development in Red Kidney Bean: II. Photophosphorylation and Photoreduction Appear Concomitantly but Initially are Uncoupled.
Cyclic phosphorylation with phenazine methosulfate and noncyclic phosphorylation and reduction with ferricyanide were detected in isolated chloroplasts from greening bean leaves after 3 to 4 hours of illumination. Activity commenced when rapid synthesis of chlorophyll was initiated. Rates of photophosphorylation were comparable to mature levels by 15 to 18 hours of development. Photoreduction of ferricyanide attained a peak value by 12 hours of illumination and subsequently fell to normal levels by 15 to 18 hours. With ferricyanide, the P/e(2) ratios were initially less than 0.1 but were close to 1.0 after 18 hours of illumination. The data suggested that photosystems I and II appeared concomitantly in the chloroplast but were not fully operative until later in development. Proplastids and immature chloroplasts exhibited high capacities to reduce ferricyanide in the dark. The rates of dark reduction rapidly diminished to low levels by 15 hours of illumination when normal rates of photochemical activity were observed. After a 2-to 3-day lag, a rapid increase in leaf fresh weight was noted at the time total chlorophyll content reached steady state values on a fresh weight basis. With fresh weight as an index of growth, primary leaves completed their development after 6 to 7 days of illumination.


Inhibition of Abscisic Acid Biosynthesis in Cercospora rosicola by Inhibitors of Gibberellin Biosynthesis and Plant Growth Retardants.
The fungus Cercospora rosicola produces abscisic acid (ABA) as a secondary metabolite. We developed a convenient system using this fungus to determine the effects of compounds on the biosynthesis of ABA. Inasmuch as ABA and the gibberellins (GAs) both arise via the isoprenoid pathway, it was of interest to determine if inhibitors of GA biosynthesis affect ABA biosynthesis. All five putative inhibitors of GA biosynthesis tested inhibited ABA biosynthesis. Several plant growth retardants with poorly understood actions in plants were also tested; of these, six inhibited ABA biosynthesis to varying degrees and two had no effect. Effects of plant growth retardants on various branches of the isoprenoid biosynthetic pathway may help to explain some of the diverse and unexpected results reported for these compounds. Knowledge that certain inhibitors of GA biosynthesis also have the ability to inhibit ABA biosynthesis in C. rosicola indicates the need for further studies in plants on the mode of action of these compounds.


Pharmacokinetics and biotransformation of tea polyphenols.
Tea is an infusion of the leaves of the Camellia sinensis plant and is the most widely consumed beverage in the world after water. The main chemical components in teas are phenolic compounds (tea polyphenols, mainly tea catechins). A large number of in vitro and in vivo scientific studies have supported that the tea polyphenols can provide a number of health benefits such as, reducing the incidence of coronary heart disease, diabetes and cancer. Recently, tea polyphenols have proven highly attractive as lead compounds for drug discovery programs. A clear understanding of chemistry, stability, pharmacokinetics and metabolic fate of tea will be significant to elucidate many medicinal effects by biochemical theory and pharmaceutical development. This article reviews the current literature on the pharmacoknetics and biotransformation of tea catechins. The half-lives of tea polyphenols are 2-4h and their absorption and elimination are rapid in humans. The peak times (tmax) are 1 and 3 h after oral administration and the peak plasma concentrations are low μM range. It has been reported that catechins are easily metabolized by enzyme and microbe, and the main metabolic pathways are methylation, glucuronidation, sulfation, ring-fission metabolism, and so on. The information is important to discuss some of the challenges and benefits of pursuing this family of compounds for drug discovery.


Virus-induced expression of retinoic acid inducible gene-I and melanoma differentiation-associated gene 5 in the cochlear sensory epithelium.
The inner ear has been regarded as an immunoprivileged site because of isolation by the blood-labyrinthine barrier. Several reports have indicated the existence of immune cells in the inner ear, but there are no reports showing immunocompetence of the cochlear tissue. In this report, we examined the potential involvement of retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), which are critical for initiating antiviral innate immune responses. We found that RIG-I and MDA5 are expressed in the mouse cochlear sensory epithelium, including Hensen's and Claudius' cells. Ex vivo viral infection using Theiler's murine encephalomyelitis virus revealed that the virus replicates in these cells and that protein levels of RIG-I and MDA5 are up-regulated. Furthermore, the critical antiviral transcription factor, interferon (IFN) regulatory factor-3, is activated in the infected cells as judged by its nuclear translocation and the accumulation of type I IFN transcripts. These results strongly suggest that RIG-I and MDA5 participate in innate antiviral responses in cochlear tissue.


Lanreotide autogel in acromegaly - a decade on.
The novel formulation of lanreotide, lanreotide (LAN) autogel (ATG), has been available in Europe since 2001 and USA from 2006 for the treatment of acromegaly. It is one of only two clinically available somatostatin analogs available for use in acromegaly. Data relating to the use of ATG in acromegaly, specifically relating to comparison to octreotide (OCT) LAR and patient acceptability and preference, have been slow to accumulate. We performed a comprehensive review of the original literature relating to development, pharmacokinetics, acceptability and clinical efficacy of ATG. LAN ATG is a novel formulation of LAN consequent on self-assembly of nanotubules in water. Diffusion between molecules within the nanotubules and surrounding tissue fluid in vivo leads to pseudo first-order pharmacokinetics. Efficacy is equivalent to the alternate long-acting somatostatin analog, OCT LAR, normalizing growth hormone and IGF-I levels in around 60 and 50% respectively. Control of tumor growth is observed in over 95% of patients, with 64% seeing a clinically significant reduction in tumor size. ATG is provided in a prefilled syringe for deep subcutaneous injection, allowing self-injection, and may be administered up to 8 weeks greatly improving convenience for the patient. The data strongly support consideration of ATG as the medical therapy of choice for patients with acromegaly.


Polymeric contrast agents for magnetic resonance imaging: synthesis and characterization of gadolinium diethylenetriaminepentaacetic acid conjugated to polysaccharides.
The synthesis and characterization of polysaccharides esterified with gadolinium diethylenetriaminepentaacetic acid (GdDTPA) are described. The results of several synthetic methods are presented for esterification of dextrans and inulin with DTPA. One method results in highly conjugated products labeled with an average of 0.4 mol of GdDTPA/mol of glucopyranose unit in dextrans of up to 70,800 average molecular weight and 0.5 mol of GdDTPA/mol of fructofuranose unit in inulin. Chromatographic and potentiometric evidence supporting the absence of significant chelate cross-linking of the conjugated polysaccharides is presented. The thermodynamic stability constant, log K (Gd3+ + L4(-)----GdL-), of the complexes was 18.0 +/- 0.2 based on an independent chelate model. In vitro ester hydrolysis of the GdDTPA-dextran 70,800 (at 37 degrees C, pH = 7.4 phosphate buffer) occurs with a half-life of 21 h. The agents exhibit T1 relaxivities ranging from 1.5 to 2.3 times that of GdDTPA at 100 MHz, and decreasing in vitro relaxivity with increasing molecular weight of the dextran carrier was observed. Phantom MRI studies indicate that the T1 and T2 effects of the complexes differ from those of GdDTPA, with the polysaccharide-bound complexes exhibiting a considerably faster drop in relative signal intensity with increased concentration in T1 and T2 weighted pulse sequences.


Schizophrenic deficit in span of apprehension.
We investigated two hypotheses about the span of apprehension task in schizophrenia: (a) schizophrenics show performance deficit on the forced-choice (FC) version but not on the full-report (FR) version, and (b) schizophrenic impairment on the FC version is greater when the display subtends a wide visual angle than when it subtends a narrow one. Schizophrenic (n = 21) and normal (n = 22) groups were tested on 3 versions of the task. A narrow-angle FC version was matched psychometrically with a wide-angle one by use of a greater number of noise letters in the narrow version. Schizophrenics reported fewer correct letters than normals on the FR version but did not differ on either the wide or the narrow FC versions. The results imply that schizophrenic deficit is not specific to the FC version and that on the FC version, visual angle is not more important than number of noise letters for demonstrating schizophrenic deficit.


40 Years of Dutch Disease Literature: Lessons for Developing Countries.
This paper surveys the "Dutch disease" literature in developing and emerging countries. It describes the original model of Dutch disease and some main extensions proposed in the theoretical literature, focusing on the ones that match developing countries' conditions. It then reviews various empirical studies that have been conducted and provides evidence that the Dutch disease is still an issue for many developing countries. Finally, it discusses the gaps in the theoretical and empirical literature for understanding the suitable policy instruments to cope with Dutch disease.


A novel eco-friendly green approach to produce particalized eggshell membrane (PEM) for skin health applications.
The eggshell membrane (ESM) is a natural bioactive material, which is increasingly utilized for various biomedical applications. However, the poor solubility of ESM limits the bioavailability of its constituents and reduces the expression of their potential bioactivity. In this study, we utilized an innovative green strategy to separate ESM from shell, and processed ESM for size reduction by cryo-grinding and homogenization to produce particalized eggshell membrane (PEM) approaching submicron dimensions, with enhanced anti-inflammatory activity and increased antimicrobial activity against skin associated pathogens. Gram-positive Staphylococcus aureus (log10 reduction = 4.5 ± 0.3) was more sensitive to PEM as compared to Gram-negative Pseudomonas aeruginosa (log10 reduction = 2.1 ± 0.3). PEM elicited a dose-dependent reduction in NO accumulation in LPS-induced RAW 264.7 macrophages, suggesting an anti-inflammatory response to ESM particles. These findings suggest that processed PEM possesses great potential as a topical ingredient in skincare applications to maintain skin health by reducing bacterial infections and inflammation.


Australian public and smallpox.
A national survey of 1,001 Australians found that most were concerned about a bioterrorist attack and were ill-informed about smallpox prevention and response. Since general practitioners were commonly identified as the initial point of care, they should become a focus of bioterrorism response planning in Australia.


Lesion of the ventral periaqueductal gray reduces conditioned fear but does not change freezing induced by stimulation of the dorsal periaqueductal gray.
Previously-reported evidence showed that freezing to a context previously associated with footshock is impaired by lesion of the ventral periaqueductal gray (vPAG). It has also been shown that stepwise increase in the intensity of the electrical stimulation of the dorsal periaqueductal gray (dPAG) produces alertness, then freezing, and finally escape. These aversive responses are mimicked by microinjections of GABA receptor antagonists, such as bicuculline, or blockers of the glutamic acid decarboxylase (GAD), such as semicarbazide, into the dPAG. In this work, we examined whether the expression of these defensive responses could be the result of activation of ventral portion of the periaqueductal gray. Sham- or vPAG electrolytic-lesioned rats were implanted with an electrode in the dPAG for the determination of the thresholds of freezing and escape responses. The vPAG electrolytic lesions were behaviorally verified through a context-conditioned fear paradigm. Results indicated that lesion of the vPAG disrupted conditioned freezing response to contextual cues associated with footshocks but did not change the dPAG electrical stimulation for freezing and escape responses. In a second experiment, lesion of the vPAG also did not change the amount of freezing and escape behavior produced by microinjections of semicarbazide into the dPAG. These findings indicate that freezing and escape defensive responses induced by dPAG stimulation do not depend on the integrity of the vPAG. A discussion on different neural circuitries that might underlie different inhibitory and active defensive behavioral patterns that animals display during threatening situations is presented.


Decree No. 966, 30 April 1988.
This Decree provides that the Executive Organ in the El Salvador Sector of Public Works is the body that will determine whether land is urban rather than nonurban and thus not subject to agrarian reform. Decisions of this body are to be final and cannot be modified by legal, judicial, or administrative order.


A complete switch of the directional selectivity in the annulation of 2-hydroxybenzaldehydes with alkynes.
Controlling reaction selectivity is an eternal pursuit for chemists working in chemical synthesis. As part of this endeavor, our group has been exploring the possibility of constructing different natural product skeletons from the same simple starting materials by using different catalytic systems. In our previous work, an isoflavanone skeleton was obtained from the annulation of a salicylaldehyde and an alkyne when a gold catalyst was employed. In this paper, it is shown that a coumarin skeleton can be efficiently obtained through an annulation reaction with the same starting materials, that is, terminal alkynes and salicylaldehydes, by simply switching to a rhodium catalyst. A plausible reaction mechanism is proposed for this new annulation based on isotopic substitution experiments.


Exploiting defects in homologous recombination repair for metastatic, castration-resistant prostate cancer.
The PROfound trial highlights that there is a benefit in testing genes involved in homologous recombination (HR) and forms the rationale for testing in all patients with metastatic, castration-resistant prostate cancer (mCRPC). This trial also demostrates that olaparib improves progression free survival (PFS), objective response rate (ORR), and time to pain progression in patients who harbor alterations in BRCA1, BRCA2, and ATM. These are groundbreaking findings - this is the first trial that demonstrates the efficacy of olaparib versus standard therapy in a genomically-selected patient population with metastatic prostate cancer. Although this trial does not demonstrate improvements in overall survival (OS), we believe that this may be an underestimation based on trial-design. Future studies of olaparib are likely to yield further promising results.


Cardiac resynchronization after left ventricular lead extraction: usefulness of angioplasty in coronary sinus stenosis.
A 68-year-old man, 54 months after having been implanted with a biventricular device, underwent successful extraction of the malfunctioning left ventricular (LV) lead using mechanical dilation. During LV lead reimplantation, venography documented stenosis of the coronary sinus (CS). To overcome the obstacle, balloon angioplasty was performed and a LV lead was then inserted into a lateral tributary of the CS. The procedure was complicated by local infection and, after 2 months, removal of the entire unit became necessary. During controlateral device implantation, a second angioplasty was carried before insertion of the new LV lead because, in the meantime, restenosis had developed in the CS.


Effects of electrodes length and insulation for transcranial electric stimulation.
The aim of this study is to investigate the effects of length and insulation of the corkscrew electrodes for transcranial motor evoked potential (tMEP) monitoring. We used the finite element method to visualize the electric field in the brain, which was generated by electrodes of different lengths (4, 7, and 12 mm). Two types of head models were generated: A model that included a subcutaneous fat layer and another without a fat layer. Two insulated needle types of conductive tip (5 and 2 mm) were studied. The stimulation threshold levels of hand tMEP were measured in a clinical setting to compare normal corkscrew and insulated 7-mm depth corkscrew. The electric field in the brain depended on the electrode depths in the no fat layer model. The deeper the electrodes reached, the stronger the electric fields generated. Electrode insulation made a difference in the fat layer models. The threshold level recordings of tMEP revealed that the 7-mm insulated electrodes showed a lower threshold than the normal electrodes by one-side replacement in each patient: 33.6 ± 9.6 mA and 36.3 ± 11.0 mA (n =16, P < 0.001), respectively. The 7-mm insulated electrodes also showed a lower threshold than the normal electrodes when both sides, electrodes were replaced: 34.4 ± 8.6 mA and 37.5 ± 9.2 mA (n =10, P = 0.003), respectively. The electrodes depth reached enough to skull is considered to be efficient. Insulation of the electrodes with a conductive tip is efficient when there is subcutaneous fat layer.


Induction of glomerular heparanase expression in rats with adriamycin nephropathy is regulated by reactive oxygen species and the renin-angiotensin system.
Heparan sulfate (HS) in the glomerular basement membrane (GBM) is important for regulation of the charge-dependent permeability. Heparanase has been implicated in HS degradation in several proteinuric diseases. This study analyzed the role of heparanase in HS degradation in Adriamycin nephropathy (AN), a model of chronic proteinuria-induced renal damage. Expression of heparanase, HS, and the core protein of agrin (to which HS is attached) was determined on kidney sections from rats with AN in different experiments. First, expression was examined in a model of unilateral AN in a time-course study at 6-wk intervals until week 30. Second, rats were treated with the hydroxyl radical scavenger dimethylthiourea (DMTU) during bilateral AN induction. Finally, 6 wk after AN induction, rats were treated with angiotensin II receptor type 1 antagonist (AT1A) or vehicle for 2 wk. Heparanase expression was increased in glomeruli of rats with AN, which correlated with HS reduction at all time points and in all experiments. Treatment with DMTU prevented the increased heparanase expression, the loss of GBM HS, and reduced albuminuria. Finally, treatment of established proteinuria with AT1A significantly reduced heparanase expression and restored glomerular HS. In conclusion, an association between heparanase expression and reduction of glomerular HS in AN was observed. The effects of DMTU suggest a role for reactive oxygen species in upregulation of heparanase. Antiproteinuric treatment by AT1A decreased heparanase expression and restored HS expression. These results suggest involvement of radicals and angiotensin II in the modulation of GBM permeability through HS and heparanase expression.


Effects of the antimicrobial peptide protegrine 1 on sperm viability and bacterial load of boar seminal doses.
The presence of bacteria adversely affects boar sperm quality of seminal doses intended for artificial insemination. Currently, the most common measure to prevent bacteriospermia is the addition of antibiotics in semen extenders; however, mounting evidence shows that microbial resistance exists. A promising alternative to replace antibiotics are antimicrobial peptides. In this study, the effects of the antimicrobial peptide protegrine 1 (PG1) on the sperm viability and bacterial load of boar seminal doses were evaluated. Three different concentrations of PG1 (2.5, 25 and 100 μg/ml) were tested over a storing period of 10 days at 17°C. Sperm viability was analysed by fluorescence microscopy (SYBR14/propidium iodide), and bacterial load was assessed by plating 100 μl of each sample in Luria-Bertani medium and incubated at 37°C for 72 hr under aerobic conditions. Protegrine 1 was effective in controlling the bacterial load in all the assessed concentrations (p < .05), reaching the lowest values at the highest concentrations of the antimicrobial peptide. Nevertheless, sperm viability was significantly (p < .05) reduced by all tested concentrations of this peptide, the most cytotoxic effects being observed at the highest PG1 concentrations. Despite these results, the use of PG1 as an alternative to antibiotics cannot be totally discarded, as further studies using the truncated form of this peptide are needed.


Oral Human Papillomavirus Infection in Children during the First 6 Years of Life, Finland.
Human papillomavirus (HPV) infections are found in children, but transmission modes and outcomes are incompletely understood. We evaluated oral samples from 331 children in Finland who participated in the Finnish Family HPV Study from birth during 9 follow-up visits (mean time 51.9 months). We tested samples for 24 HPV genotypes. Oral HPV prevalence for children varied from 8.7% (at a 36-month visit) to 22.8% (at birth), and 18 HPV genotypes were identified. HPV16 was the most prevalent type to persist, followed by HPV18, HPV33, and HPV6. Persistent, oral, high-risk HPV infection for children was associated with oral HPV carriage of the mother at birth and seroconversion of the mother to high-risk HPV during follow-up (odds ratio 1.60-1.92, 95% CI 1.02-2.74). Children acquire their first oral HPV infection at an early age. The HPV status of the mother has a major impact on the outcome of oral HPV persistence for her offspring.


Reliability of a method for evaluating porosity in denture base resins.
The method of porosity analysis by water absorption has been carried out by the storage of the specimens in pure water, but it does not exclude the potential plasticising effect of the water generating unreal values of porosity. The present study evaluated the reliability of this method of porosity analysis in polymethylmethacrylate denture base resins by the determination of the most satisfactory solution for storage (S), where the plasticising effect was excluded. Two specimen shapes (rectangular and maxillary denture base) and two denture base resins, water bath-polymerised (Classico) and microwave-polymerised (Acron MC) were used. Saturated anhydrous calcium chloride solutions (25%, 50%, 75%) and distilled water were used for specimen storage. Sorption isotherms were used to determine S. Porosity factor (PF) and diffusion coefficient (D) were calculated within S and for the groups stored in distilled water. anova and Tukey tests were performed to identify significant differences in PF results and Kruskal-Wallis test and Dunn multiple comparison post hoc test, for D results (α=0.05). For Acron MC denture base shape, FP results were 0.24% (S 50%) and 1.37% (distilled water); for rectangular shape FP was 0.35% (S 75%) and 0.19% (distilled water). For Classico denture base shape, FP results were 0.54% (S 75%) and 1.21% (distilled water); for rectangular shape FP was 0.7% (S 50%) and 1.32% (distilled water). FP results were similar in S and distilled water only for Acron MC rectangular shape (p>0.05). D results in distilled water were statistically higher than S for all groups. The results of the study suggest that an adequate solution for storing specimens must be used to measure porosity by water absorption, based on excluding the plasticising effect.


[Analysis of Clinical Efficacy and Influencing Factors of Gemcitabine-L-Asparaginase-Oxaliplatin Chemotherapy Scheme and Radiotherapy for Treatment of Early ENKTL Patients].
To analyse the clinical efficacy and its influencing factors of early ENKTL patients received chemotherapy of gemcitabine-L-asparaginase-oxaliplatin (GELOX) scheme and radiotherapy. The clinical data of 80 cases of early nasal type NK/T cell lymphoma treated during May 2013 to May 2016 were analyzed retrospectively. The earty ENKTL patients were divided into 3 groups: group I (50 cases) with GELOX after chemotherapy combined with radical radiotherapy, group II (16 cases) with GELOX after other chemotherapy combined radical radiotherapy, group III (14 cases) patients only received GELOX chemotherapy. The average cycle of chemotherapy was 3 cycles, and the total dose of irradiation was 50.20± 3.50 Gy/(20-30 times). After the treatment of 80 early ENKTL patients, the CR rate of patients was 67.50% (54/80); the CR rate of patients in I, II, III groups received chemotherapy was 45%, 10%, 18% rate respectively (P=0.029). The 2 years PFS of the 80 paaients was 79%,and 2 year OS rate was 85.00%; the 2 year PFS rate and OS rate in group 1 and 3 were 84% and 92.00%. The 2 year OS rate, PFS rate in group 1 (96%, 84%) were higher than that in group 3 (47%, 40.00%)(P=0.045,0.003) and group II (50%, 45%, P=0.001,0.00); the OS rate and PFS rate in group 2 and 3 were not statistically significant different (P=0.220,0.97). The factors that affect OS and PFS were remission or not remission after chemotherapy. Clinical use of GELOX induction chemotherapy combined with radical radiotherapy in the treatment of early ENKTL can achieve good therapeutic results.


Primary Hydatid Cyst of the Small Intestine: A Rare Case Report and Brief Review of the Literature.
Hydatid disease is an endemic disease especially in underdeveloped and developing countries affecting mostly the liver and lungs. The hydatid cysts located in other sites are mostly due to rupture of primary liver or splenic cysts. We present a primary small intestine hydatid cyst resected laparoscopically with the affected intestinal segment. As far as we know, this is the first report of a primary small intestine hydatid disease in the literature.


From flow cytometric BrdUrd data to cell population growth and doubling time.
We describe a direct way to use flow cytometric data for measuring the growth curve of a cell population. The starting point is analysis of the intrinsic informative content of the time course, after bromodeoxyuridine (BrdUrd) labeling, of the percentages of cells detected within four windows of biparametric BrdUrd-DNA histograms. We did not introduce a particular cell cycle model or use the hypothesis of exponential growth. We obtained a simple formal proof of the existence of four independent formulae connecting the flow cytometric data and the relative growth curve of the cell population. The formulae were then challenged in a number of simulated kinetic scenarios, moving away from their expected limits of validity. The results suggest additional uses of the formulae and a way of estimating cell-cycle-phase durations. Considering exponential growth in the presence of cell loss, the formulae were used to estimate the potential doubling time from a single flow cytometric measure vs. other procedures that additionally require an estimate of the duration of the phase S. The theoretical precision of the procedures may differ depending on how cell loss occurs.


Over-expression of map kinase phosphatase-1 (MKP-1) suppresses neuronal death through regulating JNK signaling in hypoxia/re-oxygenation.
A pivotal role of c-jun N-terminal kinase (JNK) on neuronal apoptosis has been demonstrated in a rodent stroke model. MAP kinase phosphatase 1 (MKP-1) is an archetypal member of the dual-specificity protein phosphatase (DUSP) family, which inactivates mitogen-activated protein kinase (MAPK) including JNK through dephosphorylation. MKP-1, one of immediate early genes in stress conditions, was induced at transcriptional level in hypoxia/re-oxygenation (H/R) in neuroblastoma N1E115 cells, however the activation of JNK was not suppressed in the acute phase of re-oxygenation. Small interference RNA-mediated knock-down of MKP-1 enhanced phospho-JNK and neuronal death that is rescued by JNK inhibitor in H/R. Conversely, conditional over-expression of MKP-1 suppressed phospho-JNK, the expression of proapoptotic genes, and neuronal death in H/R. Further the immunoreactivity of MKP-1 was detected in the neurons and partially co-localized with that of phospho-JNK in the surrounding zone of ischemia in rat MCA-O (middle cerebral artery occlusion) reperfusion model. These findings indicate that over-expression of MKP-1 could suppress neuronal death possibly through regulating JNK signaling in vitro and be a prominent neuroprotective target for the treatment of acute cerebral infarction.


Effects of a nucleoside transporter inhibitor, dilazep, on renal microcirculation in rats.
Adenosine, one of the endogenous modulators in renal hemodynamics, has recently been shown to be a mediator of tubuloglomerular feedback (TGF). Dilazep augments endogenous adenosine actions by blocking its cellular uptake. Our purpose in the present study was to clarify the effects of dilazep on renal microcirculation and the TGF mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to loop perfusion at 0-40 nl/min with artificial tubular fluid (ATF). Under dilazep administration (0.3 mg/kg+0.3 mg/kg/h i.v.) systemic BP and GFR were decreased and renal plasma flow was unaltered; as a result, the filtration fraction tended to decrease (p=0.076). Renal vascular resistance was reduced, but not to a significant degree. The reduction in EPFR by loop perfusion was similar between controls (47 +/- 2%) and rats administered dilazep i.v. (44 +/- 5%). Intraluminal application of dilazep in ATF suppressed TGF-mediated EPFR reduction to by 46 +/- 4%, 43 +/- 7%, and 37 +/- 3% at dilazep concentrations of 10(-6), 10(-5), and 10(-4) mol/l, respectively. TGF suppression with 10(-4) mol/l dilazep was reversed by co-perfusion of 10(-5) mol/l DMPX, a selective adenosine A2 receptor antagonist. DMPX alone did not affect TGF response. In conclusion, these results indicate that systemic dilazep dilates postglomerular arterioles and does not affect TGF, and thus reduces GFR. A pharmacological concentration of dilazep applied to single nephrons clearly attenuates TGF, indicating afferent arteriolar vasodilatation. Extracellular adenosine augmented by dilazep dilates glomerular vessels at both afferent and efferent sites, probably via the activation of A2 receptors.


Volume-guarantee ventilation: pressure may decrease during obstructed flow.
Two unexpected observations were made during ventilation with the Dräger Babylog 8000+ in volume-guarantee mode: (a) during complete obstruction to gas flow down the endotracheal tube (ETT), positive inspiratory pressure (PIP) was reduced to half way between the maximum inflating pressure and the positive end expiratory pressure (PEEP) even though the set expired tidal volume had not been achieved; (b) an external Dräger waveform monitor may stop displaying real-time waveforms when a tube-obstructed alarm is activated. To investigate these phenomena using a test lung. A 50 ml Dräger test lung was attached to the ventilation circuit of a Dräger Babylog 8000+. Partial obstruction to ETT flow was induced by compressing the tubing leading to the test lung, and complete obstruction was achieved by clamping. Recordings were made from the digital output of the ventilator at 125 Hz. When the ETT flow was completely obstructed during VG ventilation, a constant PIP was set midway between the set maximum and PEEP. This did not happen during partial obstruction. The external waveform monitor display froze when ETT flow was completely obstructed. During complete ETT obstruction, the PIP is set to a pressure midway between maximum PIP and PEEP even if this is less than the PIP used before the obstruction. Further research is needed to evaluate whether this reduction in PIP is associated with prolongation of precipitating events.


Race, Income, and Medical Care Spending Patterns in High-Risk Primary Care Patients: Results From the STOP-DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) Study.
Little is known about how socioeconomic status (SES) relates to the prioritization of medical care spending over personal expenditures in individuals with multiple comorbid conditions, and whether this relationship differs between Blacks and non-Blacks. We aimed to explore the relationship between SES, race, and medical spending among individuals with multiple comorbid conditions. Cross-sectional evaluation of baseline data from a randomized controlled trial. The STOP-DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) study is a completed randomized controlled trial of Duke University primary care patients with diabetes, hypertension, and chronic kidney disease. Participants underwent survey assessments inclusive of measures of socio-demographics and medication adherence. Race (Black or non-Black) and socioeconomic status (income, education, and employment). The primary outcomes were based on 4 questions related to spending, asking about reduced spending on basic/leisure needs or using savings to pay for medical care. Participants were also asked if they skipped medications to make them last longer. Multivariable logistic regression stratified by race and adjusted for age, sex, and household chaos was used to determine the independent effects of SES components on spending. Of 263 STOP-DKD participants, 144 (55%) were Black. Compared with non-Blacks, Black participants had lower incomes with similar levels of education and employment but were more likely to reduce spending on basic needs (29.2% vs 13.5%), leisure activities (35.4% vs 20.2%), and to skip medications (31.3% vs 15.1%), all P < 0.05. After multivariable adjustment, Black race was associated with increased odds of reduced basic spending (OR, 2.29; 95% CI, 1.14-4.60), reduced leisure spending (OR, 1.94; 95% CI, 1.05-3.58), and skipping medications (OR, 2.12; 95% CI, 1.12-4.04). This study was conducted at a single site in Durham, North Carolina, and nearly exclusively included insured patients. Further, the impact of the number of comorbid conditions, medication costs, or copayments was not assessed. In primary care patients with multiple chronic diseases, Black patients are more likely to reduce spending on basic needs and leisure activities to afford their medical care than non-Black patients of equivalent SES. NCT01829256.


Tissue pleiotropic effect of biotin and prebiotic supplementation in established obesity.
Combination therapies targeting multiple organs and metabolic pathways are promising therapeutic options to combat obesity progression and/or its comorbidities. The alterations in the composition of the gut microbiota initially observed in obesity have been extended recently to functional alterations. Bacterial functions involve metabolites synthesis that may contribute to both the gut microbiota and the host physiology. Among them are B vitamins, whose metabolism at the systemic, tissue or microbial level are dysfunctional in obesity. We previously reported that the combination of oral supplementation of a prebiotic (fructo-oligosaccharides, FOS) and vitamin B7/B8 (biotin) impedes fat mass accumulation and hyperglycemia in mice with established obesity. This was associated with an attenuation of dysbiosis with improved microbial vitamin metabolism. We now extend this study by characterizing whole-body energy metabolism along with adipose tissue transcriptome and histology in this mouse model. We observed that FOS resulted in increased caloric excretion in parallel with down-regulation of genes and proteins involved in jejunal lipid transport. The combined treatments also strongly inhibited the accumulation of subcutaneous fat mass, with a reduced adipocyte size and expression of lipid metabolism genes. Down-regulation of inflammatory and fibrotic genes and proteins was also observed in both visceral and brown adipose tissues and liver by combined FOS and biotin supplementation. In conclusion, oral administration of a prebiotic and biotin has a beneficial impact on the metabolism of key organs involved in the pathophysiology of obesity, which could have promising translational applications.


Nonstochastic effects of different energy beta emitters on pig skin.
Circular areas of pig skin from 1- to 40-mm diameter were irradiated with beta emitters of high, medium, and low energies, 90Sr, 170Tm, and 147Pm, respectively. The study provides information for radiological protection problems of localized skin exposures. During the first 16 weeks after irradiation 90Sr produced a first reaction due to epithelial cell death followed by a second reaction attributable to damage to the dermal blood vessels. 170Tm and 147Pm produced the epithelial reaction only. The epithelial dose response varied as a function of beta energy. The doses required to produce moist desquamation in 50% of 15- to 22.5-mm fields (ED50) were 30-45 Gy from 90Sr, approximately 80 Gy from 170Tm, and approximately 500 Gy from 147Pm. A model involving different methods of epithelial repopulation is proposed to explain this finding. An area effect was observed in the epithelial response to 90Sr irradiation. The ED50 for moist desquamation ranged from approximately 25 Gy for a 40-mm source to approximately 450 Gy for a 1-mm source. The 5-, 9-, and 19-mm 170Tm sources all produced an ED50 of approximately 80 Gy, while the value for the 2-mm source was approximately 250 Gy. It is also suggested that the area effects could be explained by different modes of epithelial repopulation after irradiation. After high energy beta irradiation repopulation would be mainly from the field periphery, while after lower energy irradiation repopulation from hair follicle epithelium would predominate.


Rearrangement of the gene for the beta chain of the T-cell receptor in T-cell chronic lymphocytic leukemia and related disorders.
Although monoclonal B-cell populations can be identified both by surface-marker analysis and by immunoglobulin-gene rearrangements, this has not been possible with T cells. We have employed cDNA probes that are specific for the entire beta chain of the T-cell receptor, and for its constant and variable regions, to investigate gene rearrangements in T-cell chronic lymphocytic leukemia and related disorders. In three malignant proliferations of helper (T4-positive) T cells, rearrangements of the beta-chain constant-region gene were readily demonstrated. A patient from the Caribbean who had adult T-cell lymphoma and antibody to human T-cell lymphotrophic virus Type I (HTLV-I), a patient with virus-negative chronic lymphocytic leukemia, and a patient with cutaneous T-cell lymphoma (Sézary variant) made up the T4-positive group. Three additional patients with chronic T8 (cytotoxic-suppressor) lymphocytosis and neutropenia were studied; in two; rearrangements were found. In all five patients with constant-region rearrangements, deletions of variable-region restriction fragments were observed as well. The presence of rearrangements of a T-cell receptor gene provides presumptive evidence for the clonal nature of T-cell proliferation and for its neoplastic character.


Act of 26 June 1987.
This Act establishes a medical assistance program for pregnant women, postpartum women, and children under one year old who are needy. The Act provides that no payments will be made for "induced abortion, diagnostic procedures done for the purpose of inducing abortion, or other procedures related to induced abortion unless the physician certifies in written form that the mother's life is in danger if the fetus is carried to term."


Neuronal activity in somatosensory cortex of monkeys using a precision grip. II. Responses To object texture and weights.
Three monkeys were trained to lift and hold a test object within a 12- to 25-mm position window for 1 s. The activity of single neurons was recorded during performance of the task in which both the weight and surface texture of the object were systematically varied. Whenever possible, each cell was tested with three weights (15, 65, and 115 g) and three textures (smooth metal, fine 200 grit sandpaper, and rough 60 grit sandpaper). Of 386 cells recorded in 3 monkeys, 45 cells had cutaneous receptive fields on the index or thumb or part of the thenar eminence and were held long enough to be tested in all 9 combinations of texture and weight. Recordings were made for the entire anterior-posterior extent of the thumb and index finger areas in somatosensory cortex including area 7b. However, the statistical analysis required a selection of only those cells for which nine complete recording conditions were available limiting the sample to cells in areas 2, 5, and 7b. Significant differences in the grip force accompanied 98% of the changes in texture and 78% of the changes in weight. Increasing the object weight also increased the force tangential to the skin surface as measured by the load or lifting force. The peak discharge during lifting was judged to be the most sensitive index of cell activity and was analyzed with a two-way analysis of variance (ANOVA). In addition, peak cell discharge was normalized to allow comparisons among different combinations of texture and weight as well as comparisons among different neurons. Overall, the peak firing frequency of 87% of the cells was significantly modulated by changes in object texture, but changes in object weight affected the peak activity of only 58% of the cells. Almost all (17/18, 94%) of the static cells were influenced by the object texture, and 81% of the dynamic cells that were active only briefly at grip and lift onset were modulated by texture. For some cells, surface texture had a significant effect on neuronal discharge that was independent of the object weight. In contrast, weight-related responses were never simple main effects of the weight alone and appeared instead as significant interactions between texture and weight. Four neurons either increased or decreased activity in a graded fashion with surface structure (roughness) regardless of the object weight (P < 0.05). Ten other neurons showed increases or decreases in response to one or two textures, which might represent either a graded response or a tuning preference for a specific texture. The firing frequency of the majority (31/45) of neurons reflected an interaction of both texture and weight. The cells with texture-related but weight-independent activities were thought to encode surface characteristics that are largely independent of the grip and lifting forces used to manipulate the object. Such constancies could be used to construct internal representations or mental models for planning and controlling object manipulation.


Functional foods: benefits, concerns and challenges-a position paper from the american council on science and health.
Functional foods can be considered to be those whole, fortified, enriched or enhanced foods that provide health benefits beyond the provision of essential nutrients (e.g., vitamins and minerals), when they are consumed at efficacious levels as part of a varied diet on a regular basis. Linking the consumption of functional foods or food ingredients with health claims should be based on sound scientific evidence, with the "gold standard" being replicated, randomized, placebo-controlled, intervention trials in human subjects. However, not all foods on the market today that are claimed to be functional foods are supported by enough solid data to merit such claims. This review categorizes a variety of functional foods according to the type of evidence supporting their functionality, the strength of that evidence and the recommended intakes. Functional foods represent one of the most intensively investigated and widely promoted areas in the food and nutrition sciences today. However, it must be emphasized that these foods and ingredients are not magic bullets or panaceas for poor health habits. Diet is only one aspect of a comprehensive approach to good health.


Partial Thickness Rotator Cuff Tears: Current Concepts.
Partial thickness rotator cuff tears are a common cause of pain in the adult shoulder. Despite their high prevalence, the diagnosis and treatment of partial thickness rotator cuff tears remains controversial. While recent studies have helped to elucidate the anatomy and natural history of disease progression, the optimal treatment, both nonoperative and operative, is unclear. Although the advent of arthroscopy has improved the accuracy of the diagnosis of partial thickness rotator cuff tears, the number of surgical techniques used to repair these tears has also increased. While multiple repair techniques have been described, there is currently no significant clinical evidence supporting more complex surgical techniques over standard rotator cuff repair. Further research is required to determine the clinical indications for surgical and nonsurgical management, when formal rotator cuff repair is specifically indicated and when biologic adjunctive therapy may be utilized.


Negative pressure wound therapy of Corynebacterium jeikeium associated granulomatous mastitis.
We present the first Corynebacterium associated therapy resistant granulomatous mastitis successfully treated with negative pressure wound therapy (NPWT). Our patient had received five different courses of antibiotic therapy, and three surgical explorations before NPWT was introduced and resulted in healing. For a successful treatment, the use of targeted antibiotic therapy, steroid therapy and in case of progressive disease, wide excision is required. When this results in a large wound cavity, NPWT seems an effective and innovative option.


[Reliabilty of intraoperative recurrent laryngeal nerve monitoring in thyroid surgery].
The intraoperative monitoring of the recurrent laryngeal nerve (NLR) is increasingly used in thyroid surgery. What has the surgeon to know about reliability and peculiarity of this method? Between 11/98 and 3/01 417 patients were operated for thyroid pathology. Vocal cord function was controlled pre- and postoperatively in all cases by laryngoscopy. Intraoperative electromygraphic NLR identification and postoperative vocal cord function were registered prospectively. Intraoperative NLR identification succeeded in 98.9 % (776/784 nerves at risk). Minor vocal cord dysfunctions were demonstrable for less than 4 weeks in 13 patients (1.6 %) associated with edema or hematoma in 11/13 cases. Complete unilateral NLR pareses was seen laryngoscopically in 16 patients (2 %). 1 patient revealed a malignant NLR infiltration. Electromygraphic NLR identification wasn't possible and followed by postoperative NLR palsy in 2 patients. In 11/13 cases with a regular intraoperative monitoring postoperative vocal cord function recovered within 8 weeks. In 2 of 4 NLR pareses persisting at the moment the follow up is longer than 12 months (permanent palsy rate 0.25 %). NLR identification during thyroid surgery is improved by intraoperative monitoring. In cases with difficult thyroid preparation the vagal nerve may be stimulated for indirect proof of NLR integrity.


Duodenal rapeseed oil infusion in early and midlactation cows. 5. Milk fatty acids and adipose tissue lipogenic activities.
Lipogenic activities of perirenal adipose tissue were investigated in early (wk 3) and midlactation (wk 19 to 26) cows that received a duodenal rapeseed oil infusion (1.0 to 1.1 kg/d). In midlactation, oil infusion resulted in a decreased rate of fatty acid synthesis from acetate and a decreased rate of the activities of fatty acid synthetase and glucose-6-phosphate dehydrogenase, whereas lipoprotein lipase activity tended to increase. The rate of glucose incorporation into glyceride-glycerol and the activities of glycerol-3-phosphate dehydrogenase and malic enzyme were not significantly affected. Fatty acid C14:0 content of perirenal adipose tissue was decreased, and fatty acid C18:2 and C18:3 contents were increased in oil-infused cows. In early lactation, rates of acetate incorporation into fatty acids and activities of fatty acid synthetase and lipoprotein lipase were very low. Activities of glucose-6-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase were lower in the early than in the midlactation trial. Oil infusion did not change the measured parameters. In both trials, percentages and yields of milk fatty acids C18:1, C18:2, and C18:3 were increased, whereas those of C14:0 and C16:0 were decreased by oil. Calculated transfer rates of absorbed fatty acid C18:2 from oil to milk fat were 16 to 26%. Results suggested that oil fatty acids affected adipose and mammary de novo lipogenesis in a direct way without affecting fatty acid esterification in adipose tissue or total fat secretion in mammary tissue.


Co-infection of human parvovirus B19 in Vietnamese patients with hepatitis B virus infection.
Human parvovirus B19 (B19) has been identified in the serum of hepatitis B virus (HBV) infected patients. However, the effect of B19-infection on the course of HBV-associated liver disease has not previously been investigated. We examined the prevalence of B19-DNA in HBV-infected Vietnamese patients and analysed the association between co-infection and the clinical outcome of HBV-infection. Serum samples from 399 HBV-infected patients and 64 healthy individuals were analysed for the presence of B19-DNA by PCR and DNA-sequencing. B19-DNA was detected in 99/463 (21.4%) individuals. The proportion of HBV-infected patients who were also co-infected with B19 was higher than the healthy controls (P<0.001). B19-DNA was detected more frequently in patients with HBV-associated hepatocellular carcinoma compared to patients with acute and chronic HBV, HBV-associated liver cirrhosis and healthy subjects (P<0.006). A positive correlation was also found between B19-DNA loads and both serum HBV-DNA loads and alanine aminotransferase (rho>0.250 and P<0.05). Our findings demonstrate that B19-infection is frequent in HBV-infected Vietnamese patients. Also, a significant correlation exists between HBV/B19 co-infection and a greater likelihood of progression to more severe hepatitis B-associated liver disease. Further studies are required to determine the role of B19-infection on HBV-associated pathogenesis.


[Genetic aspects of tuberculous infection in adolescents].
Comparative study of the distribution of antigens of HLA-A, B, and C, as well as somato- and phenotype in 234 adolescents has revealed that HLA-A11 and HLA-B12 antigens may indicate a predisposition to tuberculosis and HLA-A28, HLA-B8, and HLA-B51 antigens are involved in its prevention. It has been found that there is predominance of persons having severe forms of somatotype (dolychobrachymorphic) and that there is also a high phenotype stigmatization in adolescents with different manifestations of tuberculous infection.


Trends in hospital service provision.
In this paper, trends in hospital service provision are measured using data on the numbers and nature of hospitals, on hospital expenditure and on hospital activity over recent years. The number of public acute care hospitals was fairly stable, however, bed numbers decreased. Hospital numbers rose for private hospitals, as did numbers of beds, particularly for group for-profit private hospitals. Recurrent health expenditure on hospitals as a proportion of all recurrent health expenditure fell, although it rose for private hospitals, and real increases in expenditure occurred for both public acute and private hospitals. Population rates for separations and patient days rose for private hospitals and were stable and fell, respectively, for public acute hospitals. Average length of stay decreased for both public acute and private hospitals, with increasing numbers of separations occurring on a same day basis. Increasing proportions of procedures were undertaken during same day stays, and in private hospitals. Separation rates varied geographically, with highest rates overall, and for public hospitals and overnight separations, for patients resident in remote centres and other remote areas. Highest rates for private hospitals were for patients resident in capital cities, other metropolitan centres and large rural centres.


Evidence for a correlation between nitric oxide formation by cleavage of organic nitrates and activation of guanylate cyclase.
According to our present understanding organic nitrates like glycerine trinitrate mediate their pharmacological effect by an intracellular stimulation of the enzyme guanylate cyclase (E.C. 22.214.171.124.) [1, 10]. The exact molecular mechanism underlying the process of enzyme activation is still a matter of controversial discussion. But there is general agreement in literature about the fact that organic nitrate compounds are able to activate the enzyme guanylate cyclase only in the presence or by the interaction of the amino acid cysteine [3, 5]. The stimulatory activity of nitric oxide-containing compounds may be due, at least in part, to the formation of active, unstable intermediate S-nitrosothiols, i.e. S-nitrosocysteine in case of the organic nitrates [7]. According to Craven and DeRubertis [2], the active intermediates of guanylate cyclase stimulation are represented by nitric oxide-heme complexes. There is, however, substantial evidence that the organic nitrates have to be cleaved before they become biologically active. During the transformation which takes place in the presence of cysteine or by means of enzymatic catalysis, nitric oxide radicals are reductively split off the molecule from which (via the intermediate formation of salpetric acid) the nitric oxide is liberated as the essential stimulatory agent. In this study we examined the transformation of glycerine trinitrate and other organic nitrates under the influence of different thiols and a purified soluble rat liver guanylate cyclase preparation. At the same time the stimulation of guanylate cyclase in the presence of the thiols mentioned was quantitatively estimated. Only in case of cysteine did we find a strict correlation between the liberation of nitric oxide from different organic nitrates and the degree of enzyme activation. Several other thiols were also able to liberate nitric oxide, but surprisingly enough, there was no equivalent stimulation of guanylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)


H-ATPase Activity from Storage Tissue of Beta vulgaris: IV. N,N'-Dicyclohexylcarbodiimide Binding and Inhibition of the Plasma Membrane H-ATPase.
The molecular weight and isoelectric point of the plasma membrane H(+)-ATPase from red beet storage tissue were determined using N,N'-dicyclohexylcarbodiimide (DCCD) and a H(+)-ATPase antibody. When plasma membrane vesicles were incubated with 20 micromolar [(14)C]-DCCD at 0 degrees C, a single 97,000 dalton protein was visualized on a fluorograph of a sodium dodecyl sulfate polyacrylamide gel. A close correlation between [(14)C]DCCD labeling of the 97,000 dalton protein and the extent of ATPase inhibition over a range of DCCD concentration suggests that this 97,000 dalton protein is a component of the plasma membrane H(+)-ATPase. An antibody raised against the plasma membrane H(+)-ATPase of Neurospora crassa cross-reacted with the 97,000 dalton DCCD-binding protein, further supporting the identity of this protein. Immunoblots of two-dimensional gels of red beet plasma membrane vesicles indicated the isoelectric point of the H(+)-ATPase to be 6.5.


Therapeutic Effect of Long-Term Epidural Block in Rats with Pregnancy Induced Hypertension.
Pregnancy induced hypertension (PIH) causes a variety of systemic disorders that negatively affect the maternal placenta and fetal growth. Epidural sympathetic block elicits symptoms of decreased blood pressure. This study was designed to determine the therapeutic effect of long-term epidural block in rats with PIH. Forty healthy pregnant Sprague Dawley rats were randomized into four groups with each group consisting of 10 rats. On gestation day (GD) 14, rats in control group underwent a sham procedure; rats in RUPP group were operated on to obtain reduced uterine perfusion pressure (RUPP); rats in RUPP plus normal saline (NS) group were also subjected to the RUPP procedure and underwent epidural block with 25 μl normal saline twice daily until delivery; rats in RUPP plus epidural block (EB) group were treated as those in RUPP plus NS group except that an epidural block with 25 μl of 0.125% bupivacaine was administered two times per day until delivery. On GD 20, blood pressure was measured in all groups before delivery, and blood samples were collected in order to quantify the serum concentrations of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1). The mean arterial pressure (MAP) of rats in RUPP group (147.6 ± 6.0 mmHg) was markedly increased when compared with control group (80.8 ± 4.6 mmHg) (p < 0.05). The MAP of rats in RUPP plus EB group (114.4 ± 7.2 mmHg) was clearly decreased in contrast with RUPP group but was still higher than in control group (p < 0.05). The variation of fetal weight in all groups followed a similar trend to that of MAP. However, there were no significant differences between control group and RUPP plus EB group with respect to placental weight (p = 0.186). Variation in MAP was positively correlated with the expression of sFlt-1 in each group but was negatively correlated with VEGF. This study demonstrates that long-term epidural block decreases blood pressure in PIH rats and improves the serum concentrations of VEGF and sFlt-1. Taken together, long-term epidural block may have a potential role in PIH treatment.


Panmasala chewing induces deterioration in oral health and its implications in carcinogenesis.
ABSTRACT Panmasala containing tobacco was introduced in the Indian market during the 1970s. Panmasala consists of areca nut (betel nut), catechu, lime, cardamom, spices, and unspecified flavoring agents, etc., with tobacco locally known as gutkha or without tobacco (Plain or sada), and consumed abundantly in India and also other parts of the world, predominantly in South East Asian countries. Available studies demonstrate that the habits of chewing panmasala gutkha or plain by students and adolesescents are on the increase, which may lead to deterioration of oral health and other organ systems. Based on the experimental as well as clinical studies available on panmasala as well as on different components of panmasala, this review suggests that it has the potential in causation of various oral diseases such as Oral Sub Mucosis Fibrosis (OSMF) and leucoplakia which may lead to oral cancer. Studies reviewed on these chewing mixtures also reveal that it is likely to be carcinogenic, as tobacco and areca nut have carcinogenic potential and both have encompassing addictive potential leading to dependence on chewing mixture containing areca nut and tobacco. These mixtures might not only lead to cancer but may also affect other organs of the body, including oral hard tissues in the form of dental attrition and sensitivity. There is a need to consider the potential health hazards associated with the habits of these products, especially oral cancer. More research is needed to find out early changes which could be reversible and also intervention measures through education to desist people in indulging in such habits.


GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients.
We have genotyped 657 Norwegian men, including 282 lung cancer patients (147 non-operable and 135 operable) and 375 healthy referents (210 smokers and 165 non-smokers), to study the possibility that glutathione S-transferase M1 (GSTM1)-null and/or N-acetyl transferase 2 (NAT2)-slow genotypes confer susceptibility towards lung cancer in smokers. Compared with smoking referents, there was a significant over-representation of the GSTM1-null genotype among patients with squamous cell carcinoma (SQ) [odds ratio (OR) = 1.7, 95% confidence interval (95%CI) = 1.1-2.7], and the NAT2-slow genotype among patients with large cell carcinoma or mixed histological diagnosis (LM) (OR = 2.5, 95%CI = 1.0-6.1). In contrast to operable patients, non-operable patients showed a clear over-representation of slow genotypes if they were younger (</= 63 years; versus older: OR = 3.9, 95%CI = 1.7-8.8) or younger light smokers [</= 30 pack-years (PY); versus heavy smokers: OR = 5.7, 95%CI = 1.4-23.3]. Among younger light smokers, the slow genotype appeared to be associated with an increased risk of developing non-operable tumours only (OR = 6.3, 95%CI = 1.9-20.4), especially other types of tumours than SQ (OR = 10.8, 95%CI = 1.4-83.9). The null genotype (OR = 3.9, 95%CI = 1.1-13.5) and the null/slow combination (OR = 4.5, 95%CI = 1.5-13.8) seemed to increase the risk for non-operable SQ only. These results are supported by logistic regressions of patients allowing interactions between tumour type (or treatment) and PY (or age), and indicate that the GSTM1-null genotype could be an important susceptibility factor for SQ while the NAT2-slow genotype may have an impact on other types of lung cancer. Individuals with the GSTM1-null and/or NAT2-slow genotypes may constitute susceptible groups with increased risk to contract non-operable lung cancer at younger age and lower smoking dose.


Swan-Ganz catheter-induced severe complications in cardiac surgery: right ventricular perforation, knotting, and rupture of a pulmonary artery.
The role of Swan-Ganz catheterization for cardiac surgery and perioperative management has recently been scrutinized. Prospective observational study for serious complications related to Swan-Ganz catheterization. 7150 patients undergoing cardiac operations at a major European heart center and academic setting. 3730 Swan-Ganz catheter placements for cardiac surgery (7.5 French Swan-Ganz Catheter Baxter, heparin coated). We observed four serious complications related to Swan-Ganz catheterization and placement (0.1%): A right ventricular free wall perforation occurred, one trouble with knotting, and two pulmonary artery ruptures. The right ventricular perforation was controlled with a suture, the knot was tightened, and the catheter withdrawn through insertion. The first case of pulmonary artery rupture was treated conservatively. All of these patients survived. The other pulmonary artery rupture occurred during coronary artery bypass grafting. Emergency lobectomy was performed. This patient died due to bleeding during the early postoperative course. The incidence of serious Swan-Ganz catheter complications in our patient population is comparable to the incidence reported in the literature. Based on these results the use of Swan-Ganz catheters in cardiac surgery is still justified since the rate of associated serious complications is extremely low. Despite the rare occurrence of serious complications and the infrequent fatal outcomes, the benefit of its use in selected cases of cardiac surgery overweight its associated complications.


The H1 histamine receptor blocker, chlorpheniramine, completely prevents the increase in REM sleep induced by immobilization stress in rats.
Chlorpheniramine is a selective antagonist of the H1 histaminergic receptor subtype and its effects in humans include somnolence. Chlorpheniramine affects sleep in rats, mainly by decreasing REM sleep. On the other hand, stress by immobilization induces an important increase in the percentage of REM sleep. In this study we analyzed the effects of blocking histaminergic receptors on REM sleep induced by immobilization stress. Adult male Wistar rats were chronically implanted for sleep recording. Immobilization stress was induced by placing the rat in a small cylinder for 2 h. Experimental conditions were: A. Control; B. Stress; C. Stress plus vehicle and D. Stress plus chlorpheniramine. Independent experiments were done both in the dark, as well as the light period. Results showed that the increase in REM sleep observed after immobilization stress was completely abolished by chlorpheniramine, both in the dark and in the light phase. Furthermore, the decrease in REM sleep was significant even when compared to the non-stressed control rats. REM sleep latency was also significantly longer during both light phases. The present results suggest that REM sleep is quite sensitive to histaminergic blockage. It is possible that chlorpheniramine is also blocking the cholinergic mechanisms generating REM sleep.


Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist.
Histone deacetylase inhibitors (HDACi) and agents such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL receptor (TRAIL-R) antibodies are anticancer agents that have shown promise in preclinical settings and in early phase clinical trials as monotherapies. Although HDACi and activators of the TRAIL pathway have different molecular targets and mechanisms of action, they share the ability to induce tumor cell-selective apoptosis. The ability of HDACi to induce expression of TRAIL-R death receptors 4 and 5 (DR4/DR5), and induce tumor cell death via the intrinsic apoptotic pathway provides a molecular rationale to combine these agents with activators of the TRAIL pathway that activate the alternative (death receptor) apoptotic pathway. Herein, we demonstrate that the HDACi vorinostat synergizes with the mouse DR5-specific monoclonal antibody MD5-1 to induce rapid and robust tumor cell apoptosis in vitro and in vivo. Importantly, using a preclinical mouse breast cancer model, we show that the combination of vorinostat and MD5-1 is safe and induces regression of established tumors, whereas single agent treatment had little or no effect. Functional analyses revealed that rather than mediating enhanced tumor cell apoptosis via the simultaneous activation of the intrinsic and extrinsic apoptotic pathways, vorinostat augmented MD5-1-induced apoptosis concomitant with down-regulation of the intracellular apoptosis inhibitor cellular-FLIP (c-FLIP). These data demonstrate that combination therapies involving HDACi and activators of the TRAIL pathway can be efficacious for the treatment of cancer in experimental mouse models.


Compressive elasticity of three-dimensional nanofiber matrix directs mesenchymal stem cell differentiation to vascular cells with endothelial or smooth muscle cell markers.
The importance of mesenchymal stem cells (MSC) in vascular regeneration is becoming increasingly recognized. However, few in vitro studies have been performed to identify the effects of environmental elasticity on the differentiation of MSC into vascular cell types. Electrospinning and photopolymerization techniques were used to fabricate a three-dimensional (3-D) polyethylene glycol dimethacrylate nanofiber hydrogel matrix with tunable elasticity for use as a cellular substrate. Compression testing demonstrated that the elastic modulus of the hydrated 3-D matrices ranged from 2 to 15 kPa, similar to the in vivo elasticity of the intima basement membrane and media layer. MSC seeded on rigid matrices (8-15 kPa) showed an increase in cell area compared with those seeded on soft matrices (2-5 kPa). Furthermore, the matrix elasticity guided the cells to express different vascular-specific phenotypes with high differentiation efficiency. Around 95% of MSC seeded on the 3-D matrices with an elasticity of 3 kPa showed Flk-1 endothelial markers within 24h, while only 20% of MSC seeded on the matrices with elasticity >8 kPa demonstrated Flk-1 marker. In contrast, ∼80% of MSC seeded on 3-D matrices with elasticity >8 kPa demonstrated smooth muscle α-actin marker within 24h, while fewer than 10% of MSC seeded on 3-D matrices with elasticity <5 kPa showed α-actin markers. The ability to control MSC differentiation into either endothelial or smooth muscle-like cells based purely on the local elasticity of the substrate could be a powerful tool for vascular tissue regeneration.


Level of implementation of best practice policies for creating healthy food environments: assessment by state and non-state actors in Thailand.
To determine and compare the level of implementation of policies for healthy food environments in Thailand with reference to international best practice by state and non-state actors. Data on the current level of implementation of food environment policies were assessed independently using the adapted Healthy Food Environment Policy Index (Food-EPI) by two groups of actors. Concrete actions were proposed for Thai Government. A joint meeting between both groups was subsequently held to reach consensus on priority actions. Thailand. Thirty state actors and twenty-seven non-state actors. Level of policy implementation varied across different domains and actor groups. State actors rated implementation levels higher than non-state actors. Both state and non-state actors rated level of implementation of monitoring of BMI highest. Level of implementation of policies promoting in-store availability of healthy foods and policies increasing tax on unhealthy foods were rated lowest by state and non-state actors, respectively. Both groups reached consensus on eleven priority actions for implementation, focusing on food provision in public-sector settings, food composition, food promotion, leadership, monitoring and intelligence, and food trade. Although the implementation gaps identified and priority actions proposed varied between state and non-state actors, both groups achieved consensus on a comprehensive food policy package to be implemented by the Thai Government to improve the healthiness of food environments. This consensus is a platform for continued policy dialogue towards cross-sectoral policy coherence and effective actions to address the growing burden of non-communicable diseases and obesity in Thailand.


The role of breast MR imaging in pre-operative determination of invasive disease for ductal carcinoma in situ diagnosed by needle biopsy.
To evaluate whether magnetic resonance (MR) imaging features can predict the presence of occult invasion in cases of biopsy-proven pure ductal carcinoma in situ (DCIS). We retrospectively reviewed 92 biopsy-proven pure DCIS in 92 women who underwent MR imaging. The following MR imaging findings were compared between confirmed DCIS and invasive breast cancer (IBC): lesion size, type, morphological and kinetic assessments by ACR BI-RADS MRI, and findings of fat-suppressed T2-weighted (FS-T2W) imaging. Sixty-eight of 92 (74%) were non-mass-like enhancements (NMLE) and 24 were mass lesions on MR imaging. Twenty-one of 68 (31%) NMLE and 13 of 24 (54%) mass lesions were confirmed as IBC. In NMLE lesions, large lesions (P = 0.007) and higher signal intensities (SI) on FS-T2W images (P = 0.032) were significantly associated with IBC. Lesion size remained a significant independent predictor of invasion in multivariate analysis (P = 0.032), and combined with FS-T2W SIs showed slightly higher observer performances (area under the curve, AUC, 0.71) than lesion size alone (AUC 0.68). There were no useful findings that enabled the differentiation of mass-type lesions. Breast MR imaging is potentially useful to predict the presence of occult invasion in biopsy-proven DCIS with NMLE. MR mammography permits more precise lesion assessment including ductal carcinoma in situ A correct diagnosis of occult invasion before treatment is important for clinicians This study showed the potential of MR mammography to diagnose occult invasion Treatment and/or aggressive biopsy can be given with greater confidence MR mammography can lead to more appropriate management of patients.


Hormonal vitamin D up-regulates tissue-specific PD-L1 and PD-L2 surface glycoprotein expression in humans but not mice.
PD-L1 (programmed death ligand 1) and PD-L2 are cell-surface glycoproteins that interact with programmed death 1 (PD-1) on T cells to attenuate inflammation. PD-1 signaling has attracted intense interest for its role in a pathophysiological context: suppression of anti-tumor immunity. Similarly, vitamin D signaling has been increasingly investigated for its non-classical actions in stimulation of innate immunity and suppression of inflammatory responses. Here, we show that hormonal 1,25-dihydroxyvitamin D (1,25D) is a direct transcriptional inducer of the human genes encoding PD-L1 and PD-L2 through the vitamin D receptor, a ligand-regulated transcription factor. 1,25D stimulated transcription of the gene encoding PD-L1 in epithelial and myeloid cells, whereas the gene encoding the more tissue-restricted PD-L2 was regulated only in myeloid cells. We identified and characterized vitamin D response elements (VDREs) located in both genes and showed that 1,25D treatment induces cell-surface expression of PD-L1 in epithelial and myeloid cells. In co-culture experiments with primary human T cells, epithelial cells pretreated with 1,25D suppressed activation of CD4+ and CD8+ cells and inhibited inflammatory cytokine production in a manner that was abrogated by anti-PD-L1 blocking antibody. Consistent with previous observations of species-specific regulation of immunity by vitamin D, the VDREs are present in primate genes, but neither the VDREs nor the regulation by 1,25D is present in mice. These findings reinforce the physiological role of 1,25D in controlling inflammatory immune responses but may represent a double-edged sword, as they suggest that elevated vitamin D signaling in humans could suppress anti-tumor immunity.


[Experimental study on intraperitoneal sequential MTX/5-FU therapy for peritoneal seeding in comparison with intravenous administration].
Sequential MTX/5-FU therapy (intravenous route) is powerful chemotherapy especially for poorly differentiated adenocarcinoma of the stomach and its peritoneal metastases. The authors had proposed the idea of intraperitoneal sequential MTX/5-FU chemotherapy for potential peritoneal metastases and micrometastases from advanced gastric carcinoma. This experimental study was planned to confirm this experimentally. Peritoneal seeding model of nude mice was made by the intraperitoneal inoculation of human gastric cancer cell line MKN-45. Control group (n = 5) had no treatment. The intraperitoneal (i.p.) group and intravenous (i.v.) group underwent the treatments on the 7th, 14th, and 21st day after cell implantation. Experimental chemotherapies consisted of intraperitoneal injection of MTX (15 mg/kg, 1.5 ml saline) and 5-FU (50 mg/kg, 1.0 ml saline) for i.p. group and intravenous injection of MTX (15 mg/kg, 0.2 ml saline) and 5-FU (50 mg/kg, 0.2 ml saline) for i.v. group. Interval time between MTX and 5-FU administration was 2 hours. On the 35th day after the cell implantation necropsies were performed. Counting of peritoneal metastatic nodules revealed the number of nodules of control group. (14.2 +/- 6.7) > i.v. group (5.3 +/- 4.1) > i.p. group (0.41 +/- 0.7) (p < 0.05). Weight of omental tumors showed Control group (0.246 +/- 0.136 g) > i.v. group (0.140 +/- 0.068 g) > i.p. group (0.051 +/- 0.017 g) (i.v.-i.p., p < 0.01). The mouse body weight decrease less in the i.p. group than in the i.v. group (p < 0.05) throughout this experiment. The results of this experiment demonstrated intraperitoneal sequential MTX/5-FU therapy was more effective than intravenous sequential MTX/5-FU therapy for potential peritoneal seeding and peritoneal micrometastases from the gastric cancer. Moreover, the side effect of intraperitoneal administration was milder than by the intravenous route.


[Salvage therapy by hemicortical excision and reconstruction for low-grade malignant bone tumour].
To treat low-grade limb malignant tumors with hemicortical excision and reconstruction of the defect with recycled pasteurized autograft. From January 2005 to January 2011, 10 patients [age (27.0±6.5) years] suffering from low-grade limb malignant tumors were treated with hemicortical excision and reconstruction of the defect with recycled pasteurized autograft: 7 were histopathologically diagnosed as parosteal osteosarcoma, and 3 as peripheral chondrosarcoma. According to the Enneking staging system, 8 were in Stage IA and 2 were in IB. All the patients were followed-up for (50±23) months. All the patients had bony union at the last follow-up. The length of tumor bone resection was (9.5±2.7) cm, operation time was (150±45) min, intraoperative blood loss was (1000±350) mL, and drainage volume was (450±200) mL. The only fracture in the host bone during the operation was treated by internal fixation. Local recurrence occurred in 1 patient was treated by a wide operative margin and reconstruction with a prosthesis. There was no distal metastasis. A ccording to the Enneking system, 9 patients had excellent results and 1 had good results. Hemicortical excision for low-grade limb malignant tumors is safe and effective.


Neuro-ophthalmic, radiographic, and pathologic manifestations of adult-onset Alexander disease.
A 61-year-old woman had a 3-year history of imbalance. Eye movement studies revealed square-wave jerks, gaze paretic nystagmus, rebound nystagmus, impaired smooth pursuit, impaired optokinetic nystagmus, and abnormal fixation suppression of vestibular nystagmus. A brain magnetic resonance imaging study showed extensive areas of increased signal from the middle cerebellar peduncles and dentate nuclei, which enhanced with gadolinium. Histopathological analysis of a needle biopsy specimen of the left cerebellar peduncle revealed diffuse gliosis in the presence of symmetrically distributed areas of demyelination. There were associated Rosenthal fibers. Clinicopathologic correlation supported a diagnosis of Alexander disease. An adult patient with a history of progressive imbalance, ocular motility abnormalities consistent with cerebellar and/or brainstem dysfunction, and diffuse, symmetric hyperintense magnetic resonance imaging signals in brainstem and cerebellar white matter should suggest a diagnosis of adult-onset Alexander disease.


Costs associated with symptomatic systolic heart failure.
To investigate whether the extent of systolic dysfunction is a useful predictor of the costs of healthcare and social support for patients with heart failure. Cross-sectional study with collection of cost data attributed to management of heart failure in the previous year. Four primary-care practices in Scotland. Patients receiving long term therapy with loop diuretics for suspected heart failure. Two-dimensional and Doppler echocardiography. Two hypotheses were tested: (i) the proportion of patients incurring costs is higher in patients with abnormal left ventricular (LV) function; and (ii) the median cost per patient that incurs costs is higher in patients with abnormal LV function. Of the 226 patients in the study, 67 (30%) had abnormal systolic function. In comparison with the remaining 159 patients, they had higher healthcare costs [560 Pounds vs 440 Pounds per patient year (1994/1995 values)], were more likely to incur hospital inpatient or outpatient costs [Odds ratio (OR): 2.02; 95% confidence interval (CI): 1.06 to 3.84] and had significantly higher primary-care costs (mean 292 Pounds vs 231 Pounds per patient year; p = 0.02, Mann Whitney test). In contrast, they were no more likely to incur social support costs (OR: 1.22; 95% CI: 0.52 to 2.86) and the mean cost of social support per patient year was lower (234 Pounds vs 373 Pounds). Patients with objectively measured systolic dysfunction incurred significantly higher healthcare costs in the year before diagnosis. This suggests that treatment that improves systolic function will reduce healthcare costs, even in a primary-care population with relatively mild congestive heart failure.


Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation.
We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398X optineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration.


Vitamin B6 status improves in overweight/obese women following a hypocaloric diet rich in breakfast cereals, and may help in maintaining fat-free mass.
To analyze the changes in vitamin B6 status in women following slightly hypocaloric diets based on the relative increase consumption of foods whose intakes are below those recommended, and to study how these changes influence the proportion of fat-free mass. Intervention study of two slightly hypocaloric diets: diet V (increased consumption of vegetables), or diet C (increased consumption of cereals, especially breakfast cereals). A total of 49 women with a body mass index (BMI) of 25-35 kg/m2. Dietetic, anthropometric and biochemical data were collected at the start of the study and at 2 and 6 weeks. Both the C and V subjects showed a reduction in their energy intake, body weight, BMI and fat mass. Pyridoxine intake increased in both groups and plasma pyridoxal phosphate (PLP) levels increased only with diet C. An association was found between the increase in plasma PLP at 6 weeks and the increase in pyridoxine intake (r=0.451; P<0.01). Multiple regression analysis showed a positive association between the increase in PLP at the end of the study and the increases in the pyridoxine intake, B6 density or B6/protein ratio. At the end of the study, and only in those women whose PLP levels were increased, the higher the increase in PLP level, the higher the increase in fat-free mass percentage (r=0.4426, P<0.05). Interventions aimed at weight control should also try to maintain or improve nutritional status. A diet rich in cereals (especially fortified breakfast cereals) appears to be useful in improving vitamin B6 status. Such an improvement could help maintain fat-free mass during periods of weight loss.


Use Patterns, Knowledge Diversity and Drivers for the Cultivation of the Miracle Plant [Synsepalum dulcificum (Schumach & Thonn.) Daniell] in Benin and Ghana.
Despite the growing interest in the miracle plant worldwide due to its numerous applications, the threats and the wild harvest of the species hamper its sustainable utilisation. Moreover, traditional knowledge so far documented on the species is limited to a narrow geographical coverage of its natural distribution range, which is West and Central Africa. This study analysed the use variation and knowledge acquisition pattern of the miracle plant among West African sociolinguistic groups and deciphered the drivers of populations' willingness and readiness to engage in cultivating the species. Semi-structured interviews were conducted with 510 respondents purposively selected from nine sociolinguistic groups in Benin and Ghana using the snowball sampling approach. Information was collected on respondents' socio-demographic profile, miracle plant ownership, plant parts used and preparation methods, knowledge of the species bioecology, perceived threats on the species, willingness to cultivate, maximum acreage to allocate to the species and maximum price to pay for a seedling. Descriptive statistics, generalized linear models, classification and regression tree models were used for data analysis. The miracle plant ownership mode depended on the age category. Sociolinguistic affiliation, level of schooling, migratory status and religion significantly affected the number of trees owned. We recorded 76 uses belonging to six use categories. The overall use-value of the miracle plant significantly varied according to the respondent sociolinguistic affiliation, main activity and religion. Men were the main source of knowledge and knowledge is mainly acquired along the family line. Knowledge related to food and social uses was mostly acquired from parents and people of the same generation, while magico-therapeutic and medicinal use-related knowledge were inherited from parents and grandparents. Sociolinguistic affiliation, awareness of taboos and market availability were the most important drivers of respondent willingness to cultivate the miracle plant. While the respondent's level of schooling and perception of plant growth rate determined the maximum acreage they were willing to allocate to the species in cultivation schemes, their main activity, sociolinguistic affiliation and knowledge of the species time to fruiting drove the maximum purchase price they were willing to offer for a seedling of the species. Our findings provide key information for the promotion of miracle plant cultivation in the study area.


Inhibition of tumor cell growth by Triton X-100 through specific effects on cell-cycle-regulatory components.
A cross-linked form of the detergent Triton X-100, called Triton WR-1339, has been shown to reduce the spread of tumor cells in laboratory animals. However, some of these effects were controversial, probably due to the use of different tumor cell lines and varying sites of injection. In order to better understand these processes, we have used Triton X-100 and performed a molecular analysis of its growth-inhibitory function. Using the T24 bladder carcinoma cell line, we have shown that treatment of cells with this detergent caused a potent antiproliferative effect resulting from the downregulation of the key cell cycle regulators, the cyclin-dependent kinases (CDKs). CDK activity was lost due to a twofold effect, the increased expression of the CDK inhibitors p21(Cip1) and p27(Kip1) in combination with the reduced expression of cyclin A, a regulatory CDK subunit that is essential for CDK function. Taken together, our results provide a molecular basis for the antiproliferative effects of the Triton detergent, namely its differential effects on various parts of the cell cycle machinery.


Light and acetate regulate a mitochondrial malate dehydrogenase.
A malate dehydrogenase was purified from the unicellular green alga Chlorogonium elongatum Dangeard. The enzyme was localized in the mitochondria by immunogold electron microscopy and was found to be present on the cristae. The concentration of the enzyme is regulated by acetate and light. In cells cultured heterotrophically with acetate as carbon source the activity and the concentration of the enzyme is 5- to 6-fold higher than in autotrophic cells. In mixotrophically cultured cells (light and acetate) the enzyme level attains only half of the value of that in heterotrophic cells. Acetate induces an increase of the enzyme concentration while light has an inhibitory effect on this process.


Allergen immunotherapy for food allergy from the Asian perspective: key challenges and opportunities.
Introduction: Prevalence of food allergy is rising in different regions of the world. Asia has not been spared from this epidemic, but epidemiological data have revealed a different pattern of food allergens in this continent. Allergen-specific immunotherapy (AIT) for food allergy, which has been revolutionary as the main focus of research in recent years, needs to be adapted for the different populations in Asia. Areas covered: Recent evidence shows increasing popularity and superiority of AIT over strict food avoidance as the cornerstone of food allergy management. Asia is a distinctive continent with specific food allergy triggers, in particular, seafood, and wheat. Peanut, on the contrary, is not a common food allergen in most parts of Asia. The common Asian food allergens, as well as the rapidly developing food-specific AIT in this region will be covered in this article. Expert commentary: Evidence on oral immunotherapy for wheat allergy and preclinical data on shellfish AIT are promising. Further work should be done on resolving cross-sensitization between environmental allergens with wheat and shellfish allergens, and a modified AIT approach to enhance the safety and effectiveness of food-specific immunotherapy.


Adenovirus entry into host cells: a role for alpha(v) integrins.
The mechanism(s) by which nonenveloped viruses enter host cells is poorly understood. The recent identification of cell-surface alpha(v) integrins as receptors for adenovirus internalization has shed much light on this process. In addition, analysis of alpha(v) integrins as internalization receptors for adenovirus has provided further insights into the biology of integrins.


Analysis of restriction profiles of mitochondrial DNA from Sporothrix schenckii.
Mitochondrial DNA (mtDNA) diversity was analyzed in 42 clinical isolates of Sporothrix schenckii from Mexico (n = 29), Guatemala (n = 4) and Colombia (n = 9). Based on HaeIII restriction digestion profiles, the isolates were classified into eight types. In addition to 24 mtDNA types previously reported in another study, 6 new types were found in this study. Most of the strains belong to type 14 and type 30, the former restricted to Mexico, whereas the latter was distributed in Mexico, Guatemala and Colombia. The new types (25-30) were identified in Mexico, Guatemala and Colombia. Restriction-fragment length polymorphism in mtDNA of S. schenckii revealed high levels of genetic variation attributable to differences in restriction sites as well as in mtDNA size. Based on genetic distances S. schenckii types were clustered into two main groups.


Novel RHAG allele encoding the Rh(null) phenotype in Brazil.
Rhnull is a rare phenotype characterized by the loss of Rh antigen expression. This phenotype can be related to several molecular backgrounds. In this study, we show a novel allele in a Brazilian pregnant woman encoding the Rhnull phenotype due to a change in RHAG exon2 c.310C>T, which leads to a premature stop codon (Gln104Stop).


Review: Glycation of human serum albumin.
Glycation involves the non-enzymatic addition of reducing sugars and/or their reactive degradation products to amine groups on proteins. This process is promoted by the presence of elevated blood glucose concentrations in diabetes and occurs with various proteins that include human serum albumin (HSA). This review examines work that has been conducted in the study and analysis of glycated HSA. The general structure and properties of HSA are discussed, along with the reactions that can lead to modification of this protein during glycation. The use of glycated HSA as a short-to-intermediate term marker for glycemic control in diabetes is examined, and approaches that have been utilized for measuring glycated HSA are summarized. Structural studies of glycated HSA are reviewed, as acquired for both in vivo and in vitro glycated HSA, along with data that have been obtained on the rate and thermodynamics of HSA glycation. In addition, this review considers various studies that have investigated the effects of glycation on the binding of HSA with drugs, fatty acids and other solutes and the potential clinical significance of these effects.


Group delay and chromatic dispersion of thin-film-based, narrow bandpass filters used in dense wavelength-division-multiplexed systems.
Theoretical analysis is made for thin-film-based, 200- and 100-GHz narrow bandpass filters with respect to the intensity response as well as to the chromatic dispersion. The results indicate that the narrower the passband, the higher the chromatic dispersion. The maximum chromatic dispersion appears at the edges of the 0.5-dB passband, owing to the fast change of the group delay in the region. The deviation of chromatic dispersion induced by manufacturing error is simulated. Effective-medium approximation layers are added to simulate the contribution of surface roughness and the mixture interfaces to the passband ripple as well as the chromatic dispersion. The simulations are compared with the experimental results. The measured chromatic dispersion matches the general trend of the theoretical calculation. The imperfect surface and layer mismatch induce additional ripples across the 0.5-dB passband. The maximum chromatic dispersion within a 0.5-dB passband is 20.7 and 54.9 ps/nm for 200- and 100-GHZ narrow bandpass filters, respectively.