Expression of CD63 in Lung Tissue of Guinea Pigs Dying of Anaphylactic Shock.
Objective To study the protein expression of cluster of differentiation 63 (CD63) in lung tissues of guinea pigs that died of anaphylactic shock and discuss the diagnostic value of CD63 for death from anaphylactic shock. Methods Twenty guinea pigs were randomly divided into control group, anaphylactic shock immediate death group, cold storage group (4 ℃ for 48 h) and frozen group (-20 ℃ for 7 d). The animal model of guinea pigs that died of anaphylactic shock was established with human mixed serum injection. The expression changes of CD63 protein and CD63 mRNA in lung tissues were detected by hematoxylin-eosin (HE) staining, immunohistochemical staining, Western blotting, enzyme-linked immunosorbent assay (ELISA) and real-time RT-PCR. Results HE staining results showed congestion, and edema of lung tissues, and eosinophil infiltration in the anaphylactic shock groups. Western blotting analysis results showed that the expression of CD63 protein in the lung tissues of guinea pigs that died of anaphylactic shock was significantly higher than that in the control group (P<0.05). Comparison between the anaphylactic shock groups was made, and the differences had no statistical significance. The results of immunohistochemical staining and real-time RT-PCR were consistent with that of Western blotting. ELISA results showed that CD63 protein expression in the immediate death group was higher than that in the control group (P<0.05). Conclusion The expression of CD63 protein and CD63 mRNA in the lung tissues of guinea pigs that died of anaphylactic shock is significantly enhanced. Animal carcasses which were put in cold storage for 48 h and frozen for 7 d do not affect the examination of the above indicators. CD63 protein is expected to become an auxiliary diagnostic indicator of death from anaphylactic shock.


Assay for antiviral activity of herbal extracts using their absorbed sera.
We evaluated an antiviral assay procedure using serum obtained from guinea pigs administered 32 herbal extracts. In this assay, 21 of the 32 showed anti-herpes simplex virus type 1 (HSV-1) activity in serum. Ten of the 21 exhibited therapeutic anti-HSV-1 activity, and this was consistent with our previous results that 12 of the 32 were effective in murine infection models. Therefore, the serum pharmacological assay procedure was suitable for the selection of possible herbal extracts with biological activity in vivo as a pre-screening method before animal experiments.


Technical considerations in the application of intensity-modulated radiotherapy as a concomitant integrated boost for locally-advanced cervix cancer.
The technical aspects of IMRT applied to cervix cancer are discussed in this paper, as well as issues related to tumor delineation, target volume definitions, inverse planning, and IMRT delivery. A theoretical example illustrating how IMRT can accurately mimic dose distributions obtained using conventional planning plus HDR brachytherapy is also shown. The notion of clinical optimization parameters is introduced to account for the radiation delivery variables, which affect the overall treatment time. This is especially relevant to the possible introduction of intrafractional movement and resulting inaccuracy, as well as facility efficiency.


Development and Application of an RT-PCR to Differentiate the Prevalent NA-PRRSV Strains in China.
PRRSV features with genetic diversity and high mutation which leads to the emergence of a multiple of circulating virus strains with different virulence. North American (genotype 2) PRRSV (NA-PRRSV) can be divided into classical PRRSV (C-PRRSV), highly pathogenic PRRSV (HP-PRRSV), and NADC30-like PRRSV (NL-PRRSV) according to their genomic characteristics and pathogenicity. So far, the above three subtypes of NA-PRRSV are now circulating in China. In this study, a reverse transcript polymerase chain reaction (RT-PCR) was established to simultaneously differentiate three subtypes of NA-PRRSV. The established RT-PCR can be applied to PRRSV-infected samples originated from both supernatant of cell culture and pig tissues and showed specificity exclusively to PRRSV. The sensitivity of RT-PCR showed the minimum RNA detection was 0.04ng/µl. The established RT-PCR was next used to differentiate the subtypes of 29 NA-PRRSV isolated in 2016 and the results showed that HP-PRRSV is still the dominant circulating virus strain in the presence of NADC30-like PRRSV in Henan province.


Irreversible inhibition of the bacterial cysteine protease-transpeptidase sortase (SrtA) by substrate-derived affinity labels.
We report on the first synthesis, kinetic evaluation and application of novel substrate-derived inhibitors against the Staphylococcus aureus cysteine protease-transpeptidase, sortase (staphylococcal surface protein sorting A, SrtA). The peptidyl-diazomethane and peptidyl-chloromethane analogues, Cbz (benzyloxycarbonyl)-Leu-Pro-Ala-Thr-CHN(2) (I) and Cbz-Leu-Pro-Ala-Thr-CH(2)Cl (II) respectively were found to act as time-dependent irreversible inhibitors of recombinant sortase (SrtA(DeltaN)). The peptidyl-chloromethane analogue (II) was the most powerful with an inhibitor specificity constant (k(i)/K(i)) of 5.3x10(4) M(-1).min(-1), approx. 2-fold greater than that determined for the peptidyl-diazomethane (I). Additionally, using Western-blot analysis, we have been able to demonstrate that a biotinylated version of the peptidyl-diazomethane analogue, biotin-Ahx (aminohexanoyl)-Leu-Pro-Ala-Thr-CHN(2) (III), can be used as an affinity label to detect the presence of wild-type SrtA in crude cell lysates prepared from S. aureus.


The dark side of the mycorrhiza.
Plant association with arbuscular mycorrhizal (AM) fungi is usually regarded as mutualistic. However, this positive effect could disappear if the benefit of the fungal-plant association changes with colonization density. In order to test the conditionality of this interaction, we evaluated plant performance and tolerance to defoliation across five levels of commercial AM fungal inoculum concentrations. Additionally, we evaluated if plant performance and tolerance were similarly affected by a whole soil community collected under a native congener. Along the gradient of inoculation, plant performance exhibited a peak at intermediate inoculum concentration, indicating the presence of an optimum level of AM fungal concentration that maximized AM fungal benefit. Root colonization by fungal hyphae increased linearly across the experimental inoculation gradient. Paralleling root colonization, plant tolerance to defoliation decreased linearly along the inoculum gradient. Plant performance was similar under the whole soil and commercial treatments. Our results show a negative correlation between tolerance to defoliation and AM fungal inoculum concentration, indicating that AM fungi colonization could constrain the evolution of plant tolerance to herbivory.


An economic approach to energy budgets: HOW many resources should living organisms spare?
Ramsey's economic theory of saving (RTS) estimates how much of its commodities a nation should save to safeguard the well-being of future generations. Since RTS retains many attractive qualities such as simplicity, strength, breadth and generality, here we ask if it would be useful to investigate biophysical issues. Specifically, we focus on a biological topic that lends itself as a backdrop for the study of the imbalance between intake and expenditure, i.e., the evaluation of the multicellular living organisms' energetic requirements and constraints. Our problem is to find at each time the optimum distribution and the right balance of the cellular energy budget between consumption and storage: how much must a living organism spare to increase its chances of survival over long periods? To give an operational example, we discuss the ATP requirements in the central nervous system during the spontaneous and the evoked activity of the brain, showing that the experimentally detected values of energetic expenditure during neural computations match well with the estimations provided by RTS. Suggesting how to find the optimum allocation of the available energy between expenditure and saving at each time, RTS approaches to biological energy budgets may have a wide range of experimental applications, such as: a) optimization of the long-term survival chances of either immortalized cell cultures, or beneficial bacterial colonies and exogenous probiotic mixtures; b) eradication of detrimental biofilms, such as, e.g., heart valves' Streptococcus colonies; c) novel anti-stress and anti-ageing strategies.


Association between Genetic Variations Affecting Mean Telomere Length and the Prevalence of Hypertension and Coronary Heart Disease in Koreans.
In this study, we investigated whether the single nucleotide polymorphisms (SNPs) associated with telomere length (TL) were associated with the incidence of hypertension (HTN)/coronary heart disease (CHD) and cardiovascular risk factors in the Korean population. Data from 5,705 (ages 39-70) participants in the Korean Genome Epidemiology Study (rural Ansung and urban Ansan cohorts) were studied. Twelve SNPs known to be associated with telomere biology were tested for an association with HTN/CHD. As results, no significant associations were found between the selected TL-related SNPs and prevalence of HTN and CHD. Among non-alcohol users, subjects with minor alleles in rs1269304 and rs10936601 (TERC and LRRC34, respectively) exhibited a higher rate of CHD occurrence (odds ratio [OR], 1.862; 95% confidence intervals [CIs], 1.137, 3.049; OR, 1.855; 95% CIs, 1.111, 2.985; respectively). However, alcohol users with minor alleles in rs398652 (PELI2) were significantly associated with higher HTN prevalence (OR, 1.179; 95% CIs, 1.040, 1.336). Of the 3 SNPs related to disease outcomes, rs1296304 was significantly associated with increased levels of diastolic blood pressure (β estimate, 0.470; 95% CIs, 0.013, 0.926). The minor allele in rs398652 was significantly associated with higher levels of body mass index (OR, 0.128; 95% CIs, 0.010, 0.246) and γ-glutamyl transpeptidase (OR, 0.013; 95% CIs, 0.001, 0.024). In conclusion, there were no significant associations between the selected TL-related SNPs and the occurrence of HTN/CHD in Koreans. However, the results suggest the presence of a possible interaction between related SNPs and alcohol behavior associated with HTN/CHD occurrence.


Variable δ(15)N diet-tissue discrimination factors among sharks: implications for trophic position, diet and food web models.
The application of stable isotopes to characterize the complexities of a species foraging behavior and trophic relationships is dependent on assumptions of δ(15)N diet-tissue discrimination factors (∆(15)N). As ∆(15)N values have been experimentally shown to vary amongst consumers, tissues and diet composition, resolving appropriate species-specific ∆(15)N values can be complex. Given the logistical and ethical challenges of controlled feeding experiments for determining ∆(15)N values for large and/or endangered species, our objective was to conduct an assessment of a range of reported ∆(15)N values that can hypothetically serve as surrogates for describing the predator-prey relationships of four shark species that feed on prey from different trophic levels (i.e., different mean δ(15)N dietary values). Overall, the most suitable species-specific ∆(15)N values decreased with increasing dietary-δ(15)N values based on stable isotope Bayesian ellipse overlap estimates of shark and the principal prey functional groups contributing to the diet determined from stomach content analyses. Thus, a single ∆(15)N value was not supported for this speciose group of marine predatory fishes. For example, the ∆(15)N value of 3.7‰ provided the highest percent overlap between prey and predator isotope ellipses for the bonnethead shark (mean diet δ(15)N = 9‰) whereas a ∆(15)N value < 2.3‰ provided the highest percent overlap between prey and predator isotope ellipses for the white shark (mean diet δ(15)N = 15‰). These data corroborate the previously reported inverse ∆(15)N-dietary δ(15)N relationship when both isotope ellipses of principal prey functional groups and the broader identified diet of each species were considered supporting the adoption of different ∆(15)N values that reflect the predators' δ(15)N-dietary value. These findings are critical for refining the application of stable isotope modeling approaches as inferences regarding a species' ecological role in their community will be influenced with consequences for conservation and management actions.


Alcohol dehydrogenase and an inactivator from rice seedlings.
Alcohol dehydrogenase (ADH) was measured in the various organs of rice seedlings (Oryza sativa) growing in air. In extracts from ungerminated seeds, the ADH is stable, but in extracts from seedlings more than 2 days old the enzyme initially present loses activity in a time- and temperature-dependent fashion, due to the presence of an inactivating component which increases with age in roots and shoots. The inactivation can be prevented completely by dithiothreitol, and when this is included in the extraction medium the apparent loss of total ADH in roots and shoots with age is not observed. In seedlings grown in N(2), ADH levels in coleoptile extracts are higher than those in air, the enzyme is stable, and no inactivator can be detected. When seedlings grown for 5 days in air were transferred to N(2) for 3 days, ADH levels increased and there was a decline in inactivator activity. Transfer back to air after 1 day in N(2) led to loss of the accumulated ADH and increase in inactivator. These reciprocal changes and the fact that the inactivator is absent from coleoptiles of seedlings grown in N(2) appear to suggest a regulatory role for the inactivator in vivo. However, it is clear that high levels of inactivator and ADH can exist in cells of seedlings grown in air for long periods without loss of enzyme activity, and it is argued that they must normally be separately compartmented.


[Kearns-Sayre syndrome with GH deficiency].
A case of Kearns-Sayre syndrome with failure to thrive, cytochrome oxidase deficiency in muscle fibers, mtDNA deletion and deficient GH responses to stimulation tests is reported. The patient, when 9 years old, was treated with GH without significant improvement in growth velocity. The opportunity of search for GH deficiency in children with Kearns-Sayre syndrome and failure to thrive is stressed.


Pain assessment during blood collection from sedated and mechanically ventilated children.
This study assessed pain and observed physiological parameters in sedated and mechanically ventilated children during a routine procedure. This observational study was performed in a pediatric intensive care unit. Thirty-five children between 1 month and 12 years of age were assessed before, during, and five minutes after an arterial blood collection for gas analysis (painful procedure). Face, Legs, Activity, Cry and Consolability scale was used to assess pain. In addition, patients' heart rate, respiratory rate, peripheral saturation of oxygen and blood pressure (diastolic and systolic) were recorded. COMFORT-B scale was applied before the pain and physiological parameter assessments to verify sedation level of the subjects. There was an increase in Face, Legs, Activity, Cry and Consolability score (p = 0.0001) during painful stimuli. There was an increase in heart rate (p = 0.03), respiratory rate (p = 0.001) and diastolic blood pressure (p = 0.006) due to pain caused by the routine procedure. This study suggests that assessments of pain using standard scales, such as Face, Legs, Activity, Cry and Consolability score, and other physiological parameters should be consistently executed to optimize pain management in pediatric intensive care units.


[A case of postoperative multiple hepatic metastasis from gastric cancer successfully treated by percutaneous microwave coagulation therapy and hepatic arterial infusion chemotherapy].
A 61-year-old male who underwent radical resection for gastric cancer was diagnosed with multiple hepatic metastasis 2 years and 2 months after the surgery. He first underwent percutaneous microwave hepatic coagulation therapy with segmental hepatic blood flow occlusion and obtained complete coagulation of the main tumor. Consecutively, he received hepatic arterial infusion chemotherapy (FAP: 5-FU, cisplatin, adriamycin) against residual multiple hepatic tumors. These hepatic recurrent lesions disappeared completely after 3 sessions of arterial infusion chemotherapy. At present, this patient is alive with no recurrent lesions, 1 year and 6 months from the beginning of treatment for hepatic metastasis. Recently, we tried hepatic arterial infusion chemotherapy (FAP) in four cases in which the recurrence from gastric cancer was not only in the liver but elsewhere. The response rate (CR and PR) was 75% and no major side effects were observed. In conclusion, some cases can obtain longer survival if the multimoderate therapy including hepatic arterial infusion chemotherapy (FAP) and microwave coagulation therapy are effective.


Electrocardiographic ST-segment elevation: correct identification of acute myocardial infarction (AMI) and non-AMI syndromes by emergency physicians.
To determine the emergency physician's (EP's) ability to identify the cause of ST-segment elevation (STE) in a hypothetical chest pain patient. Eleven electrocardiograms (ECGs) with STE were given to EPs; the patient in each instance was a 45-year-old male with a medical history of hypertension and diabetes mellitus with the chief complaint of chest pain. The EP was asked to determine the cause of the STE and, if due to acute myocardial infarction (AMI), to decide whether thrombolytic therapy (TT) would be administered (the patient had no contraindication to such treatment). Rates of TT administration were determined; appropriate TT administration was defined as that occurring in an AMI patient, while inappropriate TT administration was defined as that in the non-AMI patient. Four hundred fifty-eight EPs completed the questionnaire; levels of medical experience included the following: postgraduate year 2-3, 193 (42%); and attending, 265 (58%). The overall rate of correct interpretation of the study ECGs was 94.9% (4,782 correct interpretations out of 5,038 instances). Acute myocardial infarction with typical STE, ventricular paced rhythm, and right bundle branch block were never misinterpreted. The remaining conditions were misinterpreted with rates ranging between 9% (left bundle branch block, LBBB) and 72% (left ventricular aneurysm, LVA). The overall rate of appropriate thrombolytic agent administration was 83% (1,525 correct administrations out of 1,832 indicated administrations). The leading diagnosis for which thrombolytic agent was given inappropriately was LVA (28%), followed by benign early repolarization (23%), pericarditis (21%), and LBBB without electrocardiographic AMI (5%). Thrombolytic agent was appropriately given in all cases of AMI except when associated with atypical STE, where it was inappropriately withheld 67% of the time. In this survey, EPs were asked whether they would give TT based on limited information (ECG). Certain syndromes with STE were frequently misdiagnosed. Emergency physician electrocardiographic education must focus on the proper identification of these syndromes so that TT may be appropriately utilized.


[Glutamine and branched-chain amino acids--practical importance of their metabolic relations].
Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) represent important precursors in the synthesis of glutamine and alanine in the skeletal muscle. Enhanced oxidation of BCAAs can cover the elevated demands of the body on glutamine and alanine during severe illnesses (sepsis, polytrauma, burns). The sufficient supply of the BCAAs in such conditions is facilitated by increased proteolysis in skeletal muscle. However, it can result in muscle wasting and negative protein balance. While concentrations of the BCAAs and alanine are rarely significantly altered, a marked decrease in glutamine concentration, particularly in skeletal muscle, is frequently observed. Glutamine is therefore considered to be a conditional essential amino acid. The manuscript describes the metabolic relations between BCAAs and glutamine, and explains the importance of the recycling of BCAAs and their ketoanalogues between the liver and skeletal muscle. Finally, it is suggested that the favourable effect of glutamine administration on protein metabolism is related to changes in BCAA metabolism.


Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study.
Tofacitinib is the first oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously treated with methotrexate. We used MarketScan® databases (2011-2014) to study methotrexate-exposed patients with RA who were newly prescribed tofacitinib, DMARDs other than methotrexate, and biologics. The date of first prescription was defined as the cohort entry. The therapy was considered effective if all of the following criteria from a claims-based algorithm were achieved at the first year of follow-up: high adherence, no biologic or tofacitinib switch or addition, no DMARD switch or addition, no increase in dose or frequency of index drug, no more than one glucocorticoid joint injection, and no new/increased oral glucocorticoid dose. The safety outcome was serious infections requiring hospitalization. Non-TNF biologics comprised the reference group. We included 21,832 patients with RA, including 0.8% treated with tofacitinib, 24.7% treated with other DMARDs, 61.2% who had started therapy with TNFi, and 13.3% treated with non-TNF biologics. The rates of therapy effectiveness were 15.4% for tofacitinib, 11.1% for DMARDs, 18.6% for TNFi, and 19.8% for non-TNF biologics. In adjusted analyses, tofacitinib and non-TNF biologics appeared to have similar effectiveness rates, whereas DMARD initiators were less effective than non-TNF biologics. We could not clearly establish if tofacitinib was associated with a higher rate of serious infections. In patients with RA previously treated with methotrexate, our comparisons of tofacitinib with non-TNF biologics, though not definitive, did not demonstrate differences with respect to hospitalized infections or effectiveness.


Methoxy-Group Control of Helical Pitch in Stereoregular Poly(2-ethynylmethoxynaphthalene) Prepared by Rhodium Complex Catalyst.
The position of the methoxy group in a poly(n-methoxy-2-ethynylnaphthalene) (PnMeO2EN) was found to control the helical pitch of the π-conjugated polymer in the solid state. These PnMeO2ENs were stereoregularly synthesized using an Rh-complex catalyst in ethanol or toluene as the solvent. The helical structure in the solid phase was confirmed by conventional analytical methods, namely diffuse reflective ultraviolet⁻visible light (UV⁻Vis) and Raman spectroscopies, X-ray diffraction, and 13C cross-polarization magic angle spinning NMR spectroscopy, together with molecular mechanics calculations, because the as obtained polymers were insoluble in common solvents. The color of poly(6-methoxy-2-ethynylnaphthalene) (P6MeO2EN) (yellow or red) depended on the polymerization solvent, whereas no such dependency was observed for the yellow-colored P7MeO2EN and P8MeO2EN. The helical structures energetically optimized by molecular mechanics indicate that the red- and yellow-colored P6MeO2ENs form contracted and stretched helices, respectively. Due to the relatively unconstrained rotations of the 6-methoxynaphthyl moieties, the methoxy groups in P6MeO2EN are less sterically hindered along the helical axis. On the contrary, P7MeO2EN and P8MeO2EN have stretched helices due to the considerable steric hindrance imparted by their methoxy groups. The thermal cis-to-trans isomerization of P6MeO2EN in the contracted-helix form required a somewhat higher temperature than that of the stretched helix.


Sleep Deprivation Enhances Cocaine Conditioned Place Preference in an Orexin Receptor-Modulated Manner.
Drug addiction and withdrawal are characterized by sleep disruption, but the effects of sleep disruption on these states are not well characterized. Sleep deprivation (SD) immediately before the cocaine conditioning trials enhanced cocaine conditioned place preference (CPP) in a dose-dependent manner (3, 8 mg/kg but not 15 mg/kg) in mice. SD immediately before the postconditioning test also enhanced cocaine CPP preference in a dose-dependent manner (8 mg/kg, but not 3, 15 mg/kg). Exposure to orexin-receptor antagonism (1 mg/kg SB 334867, an orexin 1 receptor antagonist; OX1R) just before cocaine-conditioning trials or the postconditioning test attenuated SD-enhanced preference. This suggests a potential therapeutic role for the manipulation of the orexin system to mitigate drug seeking, especially in the context of sleep loss before drug exposure.


Edoxaban for Venous Thromboembolism Treatment-The New Kid on The Block for Latin America. A Practical Guide.
Edoxaban, a direct factor Xa inhibitor (FXa), is the fourth direct oral anticoagulant (DOAC) approved for clinical use in the treatment of venous thromboembolism (VTE) in Latin America, following global approvals for this indication. Edoxaban features some particular characteristics when compared to the previously approved DOACs. This review summarizes the main properties of edoxaban, the outcomes results of its pivotal global clinical trials and the peculiar clinical features of this compound. This practical guide aims to help Latin America clinicians understand edoxaban, its proper indication and its use for the appropriate patients with VTE.


Dietary Lasia spinosa Thw. Improves Growth Performance in Broilers.
This study aimed to evaluate the effects of dietary Lasia spinosa Thw. (LST) powder supplementation on growth performance, blood metabolites, antioxidant status, intestinal morphology, and cecal microbiome in broiler chickens. A total of 400 1-day-old male Guangxi partridge broilers (initial body weight: 42.52 ± 0.06 g) were randomly allotted to 4 dietary treatments: LST0 group (a basal diet), LST1 group (a basal diet with 1% LST powder), LST2 group (a basal diet with 2% LST powder), LST4 group (a basal diet with 4% LST powder), 10 replicates for each treatment, and 10 broilers in each treatment group. Results indicated that the average daily feed intake of broilers during 22-42 days and the average daily gain of chickens during 1-42 days significantly increased by dietary supplementation of LST powder (p < 0.01), while the feed conversion ratio during the overall periods was decreased by dietary supplementation of LST powder (p < 0.01). Except for the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver (p > 0.05), the levels of SOD, catalase (CAT) and GSH-Px in serum, liver, and breast muscle were significantly increased in the LST supplemented groups (p < 0.05), while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in serum, liver, and breast muscle were significantly decreased in the LST supplemented groups (p < 0.05). Furthermore, the levels of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased by the addition of dietary LST powder (p < 0.01), while the levels of HDL-C, Ca, Fe, Mg, and P were linearly increased by the addition of dietary LST powder (p < 0.01). With respect to the gut morphometric, crypt depth was significantly decreased by LST supplementation (p < 0.05), while villus height and the ratio of villus height to crypt depth were notably increased by LST supplementation (p < 0.05). Sequencing of 16S ribosomal RNA (16S rRNA) from the cecal contents of broilers revealed that the composition of the chicken gut microbiota was altered by LST supplementation. The α-diversity of microbiota in broilers was increased (p < 0.05) in the LST1 group, but was decreased (p < 0.05) in the LST2 and LST4 groups compared with the LST0 group. The differential genera enriched in the LST1 group, such as Bacillus, Odoribacter, Sutterella, Anaerofilum, Peptococcus, were closely related to the increased growth performance, antioxidant status, intestinal morphology, Ca, Mg, and reduced blood lipid in the treated broilers.


[Suggestions concerning serological diagnosis of echinococcosis in Poland].
It has been suggested to change the present way of serological diagnosis of echinococcosis in Poland which utilizes immunoelectrophoresis for confirmation of positive results in a screening test. Diagnostic procedure should be indicated with a sensitive test, such as indirect haemagglutination or immunoenzymatic assay, and every positive result should be verifies later using a Western-blot method in order to detect the most specific reaction with 8 kDa fraction of Echinococcus antigen. Further diferentiation of the infecting species may be accomplished with the aid of Em2 plus ELISA test which detects antibodies specific for E. multilocularis.


Hydroxyurea for sickle cell disease.
Sickle cell disease is one of the most common inherited diseases world wide. It is associated with life long morbidity and a reduced life expectancy. Hydroxyurea, a chemotherapeutic drug taken by mouth, raises fetal haemoglobin and, as such, is expected to ameliorate some of the clinical problems of sickle cell disease. To assess the effects of hydroxyurea therapy in sickle cell disease patients of all types, of any age, regardless of setting. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialised register of controlled trials for haemoglobinopathies, which comprises references identified from comprehensive electronic database searches, hand-searching relevant journals, and hand-searching abstract books of conference proceedings. Date of the most recent search(es): November 2000. All randomised or quasi-randomised controlled trials comparing the use of oral hydroxyurea for one month or longer with placebo, standard therapy or other interventions for the treatment of patients with sickle cell disease. Both reviewers independently assessed trial quality and extracted data from the two studies included. Twenty trials were found of which two trials, which reported results from a total of 324 adults and children were suitable for inclusion in the review. From the data provided in the published reports only one study (the MSH study to the United States of America) could be analysed. This study showed marked differences in favour of hydroxyurea treatment as compared with placebo in terms of annual crisis rate, use of transfusions, and life-threatening complications (in particular, the acute sickle chest syndrome). No serious adverse effects were reported from either study. While hydroxyurea appears both effective and safe in the severely affected SS adults over a two year period; further studies are required to elucidate its role in other patient groups and for other conditions.


The Fucoxanthin Chlorophyll a/c-Binding Protein in Tisochrysis lutea: Influence of Nitrogen and Light on Fucoxanthin and Chlorophyll a/c-Binding Protein Gene Expression and Fucoxanthin Synthesis.
We observed differences in lhc classification in Chromista. We proposed a classification of the lhcf family with two groups specific to haptophytes, one specific to diatoms, and one specific to seaweeds. Identification and characterization of the Fucoxanthin and Chlorophyll a/c-binding Protein (FCP) of the haptophyte microalgae Tisochrysis lutea were performed by similarity analysis. The FCP family contains 52 lhc genes in T. lutea. FCP pigment binding site candidates were characterized on Lhcf protein monomers of T. lutea, which possesses at least nine chlorophylls and five fucoxanthin molecules, on average, per monomer. The expression of T. lutea lhc genes was assessed during turbidostat and chemostat experiments, one with constant light (CL) and changing nitrogen phases, the second with a 12 h:12 h sinusoidal photoperiod and changing nitrogen phases. RNA-seq analysis revealed a dynamic decrease in the expression of lhc genes with nitrogen depletion. We observed that T. lutea lhcx2 was only expressed at night, suggesting that its role is to protect \cells from return of light after prolonged darkness exposure.


Spatial traffic noise pollution assessment - A case study.
Spatial assessment of traffic noise pollution intensity will provide urban planners with approximate estimation of citizens exposure to impermissible sound levels. They could identify critical noise pollution areas wherein noise barriers should be embedded. The present study aims at using the Geographic Information System (GIS) to assess spatial changes in traffic noise pollution in Tehran, the capital of Iran, and the largest city in the Middle East. For this purpose, while measuring equivalent sound levels at different time periods of a day and different days of a week in District 14 of Tehran, wherein there are highways and busy streets, the geographic coordination of the measurement points was recorded at the stations. The obtained results indicated that the equivalent sound level did not show a statistically significant difference between weekdays, and morning, afternoon and evening hours as well as time intervals of 10 min, 15 min and 30 min. Then, 91 stations were selected in the target area and equivalent sound level was measured for each station on 3 occasions of the morning (7:00-9:00 a.m.), afternoon (12.00-3:00 p.m.) and evening (5:00-8:00 p.m.) on Saturdays to Wednesdays. As the results suggest, the maximum equivalent sound level (Leq) was reported from Basij Highway, which is a very important connecting thoroughfare in the district, and was equal to 84.2 dB(A), while the minimum equivalent sound level (Leq), measured in the Fajr Hospital, was equal to 59.9 dB(A). The average equivalent sound level was higher than the national standard limit at all stations. The use of sound walls in Highways Basij and Mahallati as well as widening the Streets 17th Shahrivar, Pirouzi and Khavaran, benchmarked on a map, were recommended as the most effective mitigation measures. Additionally, the research findings confirm the outstanding applicability of the Geographic Information System in handling noise pollution data towards depicting noise pollution intensity caused by traffic.


Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival.
Malignancy increases sepsis incidence 10-fold and elevates sepsis-associated mortality. Advances in treatment have improved survival of cancer patients shortly after sepsis, but there is a paucity of information on how sepsis impacts cancer growth, development, and prognosis. To test this, cecal ligation and puncture surgery was performed on B16 melanoma-bearing mice to show that sepsis has detrimental effects in hosts with advanced tumors, leading to increased mortality. Surprisingly, mice experiencing cecal ligation and puncture-induced sepsis earlier during tumor development exhibited CD8 T cell-dependent attenuation of tumor growth. Sepsis-resistant CD8 tumor-infiltrating T cells showed increased in vivo activation, effector IFN-γ cytokine production, proliferation, and expression of activation/inhibitory PD-1/LAG-3 receptors because of a sepsis-induced liberation of tumor Ags. Sepsis-reinvigorated CD8 tumor-infiltrating T cells were also amenable to (anti-PD-L1/LAG-3) checkpoint blockade therapy, further prolonging cancer-associated survival in sepsis survivors. Thus, sepsis has the capacity to improve tumor-specific CD8 T cell responses, leading to better cancer prognosis and increased survival.


Long- and medium-chain fatty acid oxidation is increased in exercise-trained human skeletal muscle.
The purpose of this study was to test the hypothesis that skeletal muscle fatty acid oxidation is enhanced by increased entry into the mitochondria with exercise training. Muscle was obtained from young ( approximately 24 years) sedentary (n = 13) and endurance-trained (n = 10) volunteers and oxidation studied by measuring (14)CO(2) production from labeled medium-chain (MCFA) or long-chain (LCFA) fatty acids in muscle homogenate preparations. LCFA (palmitate) oxidation was (P <.05) approximately 34% higher in the trained than sedentary subjects (26.9 +/- 3.0 v 17.8 +/- 1.3 nmol CO(2)/g x h). MCFA (octanoate) oxidation was also about 26% higher (P <.05) in the trained subjects (21.7 +/- 2.1 v 16.1 +/- 2.0 nmol CO(2)/g x h). To examine the roles of carnitine-mediated transport and mitochondrial content, we also measured carnitine palmitoyltransferase I (CPT1), carnitine octanoyl transferase (COT), and citrate synthase (CS) activities. CPT1 and CS activity were significantly (P <.05) higher (approximately 25%) in the endurance-trained subjects; there was no difference in COT activity. These data suggest that adaptations at the level of CPT1 and processes distal to this step may contribute to increases in LCFA or MFCA oxidation with exercise training. In contrast, carnitine-mediated transport (COT) does not appear to contribute to an enhancement in MCFA oxidation with exercise training.


Neddylation positively regulates the ubiquitin E3 ligase activity of parkin.
Mutations in the parkin gene underlie a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinsonism (AR-JP). Dysfunction of parkin, a ubiquitin E3 ligase, has been implicated in the accumulation of ubiquitin proteasome system-destined substrates and eventually leads to cell death. However, regulation of parkin enzymatic activity is incompletely understood. Here we investigated whether the ubiquitin E3 ligase activity of parkin could be regulated by neddylation. We found that parkin could be a target of covalent modification with NEDD8, a ubiquitin-like posttranslational modifier. In addition, NEDD8 attachment caused an increase of parkin activity through the increased binding affinity for ubiquitin-conjugating E2 enzyme as well as the enhanced formation of the complex containing parkin and substrates. These findings point to the functional importance of NEDD8 and suggest that neddylation is one to the diverse modes of parkin regulation, potentially linking it to the pathogenesis of AR-JP.


Absence of Variable Fluorescence from Guard Cell Chloroplasts of Stenotaphrum secundatum.
The lack of detectable variable fluorescence from guard cell chloroplasts in both the albino and green portions of variegated leaves of St. Augustine grass (Stenotaphrum secundatum var variegatum A.S. Hitchc.) is reported. Fluorescence was measured either with a highly sensitive, modified fluorescence microscope which was capable of recording fluorescence induction curves from single chloroplasts, or with a spectrofluorometer. Both fast and slow fluorescence transients from S. secundatum guard cells showed a rapid rise and then remained at a steady level. Neither variable fluorescence increase (induction) nor decrease (quenching), properties normally associated with photosystem II, was observed from these chloroplasts. These fluorescence kinetics did not change either with alterations of the specimen preparation procedure or with alterations of the excitation light intensities and wavelengths. These results indicate that guard cell chloroplasts in this variety of S. secundatum do not conduct normal photosystem II electron transport. Light regulation of stomatal conductance in intact leaves of this plant did occur, however, and was similar to light regulation observed in other species. The conductance of the green portion of the leaves was much greater in the light than in the dark, and was much greater than the conductance of the albino portion of the leaves. Stomata in the green portion of the leaves also showed greater opening in blue light than in red light. These results provide evidence that stomatal regulation in this variety of S. secundatum does not rely on photosystem II electron transport in guard cell chloroplasts.


In the eye of the beholder: does the master see the SameSpots as the novice?
Historically, the use of two-dimensional electrophoresis (2-DE) in quantitative proteomics has been hampered by significant technical variance. Over the past decade, a range of technological leaps have reduced the overall variance of 2-DE, thus turning the technology into a robust platform for quantitative intact proteomics. However, as the confounding gel-to-gel variation improves, the variance arising from the subsequent image analysis becomes more prominent. Limitations in image alignment and spot detection of previous generations of 2-DE analysis software have demanded considerable user-intervention and manual editing, resulting in introduction of a large degree of subjectivity and software-induced variance. We evaluated the performance of SameSpots, representing a new generation of 2-DE image analysis software, using both DIGE and traditional single-stain 2-DE approaches. Evaluations of the software-induced variance in relation to other sources of variance, as well as the subjectivity through comparison of analyses performed by an expert user and a novice lab-user, were performed. In terms of statistical power, the less-experienced user achieved the better results, but no discernible difference was detected in multivariate comparisons between the users. In conclusion, we found that SameSpots represents improvements both in reproducibility and objectivity in relation to previous generations of 2-DE analysis software.


Transmission characteristics of low pathogenic avian influenza virus of H7N7 and H5N7 subtypes in layer chickens.
Low pathogenic avian influenza virus (LPAIv) infections of H5 and H7 subtypes in poultry are notifiable to the OIE, hence surveillance programmes are implemented. The rate at which LPAIv strains spread within a flock determines the prevalence of infected birds and the time it takes to reach that prevalence and, consequently, optimal sample size and sampling frequency. The aim of this study was to investigate the transmission characteristics of an H7N7 and an H5N7 LPAIv in layer chickens. Two transmission experiments were performed, which consisted of 30 (first experiment) and 20 (second experiment) pairs of conventional layers, respectively. At the start of the experiments, one chicken per pair was inoculated with LPAIv and the other chicken was contact-exposed. Occurrence of infection was monitored by regularly collecting tracheal and cloacal swab samples, which were examined for the presence of virus RNA by RT-PCR. The results of the test were used to estimate the transmission rate parameter (β), the infectious period (T) and the basic reproduction ratio (R(0)). In addition, egg production and virus shedding patterns were quantified. For the H7N7 virus, the β, T and R(0) estimates were 0.10 (95% confidence interval (CI): 0.04-0.18) day(-1), 7.1 (95% CI: 6.5-7.8) days and 0.7 (95% CI: 0.0-1.7), respectively. With the H5N7 virus, only a few inoculated chickens (5 out of 20) became infected and no transmission was observed. This study shows that transmission characteristics of LPAIv strains may vary considerably, which has to be taken into account when designing surveillance programmes.


The current treatment of ductal carcinoma in situ.
A consensus conference was held in April, 1999, to help sift through the maze of controversy surrounding the treatment of mammographically detected ductal carcinoma in situ (DCIS). Members of the panel included approximately 30 DCIS experts, who addressed issues relating diagnosis, treatment, treatment of breast (and axilla), adjuvant therapy, among others. The panel agreed that the goal of treatment for DCIS is breast conservation and attempted to divide the population of patients with DCIS into subsets who are appropriately treated by mastectomy, radiation therapy, or by excision alone. Major criteria for breast conservation include small size of area of DCIS, clear surgical margins, and favorable biology. Neither axillary dissection nor sentinel node biopsy is appropriate for DCIS treated by breast conservation. The role of tamoxifen is currently under study, and although approved by the FDA for "risk reduction," its use in patients with DCIS is uncertain.


Localization of the delta subunit in the Escherichia coli F(1)F(0)-ATPsynthase by immuno electron microscopy: the delta subunit binds on top of the F(1).
The binding site of the delta subunit in the F(1)F(0)-ATPsynthase from Escherichia coli has been determined by electron microscopy of negatively stained, antibody-decorated enzyme molecules. The images show that the antibody is bound at the very top of the F(1) domain indicating that at least part of delta is bound in the dimple formed by the N termini of the alpha and beta subunits. The data may explain why there is only one binding site for delta on the F(1) despite there being three identical alphabeta pairs. The finding also implies that the b subunits of the F(0) have to extend all the way from the membrane surface to the very top of the F(1) domain to make contact with the delta subunit.


Indolent intracranial mucormycosis: case report.
We present a patient with isolated intracranial mucormycosis that remained indolent for several months. The mucormycosis formed a mass in the prepontine cistern, probably spreading from the sphenoid sinus. We propose that at least some cases of what is considered isolated CNS mucormycosis develop from such unrecognized indolent infections. Mucormycosis may present as a mass in the basilar cisterns, especially in immunocompromised patients.


[A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy].
The premortem diagnosis of cytomegalovirus (CMV) pneumonia is usually difficult, and mortality of it is high. A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy is reported. The patient was a 76-year-old man. Under diagnosis as lung cancer, the right lower lobectomy was performed. After operation, pneumonia occurred on the nonoperated side and in a few days reticular shadows rapidly spread to the whole lung. Although pulse steroid therapy was performed, the interstitial pneumonitis improved only a little. Then intranuclear inclusion body-bearing giant cells were found in sputum obtained by bronchoscopy. So we diagnosed the interstitial pneumonitis as CMV pneumonia and ganciclovir was administrated. CMV pneumonia had improved for two weeks and the patient has no recurrence. When interstitial pneumonitis develop in patients after operation or steroid therapy, the differential diagnosis should include the possibility of CMV pneumonia.


[The organizational approaches to the quality management in the laboratorial examinations].
The results of the quality investigation of laboratory services operations of the city of Saratov and Saratov Oblast are presented. The issue of organization and quality of carrying out the laboratorial examinations is analyzed. The suggestions related to the clinical laboratorial examinations quality management are exposed.


Psychiatry in eastern Europe today: mental health status, policies, and practices.
The author describes the impact of the recent social and political changes in Eastern Europe on psychiatrists and psychiatry. The observations contained in this paper are drawn from his personal experiences as a practicing psychiatrist in East Germany who also served as a member of the Executive Committee of the World Psychiatric Association from 1984 to 1989. The practice of psychiatry in Eastern Europe before the recent social and political changes was highly variable depending on the country, the locale of practice, and the social and political positions of the involved psychiatrists. Adapting to the recent changes will be very difficult, and it will be a long time before the modernization of psychiatric practice in Eastern Europe takes place. Psychiatrists in the Western world can play an important part in the future development of psychiatry in Eastern Europe. Their understanding of the current situation and the historical forces that shaped it is extremely important to the psychiatrists of Eastern Europe.


Applying the SAGE technique to study the effects of electromagnetic field on biological systems.
Identification of genes alternatively expressed in electromagnetic field (EMF)-exposed cells could provide direct evidence for biological effects of EMF. As there are a few indications so far for certain genes to be influenced by EMF, genome-wide scans of the transcriptome appear to be necessary. Among the several technologies used for genome-wide gene expression analysis, serial analysis of gene expression (SAGE) is one promising method, which seems particularly applicable for EMF research. This review provides a brief description of the features of gene expression, illustrates the basic principle of SAGE, and discusses the advantages and limitations of SAGE as well as examples of application. This information should help investigators determine if the SAGE technique is an optimal method for evaluating the biological effects of EMF.


Regional decreases in NK-3, but not NK-1 tachykinin receptor binding in dystonic hamster (dt(sz)) brains.
Although the pathophysiology of primary dystonias is currently unknown, it is thought to involve changes in the basal ganglia-thalamus-cortex circuit, particularly activity imbalances between direct and indirect striatal pathways. Substance P, a member of the tachykinin family of neuropeptides, is a major component in the direct pathway from striatum to basal ganglia output nuclei. In the present study quantitative autoradiography was used to examine changes in neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptors in mutant dystonic hamsters (dt(sz)), a well characterized model of paroxysmal dystonia. NK-1 receptors were labeled in 10 dystonic brains and 10 age-matched controls with 3 nM [(3)H]-[Sar(9), Met(O(2))(11)]-SP. NK-3 binding sites were labeled in adjacent sections with 2.5 nM [(3)H]senktide. NK-1 binding was found to be unaltered in 27 brain areas examined. In contrast, NK-3 binding was significantly reduced in layers 4 and 5 of the prefrontal (-46%), anterior cingulate (-42%) and parietal (-45%) cortices, ventromedial thalamus (-42%) and substantia nigra pars compacta (-36%) in dystonic brains compared to controls. The latter effects may be particularly relevant in view of evidence that activation of NK-3 receptors on dopaminergic neurons in the substantia nigra pars compacta can increase nigrostriatal dopaminergic activity. Since previous studies indicated that a reduced basal ganglia output in mutant hamsters is based on an overactivity of the direct pathway which also innervates substantia nigra pars compacta neurons, the decreased NK-3 binding could be related to a receptor down-regulation. The present finding of decreased NK-3 receptor density in the substantia nigra pars compacta, thalamic and cortical areas substantiates the hypothesis that disturbances of the basal ganglia-thalamus-cortex circuit play a critical role in the pathogenesis of paroxysmal dystonia.


Comparative study of the extent of palatal lengthening by different methods.
Palatal lengthening is often emphasized in performing palatoplasty. However, definitive data regarding the method of measuring palatal length and the extent of palatal lengthening expressed quantitatively have not been reported. The authors have devised an easy method of measuring palatal length that can be expressed quantitatively, and they examined the characteristics of various methods of palatoplasty that are presently used commonly. A paper ruler was used to measure both a straight-line and a curved distance while the patient was under general anesthesia before and immediately after the palatoplasty. According to this study, the straight-line distance was lengthened to a significantly greater degree than the curved distance was after pushback palatoplasty for incomplete types of cleft palate and two-flap palatoplasty for complete types. Furlow double-opposing Z-palatoplasty and two-flap palatoplasty appeared to allow for greater palatal lengthening than the pushback palatoplasty. Further investigations will be undertaken to determine the correlation between the extent of palatal lengthening and speech development.


Magnetic Field-Induced Self-Assembly of Conjugated Block Copolymers and Nanoparticles at the Air-Water Interface.
Here, we report the magnetic field-induced self-assembly of a conjugated block copolymer, poly(3-hexylthiopene)-block-poly(ethylene glycol) (P3HT-b-PEG), and iron oxide nanoparticles (IONPs) at the air-water interface. Binary self-assembly of P3HT-b-PEG and IONPs at the interface results in nanoparticle-embedded P3HT-b-PEG nanowire arrays with a micrometer-scale domain size. Under the magnetic field, the field-induced magnetic interaction significantly improves the degree of order, generating long-range ordered, direction-controlled nanoarrays of P3HT-b-PEG and IONPs, where IONPs are aligned in the direction of the magnetic field over a sub-millimeter scale. The size of IONPs is an important factor for the formation of an ordered assembly structure at the nanometer scale, as it dictates the magnetic dipole interaction and the entropic interaction between nanoparticles and polymers. The consideration of magnetic dipole interactions suggests that the field-induced self-assembly occurs through the formation of intermediate magnetic subunits composed of short IONP strings along the semirigid P3HT nanowires, which can be aligned through the magnetic interactions, ultimately driving the long-range ordered self-assembly. This study demonstrates for the first time that the magnetic field-induced self-assembly can be used to generate macroscopically ordered polymer films with a nanometer-scale order in low fields.


Prevalence of hepatitis B virus infections in nonhuman primates.
The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in nonhuman primates. Serum samples from Europe, Thailand and Vietnam were analyzed. Sera obtained from 262 apes and 454 monkeys were tested for HBV infection serologically and for HBV DNA using nested PCR (nPCR). A total number of 198 ape sera and all but one (Cercopithecus aethiops) of the 4543 monkey sera had no serological signs of HBV infection. Among the 64 of 262 (24.4%) seropositive ape sera, we found, as in humans, different stages of HBV infection: very early HBV infection, active infection with high level of infectivity, virus carriers with low infectivity, and passed HBV infection. In the cases with passed infection, 47.8% harbored HBV DNA in the presence of protective antibodies to the HBV surface antigen (HBsAb). This indicates HBV persistence in apes despite immune control. In contrast to apes, in monkeys HBV infection is a very rare event.


The relationship between acquaintance with a SARS-CoV-2 death, positive SARS-CoV-2 test results, and sleep duration among college students in fall 2020.
The aim of this study was to test whether two SARS-CoV-2 experiences, knowing someone who had died of SARS-CoV-2 infection and having received a positive SARS-CoV-2 test result, were associated with shorter sleep duration among undergraduate students. An online cross-sectional study was conducted at a large public Midwestern university in September 2020 (fall semester). Self-reported average sleep duration and the exposures of interest, knowing someone who died from a SARS-CoV-2 infection and their own SARS-CoV-2 test result, were collected from 1,058 undergraduate study participants. Respondents who knew someone who had died of a SARS-CoV-2 infection were more likely to report having a short sleep duration, compared to respondents who did not know someone who had died of a SARS-CoV-2 infection (aOR = 1.80, 95% CI: 1.14, 2.79). However, those with a positive SARS-CoV-2 test result were less likely to report a short sleep duration, compared to respondents without a positive test history (aOR = 0.47, 95% CI: 0.21, 0.91). These findings suggest that college students' knowing someone who had died of SARS-CoV-2 infection and having received a positive SARS-CoV-2 test result are associated with sleep duration. However, different experiences may impact sleep differently, so further research is warranted to better understand how unusual events impact the sleep of college students.


The parallel helices of the intermediate filaments of alpha-keratin.
Recent Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection technique (ATR) has been applied to alpha-keratin fibers (horse-hair) extended in water both at 21 and 95 degrees C. Infrared absorption bands in the Amide 1 region indicated that at extensions to 40-50% strain in water at 21 degrees C alpha-helices had completely disappeared and parallel beta-sheets were formed [Appl. Spectrosc. 55 (2001) 552]. However, when the hair fibers were extended to the same strain at 95 degrees C in water the result was the formation of anti-parallel beta-sheets. These results suggest that the relatively more stable anti-parallel beta-state [Polymer 10 (1969) 810] is only attained in extended alpha-keratin fibers at elevated temperatures and must result from major molecular rearrangement. It was concluded that the alpha-helices in the intermediate filaments (IFs) of alpha-keratin fibers must be parallel. This is in contrast to the previously accepted orientation of anti-parallel alpha-helices, based primarily on findings of X-ray diffraction studies of the structure of beta-keratin in highly extended fibers [Polymer 10 (1969) 810; Keratins, IL: Thomas Springfield (1972); Nature 316 (1985) 767].


Pneumocystis jirovecii Pneumonia in an Immunocompetent Japanese Man: A Case Report and Literature Review.
We herein report the case of a 37-year-old immunocompetent man who died from Pneumocystis jirovecii pneumonia (PCP). He was initially treated for an acute exacerbation of interstitial pneumonia; however, the elevation of the patient's serum (1-3) β-D glucan (BG) level suggested the possibility of PCP and sulfamethoxazole trimethoprim was added. A postmortem pathological examination and retrospective Grocott's methenamine silver (GMS) staining of the bronchoalveolar lavage fluid (BALF), which was obtained on the day of admission, revealed PCP. The present case suggests that it is essential to perform a BG assay and GMS staining of BALF specimens when patients show diffuse ground-glass opacity on chest computed tomography, regardless of their immune status.


How pharmacists are rated as a source of drug information by physician assistants.
A study to examine physician assistants' (PAs) views of drug information sources was undertaken in a sample of practicing PAs in Georgia. Analysis of Kendall's coefficient of concordance statistic indicated Pharm.D.s were ranked highest as being good sources of drug information of the six categories listed. Next in descending order of classification as good sources of drug information were the categories of journal articles, physicians, non-Pharm.D. pharmacists, detail persons, and physician assistants. A significant correlation was found between PA contact with pharmacists and the classification of pharmacists as good sources of drug information. The difference in rating between Pharm.D.s and journal articles and physicians was not significantly different, but the rating differences between these categories and each of the other sources were statistically significant. Pharm.D. pharmacists were rated higher as a source of drug information than were non-Pharm.D. pharmacists. Results indicate pharmacists are viewed positively as sources of drug information for PAs, and that view increases with contact with pharmacists.


CBP/cycA, a CCAAT-binding protein necessary for adhesion-dependent cyclin A transcription, consists of NF-Y and a novel Mr 115,000 subunit.
Cells of most tissues, with the exception of hematopoietic cells, require adhesion to an appropriate surface to grow. Cyclin A is needed for cell cycle progression at the G1-S transition, and appearance of cyclin A mRNA and protein in late G1 has been shown to be dependent on adhesion-initiated signals in normal rat kidney fibroblasts. Previously, we have reported that the adhesion-dependent activation of cyclin A transcription in late G1 is mediated by CBP/cycA (CCAAT-binding protein for cyclin A gene), a novel CCAAT-binding protein. Specific binding of CBP/cycA, a Mr 30,000/40,000/115,000 heterotrimeric protein complex, to the CCAAT element of the cyclin A promoter was detectable in growing but not in G0-arrested or nonadherent normal rat kidney cells. Here, we demonstrate that the Mr 30,000/40,000 subunits of CBP/cycA are identical with NF-YA and NF-YB, the two subunits of NF-Y. In addition, we show that, aside from CBP/cycA, NF-Y itself also binds to the CCAAT element of the cyclin A promoter. But, whereas the binding of CBP/cycA is adhesion and cell cycle dependent and correlates with the expression of cyclin A in late G1 phase, NF-Y itself seems to bind in a cell cycle-independent manner.


Genes devoid of full-length transposable element insertions are involved in development and in the regulation of transcription in human and closely related species.
Transposable elements (TEs) are major components of mammalian genomes, and their impact on genome evolution is now well established. In recent years several findings have shown that they are associated with the expression level and function of genes. In this study, we analyze the relationships between human genes and full-length TE copies in terms of three factors (gene function, expression level, and selective pressure). We classified human genes according to their TE density, and found that TE-free genes are involved in important functions such as development, transcription, and the regulation of transcription, whereas TE-rich genes are involved in functions such as transport and metabolism. This trend is conserved through evolution. We show that this could be explained by a stronger selection pressure acting on both the coding and non-coding regions of TE-free genes than on those of TE-rich genes. The higher level of expression found for TE-rich genes in tumor and immune system tissues suggests that TEs play an important role in gene regulation.


Interleukin-4 inhibits growth of multiple myelomas by suppressing interleukin-6 expression.
Unfractionated bone marrow (BM) cells obtained from patients with multiple myeloma (MM) exhibit high levels of interleukin (IL)-6. Secretion of IL-6 by these cells as well as spontaneous plasma cell proliferation can be abrogated by neutralizing anti-IL-6 monoclonal antibody (MoAb). Treatment of BM cells with recombinant human (rh)IL-4 at doses of 50 to 250 U/mL blocked endogenous IL-6 synthesis in a dose-dependent fashion and was associated with significant reduction of plasma cell growth that could be reversed by exogenous rhIL-6. Enrichment of BM cells from MM patients for plasma cells and adherent cells and analysis of IL-6 mRNA in these subpopulations by means of quantitative polymerase chain reaction (PCR) showed that adherent BM cells accounted for most of the synthesis of IL-6 transcripts, whereas plasma cells displayed negligible levels of IL-6 mRNA only. These results suggest therapeutic evaluation of rhIL-4 in patients with plasma cell neoplasms.


Endothelin antagonism in end-organ damage of spontaneously hypertensive rats. Comparison with angiotensin-converting enzyme inhibition and calcium antagonism.
High blood pressure results in cardiac hypertrophy and fibrosis, increased thickness and stiffness of large artery walls, and decreased renal function. The objective of our study was to assess the role of endothelin, angiotensin II, and high blood pressure in the end-organ damage observed in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 10 weeks with either a mixed endothelin-A and endothelin-B receptor antagonist, bosentan (100 mg/kg per day), an angiotensin-converting enzyme inhibitor, enalapril (10 mg/kg per day), or a long-acting calcium antagonist, mibefradil (20 mg/kg per day). A group of SHR was left untreated, and a group of normotensive Wistar rats was used as control. At the end of treatment, maximal coronary blood flow was measured in isolated perfused hearts. Cardiac hypertrophy and fibrosis, aortic medial thickness, and extracellular matrix content were evaluated by quantitative morphometry. Proteinuria and urea and creatinine clearances were measured, and renal histopathology was assessed. SHR exhibited cardiac hypertrophy, perivascular fibrosis, and decreased maximal coronary blood flow. Aortic medial thickness was increased, whereas elastin density was decreased. Finally, SHR showed decreased urinary excretion and decreased urea and creatinine clearances. No renal histological lesions were observed. Although bosentan did not affect blood pressure, it normalized renal function and slightly decreased left ventricular hypertrophy and fibrosis. Enalapril and mibefradil were both effective in significantly decreasing blood pressure, left ventricular hypertrophy, and aortic medial thickness and improving coronary blood flow, but in contrast to bosentan, they did not improve creatinine clearance. We conclude that in SHR, high blood pressure plays a major role in end-organ damage and that endothelin may partly mediate renal dysfunction and cardiac remodeling independently of a direct hemodynamic effect.


Structural Perspectives on Extracellular Recognition and Conformational Changes of Several Type-I Transmembrane Receptors.
Type-I transmembrane proteins represent a large group of 1,412 proteins in humans with a multitude of functions in cells and tissues. They are characterized by an extracellular, or luminal, N-terminus followed by a single transmembrane helix and a cytosolic C-terminus. The domain composition and structures of the extracellular and intercellular segments differ substantially amongst its members. Most of the type-I transmembrane proteins have roles in cell signaling processes, as ligands or receptors, and in cellular adhesion. The extracellular segment often determines specificity and can control signaling and adhesion. Here we focus on recent structural understanding on how the extracellular segments of several diverse type-I transmembrane proteins engage in interactions and can undergo conformational changes for their function. Interactions at the extracellular side by proteins on the same cell or between cells are enhanced by the transmembrane setting. Extracellular conformational domain rearrangement and structural changes within domains alter the properties of the proteins and are used to regulate signaling events. The combination of structural properties and interactions can support the formation of larger-order assemblies on the membrane surface that are important for cellular adhesion and intercellular signaling.


Spermatogonia-dependent expression of testicular genes in mice.
Spermatogenesis is initiated by the interaction of germ cells and somatic cells in seminiferous tubules. We used cDNA microarrays and representational difference analysis to identify genes that are expressed in the testis of the jsd/jsd mutant mouse, which contains only type A spermatogonial germ cells and Sertoli cells, but not in the testis of the W/W(v) mutant mouse, where Sertoli cells but few germ cells are present. We isolated 20 known genes and 4 novel genes, including 2 genes encoding lipocalin family members (prostaglandin D synthetase and 24p3) and 2 tumor suppressors (protein tyrosine phosphatase TD14 and Sui1). All 24 of these jsd/jsd-derived genes were highly expressed in the cryptorchid testis as well as in the jsd/jsd testis. This indicates that their selective expression is not directly caused by the as-yet-uncharacterized jsd gene product, but is rather correlated to the cessation of spermatogonial differentiation. In situ hybridization analysis and flow cytometric sorting followed by reverse transcriptase-PCR revealed that these genes are expressed in both the spermatogonial germ cells and the somatic cells in the developing gonads and adult testes. As the mRNAs of these jsd/jsd-derived genes were barely detectable in the W/W(v) testis, we propose that early spermatogonial germ cells regulate the expression of a group of testicular genes.


Burst characteristics of dentate gyrus granule cells: evidence for endogenous and nonsynaptic properties.
1. Hippocampal slices bathed in 8 mM potassium and 0-added calcium exhibited spontaneous epileptiform activity in the dentate gyrus. Extracellular recording revealed recurrent prolonged bursts of population spikes and an associated negative DC shift. These episodes were very similar to the in vivo phenomenon termed maximal dentate activation (MDA). Therefore this in vitro activity will be referred to as MDA-like activity or events. 2. During the MDA-like activity, the individual granule cells exhibited a sustained depolarization that matched the duration of the negative extracellular DC shift. At the beginning of the MDA-like activity, there was a burst of action potentials. After the burst, most granule cells either continued to fire action potentials regularly or in bursts. Some cells exhibited this initial burst of activity and then a dramatic reduction in firing rate. This reduction in rate was followed by a gradual increase in the amplitude and frequency of the epileptiform activity recorded during the remainder of the MDA-like event. 3. Before and between MDA-like events, spontaneous cellular activity consisted of single action potentials and bursts of action potentials on a depolarizing envelope. In addition, depolarizing potentials, up to 13 mV, were recorded. There were no extracellular field potentials associated with these intracellularly recorded potentials. 4. In the 8 mM potassium, 0-added calcium test solution, the membrane potential threshold for burst production was significantly lower than in normal potassium and calcium medium. 5. The effect of depolarizing and hyperpolarizing current injections on the amplitude and frequency of the epileptiform activity was tested. Current injection had no effect on the frequency of the epileptiform activity recorded during the MDA-like events. However, the frequency of the cellular bursts between MDA-like events was very sensitive to current injection. Depolarizing current increased the frequency, and hyperpolarizing current decreased the frequency of the spontaneous activity. 6. This study has shown that in 8 mM potassium and 0-added calcium the granule cells of the dentate gyrus are capable of generating spontaneous bursts that appear to be mediated by endogenous mechanisms. In addition, synchronized epileptiform discharges were recorded from the granule cells at regular intervals that appear were recorded from the granule cells at regular intervals that appear to be mediated by exogenous nonsynaptic mechanisms.


A comparative study of a new selective beta 2-adrenoceptor agonist, procaterol and salbutamol in asthma.
The effects of single oral doses of a new selective beta 2-adrenoceptor agonist procaterol (0.05 mg and 0.1 mg) and salbutamol (4 mg) on ventilatory function, were compared in 24 asthmatic patients. A bronchodilator effect of similar duration and magnitude followed all three treatments with no evidence of a dose-related response in the case of procaterol. There was no significant difference in blood pressure or heart rate responses or pattern of unwanted effects. We conclude that procaterol and salbutamol are clinically similar with oral dosing and that the maximum effective dose of procaterol is not greater than 0.05 mg.


Salinity Effects on Photosynthesis, Carbon Allocation, and Nitrogen Assimilation in the Red Alga, Gelidium coulteri.
The long-term effects of altered salinities on the physiology of the intertidal red alga Gelidium coulteri Harv. were assessed. Plants were transfered from 30 grams per liter salinity to media with salinities from 0 to 50 grams per liter. Growth rate, agar, photosynthesis, respiration, and various metabolites were quantified after 5 days and 5 weeks adaptation. After 5 days, growth rates were lower for plants at all altered salinities. Growth rates recovered from these values with 5 weeks adaptation, except for salinities of 10 grams per liter and below, where tissues bleached and died. Photosynthetic O(2) evolution was lower than control values at both higher and lower salinities after 5 days and did not change over time. Carbon fixation at the altered salinities was unchanged after 5 days, but decreased below 25 grams per liter and above 40 grams per liter after 5 weeks. Respiration increased at lower salinities. Phycobili-protein and chlorophyll were lower for all altered salinities after 5 days. These decreases continued at lower salinities, then were stable after 5 weeks. Chlorophyll recovered over time at higher salinities. Decreases in protein at lower salinities were quantitatively attributable to phycobili-protein loss. Total N levels and C:N ratios were nearly constant across all salinities tested. Carbon flow into glutamate and aspartate decreased with both decreasing and increasing salinities. Glycine, serine, and glycolate levels increased with both increasing and decreasing salinity, indicating a stimulation of photorespiration. The cell wall component agar increased with decreasing salinity, although biosynthesis was inhibited at both higher and lower salinities. The storage compound floridoside increased with increasing salinity. The evidence suggests stress responses to altered salinities that directly affected photosynthesis, respiration, and nitrogen assimilation and indirectly affected photosynthate flow. At low salinities, respiration and photorespiration exceeded photosynthesis with lethal results. At higher salinities, although photosynthesis was inhibited, respiration was low and carbon fixation adequate to offset increased photorespiration.


The clinical significance of MAGEA3 expression in pancreatic cancer.
The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent-to-cure surgery for PDAC. Total RNA from paraffin-embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe-based quantitative real-time RT-PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log-rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0-4.4, p = 0.041; and HR 3.7, 95% CI: 1.8-7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune-based therapy.


Surface changes during the arrest of active enamel carious lesions in vivo. A scanning electron microscope study.
The present study examines early enamel surface alterations taking place when active carious lesions enter an arrested stage. Orthodontic bands with a standardized space for plaque accumulation were used to produce incipient carious lesions on the buccal surface of all four first premolars of four young adolescents. The premolars were to be extracted for orthodontic reasons. After 4 weeks of local cariogenic challenge, all teeth were debanded. In each patient one tooth was extracted at the time of debanding. The remaining premolars were extracted 1, 2, and 3 weeks after re-exposure to the oral environment. No fluoride was added during the entire test period, and the patients were told to maintain usual oral hygiene. Scanning electron microscope examination of the experimental surface areas disclosed a gradual wearing away of the outermost crystals during the 3 weeks of observation. This was associated with a leveling off of surface irregularities and the development of a multitude of scratches. The observed attrition of the porous surface in the lesion area indicates that functional wear and toothbrushing were responsible for the arrestment by disturbance and removal of bacterial deposits.


International survey on willingness-to-pay (WTP) for one additional QALY gained: what is the threshold of cost effectiveness?
Although the threshold of cost effectiveness of medical interventions is thought to be 20 000- 30 000 UK pounds in the UK, and $50 000-$100 000 in the US, it is well known that these values are unjustified, due to lack of explicit scientific evidence. We measured willingness-to-pay (WTP) for one additional quality-adjusted life-year gained to determine the threshold of the incremental cost-effectiveness ratio. Our study used the Internet to compare WTP for the additional year of survival in a perfect status of health in Japan, the Republic of Korea (ROK), Taiwan, Australia, the UK, and the US. The research utilized a double-bound dichotomous choice, and analysis by the nonparametric Turnbull method. WTP values were JPY 5 million (Japan), KWN 68 million (ROK), NT$ 2.1 million (Taiwan), 23 000 UK pounds (UK), AU$ 64 000 (Australia), and US$ 62 000 (US). The discount rates of outcome were estimated at 6.8% (Japan), 3.7% (ROK), 1.6% (Taiwan), 2.8% (UK), 1.9% (Australia), and 3.2% (US). Based on the current study, we suggest new classification of cost-effectiveness plane and methodology for decision making.


Critical Role of IP-10 on Reducing Experimental Corneal Neovascularization.
To address the role of interferon-induced protein of 10 kDa (IP-10) in the course of corneal neovascularization (CrNV) in a mouse model of experimental corneal neovascularization. BALB/c mice that were 7- to 8-week-old male were included in the study. Corneal injury was induced by NaOH. Mice were randomly divided into 2 groups of IP-10 and vehicle. The alkali-treated eyes received 5 μl of 5 μg/ml IP-10 dissolved in 0.2% sodium hyaluronate for IP-10-treated group, or 5 μl of 0.2% sodium hyaluronate for vehicle-treated group twice a day for 7 days immediately after the alkali injury. 2 weeks after alkali injury, corneas were removed and used for whole mount CD31 staining. The percentages of neovascularization on corneal photographs were examined with digital image analysis. In other experiments, at indicated time intervals, the corneas were removed. Angiogenic factor expression in the early phase after injury was quantified by real-time PCR and western blot. The VEGF expression in macrophages infiltrating into burned corneas was examined by Flow cytometry (FCM) and immunofluorescence. Tube formation and cell proliferation of human retinal endothelial cells (HRECs) were detected after being stimulated with IP-10 in vitro. The mRNA and protein expression of IP-10 and C-X-C motif chemokine receptor 3 (CXCR3) was augmented after the alkali injury (p < 0.05). Compared with vehicle-treated mice, IP-10-treated mice exhibited reduced CrNV 2 weeks after injury, as evidenced by diminished CD31-positive areas (p < 0.05). Concomitantly, the intracorneal mRNA and protein expression enhancement of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was lower in IP-10-treated mice than in vehicle-treated mice after injury (p < 0.05). Moreover, IP-10 inhibited HREC tube formation and proliferation in vitro. IP-10-treated mice exhibited reduced alkali-induced CrNV through decreasing intracorneal VEGF and bFGF expression, and inhibiting endothelial cell proliferation and tube formation.


Scleromyxedema (Arndt - Gottron Syndrome) Developing Under Tenofovir Treatment for Hepatitis B: Unique Presentation in a Bulgarian Patient!
Scleromyxedema, also referred to as the Arndt-Gottron (S-AG) syndrome or the systemic form of Lichen myxedematosus (LM), is a cutaneous mucinosis with a chronic course and high lethality from systemic involvement of other organs and systems. Interesting in several aspects is the association between scleromyxedema and viral hepatitis about: 1) hepatitis virus infection as a possible etiological factor for the development of scleromyxedema, 2) antiretroviral therapy for the treatment of hepatitis as a method of reversing scleromyxedema and 3) antiviral drugs as inducers of scleromyxedema. We present a 53-year old patient who for nine months had been on tenofovir disoproxil 245 mg (0-0-1) therapy for chronic hepatitis B. Three months after the start of antiviral therapy (i.e. for a period of 6 months), the patient observed swelling, itching and hardening of the skin on the face, ears and hands, which subsequently spread throughout the trunk. Subsequent histological study of a skin biopsy revealed changes of scleromyxedema at an advanced stage, though immunoelectrophoresis of serum and urine excluded the presence of paraproteinaemia or para proteinuria. Systemic antihistamine and topical corticosteroid therapy were instituted. Bone involvement with possible plasmacytoma was excluded, and a myelogram showed evidence of an erythroblastic reaction of bone marrow. We believe that drug-induced scleromyxedema is a rare but possible phenomenon. We describe the first case of tenofovir-induced scleromyxedema within the framework of chronic hepatitis B treatment.


Chloramphenicol acetyltransferase as selectable marker for plastid transformation.
Chloroplast transformation remains a demanding technique and is still restricted to relatively few plant species. The limited availability of selectable marker genes and the lack of selection markers that would be universally applicable to all plant species represent some of the most serious technical problems involved in extending the species range of plastid transformation. Here we report the development of the chloramphenicol acetyltransferase gene cat as a new selectable marker for plastid transformation. We show that, by selecting for chloramphenicol resistance, tobacco chloroplast transformants are readily obtained. Transplastomic lines quickly reach the homoplasmic state (typically in one additional regeneration round), accumulate the chloramphenicol acetyltransferase enzyme to high levels and transmit their plastid transgenes maternally into the next generation. No spontaneous antibiotic resistance mutants appear upon chloramphenicol selection. Several lines of evidence support the assumption that plant mitochondria are also sensitive to chloramphenicol suggesting that the chloramphenicol acetyltransferase may be a good candidate selectable marker for plant mitochondrial transformation.


Predictors of Social Media Use in Two Family Generations.
Older adults have recently begun to adopt social media in increasing numbers. Even so, little is known about the factors influencing older adults' social media adoption. Here, we identify factors that predict the use of social media among older adults (aged 68-73) and compare them to those of their adult children (aged 19-56) using population-based data from Finland. As predictors for social media use, we utilized demographic factors as well as characteristics of the respondents' social lives. In addition, we test whether social media use in older adults is predicted by the social media use of their adult children. The data used in this study uniquely enable the study of this question because actual parent-child dyads are identifiable. In both generations, women and those with higher education were more likely to use social media. Predictors specific to men of the older generation were being divorced and younger, and predictors specific to women of the older generation were having better health and more frequent contact with friends. A higher number of children predicted use in both men and women in the older generation. As for the younger generation, specific predictors for social media use in women were younger age, divorce, higher number of children, and more frequent contact with friends. For men in the younger generation, there were no significant predictors for social media use besides higher education, which predicted social media use in all groups. Finally, social media use in a parent representing the older generation was predicted by the social media use of their adult children. This study provides novel information on the predictors of the use of social media in two family generations.


Measurement of DNA damage induced by irradiation with gamma-rays from a TRIGA Mark II research reactor in human cells using Fast Micromethod.
The Fast Micromethod is a novel quick and convenient microplate assay for determination of DNA single-strand breaks. This method measures the rate of unwinding of cellular DNA upon exposure to alkaline conditions using a fluorescent dye which preferentially binds to double-stranded DNA. Here we applied this method to determine the levels of DNA single-strand breaks in HeLa cells induced by y-irradiation deriving from fission isotopes and activation products at the TRIGA Mark II research reactor in Mainz. An increased strand scission factor (SSF) value, which is indicative for DNA damage, was found at doses of 1 Gy and higher. A similar increase in SSF value, which further increased in a dose-dependent manner, was found in human peripheral blood mononuclear cells after irradiation with 6 MV X-rays from a linear accelerator to give a total exposure of 0.5 to 10 Gy.


Sex-specific regionality of liver metabolism during starvation; with special reference to the heterogeneity of the lobular periphery.
Staining procedures for glucose-6-phosphatase and 3-hydroxybutyrate dehydrogenase activity and for glycogen were used to investigate adaptive changes in the regionality of hepatic gluconeogenesis and ketogenesis in fasting male and female rats. A reciprocal distribution of gluconeogenic and ketogenic capacities was found in both sexes, but male and female animals were different with respect to: a) the time necessary for full induction of glucose-6-phosphatase activity (24 h in females, 48 h in males); b) the overall activity of 3-hydroxybutyrate dehydrogenase; and c) glycogen content. The activity of the latter enzyme and the glycogen content did increase with time of starvation, but at all times, were higher in males, than in females. Results, thus, indicate that the extent to which ketone bodies replace glucose as major fuel for the brain is larger in males than in females. This may explain the delayed induction of glucose-6-phosphatase activity and the higher glycogen content in the male during starvation. Distributions of enzyme activities and of glycogen, furthermore, revealed the heterogeneity of the lobular periphery, i.e. functional differences among sinusoids dependent upon whether they originate from the portal tract or the vascular septum, and thus confirm the lobular concept proposed by Matsumoto et al. (1979).


The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use.
Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity.


Reevaluation of the cyanide resistance of seed germination.
Although high levels of KCN (53 micromoles per gram fresh weight of seed, corresponding to 3.2 millimolar) failed to block germination of lettuce seeds incubated in covered Petri dishes, the same levels totally blocked germination in sealed dishes. Inhibition was reversed by removing the seal. Placement of KCN remote from seeds also blocked germination in closed systems. Cyanide effectiveness was enhanced by acidifying the KCN solution but negated by the presence of a trap containing strong alkali. Low levels of aqueous HCN (2.6 micromoles HCN per gram, corresponding to 0.16 millimolar) injected into sealed dishes gave maximal inhibition of germination, suggesting that the effectiveness of KCN was due to formation of HCN in KCN solutions. Studies with nine additional crop species generally supported the interpretation that cyanide inhibition of germination has been underestimated in the past due to escape of volatile HCN from open systems.


[Does isolated TSH elevation need treatment? Study of risk factors for the development of manifest hypothyroidism].
Isolated elevations of basal TSH levels are frequently observed in the general population. In a prospective study we analyzed the spontaneous evolution of thyroid function over time in such patients. The mean observation period was 5.4 (0.5-12) years. During the follow-up period 20% of these patients developed overt hypothyroidism. The risk of developing hypothyroidism was determined primarily by the initial TSH value and an additive effect was found for the thyroid antibodies and the thyroidal reserve (delta-T3) after TRH stimulation (Cox proportional hazard model). The cumulative risk for overt hypothyroidism after 10 years was only 22% for a mean TSH level of 12 mU/l for patients with negative thyroid antibodies and a good thyroidal reserve (low-risk), but increased to 63% for patients with positive antibodies and impaired T3 reserve (high-risk). Therefore, patients with isolated elevation of TSH can be divided into two subgroups according to the results of TSH, antibody status and T3 reserve: (1) In the "low-risk group" with good prognostic factors the patients should be followed up by periodic laboratory testing only (TSH, FT4, every 2-3 years). (2) In the "high-risk group" with clearly abnormal parameters, however, frequent controls are mandatory (every 6-12 months) or treatment with thyroxine may be indicated.


A new metabolic labelling medium for Trichomonas vaginalis and Tritrichomonas foetus using 35S methionine.
A metabolic labelling medium was devised for Trichomonas vaginalis and Tritrichomonas foetus utilizing 35S methionine. T. vaginalis cultured for 24h in the medium took up approximately 27% of the available label and increased greater than two fold in number. Counts per microgram of protein were 32,555 +/- 10% between different strains or identical strains in different labelling runs. T. foetus took up approximately 5% of the available label and increased greater than two fold in 24h. This resulted in specific labelling of 12,704 cpm/ug protein +/- 10% between different runs with the same strain.


Failure in distinguishing colored noise from chaos using the "noise titration" technique.
Identifying chaos in experimental data-noisy data-remains a challenging problem for which conclusive arguments are still very difficult to provide. In order to avoid problems usually encountered with techniques based on geometrical invariants (dimensions, Lyapunov exponent, etc.), Poon and Barahona introduced a numerical titration procedure which compares one-step-ahead predictions of linear and nonlinear models [Proc. Natl. Acad. Sci. U.S.A. 98, 7107 (2001)]. We investigate the aformentioned technique in the context of colored noise or other types of nonchaotic behaviors. The main conclusion is that in several examples noise titration fails to distinguish such nonchaotic signals from low-dimensional deterministic chaos.


Quantitative Follow-Up Assessment of Patients with Interstitial Lung Disease by 3D-Curved High-Resolution CT Imaging Parallel to the Chest Wall.
We evaluated the progression of interstitial lung disease (ILD) by three-dimensional curved high-resolution computed tomography (3D-cHRCT) at a constant depth from the chest wall and compare the results to pulmonary function test (PFT) results on a follow-up assessment. We reviewed the patients with ILD who underwent HRCT and concurrent PFTs at least twice from April 2008 to December 2014. Forty-five patients with ILD were enrolled. 3D-cHRCT images of the lung at various depths from the chest wall were reconstructed, and total area (TA), high-attenuation area (HAA) >-500 HU, and %HAA ([HAA/TA] × 100) were calculated. The TA, HAA, and %HAA ratios (follow-up to baseline) were assessed for use in the diagnosis of physiologically progressive ILD (defined as; forced vital capacity [FVC] ratio <0.9 or %diffusing capacity of the lung for carbon monoxide [%DLCO] ratio <0.85 [follow-up to baseline]). Of all ratios obtained from 3D-cHRCT images at 5-30mm depths, the %HAA ratio at 20-mm had the largest area under the receiver operating characteristic curve (0.815, 95 % confidence interval 0.677-0.953). By univariate logistic regression analysis, TA, HAA, and %HAA ratios at 20-mm showed significant correlations with physiologically progressive ILD. 3D-cHRCT imaging performed in parallel with the chest wall offers novel quantitative parameters that are useful for following ILD.


Nonsmooth Continuous-Time Distributed Algorithms for Seeking Generalized Nash Equilibria of Noncooperative Games via Digraphs.
In this article, the problem of distributed generalized Nash equilibrium (GNE) seeking in noncooperative games is investigated via multiagent networks, where each player aims to minimize his or her own cost function with a nonsmooth term. Each player's cost function and feasible action set in the noncooperative game are both determined by actions of others who may not be neighbors, as well as his/her own action. Particularly, feasible action sets are constrained by private convex inequalities and shared linear equations. Each player can only have access to his or her own cost function, private constraint, and a local block of shared constraints, and can only communicate with his or her neighbours via a digraph. To address this problem, a novel continuous-time distributed primal-dual algorithm involving Clarke's generalized gradient is proposed based on consensus algorithms and the primal-dual algorithm. Under mild assumptions on cost functions and graph, we prove that players' actions asymptotically converge to a GNE. Finally, a simulation is presented to demonstrate the effectiveness of our theoretical results.


Healthcare Access and Utilization among Korean Americans: The Mediating Role of English Use and Proficiency.
The literature suggests that Korean Americans underutilize health services. Cultural factors and language barriers appear to influence this pattern of low utilization but studies on the relationships among length of stay in the US, English use and proficiency, and utilization of health services among Korean Americans have yielded inconsistent results. This study examines whether English language use and proficiency plays a mediating role in the relationships between length of stay in the US and health insurance coverage, access to and use of care. Structural equation modeling was used for mediation analysis with multiple dependent variables among Korean Americans (N = 555) using baseline data from a large trial designed to increase Hepatitis B testing. The results show 36% of the total effect of proportion of lifetime in the US on having health insurance was significantly mediated by English use and proficiency (indirect effect = 0.166, SE = 0.07, p<.05; direct effect = 0.296, SE = 0.13, p<.05). Proportion of lifetime in the US was not associated with usual source of care and health service utilization. Instead, health care utilization was primarily driven by having health insurance and a usual source of care, further underscoring the importance of these factors. A focus on increasing English use and proficiency and insurance coverage among older, female, less educated Korean Americans has the potential to mitigate health disparities associated with reduced access to health services in this population.