Gemcitabine and radiation therapy for non-small cell lung cancer.
Patients with stage III non-small cell lung cancer (NSCLC) frequently progress either within the irradiated field or systemically, due to uncontrolled microscopic dissemination present before the time of initial diagnosis. The use of combined modality therapy has led to improved survival rates in recent years. In particular, the use of cisplatin and vinblastine as induction chemotherapy is supported by two large randomized clinical trials. Nevertheless, the large majority of patients still die of progressive disease, thus providing a rationale for the integration of new active agents into the overall treatment plan of these patients. Gemcitabine has demonstrated significant single-agent activity in NSCLC. In addition, preclinical and early clinical data indicate that it is a powerful radiation enhancer. Clinical trials investigating this drug with concurrent radiation therapy in NSCLC are reviewed.


Tourette syndrome and HLA.
Five kindreds with multiple individuals manifesting Tourette syndrome (TS) or related abnormal movements were evaluated for linkage between TS and HLA-A, B, C and DR antigens. Families were selected to have a constellation of affected individuals which gave the appearance of transmission of a major susceptibility gene. All kindreds had at least two clearly affected first or second degree relatives. Although developmental neurobehavioral disorders are candidates for showing a relationship to specific tissue antigens, we found no evidence for a close linkage between a gene locus determining susceptibility to TS and the HLA loci.


Strength and Motion in the Shoulder, Elbow, and Hip in Softball Windmill Pitchers.
Softball pitching is a ballistic, complex movement that requires an underhand windmill motion to create force and ball velocity. In addition to proper pitch biomechanics, upper and lower extremity strength and joint motion likely contribute to ball location accuracy and velocity. Yet, the number of studies reporting muscle strength and joint range of motion among softball pitchers is scarce. To assess differences between throwing and nonthrowing shoulder, elbow, and hip (lead and trail leg) strength and range of motion (ROM) in high school and collegiate level softball windmill pitchers. Cross-sectional study. Thirty-three female softball pitchers (24 high school, 9 collegiate) were recruited from local teams. Goniometric joint ROM and handheld dynamometer strength measurements of the bilateral shoulders, elbows, and hips were measured. Goniometric joint ROM of the bilateral elbows (flexion, extension), shoulders, and hips (flexion, extension, internal rotation [IR], external rotation [ER]). Handheld dynamometer strength measurements of the bilateral shoulders (flexion, extension, abduction, IR, ER), elbows (flexion, extension), and hips (flexion, extension, IR, ER, abduction). Across all pitchers, there was greater shoulder flexion ROM in the nonthrowing limb than in the throwing limb (P = .004). There was greater hip extension in the lead leg than trail leg. Among high school pitchers, there was greater shoulder ER (x = 105.792 ± 7.11) than collegiate pitchers (x = 100.1 ± 6.92), P = .05. There was no difference in total arc of shoulder rotational motion (ER+ IR) between throwing and nonthrowing limbs across all pitchers, nor between high school and collegiate pitchers. Strength measures demonstrated greater throwing limb shoulder abduction (P = .006) and IR strength (P = .001) than the nonthrowing shoulder across all pitchers. Elbow flexion strength was significantly greater than the nonthrowing side (P = .001). No difference was noted in hip strength between lead and trail lower extremities. Developing normative data for softball pitchers upper and lower extremity strength and range of motion may allow providers to assess players more comprehensively and identify athletes out of the expected value range. This information may help in guiding strength and conditioning programs for softball pitchers. III.


Determination of phenazopyridine in human plasma via LC-MS and subsequent development of a pharmacokinetic model.
This paper describes a new LC-MS method for the determination of phenazopyridine and the subsequent development of a pharmacokinetic model for phenazopyridine in vivo. Phenazopyridine hydrochloride is a strong analgesic used in the treatment of urinary tract infections. Although it has been used as a clinical treatment for a very long time, pharmacokinetic data and suitable methods for its determination in plasma are currently lacking. The study described in this paper used high performance liquid chromatography-mass spectrometry, HPLC-MS, to determine the plasma concentrations of phenazopyridine in human subjects after oral administration. After liquid-liquid extraction, the phenazopyridine in the plasma was analyzed on a C18 column under SIM mode. A double-peak phenomenon was observed in most of the concentration-time profiles of the subjects. Although some drugs are known to cause this phenomenon, phenazopyridine has not been reported to do so. Several possible causes were analyzed in order to obtain an explanation. We proposed a two-site absorption compartment model to fit the concentration data in vivo, which has one more absorption site than the classical one-compartment model. The model describes the concentration profiles in different dose groups well and could provide an explanation for the double-peak phenomenon. The three dose groups exhibited similar model parameters and a linear pharmacokinetic process over the dose range used.


Recrystallization of dihydromyricetin from Ampelopsis grossedentata and its anti-oxidant activity evaluation.
A fast and efficient method for purification of dihydromyricetin (3,5,7,3',4',5'-six hydroxy-2,3-dihydro flavonol; DMY) from Ampelopsis grossedentata was created by crystallization eight times at 25°C, and a purity of 98% was finally achieved. The purified DMY exhibited high oxygen radical absorbance capacity (ORAC) (30.21 μmol Trolox equiv/mg) and strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (half-maximal inhibitory concentration [IC50]=0.235 μg/mL). The addition of DMY could also effectively attenuate 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced human erythrocyte hemolysis and cupric chloride (CuCl2)-induced human plasma lipid peroxidation via inhibition of intracellular reactive oxygen species (ROS) generation. It was also found that DMY (>12 μg/mL) treatment significantly inhibited intracellular malondialdehyde (MDA) formation. Meanwhile, DMY treatment significantly inhibited the obvious increase of anti-oxidant enzymes levels (superoxide dismutase [SOD]; glutathione peroxidase [GPX], and catalase [CAT]) induced by AAPH radicals, suggesting that stress defense mechanisms are associated with protection of DMY against intracellular oxidation.


The Physical Properties and Self-Assembly Potential of the RFFFR Peptide.
The self-assembly of fibers from peptides has attracted a tremendous amount of attention due to its many applications, such as in drug-delivery systems, in tissue engineering, and in electronic devices. Recently, the self-assembly potential of the designer peptide RFFFR has been reported. Here it is experimentally verified that the peptide forms fibers that are entangled and form solid spheres without water inside. Upon dilution below the critical fiber concentration, the fibers untangle and become totally separated prior to dissolution. These structures readily bind thioflavin T, resulting in a characteristic change in fluorescent properties consistent with β-sheet-rich amyloid structures with aromatic/hydrophobic grooves. The circular dichroism spectroscopy data are dominated by a π→π* transition, thus indicating that the fibers are stabilized by π-stacking. Contrary to what was expected, the dissolution of the spheres/fibers results in increasing fluorescence anisotropy over time. This is explained in terms of HomoFRET between phenylalanine residues with a T-shaped π-stacking mode, which was determined in another study to be the dominant mode through atomistic simulations and semiempirical calculations. Kelvin probe force microscopy measurements indicate that the spheres and fibers have a conductivity comparable to that of gold. Hence, these self-assembled structures might be applicable in organic solid-state electronic devices. The dissolution properties of the spheres further suggest that they might be used as drug-delivery systems.


Direct observation of lipid bilayer disruption by poly(amidoamine) dendrimers.
Atomic force microscopy (AFM) is employed to observe the effect of poly(amidoamine) (PAMAM) dendrimers on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers. Aqueous solutions of generation 7 PAMAM dendrimers cause the formation of holes 15-40 nm in diameter in previously intact bilayers. This effect is observed for two different branch end-groups--amine and carboxyl. In contrast, carboxyl-terminated core-shell tectodendrimer clusters do not create holes in the lipid membrane but instead show a strong affinity to adsorb to the edges of existing bilayer defects. A possible mechanism for the formation of holes in the lipid bilayer is proposed. The dendrimers remove lipid molecules from the substrate and form aggregates consisting of a dendrimer surrounded by lipid molecules. Dynamic light scattering (DLS) measurements as well as 31P NMR data support this explanation. The fact that tectodendrimers behave differently suggests that their cluster-like architecture plays an important role in their interaction with the lipid bilayer.


Hospital communication about drugs: the effect of language on accuracy.
To review some of the problems associated with the prescription, supply and administration of drugs in a multicultural environment. Staff questionnaire. Most respondents indicated the information received from the pharmacy was satisfactory, that they had read a recent therapeutic bulletin and that they could describe prescription handwriting as 'clear and reasonable'. There was general difficulty in understanding the meaning of Latin abbreviations and a demonstrated failure to absorb recently circulated information.


Ataxic sensory neuronopathy in a patient with systemic lupus erythematosus.
The occurrence of ataxic sensory neuronopathy (ASN) is rare in patients with connective tissue diseases (CTDs). ASN has been described in case reports and case series in patients with CTDs, mostly Sjögren's syndrome, and most often occurring during middle or old age. ASN in association with systemic lupus erythematosus (SLE) is extremely rare; there has been only one reported case in the literature. In addition, to our knowledge, adolescent onset of symptoms in CTD-associated ASN has not been reported previously. We report the case of a young woman who presented with ASN, characterized by sensory ataxia, with elevated antinuclear antibodies, leukopenia and anemia; she fulfilled the diagnostic criteria for SLE about 7 years after the onset of sensory ataxia. Our case points out that ASN may be the initial presenting feature of SLE. SLE should be included in the differential diagnosis of ASN, especially in patients of young age.


Exercise, natural immunity, and tumor metastasis.
Exercise has been shown to reduce the growth of primary tumors and to enhance certain aspects of host natural immunity. The question of whether these are independent phenomena or are casually related has not been systematically evaluated. This paper presents information concerning the methodological difficulties in studying proposed relationships between exercise and cancer, focusing specifically on tumor metastasis, the process by which malignant cells disseminate to distant organs and establish new colonies. This paper also focuses on how natural immune processes and tumor cells exert bidirectional influences on each other. It is suggested that the direction of the impact of exercise on the control of metastatic spread of neoplastic cells will reflect, in part, the sensitivity of the specific tumor to cytolysis by natural immune mechanisms, the route of dissemination, the timing of exercise relative to tumor exposure, and whether exercise acts as a distress or eustress state.


Mid-term outcomes in unbalanced complete atrioventricular septal defect: role of biventricular conversion from single-ventricle palliation.
Management strategy for unbalanced complete atrioventricular septal defects (CASVSDs) includes single-ventricle (SV) palliation and primary or staged biventricular (BiV) repair. More recently, BiV conversion (BiVC) from SV palliation and staged BiV recruitment (BiVR) have also been advocated. This study assesses mid-term outcomes in patients with unbalanced CASVSDs according to management strategy. Consecutive patients with unbalanced CASVSDs who underwent surgery at a tertiary care centre from January 2000 to February 2016 with institutional review board approval. The index surgery was defined as the first palliation procedure for the SV group, a BiV repair for the BiV repair group and conversion or the first procedure for recruitment for the BiVC/BiVR group. Kaplan-Meier and Cox regression were used for time-to-event analysis of death/transplant and unplanned reinterventions that occurred after the index surgery. There were 212 patients: 82 (38.7%) had SV palliation, 67 (31.6%) had BiV repair and 63 (29.7%) had BiVC/BiVR, respectively; 50 patients had undergone a successful BiVC. There were 93 (43.9%) boys; 51 (24%) patients had Down syndrome; and 101 (48%) patients had heterotaxy. In the entire cohort, there were 40 (18.9%) deaths, 110 (51.9%) reinterventions, 82 (38.7%) surgical reinterventions and 70 (33%) catheter reinterventions, with some patients having more than 1 reintervention. Median length of follow-up was 35 (range 1-192) months. The BiVC/BiVR group had a transplant-free survival benefit similar to that of the primary BiV repair group compared with the SV group. The BiV repair group needed fewer catheter-based reinterventions compared with the SV and BiVC/BiVR groups. BiVC or BiVR from an SV pathway can be achieved with low rates of mortality and morbidity in patients with unbalanced CASVSDs.


Sensemaking and cognitive shifts - learning from dissemination of a National Quality Register in health care and elderly care.
Purpose The purpose of this study is to examine and establish how sensemaking develops among a group of external change agents (ECAs) engaged to disseminate a national quality register nationwide in Swedish health care and elderly care. To study the emergent sensemaking, the theoretical concept of cognitive shift has been used. Design/methodology/approach The data collection method included individual semi-structured interviews, and two sets of interviews (initial sensemaking and renewed sensemaking) have been conducted. Based on a typology describing how ECAs interpret their work, structural analyses and comparisons of initial and renewed sensemaking are made and illuminated in spider diagrams. The data are then analyzed to search for cognitive shifts. Findings The ECAs' sensemaking develops. Three cognitive shifts are identified, and a new kind of issue-related cognitive shift, the outcome-related cognitive shift, is suggested. For the ECAs to customize their work, they need to be aware of how they interpret their own work and how these interpretations develop over time. Originality/value The study takes a novel view of the interrelated concepts of sensemaking and sensegivers and points out the cognitive shifts as a helpful theoretical concept to study how sensemaking develops.


Three-dimensional Printing in Anatomy Education: Assessing Potential Ethical Dimensions.
New technological developments have frequently had major consequences for anatomy education, and have raised ethical queries for anatomy educators. The advent of three-dimensional (3D) printing of human material is showing considerable promise as an educational tool that fits alongside cadaveric dissection, plastination, computer simulation, and anatomical models and images. At first glance its ethical implications appear minimal, and yet the more extensive ethical implications around clinical bioprinting suggest that a cautious approach to 3D printing in the dissecting room is in order. Following an overview of early groundbreaking studies into 3D printing of prosections, organs, and archived fetal material, it has become clear that their origin, using donated bodies or 3D files available on the Internet, has ethical overtones. The dynamic presented by digital technology raises questions about the nature of the consent provided by the body donor, reasons for 3D printing, the extent to which it will be commercialized, and its comparative advantages over other available teaching resources. In exploring questions like these, the place of 3D printing within a hierarchical sequence of value is outlined. Discussion centers on the significance of local usage of prints, the challenges created by regarding 3D prints as disposable property, the importance of retaining the human side to anatomy, and the unacceptability of obtaining 3D-printed material from unclaimed bodies. It is concluded that the scientific tenor of 3D processes represents a move away from the human person, so that efforts are required to prevent them accentuating depersonalization and commodification.


Improvement of ethanol production in very high gravity fermentation by horse gram (Dolichos biflorus) flour supplementation.
To determine the effect of osmotic stress on yeast and to investigate the protective role of horse gram flour during very high gravity (VHG) ethanol fermentation. Saccharomyces cerevisiae was inoculated into high sugar (30-40%, w/v) containing medium with and without supplementation of horse gram flour. The fermentation experiments were carried out in batch mode. The effect of 4 or 6% of horse gram flour to the medium on the metabolic behaviour and viability of yeast was studied. Significant increase in ethanol yield up to 50% and dramatic decrease in glycerol production up to 100% was observed in the presence of horse gram flour. The fermentation rate was increased from 3 to 5 days with increased viable cell count. The physical and chemical factors of horse gram flour may aid in reducing the osmotic stress of high gravity fermentation of ethanol as well as enhancing ethanol yield. It was found that horse gram flour not only reduced fermentation time but also enhanced ethanol production by better utilization of sugar. Production of high ethanol concentration by using VHG sugar fermentation eliminates the expensive steps in the conventional process and saves time.


Global satellite monitoring of climate-induced vegetation disturbances.
Terrestrial disturbances are accelerating globally, but their full impact is not quantified because we lack an adequate monitoring system. Remote sensing offers a means to quantify the frequency and extent of disturbances globally. Here, we review the current application of remote sensing to this problem and offer a framework for more systematic analysis in the future. We recommend that any proposed monitoring system should not only detect disturbances, but also be able to: identify the proximate cause(s); integrate a range of spatial scales; and, ideally, incorporate process models to explain the observed patterns and predicted trends in the future. Significant remaining challenges are tied to the ecology of disturbances. To meet these challenges, more effort is required to incorporate ecological principles and understanding into the assessments of disturbance worldwide.


The antibody response to fungal melanin in mice.
Melanins are associated with virulence in several important human pathogens, but little is known about the immune response to this ubiquitous biologic compound. We hypothesized that melanin produced by the fungus Cryptococcus neoformans was immunogenic. C. neoformans melanin was purified from melanized fungal cells and was used to immunize C57BL/6, BALB/c, and T cell-deficient (nude) BALB/c mice. The Ab response was evaluated by ELISA, immunofluorescence, and agglutination. The results demonstrate that melanin can be immunogenic, and the humoral immune response is T cell independent. Furthermore, the experiments demonstrate 1) a sensitive ELISA for the measurement of Ab to melanin, 2) that mice mount an intense Ab response to fungal melanin that includes Abs of IgM and IgG isotypes, 3) that melanins from different sources have cross-reactive epitopes, and 4) melanin in the cell wall of melanized yeast cells reacts with Abs raised to L-dopa C. neoformans melanin. The biologic significance of Ab to melanin remains to be determined, but the development of Ab suggests that this amorphous insoluble polymer can stimulate the immune system. The serologic techniques described here may prove useful for the evaluation of Ab responses to melanin in a variety of diseases.


Patient communication skills training: a review with implications for cancer patients.
Although considerable attention has been given to physicians' communication, relatively little research has been directed to patients' communicative contributions to the medical interview. The research in patient communication skills training within the context of primary care is reviewed and implications are discussed for applying skills training in a cancer environment.


Mobilization and collection of peripheral blood stem cells in multiple myeloma patients older than 65 years.
Over the past 10 years, the incidence of multiple myeloma (MM) has been greater among individuals >65 years old than in younger age groups. This retrospective study of peripheral blood stem cell mobilization and harvesting examined patients of various age groups who were afflicted with this pathology. One group of 17 patients ≥65 years of age with MM (group A) were mobilized between 2002 and 2009 and compared with 33 consecutive patients of younger ages with the same diagnosis treated in 2008 and 2009 (group B). The 2 populations had a similar gender distribution; their median ages were 66 and 52 years, respectively. A successful mobilization was defined as a collection of ≥2.5 × 10(6) CD34+/kg body weight. The mobilization used filgrastim (16 μg/kg/d) with the beginning of the harvest on the fifth day. The median number of outpatient apheresis procedures per patient was 2 in group A and 1 in group B. There were no incidents or serious adverse reactions. Patients in group A collected 4.68 × 10(6) CD34+ cells/kg and for group B 3.30 × 10(6)/kg. The group A patients required a greater number of apheresis procedures to collect the appropriate graft. In conclusion, mobilization with growth factors and PHSP harvest by apheresis was safe with reasonable costs for subjects including those aged ≥65 years, resulting in an option for autologous transplantation.


Long-term maintenance of immunity in patients with common variable immune deficiency by plasma transfusion.
The AIDS crisis and the fear of blood product contamination stimulated the development of a designated plasma collection and transfusion for patients with common variable immune deficiency. Four patients have been maintained over 1 year; 5 years and 10 months; 8 years and 7 months; and 12 years. A new crisis affecting commercial IgG manufacturing, owing to recalls, has made the life saving product scarce, threatening patients' health maintenance. Our experience over a long time has demonstrated that plasma transfusion is equivalent to management with commercial IgG. The program of product collection and patient management includes testing the collected plasma for IgG content, selecting ABO compatible plasma, and following patients with IgG trough levels, prior to each transfusion, to assure sufficient immune globulin administration.


Cryoprecipitate coagulum pyelolithotomy.
Coagulum pyelolithotomy is a useful adjunct in the extraction of renal calculi. Unfortunately, a superior coagulum (pooled fibrinogen) is no longer available in the United States. Experience has shown that the better coagula have a high fibrinogen content. A suitable alternate source of fibrinogen is present in cryoprecipitate. Experience with this new coagulum and its use are presented.


Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets.
The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose. From the resulting insulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P less than 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.


Survival on biventricular mechanical support with the Centrimag® as a bridge to decision: a single-center risk stratification.
Temporary mechanical assist devices are increasingly being used as a lifesaving bridge to decision in patients requiring cardiopulmonary resuscitation. We report our single-center experience with biventricular Centrimag® pumps over a five-year period. Data was retrospectively collected in consecutive patients who required biventricular support from 2008 to 2013. Patients who were supported with central cannulation using the Centrimag® system were analyzed. In addition to demographic information, data pertaining to indications, outcomes and mortality were collected. The cohort consisted of 48 patients (19 women and 29 men, mean age of 56 years). The median duration of support was 14 days. The median duration to patient expiration while still on the Centrimag® was 12 days. Thirty-day survival was 56% (27/48). Nine patients were explanted to recovery, while fourteen patients were converted to a durable LVAD, two of whom were then transplanted. We stratified patients into two groups. Group I comprised patients who were either explanted to recovery, converted to durable LVAD or transplanted (23/48) and Group II consisted of patients who either died on the Centrimag® or were explanted for withdrawal of care (25/48). Statistical analysis did not reveal any clinically significant differences between the two groups in terms of age, sex, etiology, hemodynamic, co-morbidities or laboratory parameters. The biventricular Centrimag® can be used as a bridge to decision in patients with thirty-day survival of >50%. Parameters to predict 30-day survival in this high-risk cohort continue to remain elusive.


[Health economic analysis of the effects of offered complementary medical procedures on health insurance].
A randomized trial is being conducted to determine whether the offer of unconventional medicine as a health benefit by the health insurance funds has a substitutional or additional effect on the use of conventional medicine. For this purpose, a stratified random sample of 5000 enrollees of the largest Swiss health insurance fund is receiving, as an experiment group, an insurance supplement for unconventional medicine during the next three years free of charge. The rest of the insured population with comparable health insurance but without coverage of unconventional medicine is the control group. The third group to be examined are insured persons who have already chosen the unconventional health insurance supplement on their own account. Data of inpatient and outpatient costs and use of conventional and unconventional health services will be collected and analyzed. The third group with self-selected insurance supplement for unconventional medicine will be compared systematically with the other two groups. A further random sample of persons from each of the three groups will be interviewed at different points of time about their health perceptions.


[Association between hypertensive cerebrovascular stroke and renin-angiotensin system gene polymorphism from Chinese cohort in Shanghai].
To evaluate the association between hypertensive cerebrovascular stroke and renin-angiotensin system gene polymorphism from Chinese cohort. The polymorphisms of angiotensinogen(AGT) and angiotensin-converting enzyme(ACE) from 257 cases of simple essential hypertension(EH) and 218 cases of hypertensive stroke(131 hemorrhagic cases and 87 ischemic cases were detected by PCR-RFLP. The frequencies of DD genotype and D allele of ACE gene in ischemic stroke were significantly higher than those in hemorrhagic stroke and EH, and the odds ratios(OR) of DD/II genotype were 3.25(2.20-4.79) and 2.87(2.03-4.06), while the OR of D/I allele were 1.83(1.38-2.43) and 1.69(1.27-2.24) respectively. Otherwise, there was no difference in frequency distribution of Met235Thr mutation polymorphism and DD+TT/non DD non TT combined among the three groups. The I/D polymorphism of ACE gene may be one of the risk factors and susceptible genetic markers for ischemic stroke with essential hypertension in Chinese.


p53 alterations predict tumor response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma: a prospective series.
The tumor suppressor gene p53 plays a crucial role in cell cycle control and apoptosis in response to DNA damages. p53 gene mutations and allelic losses at 17p are one of the most common genetic alterations in primary head and neck squamous cell carcinoma (HNSCC). Alterations of the p53 gene have been shown to contribute to carcinogenesis and drug resistance. In this prospective series, patients with HNSCC were treated with cisplatin-fluorouracil neoadjuvant chemotherapy. p53 status was characterized in 106 patients with HNSCC (p53 mutations, allelic losses at p53 locus, and plasma anti-p53 antibodies) to determine the existence of a relationship between p53 gene status and response to neoadjuvant chemotherapy. Exons 4 to 9 of the p53 gene were analyzed, and mutations were found in 72 of 106 patients with HNSCC. p53 mutations were associated with loss of heterozygosity at chromosome 17p (P <.001). The prevalence of p53-mutated tumors was higher in the group of patients with nonresponse to neoadjuvant chemotherapy than in the group of responders (81% v 61%, respectively; P <.04). When compiling p53 mutations and anti-p53 antibodies in plasma, the correlation between p53 status and response to chemotherapy was significant (87% v 57%, respectively; P =.003). A multivariate analysis showed that p53 status is an independent predictive factor of response to chemotherapy. This prospective study suggests that p53 status may be a useful indicator of response to neoadjuvant chemotherapy in HNSCC.


Memory Retrieval from First Principles.
The dilemma that neurotheorists face is that (1) detailed biophysical models that can be constrained by direct measurements, while being of great importance, offer no immediate insights into cognitive processes in the brain, and (2) high-level abstract cognitive models, on the other hand, while relevant for understanding behavior, are largely detached from neuronal processes and typically have many free, experimentally unconstrained parameters that have to be tuned to a particular data set and, hence, cannot be readily generalized to other experimental paradigms. In this contribution, we propose a set of "first principles" for neurally inspired cognitive modeling of memory retrieval that has no biologically unconstrained parameters and can be analyzed mathematically both at neuronal and cognitive levels. We apply this framework to the classical cognitive paradigm of free recall. We show that the resulting model accounts well for puzzling behavioral data on human participants and makes predictions that could potentially be tested with neurophysiological recording techniques.


[The role of prostaglandins and Cyclooxygenase in pathogenesis of chronic endometritis].
The purpose: to present the modern data of cyclooxygenase role (COX) in the development of chronic endometritis.106 references on the role of COX-1 and COX-2 in the development of chronic endometritis in patients of reproductive age, published in the Medline database, Pubmed, Scopus were analyzed; 14 sources are included in this review. Prostaglandins (PG) play an important role in maintaining inflammatory process in the endometrium. Nevertheless, the production of PG and leukotrienes (LTS) - lipid mediators, which, along with PG, play a major role in the inflammatory process of the inflamed uterus, is not fully understood. Cyclooxygenase-2, the enzyme having various physiological functions, is involved in reproduction, where its role is polyfunctional. It has been established that the inhibition of cyclooxygenase pathways, blocking the synthesis of prostaglandins, eliminates the effects of many pro-inflammatory cytokine involved in the pathogenesis of chronic endometritis. Conclusion. The role of cyclooxygenase in the development of chronic endometritis is interesting; on the basis of the acquired knowledge, we can plan the use of drugs that inhibit the cyclooxygenase pathway (NSAIDs) in the treatment of chronic endometritis - as a method of pathogenetic therapy. The issue is not fully understood. Further research is needed in this sphere.


Default-mode network dysfunction and cognitive impairment in progressive MS.
This study explores default-mode network (DMN) abnormalities in patients with secondary progressive (SP) and primary progressive (PP) multiple sclerosis (MS) and whether such abnormalities correlate with cognitive impairment and damage to selected white matter (WM) fiber bundles, quantified using diffusion tensor (DT) MRI tractography. Resting state (RS) functional MRI and DT MRI data were acquired from 33 patients with SPMS, 24 patients with PPMS, and 24 controls. Independent component analysis (ICA) was used to identify the DMN. SPM5 was used to assess within- and between-group activations. Between-group differences in DMN activity were found in the left medial prefrontal cortex (mPFC), left precentral gyrus (PcG), and anterior cingulate cortex (ACC). Compared to controls, patients with SPMS had reduced activity in the mPFC (p = 0.01) and PcG (p = 0.02), while patients with PPMS had reduced activity in the PcG (p = 0.008) and the ACC (p = 0.002). Compared to patients with PPMS, patients with SPMS had increased ACC activity (p = 0.04). Reduction of RS activity in the ACC was more pronounced in cognitively impaired vs cognitively preserved patients with MS (p = 0.02). In patients with MS, DMN abnormalities correlated with the PASAT and word list test scores (r values ranging from 0.35 to 0.45) and DT MRI changes in the corpus callosum and the cingulum (r values ranging from 0.82 to 0.87). These results suggest that a dysfunction of the anterior components of the default-mode network may be among the factors responsible for the accumulation of cognitive deficits in patients with progressive multiple sclerosis.


Benzo(a)pyrene induces lung toxicity and inflammation in mice: prevention by carvacrol.
Benzo(a)pyrene (B(a)P) is an environmental pollutant which causes various lung toxicities. The present study was designed to evaluate the protective effects of carvacrol, a monoterpenic phenol against B(a)P-induced lung toxicity. In this study, Swiss albino mice were pretreated with carvacrol (25 mg/kg and 50 mg/kg) orally for 7 consecutive days before administering oral B(a)P (125 mg/kg). Preventive efficacy of carvacrol was assessed in terms of membrane oxidation, antioxidant enzyme activities, histopathological changes, and inflammatory (iNOS, NF-κB, and COX-2) markers. Carvacrol pretreatment in the two doses restored B(a)P-induced lipid peroxidation and increased the activities of antioxidant enzymes. Protein expressions of iNOS, NF-κB, and COX-2 in the lung tissue were found to be upregulated by B(a)P. Carvacrol treatment, however, downregulated their expressions by decreasing the marker of positive stained cells and restored the histopathological architecture of lung tissue. Our results suggest that carvacrol can be used as a protective agent against B(a)P-induced lung toxicity and inflammation.


Estimating the precision of disc diffusion antibiotic susceptibility data published by the European committee on antimicrobial susceptibility testing.
Analysis of 163 disc diffusion data sets, 115 for bacterial species groups and 48 for types strains, published by EUCAST, was used to optimize the setting of the parameters of a standardized protocol for normalized resistance interpretation of these data. The standard deviations of the normalized distributions of these data sets, calculated using this standardized protocol, were shown to be independent of the means of their respective distributions. These standard deviations could, therefore, be used as a metric to quantify the precision of disc diffusion data sets. The median value of the standard deviations for 115 EUCAST data sets produced in multiple laboratory studies of bacterial species groups was 2.3 mm and that for the 48 EUCAST data sets produced in multiple laboratory studies of type strains was 1.5 mm. It is argued that this standardized method for estimating the precision of disc diffusion data provides a tool by which individual laboratories can assess the quality of the disc diffusion data they produce.


An investigation into the antimicrobial mechanisms of action of two contact lens biocides using electron microscopy.
Polyquaternium-1 (PQ-1) and myristamidopropyl dimethylamine (MAPD) are biocides used commercially in a contact lens disinfecting solutions. Electron microscopy was used to provide further evidence on the mechanism(s) of action of these agents against a wide range of ocular pathogens including bacteria, fungi and protozoa. Both PQ-1 and MAPD caused multiple forms of damage to the organisms tested, evidenced by structural alterations, blebbing, leakage and cell destruction. The extent of damage and the selectivity against specific type of microorganisms was consistent with the antimicrobial activity of these agents. Although electron microscopy is a powerful tool, it has its limitations when used to examine the mode of action of biocides. Indeed, there was no evidence of gross structural alteration to Acanthamoeba castellani or Aspergillus fumigatus following treatment.


A R2R3-MYB transcription factor that is specifically expressed in cotton (Gossypium hirsutum) fibers affects secondary cell wall biosynthesis and deposition in transgenic Arabidopsis.
Secondary cell wall (SCW) is an important industrial raw material for pulping, papermaking, construction, lumbering, textiles and potentially for biofuel production. The process of SCW thickening of cotton fibers lays down the cellulose that will constitute the bulk (up to 96%) of the fiber at maturity. In this study, a gene encoding a MYB-domain protein was identified in cotton (Gossypium hirsutum) and designated as GhMYBL1. Quantitative real-time polymerase chain reaction (RT-PCR) analysis revealed that GhMYBL1 was specifically expressed in cotton fibers at the stage of secondary wall deposition. Further analysis indicated that this protein is a R2R3-MYB transcription factor, and is targeted to the cell nucleus. Overexpression of GhMYBL1 in Arabidopsis affected the formation of SCW in the stem xylem of the transgenic plants. The enhanced SCW thickening also occurred in the interfascicular fibers, xylary fibers and vessels of the GhMYBL1-overexpression transgenic plants. The expression of secondary wall-associated genes, such as CesA4, CesA7, CesA8, PAL1, F5H and 4CL1, were upregulated, and consequently, cellulose and lignin biosynthesis were enhanced in the GhMYBL1 transgenic plants. These data suggested that GhMYBL1 may participate in modulating the process of secondary wall biosynthesis and deposition of cotton fibers.


Dynamic cerebral autoregulation measurement using rapid changes in head positioning: experiences in acute ischemic stroke and healthy control populations.
The ideal technique for dynamic cerebral autoregulation (dCA) assessment in critically ill patients should provide considerable variability in blood pressure (BP) but without the need for patient cooperation. We proposed using rapid head positioning (RHP) over spontaneous BP fluctuations for dCA assessment in patients with acute ischemic stroke (AIS). Cerebral blood velocity (transcranial Doppler), beat-to-beat BP (Finometer), and end-tidal CO2 (capnography) were recorded during 5-min baseline and RHP in 16 controls (8 women and 8 men, mean age: 57 ± 16 yr) and 15 patients with AIS (7 women and 8 men, mean age: 69 ± 8 yr) at two (12 ± 8 days) and three visits (13.3 ± 6.9 h, 4.8 ± 3.2 days, and 93.9 ± 11.5 days from the symptom onset), respectively. All participants were able to complete the RHP protocol without difficulty. Compared with controls, patients with AIS were hypocapnic (all visits, P < 0.0024) and hypertensive ( visit 1, P = 0.011), although BP gradually reduced after the acute phase. RHP demonstrated greater beat-to-beat BP variability (BPV) in controls ( visits 1 and 2, P < 0.001) but not in patients with AIS at any visit. Compared with controls, a reduced autoregulation index (ARI) was demonstrated in patients with AIS, at visit 2 for the baseline recording but not at other visits or during RHP. The area under the receiver-operating curve was 0.53 and 0.54 for baseline and RHP, respectively. The RHP paradigm required minimal patient cooperation and could be considered a feasible alternative for assessing dCA, mainly in conditions leading to increased BPV. The lack of BPV increase in AIS with RHP deserves further investigation. NEW & NOTEWORTHY This study used rapid head positioning (RHP) to enhance blood pressure (BP) variability (BPV) to improve BP signal-to-noise ratio and reliability of dynamic cerebral autoregulation (dCA). RHP was well accepted by controls and acute ischemic stroke (AIS); the increased BPV induced in controls was not observed in AIS, suggesting BPV at rest was already elevated. RHP did not improve detection of impaired CA in AIS; further work is needed to understand the different responses observed.


Detection of sorbitol-negative and sorbitol-positive Shiga toxin-producing Escherichia coli, Listeria monocytogenes, Campylobacter jejuni, and Salmonella spp. in dairy farm environmental samples.
Six visits were conducted to four dairy farms to collect swab, liquid, and solid dairy farm environmental samples (165 to 180/farm; 15 sample types). The objective of the study was to determine on-farm sources of Campylobacter jejuni, Salmonella spp., Listeria monocytogenes, and Shiga toxin-producing Escherichia coli (STEC), which might serve as reservoirs for transmission of pathogens. Samples were analyzed using mostly U.S. Food and Drug Administration's Bacteriological Analytical Manual protocols; however, Salmonella spp., L. monocytogenes and STEC were co-enriched in universal pre-enrichment broth. Campylobacter jejuni were enriched in Bolton broth containing Bolton broth supplement. Pathogens were isolated on agar media, typed biochemically, and confirmed using multiplex polymerase chain reaction protocols. Campylobacter jejuni, Salmonella spp., L. monocytogenes, Sorbitol-negative (SN)-STEC O157:H7, and sorbitol-positive (SP)-STEC, respectively, were isolated from 5.06%, 3.76%, 6.51%, 0.72%, and 17.3% of samples evaluated. Whereas other pathogens were isolated from all four farms, SN-STEC O157:H7 were isolated from only two farms. Diverse serotypes of SP-STEC including O157:H7, O26:H11, O111, and O103 were isolated. None of the five pathogen groups studied were isolated from bulk tank milk (BTM). Most pathogens (44.2%) were isolated directly from fecal samples. Bovine fecal samples, lagoon water, bedding, bird droppings, and rat intestinal contents constituted areas of major concern on dairy farms. Although in-line milk filters from two farms tested positive for Salmonella or L. monocytogenes, none of the pathogens were detected in the corresponding BTM samples. Good manure management practices, including control of feral animals, are critical in assuring dairy farm hygiene. Identification of on-farm pathogen reservoirs could aid with implementation of farm-specific pathogen reduction programs.


Immunotherapeutic potential of CpG oligodeoxynucleotides in veterinary species.
Innate immunity plays a critical role in host defense against infectious diseases by discriminating between self and infectious non-self. The recognition of infectious non-self involves germ-line encoded pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs). The PAMPs are the components of pathogenic microbes which include not only the cell wall constituents but also the unmethylated 2'-deoxy-ribo-cytosine-phosphate-guanosine (CpG) motifs. These CpG motifs present within bacterial and viral DNA are recognized by toll-like receptor 9 (TLR9), and signaling by this receptor triggers a proinflammatory cytokine response which, in turn, influences both innate and adaptive immune responses. The activation of TLR9 with synthetic CpG oligodeoxynucleotides (ODNs) induces powerful Th1-like immune responses. It has been shown to provide protection against infectious diseases, allergy and cancer in laboratory animal models and some domestic animal species. With better understanding of the basic biology and immune mechanisms, it would be possible to exploit the potential of CpG motifs for animal welfare. The research developments in the area of CpG and TLR9 and the potential applications in animal health have been reviewed in this article.


Combined Baccalaureate/Medical Degree Students Match Into Family Medicine Residencies More Than Similar Peers: A Matched Case-Control Study.
We sought to evaluate whether the University of New Mexico (UNM) Combined Baccalaureate/Medical Degree (BA/MD) program increases the likelihood that students match into family medicine residencies. We used binary logistic regression to predict interest and actual residency match in family medicine. We compared BA/MD participants to similar peers (one-to-one match subject design) and all other students for the nine cohorts of medical students who have matriculated into UNM School of Medicine since the inception of the BA/MD program (medical school matriculation years 2009-2017). We also investigated whether BA/MD students were more likely to select family medicine as their specialty choice at the time of matriculation using survey responses. At the time of matriculation, the differences in identifying family medicine as a first specialty choice between BA/MD, similar peers, and all other students were small and not statistically significant. However, upon graduation, 33% of BA/MD students matched into family medicine compared to 17% of similar peers, a statistically significant difference even after controlling for United States Medical Licensing Examination (USMLE) test scores and several demographic factors. The University of New Mexico Combined Baccalaureate/Medical Degree students match into family medicine at nearly twice the rate of traditional medical degree students, suggesting that the UNM BA/MD program serves to increase the growth rate of the family medicine workforce.


Isolation and Characterization of Salmonid CD4+ T Cells.
This study reports the isolation and functional characterization of rainbow trout (Oncorhynchus mykiss) CD4-1(+) T cells and the establishment of an IL-15-dependent CD4-1(+) T cell line. By using Abs specific for CD4-1 and CD3ε it was possible to isolate the double-positive T cells in spleen and head kidney. The morphology and the presence of transcripts for T cell markers in the sorted CD4-1(+)CD3ε(+) cells were studied next. Cells were found to express TCRα, TCRβ, CD152 (CTLA-4), CD154 (CD40L), T-bet, GATA-3, and STAT-1. The sorted CD4-1(+) T cells also had a distinctive functional attribute of mammalian T lymphocytes, namely they could undergo Ag-specific proliferation, using OVA as a model Ag. The OVA-stimulated cells showed increased expression of several cytokines, including IFN-γ1, IL-4/13A, IL-15, IL-17D, IL-10, and TGF-β1, perhaps indicating that T cell proliferation led to differentiation into distinct effector phenotypes. Using IL-15 as a growth factor, we have selected a lymphoid cell line derived from rainbow trout head kidney cells. The morphology, cell surface expression of CD4-1, and the presence of transcripts of T cell cytokines and transcription factors indicated that this is a CD4-1(+) T cell line. To our knowledge, this is the first demonstration of the presence of CD4-1(+)CD3ε(+) T cells in salmonids. As in mammals, CD4-1(+) T cells may be the master regulators of immune responses in fish, and therefore these findings and the new model T cell line developed will contribute to a greater understanding of T cell function and immune responses in teleost fish.


Using pulse transit delay in Z-scan to discriminate between excited-state absorption and other nonlinear processes in ZnO nanocones.
We report a new approach that uses the single beam Z-scan technique, to discriminate between excited state absorption (ESA) and two and three photon nonlinear absorption. By measuring the apparent delay or advance of the pulse in reaching the detector, the nonlinear absorption can be unambiguously identified as either instantaneous or transient. The simple method does not require a large range of input fluences or sophisticated pulse-probe experimental apparatus. The technique is easily extended to any absorption process dependent on pulse width and to nonlinear refraction measurements. We demonstrate in particular, that the large nonlinear absorption in ZnO nanocones when exposed to nanosecond 532 nm pulses, is due mostly to ESA, not pure two-photon absorption.


Chemical processing as a tool to generate ovalbumin variants with changed stability.
Processing of ovalbumin may result in proteins that differ more than 23 degrees C in denaturation temperature while the structural fold is not significantly affected. This is achieved by 1) conversion of positive residues into negative ones (succinylation); 2) elimination of negative charges (methylation); 3) reducing the proteins hydrophobic exposure (glycosylation); 4) increasing the hydrophobic exposure (lipophilization); or by 5) processing under alkaline conditions and elevated temperature (S-ovalbumin). The effect on the structural fold was investigated using a variety of biochemical and spectroscopic tools. The consequences of the modification on the thermodynamics of the protein was studied using differential scanning calorimetry and by monitoring the tryptophan fluorescence or ellipticity at 222 nm of protein samples dissolved in different concentrations of guanidine-HCl. The impact of the modification on the denaturation temperature scales for all types of modifications with a free energy change of about 1 kJ per mol ovalbumin per Kelvin (or 0.0026 kJ per mol residue per K). The nature of the covalently coupled moiety determines the impact of the modification on the protein thermodynamics. It is suggested that especially for lipophilized protein the water-binding properties are substantially lowered. Processing of globular proteins in a controlled manner offers great opportunities to control a desired functionality, for example, as texturizer in food or medical applications.


[Modern methods of diagnosis dyslipidemia ].
Dyslipidemia is abnormalities of lipid and lipoprotein metabolism. Most dyslipidemias are hyperlipidemias; that is an abnormally high level of lipids and/or lipoproteins in the blood. Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a modifiable risk factor for cardiovascular disease due to their influence on atherosclerosis. Primary dyslipidemia is usually due to genetic causes, while secondary dyslipidemia arises due to other underlying causes such as diabetes mellitus. Thus, dyslipidemia is an important factor in the development of atherosclerosis and cardiovascular diseases therefore, it is important to diagnose it in time. This review focuses on the modern methods of diagnosis of dyslipidemia.


Antibody responses of swine following infection with Mycoplasma hyopneumoniae, M. hyorhinis, M. hyosynoviae and M. flocculare.
Several mycoplasma species possessing a range of virulence have been described in swine. The most commonly described are Mycoplasma hyopneumoniae, Mycoplasma hyorhinis, Mycoplasma hyosynoviae, and Mycoplasma flocculare. They are ubiquitious in many pig producing areas of the world, and except for M. hyopneumoniae, commercial antibody-based assays are lacking for most of these. Antibody cross-reactivity among these four mycoplasma species is not well characterized. Recently, the use of pen-based oral fluids for herd surveillance is of increasing interest. Thus, this study sought to measure pig antibody responses and the level of cross-reactivity in serum and pen-based oral fluids after challenge with four species of swine mycoplasmas. Four groups of four mycoplasma-free growing pigs were separately inoculated with the different mycoplasma species. Pen-based oral fluids and serum samples were collected weekly until necropsy. Species-specific Tween 20 ELISAs were used to measure antibody responses along with four other commercial M. hyopneumoniae ELISAs. Animals from all groups seroconverted to the challenge species of mycoplasma and no evidence of cross-contamination was observed. A delayed antibody response was seen with all but M. hyorhinis-infected pigs. Cross-reactive IgG responses were detected in M. hyopneumoniae- and M. flocculare-infected animals by the M. hyorhinis Tween 20 ELISA, while sera from M. hyosynoviae and M. flocculare-infected pigs were positive in one commercial assay. In pen-based oral fluids, specific anti-M. hyopneumoniae IgA responses were detected earlier after infection than serum IgG responses. In summary, while some antibody-based assays may have the potential for false positives, evidence of this was observed in the current study.


Modified phased radiofrequency ablation of atrial fibrillation reduces the number of cerebral microembolic signals.
Phased radiofrequency (RF) ablation for atrial fibrillation is associated with an increased number of silent cerebral lesions on magnetic resonance imaging and cerebral microembolic signals (MESs) on transcranial Doppler ultrasound imaging compared with irrigated RF. The increased rate of embolic events may be due to a specific electrical interference of ablation electrodes attributed to the catheter design. The purpose of this study was to elucidate the effect of deactivating the culprit electrodes on cerebral MESs. Twenty-nine consecutive patients (60 ± 11 years, 10 female) underwent their first pulmonary vein isolation using phased RF energy. Electrode pairs 1 or 5 were deactivated to avoid electrical interference between electrodes 1 and 10 ('modified'). Detection of MESs by transcranial Doppler ultrasound was performed throughout the procedure to assess cerebral microembolism. Results were compared with the numbers of MESs in 31 patients ablated using all available electrodes ('conventional') and to 30 patients undergoing irrigated RF ablation of a previous randomized study. Ablation with 'modified' phased RF was associated with a marked decrease in MESs when compared with 'conventional' phased RF (566 ± 332 vs. 1530 ± 980; P < 0.001). This difference was mainly triggered by the reduction of MES during delivery of phased RF energy, resulting in MES numbers comparable to irrigated RF ablation (646 ± 449; P = 0.7). Total procedure duration as well as time of RF delivery was comparable between phased RF groups. Both times, however, were significantly shorter compared with the irrigated RF group (123 ± 28 vs. 195 ± 38; 15 ± 4 vs. 30 ± 9; P < 0.001, respectively). Pulmonary vein isolation with 'modified' phased RF is associated with a decreased number of cerebral microembolism especially during the delivery of ablation impulses, supporting the significance of electrical interference between ablation electrodes 1 and 10. Deactivation of electrode pairs 1 or 5 might increase the safety of this approach without an increase in procedure duration or RF delivery time.


Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.
Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity.


Q289P mutation in FGFR2 gene causes Saethre-Chotzen syndrome: some considerations about familial heterogeneity.
To describe the first report on a three-generation family presenting typical features of Saethre-Chotzen syndrome, in which the Q289P mutation in the FGFR2 gene was detected. Dysmorphological evaluation was performed by a clinical geneticist. Direct sequencing of the polymerase chain reaction-amplified coding region of TWIST and screening for the P250R mutation in the FGFR3 gene were performed. Exons IIIa and IIIc of FGFR2 were sequenced also. The mutation was confirmed by both restriction-enzyme digestion and allelic-specific polymerase chain reaction. Neither TWIST gene analysis nor analysis of the P250R mutation on gene FGFR3 showed mutation within the coding sequence. A nucleotide change from CAG to CCG in exon IIIa of the FGFR2 gene that caused a Q289P mutation was detected, although exon IIIc in the propositus was normal. These same results were detected in his mother, but no other members of the kindred presented clinical features consistent with Saethre-Chotzen syndrome. This mutation was previously reported in individuals with Crouzon and Jackson-Weiss syndromes. The FGFR2 mutation in the family with Saethre-Chotzen syndrome herein reported reinforces the idea of an interaction among TWIST and FGFR genes during development. Absence of the Q289P mutation in some affected individuals in this family is discussed.


Ibogaine and Subjective Experience: Transformative States and Psychopharmacotherapy in the Treatment of Opioid Use Disorder.
This article examines the therapeutic potential of ibogaine, a powerful oneiric alkaloid derived from Tabernanthe iboga, through exploring the subjective experiences of 44 participants from two observational treatment studies for opioid use disorder. Following treatment with ibogaine HCl, the participants (Mexico, n = 30; New Zealand, n = 14) completed the States of Consciousness Questionnaire (SCQ) to quantify the magnitude of their psychotropic experience. Participants were asked to provide written transcripts of their experiences, with those supplied being analyzed thematically through an iterative process, to produce a set of coded themes. Mean SCQ scores in many domains exceeded 0.6, the cutoff score for a "complete mystical experience," with 43% of participants achieving this in more than five of seven domains. Qualitative data described multiple phenomenological themes, including auditory and visual phenomena. Ibogaine's strong oneiric action promoted cyclic visions leading to confronting realizations involving remorse and regret for participants' actions towards others, but also release from feelings of guilt and worthlessness. Many participants reported feeling a sense of spiritual transformation. We propose that the reported experiences support the meaningfulness of ibogaine's oneiric effects as a discrete element in its capacity for healing, which is distinct from pharmacological actions associated with reduced withdrawal and craving.


[The anti-androgen flutamide in the treatment of prostatic hyperplasia].
The authors treated 23 benign prostatic hyperplasia (BPH) patients with antiandrogen flutamide. Half of the patients were treated with 500 mg, the another part with 750 mg flutamide for three months, and after 3 months brake again for 3 months. The decrease of the residual urine and an increase of the flow were observed. The subjective parameters were improved, too. In some patients side effects (gynecomastia, loss of appetite and potency) were observed. There was no different in the effect of the two doses.


Ultrafine grinding using a fluidized bed opposed jet mill: effects of feed load and rotational speed of classifier wheel on particle shape.
Circularity, aspect ratio, modelx, and pellips were employed to study the effects of process parameters, namely varying feed loads and rotational speeds of the classifier wheel, of the fluidized bed opposed jet mill on the shape of the micronized particles produced. The Shapiro-Wilk statistical test showed that 80.0% of the shape distributions of the four descriptors were not normal. Therefore, the Kruskal-Wallis test, which is a nonparametric statistical test, was employed to analyze the data. Micronized particles were more spherical and less elongated, as indicated respectively by higher median circularity and lower median modelx values when compared to unmilled lactose. These descriptors were able to indicate that the particles had been micronized. When feed loads of 250 and 350 g were used, increasing the rotational speed of the classifier wheel was found to bring about a decrease in span values of all the shape descriptors, indicating that the micronized particles were more uniform in shape. Micronized particles produced had lower median aspect ratio values than the unmilled lactose, whereas a higher feed load of 450 g resulted in the production of micronized particles that were less uniform in shape and more elliptical in nature, as reflected by the lower median pellips values. A higher feed load of 450 g caused a high level of impingement of particles on to the rotating classifier wheel, causing decreased classifier wheel efficiency, and this resulted in a less well-controlled micronization process. Thus, aspect ratio and pellips were sensitive to the changes in performance of the classifier wheel. The four shape descriptors were proposed to be used collectively as indicators for the monitoring of the micronization process.


Limits on neutrino mass from cosmic structure formation
We consider the effect of three species of neutrinos with nearly degenerate mass on the cosmic structure formation in a low-matter-density universe within a hierarchical clustering scenario with a flat Gaussian initial perturbation spectrum. The matching condition for fluctuation powers at the COBE scale and at the cluster scale leads to a strong upper limit on neutrino mass. For a flat universe with matter density parameter Omega = 0.3, we obtain m(nu)<0.6 eV for the Hubble constant H0<80 km s(-1) Mpc(-1). Allowing for the more generous parameter space limited by Omega<0.4, H0<80 km s(-1) Mpc(-1) and age t(0)>11.5 Gyr, the limit is 0.9 eV.


ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412.
The ETV6-NTRK3 (EN) fusion gene which encodes a chimeric tyrosine kinase was first identified by cloning of the t(12;15)(p13;q25) translocation in congenital fibrosarcoma (CFS). Since then, EN has been also found in congenital mesoblastic nephroma (CMN), secretory breast carcinoma (SBC) and acute myelogenous leukemia (AML). Using IMS-M2 and M0-91 cell lines harboring the EN fusion gene, and Ba/F3 cells stably transfected with EN, we demonstrated that PKC412, also known as midostaurin, is an inhibitor of EN. Inhibition of EN activity by PKC412 suppressed the activity of it downstream molecules leading to inhibition of cell proliferation and induction of apoptosis. Our data for the first time suggested that PKC412 could serve as therapeutic drug for treatment of patients with this fusion.


HA-1A. A human monoclonal antibody for the treatment of gram-negative sepsis.
HA-1A is a human monoclonal IgM antibody that binds to endotoxin. The results of the clinical trials of HA-1A demonstrate that HA-1A reduces mortality among patients with sepsis and gram-negative bacteremia. Secondary endpoints, including resolution of organ failure, discharge from intensive care unit, and discharge from the hospital, support the beneficial effects of the antibody. The antibody is well tolerated with rare side effects, including hypotension and urticarial rash. No anti-HA-1A antibodies have been detected.


Static grey-scale parathyroid ultrasonography: is high-resolution real-time technique required?
Ultrasound has been used with varying success to localise parathyroid adenomas pre-operatively. We have reviewed 61 patients with pre-operative contact-scanning grey-scale parathyroid ultrasonography and subsequent surgical exploration of all four parathyroid glands. Diagnostic accuracy was 91% considering glands examined and 63% considering patients examined. There was one false positive diagnosis. False negative diagnoses (17 adenomas and five ectopic mediastinal tumours) were mainly due to upper pole adenomas, adenomas less than 10 mm X 7 mm in size and ectopic mediastinal adenomas. Static grey-scale ultrasonography is adequate for the pre-operative localisation of parathyroid adenomas, especially when high-resolution technique is not available. In fact, the overall accuracy is comparable to the recently reported diagnostic accuracy rates with high-resolution real-time systems.


[Clinical outcome of arthroscopic posterior cruciate ligament-plasty].
Twenty-one patients were evaluated with an average follow up of 30 month after arthroscopical reconstruction of the posterior cruciate ligament using the IKDC-Evaluation Document, Lysholm-Score, KT 1000 and X-ray Complex ligament injuries and chronic instability of the knee were the indications for operative treatment. Semitendinosus--or patella ligament autografts were used. The Lysholm-Score significantly improved preoperatively to postoperatively (p < 0.01). The IKDC revealed 11 patients for group B, 7 patients for group C and 3 patients for group D. The KT 1000 measurement showed a postoperative drawer of 3.6 mm compared with the nonoperated side. Thirteen of the 21 patients showed a posterior drawer of less than 3 mm. The lateral posterior stress view of the X-ray revealed a 4.1 mm (+/- 2.9 mm) side to side difference postoperatively in comparison to 9.5 mm (+/- 3.5 mm) preoperatively. Three patients possessed radiological signs of osteoarthritis grad I by Ahlbäck. Our results recommend in patients with complex PCL-injuries as well as in cases of chronic posterior instability a complex reconstruction of the ligaments.


Current progress on internal medicine in China-2006 part I.
The growing interest has been placed in the current state of China's internal medicine from all over the world. Many data of internal medicine in China were collected by searching through some of the most prominent medical magazines published in China in 2006. Because there are many researches on the field of internal medicine, just some representative reports focusing on this topic were selected in this paper. In part I of this study, a summary of the advances made in cardiology, respiration diseases, and gastroenterology was presented.


Immunocytochemical localization of glyceraldehyde-3-phosphate dehydrogenase in cultured endothelial and smooth muscle cells.
The presence and distribution of glyceraldehyde-3-phosphate dehydrogenase (GPDH) in cultured bovine aortic endothelial cell (EC) and smooth muscle cell (SMC) were studied. For this purpose, we purified GPDH from human and bovine red blood cell (RBC) membranes and used it as antigen; anti-GPDH serum and affinity purified IgG were prepared. GPDH has been identified in the whole extracts of EC and SMC as a polypeptide having the same electrophoretic mobility as RBC protein. In addition, GPDH digested with V8 protease and analyzed by one dimensional peptide mapping presented the same pattern for the three cell types examined. Anti-RBC-GPDH cross-reacted with the polypeptide from EC and SMC. The intracellular localization of GPDH in EC and SMC was investigated by indirect immunofluorescence microscopy using affinity purified anti-GPDH. We found that the antigen exhibits a diffuse cytoplasmic distribution in both cell types; in addition, EC contained the antigen in the nucleus. The nuclear GPDH-like protein in EC has a characteristic pattern, suggesting yet unknown implications of GPDH in the cell metabolism.


Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor.
Insulin receptor complementary DNA has been cloned from an insulin-resistant individual whose receptors have impaired tyrosine protein kinase activity. One of this individual's alleles has a mutation in which valine is substituted for Gly996, the third glycine in the conserved Gly-X-Gly-X-X-Gly motif in the putative binding site fo adenosine triphosphate. Expression of the mutant receptor by transfection into Chinese hamster ovary cells confirmed that the mutation impairs tyrosine kinase activity.


Confined polar mixtures within cylindrical nanocavities.
Using molecular dynamics experiments, we have extended our previous analysis of equimolar mixtures of water and acetonitrile confined between silica walls [J. Phys. Chem. B 2009, 113, 12744] to examine similar solutions trapped within carbon nanotubes and cylindrical silica pores. Two different carbon tube sizes were investigated, (8,8) tubes, with radius R(cnt) = 0.55 nm, and (16,16) ones, with R(cnt) = 1.1 nm. In the narrowest tubes, we found that the cylindrical cavity is filled exclusively by acetonitrile; as the radius of the tube reaches approximately 1 nm, water begins to get incorporated within the inner cavities. In (16,16) tubes, the analysis of global and local concentration fluctuations shows a net increment of the global acetonitrile concentration; in addition, the aprotic solvent is also the prevailing species at the vicinity of the tube walls. Mixtures confined within silica nanopores of radius approximately 1.5 nm were also investigated. Three pores, differing in the effective wall/solvent interactions, were analyzed, (i) a first class, in which dispersive forces prevail (hydrophobic cavities), (ii) a second type, where oxygen sites at the pore walls are transformed into polar silanol groups (hydrophilic cavities), and (iii) finally, an intermediate scenario, in which 60% of the OH groups are replaced by mobile trimethylsilyl groups. Within the different pores, we found clear distinctions between the solvent layers that lie in close contact with the silica substrate and those with more central locations. Dynamical modes of the confined liquid phases were investigated in terms of diffusive and rotational time correlation functions. Compared to bulk results, the characteristic time scales describing different solvent motions exhibit significant increments. In carbon nanotubes, the most prominent modifications operate in the narrower tubes, where translations and rotations become severely hindered. In silica nanopores, the manifestations of the overall retardations are more dramatic for solvent species lying at the vicinity of trimethylsilyl groups.


Out-group threats and distress as antecedents of common in-group identity among majority and minority group members in the aftermath of a natural disaster.
The aim of the present study was to examine the role of out-group threats in fostering one-group perceptions directly and indirectly via post-traumatic stress symptoms in the aftermath of a natural disaster. We also tested whether these relationships differ depending on the ethnic group of belonging (majority vs. minority). Participants were 589 Italians and 122 immigrants from a region strongly affected by the earthquakes that struck Northern Italy in 2012. Results revealed that among Italians threat stemming from negative out-group behaviour was associated positively with post-traumatic stress symptoms and negatively with perceptions of being a common group with immigrant survivors. Among immigrants, threat posed by the out-group for economic resources was positively associated with post-traumatic stress symptoms and, indirectly, with higher one-group perceptions.


Immunohistochemical evidence for alterations in specific forms of rat hepatic microsomal cytochrome P-450 during acute carbon tetrachloride intoxication.
The response of specific forms of hepatic microsomal cytochrome P-450 to carbon tetrachloride was studied by immunohistochemical techniques in order to assess the localization and specificity of action for this hepatotoxin. Liver sections were taken from control, phenobarbital-pretreated, and 3-methylcholanthrene-pretreated male rats that had received acute (3 hr) treatment with carbon tetrachloride. The liver sections were examined after indirect immunofluorescent labeling with anti-P-450un, anti-P-450a, anti-P-450b, and anti-P-450c. Diminished fluorescence and loss of intracellular homogeneity of fluorescence were found in the centrilobular cells of liver sections from control rats incubated with anti-P-450un, anti-P-450a, and phenobarbital-pretreated, carbon tetrachloride-challenged rats incubated with anti-P-450b. In liver sections from 3-methylcholanthrene-pretreated, carbon tetrachloride-challenged rats incubated with anti-P-450c, fluorescence was diminished in periportal cells but did not show loss of intracellular homogeneity. These results provide immunohistochemical evidence for the differential effect of carbon tetrachloride on specific forms of cytochrome P-450.


Targeted mutagenesis in the progeny of maize transgenic plants.
We have demonstrated that targeted mutagenesis can be accomplished in maize plants by excision, activation, and subsequent elimination of an endonuclease in the progeny of genetic crosses. The yeast FLP/FRT site-specific recombination system was used to excise and transiently activate the previously integrated yeast I-SceI homing endonuclease in maize zygotes and/or developing embryos. An artificial I-SceI recognition sequence integrated into genomic DNA was analyzed for mutations to indicate the I-SceI endonuclease activity. Targeted mutagenesis of the I-SceI site occurred in about 1% of analyzed F1 plants. Short deletions centered on the I-SceI-produced double-strand break were the predominant genetic lesions observed in the F1 plants. The I-SceI expression cassette was not detected in the mutant F1 plants and their progeny. However, the original mutations were faithfully transmitted to the next generation indicating that the mutations occurred early during the F1 plant development. The procedure offers simultaneous production of double-strand breaks and delivery of DNA template combined with a large number of progeny plants for future gene targeting experiments.


P wave changes in body surface potential maps due to increasing heart rate during exercise in normals.
Exercise-induced changes in P maps were investigated in normal subjects (n = 20) in order to clarify the basic changes in P maps caused by exercise in patients with ischemic heart disease or by exercise-induced dysfunction of the left ventricle in patients with various heart diseases. Maps were obtained using an 87 lead-point system (HPM-6500, Chunichi-Denshi Corporation) and were recorded at rest and at heart rates up to 140/min in 20/min steps under graded bicycle ergometric exercise. P waves were divided into 3 phases (initial, middle and terminal) by locating the maximum. Maps were characterized by the distribution pattern of the positive and negative potentials in each frame. Peak voltages increased proportionally to the increase in heart rate. We observed a decrease in P wave duration concomitant with the increase in heart rate. Time from P onset to peak voltage increased slightly. We believe these findings to be due to the acceleration of sympathetic nerve tone accompanying exercise. We observed 2 patterns: type A showed the relatively short middle and terminal phases, and type B a prolongation of the middle phase and a shortening of the terminal phase. We consider the differences between types A and B to be partly due to individual differences in the degree of increase in pulmonary air volume and sympathetic nerve tone influence on the atria. In evaluating the exercise-induced P map changes, special consideration should be paid to the changes due to increase in heart rate.


Teaching the informed consent process to residents.
We believe the focus and emphasis of this committee on informed consent is unique, and that the development of an informed consent teaching process for residents will focus on the moral and ethical issues regarding informed consent. Even more important, we believe we will emphasize the patient care aspects of informed consent and also teach residents their responsibilities for long-term patient care with regard to patients' satisfaction and understanding of their disease process.


[Hyperglycemia and its control in the critically ill patient].
In the critically ill patient, hyperglycemia was believed to be a response by the body to a stressful situation. Stress-induced hyperglycemia is the consequence of increased levels of cortisol, cytokines, growth hormones, catecholamines, and glucagon resulting in the stimulation of endogenous glucose production through glycogenolysis and gluconeogenesis as well as other mechanisms including central and peripheral insulin resistance. Among other things, hyperglycemia has an effect on inflammation and function of the myocardium, kidney, central nervous system, and the immune system. The protective role of intensified insulin therapy (glycemia of 4.4-6.1 mmol/l) in the critically ill patient, as suggested by the Leuven trial, resulted in the quick and widespread adoption of this approach in practice. However, later studies did not support the Leuven trial results while pointing to the possibility of developing severe hyperglycemia. The large multicenter NICE-SUGAR study in 6,022 patients showed higher 90-day mortality in the group with tight glycemic control. The results of NICE-SUGAR led to revision of the guidelines for glycemic control in the critically, recommending to control glycemia below 10 mmol/l. The aim of this overview is to summarize available data on glycemic control in the critically ill patient.


Daily psychosocial stressors interfere with the dynamics of urine neopterin in a patient with systemic lupus erythematosus: an integrative single-case study.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by flare-ups, the causes of which are not known. In accordance with new concepts in stress research, this study investigated whether daily psychosocial stressors interfere with immunological processes in SLE. Because such processes are unique to each individual, single-case design using time-series analysis (Box and Jenkins) was applied. A 40-year-old woman with SLE (last flare-up September 1995) was interviewed initially to determine major life events and difficulties (using the Life Events and Difficulties Schedule) in the previous 2 years. She was then observed for 63 days. Urine neopterin, an immunological parameter demonstrated to parallel disease activity in SLE patients, was measured in daily overnight urine. Daily incidents were identified weekly by the Incidents and Hassles Inventory and independently rated. Intervening factors, including infections, medication, and lifestyle, were controlled. Retrospectively, data obtained from the Life Events and Difficulties Schedule indicated that major life events and difficulties had preceded the patient's last flare-up in 1995. Although there were no clinical signs of SLE during this prospective study of 63 days, cross-correlational analyses revealed that "moderately" stressful incidents associated with higher levels of emotional irritation (lag 0: +0.271, p < .05) predicted an increase in urine neopterin the following day (lag 1: +0.441, p < .05). Moreover, a 7-day cyclicity in neopterin levels that corresponded to the weekly examinations and interviews was found. This study showed a causal relationship between psychosocial stressors and urine neopterin concentrations that may be related to SLE disease activity. Furthermore, the workability of an integrative approach using single-case design and time-series analysis in psychoneuroimmunology was demonstrated for the first time.


Meridian health annual report focuses on what is 'brand new'.
The 2003-2004 annual report by Meridian Health, Neptune, N.J., is titled brand new. The high-end publication was produced especially for the healthcare system's employees, board members, shareholders and volunteers.


Antioxidative potential of raw breast meat from broiler chicks fed a dietary medicinal herb extract mix.
This study was performed to evaluate the antioxidative potential and quality of the breast meat of broiler chickens fed a dietary medicinal herb extract mix (MHEM, consisting of mulberry leaf, Japanese honeysuckle, and goldthread at a ratio of 48.5:48.5:3.0). A total of 480 one-day-old male Cobb broiler chicks were randomly allotted to 12 pens, with 40 birds per pen (replicate), and reared for 35 d. Dietary treatments consisted of a corn-soybean meal basal diet (control); a basal diet with 0.3% MHEM (T1); and a basal diet with 1% (T2) MHEM. At the end of the feeding trial, breast meat samples were excised and stored in a refrigerator at 4 degrees C to be analyzed at d 0, 3, and 7. The MHEM did not affect proximate composition of the breast meat. Total phenols content of the breast meats in the T1 and T2 diets was approximately 2 times greater than that of the control diet (P < 0.05). 1,1-Diphenyl-2-picrylhy-drazyl radical-scavenging activity and 2,2-azinobis-(3 ethylbenzothiazoline-6-sulfonic acid) cation-reduction activity were greater in the T2 diet at d 0 and in the T1 diet at d 3 compared with the control diet (P < 0.05). 2-Thiobarbituric acid-reactive substance values in the T1 and T2 diets were lower than in the control diet at d 3 and 7 and did not increase during storage, whereas the value in the control diet increased significantly. The pH of the T1 diet was significantly greater than that of the control diet at d 0 and 3. In a sensory test, panelists preferred the T1 breast meat throughout the 7-d storage period. This research indicates that dietary MHEM could increase the antioxidative potential and overall preference of breast meat during cold storage.


[Multiple pterygium syndrome].
The authors relate about a non sporadic case of "Multiple pterygium syndrome" in a child born to consanguineous parents. Clinical features of the syndrome are: short stature, articular contractures, pterygia of the neck, axillae, elbows, facial anomalies, vertebral malformation, mental retardation. The syndrome, delineated as a distinct entity by Escobar, is a rare autosomal recessive disorder with a clinical heterogeneity, which is included within the "Arthrogryposis syndromes".


Obsessive-compulsive symptoms as a manifestation of neuropsychiatric systemic lupus erythematosus.
Neuropsychiatric syndrome is a common and serious clinical manifestation of systemic lupus erythematosus (SLE), occurring in about half of all patients during the course of the disease. We report here a case of obsessive-compulsive symptoms as an unusual manifestation of neuropsychiatric SLE. A 17-year-old girl with SLE was admitted to a medical center with the chief complaint of recent-onset repeated doubt and repetitive checking, which subsided after treatment. She had recurrent and intrusive doubt about losing her belongings and tried to suppress the thoughts by mental acts of praying and repetitive checking. The central nervous system lupus involvement in this patient was confirmed by brain magnetic resonance imaging, which revealed widespread areas of abnormal high signal intensity over the internal capsules and basal ganglia, and focal lesions at the peripheral parenchyma of the frontal and parietal areas. Single photon emission computed tomography also showed decreased perfusion at the left temporal lobe. This supported the hypothesis that basal ganglia abnormalities could be the common pathophysiology of coexisting obsessive-compulsive symptoms and SLE. Moreover, increased awareness of hidden psychopathology, an accepting attitude, and careful probing for obsessive-compulsive symptoms are important while taking care of SLE patients.


[Papilloma of forestomach induced by Fusarium T-2 toxin in mice].
T-2 toxin is one of the important representatives of trichothecin metabolites of Fusarium species. Various proliferative changes in epithelia of forestomach including papillomas were induced in mice after prolonged feeding of T-2 toxin by intubation at 0.1 mg/kg, 3 times a week for 25 weeks. The incidences of hyperkeratosis, papillary hyperplasia, moderate dysplasia and papilloma were 82.9%, 28.6%, 42.9% and 14.3% respectively. The earliest papilloma in forestomach of mice occurred as early as 6th week of the experiment. While in forestomach of mice in the control group, only 4.20% hyperkeratosis and 4.2% simple hyperplasia were found, no papillary hyperplasia or papilloma occurred. The above results indicate that T-2 toxin has a selective tumorigenic effect on the forestomach which is actually the extension of the esophagus in mice. These findings may give important hint to the study of human esophageal carcinogenesis.


[Studies of fetal and neonatal isolated guinea pig lung on the effect of electric tissue resistance on the ECG].
The results of measurements of the electrical resistance of lung tissue are reported in order to estimate quantitatively the influence of air and blood filling on the conductivity. Experiments were done on isolated lung tissue of fetal and infantile guinea pigs. The ohmic resistance was measured by a minimised 4-electrode technique: isolated fetal lungs empty of air, or artificially aerated ones on the one hand, isolated lungs of infantile animals with spontaneous respiration and normal lung blood flow on the other hand. The increase of the electrical resistance produced by aeration is reduced by at least 50% by the synchronously increasing blood flow in spontaneously respired lungs. These experiments in the described animal model offer an opportunity for a more precise interpretation of the electrocardiogram of human adults changing with respiratory phases.


[Left superior vena cava: a simple diagnosis by transthoracic echocardiography. A case report].
Persistent left superior vena cava is an anomaly of the systemic venous return occurring in 0.5% of the general population. We report the case of a patient with an incidental diagnosis made during a dyspnea while he had chronic pulmonary disease. The diagnosis was suspected by the presence of a markedly dilated coronary sinus and confirmed by a simple contrast injection into the left antecubital vein. Transesophageal echocardiography and magnetic resonance imaging confirmed the existence of 2 superior vena cava with the left superior vena cava draining into the coronary sinus. This congenital anomaly is of minimal hemodynamic significance when isolated. The diagnosis can be useful for placement of central catheters from left superior approach.


Transcriptional diversity and allelic variation in nicotinic acetylcholine receptor subunits of the red flour beetle, Tribolium castaneum.
Sequence analysis of 168 cDNA clones encoding 12 nicotinic acetylcholine receptor subunits, Tcasalpha1-Tcasalpha11 and Tcasbeta1, from the red flour beetle, Tribolium castaneum, revealed extensive post-transcriptional modification and multiple alleles. The greatest diversity was found for Tcasa6, where 18 unique transcripts, as a result of alternative and optional exon usage, were seen. A novel alternative exon 8d was found in one Tcasalpha6 transcript. Tcasalpha5 transcripts did not contain previously reported exons 8-10. Six subunits had transcripts that contained unspliced introns, which introduced premature stop codons. Intron 3' splice site variants were seen at six intron boundaries across five subunits. A-to-I RNA editing was seen only in Tcasalpha6. Alleles were found for all subunit genes, except Tcasalpha1 and Tcasalpha10. Transcriptional and allelic diversity are discussed with respect to receptor function and potential interactions with insecticides.


Sustained high release at rapid stimulation rates and reduced functional autoreceptors characterize prefrontal cortex dopamine terminals.
The release of dopamine (DA) from mesocortical and nigrostriatal nerve terminal fields, as well as its modulation by auto- and heteroreceptors was investigated. Rabbit brain slices obtained from medial prefrontal cortex (PFC) and nucleus caudate (striatum) were prelabeled with [3H]DA in the presence of 0.3 microM desipramine. Neuronal depolarization was elicited by electrical stimulation. Higher stimulation-evoked overflow of [3H]DA (release) was observed from PFC than from striatal slices. At 0.3 Hz (120 pulses) release from the PFC was 60% higher than from the striatum, and at higher frequencies (10 Hz and 120 or 1200 pulses) the fraction of tissue radioactivity released from the PFC was 550% greater than that released from the striatum. These differences were not eliminated by blockade of autoreceptors with haloperidol, or by inhibition of neuronal uptake with nomifensine. These results suggest that the coupling between neuronal depolarization and DA release is more efficient in the PFC than in the striatum. This may allow the PFC terminals to sustain neurotransmission under continuous fast firing. Selective D2 agonists, as well as nonselective DA agonists, inhibited DA release in a concentration-dependent fashion from the PFC and the striatum. Their effects were blocked by l-sulpiride or haloperidol. SKF 38393, a selective D1 agonist, produced a small facilitation of release from both regions; its effects were blocked by SCH 23390 (a selective D1 antagonist). The latter was ineffective on its own. The maximal degree of inhibition of release produced by apomorphine, bromocriptine and LY-171555 was lower in the PFC than in the striatum; these differences were accentuated greatly at high stimulation rates. When the slices were stimulated at frequencies comparable to the "in vivo" firing rates for each neuronal group, apomorphine and LY-171555 were much weaker in inhibiting DA release from the PFC (10 Hz) than from the striatum (3 Hz). In the striatum, strong modulation of DA release by endogenous DA was observed; whereas little modulation was seen in the PFC. Nomifensine produced larger increases in the stimulation-evoked overflow of DA from PFC and there was no synergistic interaction between nomifensine and haloperidol in this structure. In the striatum, marked facilitation of DA overflow was observed when nomifensine and haloperidol were given together. Furthermore, haloperidol per se facilitated DA release from both brain regions; however, the degree of facilitation was frequency dependent in the striatum, but not in the PFC.(ABSTRACT TRUNCATED AT 400 WORDS)


Genome evolution: groping in the soil interstices.
Centipedes are a very old lineage of terrestrial animals. The first completely sequenced myriapod genome reveals that the blind centipede Strigamia maritima has no gene for light-sensory proteins, lacks the canonical circadian clock and possesses unusual features related to chemosensory perception.


The significance of aggression and impulsivity for self-mutilative behavior.
Self-mutilative behavior (SMB) is presented as a specific form of inwardly directed aggressiveness which is thought to be associated with problems of impulse control. Conceptual problems concerning impulsivity and impulsive aggression are discussed. Among different forms of dyscontrolled behavior, SMB is of special heuristic interest because of distinction can be made between patients committing impulsive and those committing premeditated self-harming actions. Psychometric and biological measures of impulsivity and aggressiveness were assessed in self-mutilators in comparison to depressives and normal probands. Self-mutilators were differentiated into two subgroups, those with an impulsive (ISMB) and those with a premeditated (PSMB) form of SMB, and depressives were also differentiated into two subgroups, those with a history of suicide attempts and those without. Only patients with ISMB (and depressives with a history of suicide attempts) showed an enduring tendency towards dyscontrolled patterns of behavior and cognition; therefore, SMB cannot be generally regarded as an indicator of high impulsivity or an impulse control disorder. Measures of impulsivity and aggressiveness did not behave analogically to each other and aggressive or autoaggressive modes of behavior should not be generally used as an index of impulsivity. A reduction of serotonergic activity, proved by a blunted prolactin response to D-fenfluramine, was found in all patient-groups in comparison to normal probands. Prolactin response after D-fenfluramine challenge turned out to be most blunted among self-mutilators with ISMB and among depressives with a history of suicide attempts.


Global transcriptome analysis and identification of a CONSTANS-like gene family in the orchid Erycina pusilla.
The high chromosome numbers, polyploid genomes, and long juvenile phases of most ornamental orchid species render functional genomics difficult and limit the discovery of genes influencing horticultural traits. The orchid Erycina pusilla has a low chromosome number (2n = 12) and flowers in vitro within 1 year, making it a standout candidate for use as a model orchid. However, transcriptomic and genomic information from E. pusilla remains limited. In this study, next-generation sequencing (NGS) technology was used to identify 90,668 unigenes by de novo assembly. These unigenes were annotated functionally and analyzed with regard to their gene ontology (GO), clusters of orthologous groups (COG), and KEGG pathways. To validate the discovery methods, a homolog of CONSTANS (CO), one of the key genes in the flowering pathway, was further analyzed. The Arabidopsis CO-Like (COL) amino acid sequences were used to screen for homologs in the E. pusilla transcriptome database. Specific primers to the homologous unigenes were then used to isolate BAC clones, which were sequenced to identify 12 E. pusilla CO-like (EpCOL) full-length genes. Based on sequence homology, domain structure, and phylogenetic analysis, these EpCOL genes were divided into four groups. Four EpCOLs fused with GFP were localized in the nucleus. Some EpCOL genes were regulated by light. These results demonstrate that nascent E. pusilla resources (transcriptome and BAC library) can be used to investigate the E. pusilla photoperiod-dependent flowering genes. In future, this strategy can be applied to other biological processes, marketable traits, and molecular breeding in this model orchid.


Single nucleotide polymorphism in CPT1B and CPT2 genes and its association with blood carnitine levels in acute myocardial infarction patients.
Ischemic and reperfusion injuries in acute myocardial infarction (AMI) lead to mitochondrial dysfunction in heart cells. Lipid metabolism takes place in mitochondria where carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into matrix to provide substrates for beta-oxidation. We sequenced the coding regions of CPT1B and CPT2 genes to identify the single nucleotide polymorphism (SNP) in 23 AMI patients and 23 normal subjects. We also determined blood carnitine levels in these samples to study the impact of these SNPs on carnitine homeostasis. The sequencing of coding regions revealed 4 novel variants in CPT1B gene (G320D, S427C, E531K, and A627E) and 2 variants in CPT2 gene (V368I and M647V). There were significant increases in total carnitine (54.18±3.11 versus 21.49±1.03μmol/l) and free carnitine (37.78±1.87 versus 10.06±0.80μmol/l) levels in AMI patients as compared to normal subjects. CPT1B heterozygous variants of G320D and S427C among control subjects showed significantly higher levels of total and free carnitine in the blood. The homozygous genotype (AA) of CPT2 variant V368I had significantly less blood carnitine in AMI patients. Serum troponin T was significantly less in GG genotype of CPT1B variant S427C whereas the genotype AA of CPT2 variant V368I showed significantly higher serum troponin T levels. Further studies on large number of patients are necessary to confirm the role of CPT1B and CPT2 polymorphism in AMI.