Therapeutic benefit of a combined strategy using erythropoietin and endothelial progenitor cells after transient focal cerebral ischemia in rats.
Many studies have demonstrated beneficial effects of either erythropoietin (EPO) or endothelial progenitor cell (EPC) treatment in cerebral ischemia. To improve post-ischemic tissue repair, we investigated the effect of systemic administration of endothelial colony-forming cells (ECFCs), considered as relevant endothelial progenitors due to their specific vasculogenic activity, in the presence or absence of EPO, on functional recovery, apoptosis, angiogenesis, and neurogenesis in a transient focal cerebral ischemia model in the adult rat. Experimental study. The rats were divided into four groups 24 hours after ischemia,, namely control, ECFCs, EPO, and ECFCs+EPO, and received a single intravenous injection of ECFCs (5 × 10(6) cells) and/or intraperitoneal administration of EPO (2500 UI/kg per day for 3 days). Infarct volume, functional recovery, apoptosis, angiogenesis, and neurogenesis were assessed at different time points after ischemia. The combination of EPO and ECFCs was the only treatment that completely restored neurological function. The ECFCs+EPO treatment was also the most effective to decrease apoptosis and to increase angiogenesis and neurogenesis in the ischemic hemisphere compared to controls and to groups receiving ECFCs or EPO alone. These results suggest that EPO could act in a synergistic way with ECFCs to potentiate their therapeutic benefits.


Heat Flux Sensing for Machine-Learning-Based Personal Thermal Comfort Modeling.
In recent years, physiological features have gained more attention in developing models of personal thermal comfort for improved and accurate adaptive operation of Human-In-The-Loop (HITL) Heating, Ventilation, and Air-Conditioning (HVAC) systems. Pursuing the identification of effective physiological sensing systems for enhancing flexibility of human-centered and distributed control, using machine learning algorithms, we have investigated how heat flux sensing could improve personal thermal comfort inference under transient ambient conditions. We have explored the variations of heat exchange rates of facial and wrist skin. These areas are often exposed in indoor environments and contribute to the thermoregulation mechanism through skin heat exchange, which we have coupled with variations of skin and ambient temperatures for inference of personal thermal preferences. Adopting an experimental and data analysis methodology, we have evaluated the modeling of personal thermal preference of 18 human subjects for well-known classifiers using different scenarios of learning. The experimental measurements have revealed the differences in personal thermal preferences and how they are reflected in physiological variables. Further, we have shown that heat exchange rates have high potential in improving the performance of personal inference models even compared to the use of skin temperature.


Cryptococcus neoformans var. neoformans and munia birds.
Cr. neoformans var. neoformans has been persistently demonstrated in the saprobic environment of caged munia birds at a local zoological garden. The pathogen was also cultured from the beaks, feathers and legs of these birds. It is suggested that the role of munia birds should be further investigated to understand the ecology of this important human pathogen.


Sensorineural hearing loss in posttraumatic incus dislocation.
In 34 posttraumatic incus dislocations, the initial sensorineural hearing loss (primary) after the trauma and that 11 years after trauma (late) were analyzed. Primary hearing loss measurements following the trauma showed that 53% of patients had sensorineural hearing loss of more than 10 dB for at least one of the frequencies from 1,000 to 4,000 cps, 18% for more than 30 dB. For late hearing loss after the trauma, the corresponding percentages were 50% and 15%, respectively. No reliable progression of the posttraumatic sensorineural hearing loss was found, although a few exceptions were seen. It may be concluded that sensorineural hearing loss is not a progressive disorder of the inner ear.


Mapping of serum amylase-1 and quantitative trait loci for milk production traits to cattle chromosome 4.
The present study was undertaken to confirm and refine the mapping of a quantitative trait locus in cattle for milk fat percentage that had earlier been reported to be linked to the serum amylase-1 locus, AM1. Five half-sib families from the previous study and 7 new ones were genotyped for nine microsatellite markers spanning chromosome 4. AM1 was mapped between the microsatellite markers BMS648 and BR6303. In a granddaughter design, interval mapping based on multiple-marker regression was utilized for an analysis of five milk production traits: milk yield, fat percentage and yield, and protein percentage and yield. In the families reported on previously, significant effects for fat and protein percentages were detected. In the new families, an effect on milk and fat yields was found. The most likely positions of the quantitative trait locus in both groups of families were in the same area of chromosome 4 in the vicinity of the obese locus. Direct effects of the obese locus were tested for using polymorphism in two closely linked microsatellites located 2.5 and 3.6 top downstream of the coding sequence. No firm evidence was found for an association between the obese locus and the tested traits.


'Putting words into action' project: using role play in skills training.
Research highlights the need to use experienced role-players with skilled facilitation to deliver effective communication skills training (CST) but this is challenging in a large faculty of health. In this pilot project, students from Birmingham City University's School of Acting and role-players from the Learning Disability nursing programme received role-player training (Phase I) before delivering 26 CST sessions to 520 first year BSc nursing students (Phase II), using role-plays based on clinical scenarios in adult, mental health, learning disability and children's nursing. A pre- and post-session survey assessed student confidence, with feedback gathered from role-players, and facilitators. Pre-session confidence levels in students who participated and observed the role-play were similar, and using Wilcoxon and Mann Whitney non-parametric tests, a statistically significant increase in post-session confidence levels was demonstrated across all four fields of nursing. This increase in confidence applied to role-play participating students and observers, although role-playing students gained the largest confidence increase. A Higher Education Academy Collaborative Grant extended the project in 2012/13.


Potential third-party radiation exposure from patients undergoing therapy with 131I for thyroid cancer or metastases.
The purpose of this work is to evaluate the potential third-party radiation exposure from patients undergoing therapy with 131I for ablation of residual thyroid tumor or metastases, based in part on serial measurements of exposure rates. Exposure rate measurements were performed at 1 m and 5 cm from the surface of each treated patient until patient release. Dose estimates based on measured exposure rates were compared with those based on analytic point-source (PSM) and line-source (LSM) models. Effective doses D(∞) to travelers, co-workers and sleeping partners were estimated by using the standard gamma factor (Γ) and the physical half-life or the values derived from measured data. Seven hundred ten patients were studied until the exposure at 1 m was below the constraints of 0.010 mSv. The 131I activities administered ranged from 1.85 to 11.0 GBq (median: 3.7 GBq), according to the therapeutic requirements. Based on the PSM and an experimental Γ, the mean/maximum estimated D(∞) to sleeping partners, partners, travelers, and co-workers were 2.60/20.65, 0.32/2.53, 0.96/7.59, and 0.57/4.50 mSv, respectively. Using the LSM and an experimental Γ, the D(∞) values were 2.41/19.15, 0.32/2.50, 0.83/6.62, and 0.57/4.42 mSv, respectively, while they were almost double using the theoretical Γ. The results presented, based on measured data in a large cohort of 131I-treated thyroid cancer patients, will allow more accurate estimation of potential third-party D(∞) following patient release and thus may be used to better inform physicians and hospital staff on recommendations for patient release and post-release precautions following radioiodine therapies.


Recessive resistance to plant viruses.
About half of the approximately 200 known virus resistance genes in plants are recessively inherited, suggesting that this form of resistance is more common for viruses than for other plant pathogens. The use of such genes is therefore a very important tool in breeding programs to control plant diseases caused by pathogenic viruses. Over the last few years, the detailed analysis of many host/virus combinations has substantially advanced basic research on recessive resistance mechanisms in crop species. This type of resistance is preferentially expressed in protoplasts and inoculated leaves, influencing virus multiplication at the single-cell level as well as cell-to-cell movement. Importantly, a growing number of recessive resistance genes have been cloned from crop species, and further analysis has shown them all to encode translation initiation factors of the 4E (eIF4E) and 4G (eIF4G) families. However, not all of the loss-of-susceptibility mutants identified in collections of mutagenized hosts correspond to mutations in eIF4E and eIF4G. This, together with other supporting data, suggests that more extensive characterization of the natural variability of resistance genes may identify new host factors conferring recessive resistance. In this chapter, we discuss the recent work carried out to characterize loss-of-susceptibility and recessive resistance genes in crop and model species. We review actual and probable recessive resistance mechanisms, and bring the chapter to a close by summarizing the current state-of-the-art and offering perspectives on potential future developments.


Yeast killer toxin-like anti-idiotypic antibodies.
Anti-idiotypic antibodies (anti-Ids) were raised in a rabbit against a murine monoclonal antibody (MAb) neutralizing the yeast killer toxin produced by a strain of Pichia (Hansenula) anomala. In an immunodiffusion test, the anti-Ids produced in the rabbit recognized the antigen-binding site of the MAb used as the immunogen (KT4) but not that of another heterologous MAb. The absence of any significant cross-reactivity among the anti-Ids raised in a rabbit for a heterologous MAb suggested that the anti-Ids were highly specific for unique variable-region determinants. Furthermore, the P. anomala killer toxin proved to be competing with anti-Ids for the binding site of MAb KT4. Anti-Ids against the MAb to yeast killer toxin inhibited the growth of Candida albicans, thereby mimicking the effect of the yeast killer toxin. These results suggest that, in some cases, anti-Ids might be useful tools for elucidating structure-function relationships for sensitive cell receptors.


[Home visiting nursing care for a terminal stage cancer patient with bed sore--coordination through exchanging of advice request memo as a useful tool].
Visiting nursing care service was provided to a 40s female patient, who had a terminal cancer with bed sore around the sacred bones. We started the nursing service when the patient was still cared at hospital. The nursing service we provided was coordinated by the certified nurse specialized in skin and excrement care and home visiting nurse. A smooth home care transition was resulted because of the coordination provided by the two nurses. We started coaching the family while the patient was still at the hospital with a home care instruction manual until the patient was discharged. All in all, the patient and her family were at ease with two nurses' coordinated efforts. Since the patient was cared at home, her bed sore problem got worse due to an absence of caregiver. In order to solve the bed sore problem, the visiting nurse took pictures of peeled adhesive patch and the bed sore around the sacred bones to show and consult with the certified nurse. With the advice from the certified nurse, the home visiting nurse was able to care the bed sore problem manageable in size. From this experience, we learned that a proper communication channel, in this case an advice request memo exchange, between the certified nurse and visiting nurse was a useful tool for both sides in order to properly assess the patient's medical care needs.


A critical analysis of the cycles of physical activity policy in England.
There has been increasing focus on the importance of national policy to address population levels of physical inactivity. Components of a comprehensive national physical activity policy framework include: 1) national recommendations on physical activity levels; 2) setting population goals and targets; 3) surveillance or health monitoring systems; and 4) public education. The aim of the current paper was to analyse the policy actions which have addressed each of these elements in England and to identify areas of progress and remaining challenges. A literature search was undertaken to identify past and present documents relevant to physical activity policy in England. Each document was analysed to identify content relevant to the four key elements of policy which formed the focus of the current research. Physical activity recommendations are an area where England has demonstrated a robust scientific approach and good practice; however, the physical activity campaigns in England have not been sufficiently sustained to achieve changes in social norms and behaviour. The setting of physical activity targets has been unrealistic and continuous changes to national surveillance measures have presented challenges for monitoring trends over time. Overall, physical activity policy in England has fluctuated over the past two decades. The variations and cycles in policy reflect some of the challenges in implementing and sustaining physical activity policy in the face of political changes, changes in government direction, and changing opportunities to profile active lifestyles.


Sol-gel auto combustion synthesis, characterization, and application of Tb2FeMnO6 nanostructures as an effective photocatalyst for the discoloration of organic dye contaminants in wastewater.
In this study, the auto-combustion sol-gel method was used to prepare novel Tb2FeMnO6 (TFMO) double perovskite nanoparticles. Chemical and natural fuels were used to achieve these particles with appropriate size. The resulting particles were examined via X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) techniques. Rietveld analysis was also performed to confirm the crystallinity and lattice parameters of the formed particles. The particles obtained in the presence of maleic acid were selected as the optimal sample (S4), and the particles obtained in the presence of pomegranate paste were chosen as the non-optimal sample (S8) in terms of size and morphology. Both particles were used to investigate the photocatalytic activity. Fourier transform infrared spectroscopy (FTIR), UV-Vis diffuse reflectance spectroscopy (DRS), and vibrating sample magnetometer (VSM) analyses and N2 adsorption/desorption isotherms were performed for both samples and the results were compared. Erythrosine and malachite green dyes in aqueous solutions were used as contaminants in the photocatalysis process. The results showed 22% and 20% discoloration for S4 and 41% and 30% discoloration for S8 in the presence of erythrosine and malachite green under visible light irradiation. The photocatalytic activity was investigated under UV light for S4, which showed 80% and 50% discoloration for erythrosine and malachite green, respectively. Investigating the photocatalytic activity of TFMO double perovskite nanoparticles showed that these nanoparticles could be a desirable option for mitigating water pollution.


[Tuberculosis epidemiology and disease control in Uzbekistan].
The tuberculosis situation is complicated in Uzbekistan and in other countries of the world. In the past 5 years, due to the transition from mass prophylactic examinations to the differential surveys of population groups, the annual coverage of the population to be examined by fluorographic studies has reduced from 6 to 3.5 million along with a simultaneous rise in tuberculosis detection rates from 0.1 to 0.24% and in its incidence by 33.3%. Searches for new organizational forms of tuberculosis control work are under way. The State programme on tuberculosis control and the draft law of the Republic of Uzbekistan, which regulate associated measures have been developed.


Mechanisms of sunscreen failure.
Sunscreen is used as a primary strategy to prevent sunburn and later skin cancer. However, sunscreen use has paradoxically been associated with the increasing incidence of skin cancer. One explanation for this puzzling observation is sunscreen failure (sunburn in the setting of sunscreen). Our purpose was to evaluate mechanisms of sunscreen failure in a sunscreen-using population. We carried out an epidemiologic comparison of sunburned and nonsunburned beachgoers who used sunscreen. We found that men were less likely to use sunscreen than women (chi(2) = 11.3, df = 1, P = .001), and when it was used, men were less likely to apply sunscreen to all sunlight-exposed skin (chi(2) = 18.4, df = 1, P = .0001). Swimmers who used sunscreen were significantly more likely to be sunburned compared with nonswimming sunscreen users (Fisher exact test, df = 1). Sunscreen may fail to prevent sunburn if it is washed off during swimming or if it is not applied to all exposed skin. Epidemiologic studies that link sunscreen use to skin cancer should evaluate whether sunburn occurred in this setting.


Lymphopenia as a predictor of sarcoidosis in patients with uveitis.
To investigate the hypothesis that lymphopenia is an independent predictor of sarcoidosis in new patients presenting with uveitis. Retrospective case-control study of 112 patients with sarcoidosis-associated uveitis (SAU) against 398 controls with other forms of uveitis. Of the patients with SAU, 30/112 (26.8%) had significant lymphopenia (<1.0×10(9)/L), compared with 24/398 (6.0%) for other uveitis (p≤0.0001, OR 5.7 (95% CI 3.2 to 10.3)). The mean lymphocyte count for patients with SAU was 1.43 vs 2.04 for other uveitis (p≤0.0001). Logistic regression modelling using diagnosis of SAU as the independent variable identified age, ACE levels and lymphocyte count as independent predictors of SAU. A new patient with uveitis with significant lymphopenia has a risk of sarcoidosis (from this parameter alone) of 31.6%. Significant lymphopenia (<1.0×10(9)/L) is an independent predictor of sarcoidosis in new patients presenting with uveitis. We recommend that diagnostic criteria for SAU should be modified to include this phenomenon.


[Spontaneous Disappearance of Undifferentiated Pleomorphic Primary Mesenteric Sarcoma-A Case Report].
The patient was a 49-year-old man with persistent fever since the introduction of hemodialysis(HD). Vomiting and abdominal swelling appeared 4 months after initiating hemodialysis. Computed tomography(CT)scan revealed a tumor measuring 9 cm, and disorders of passage from the jejunum. Surgery was performed, and resection was impossible because of peritoneal dissemination. Histopathological examination of the disseminated nodes suggested an undifferentiated pleomorphic sarcoma. Postoperatively, drainage from the gastric fistula was approximately 2,000mL/day. Chemotherapy was considered impossible because of HD, and palliative therapy was selected. However, the volume of drainage from the gastric fistula gradually decreased, and the disorders of passage reduced. CT scan confirmed marked reduction in the size of the intraperitoneal tumor and its subsequent disappearance. At the 2-year-and-5-month postoperative follow-up, no relapses were observed, and the course had been uneventful. Undifferentiated pleomorphic sarcomas develop in the soft tissue of adults and have a poor prognosis. However, mesenteric development is rare. Total tumorectomy is the first choice of treatment. A consensus on the usefulness of chemotherapy or radiotherapy has not been reached. Furthermore, no studies have reported spontaneous tumor disappearance in the absence of treatment. Here, we report a case of minor undifferentiated primary mesenteric sarcoma and its spontaneous disappearance and review the literature.


Long-term Survival in Head and Neck Cancer: Impact of Site, Stage, Smoking, and Human Papillomavirus Status.
Literature examining long-term survival in head and neck squamous cell carcinoma (HNSCC) with human papillomavirus (HPV) status is lacking. We compare 10-year overall survival (OS) rates for cases to population-based controls. Prospective cohort study. Cases surviving 5 years postdiagnosis were identified from the Carolina Head and Neck Cancer Study. We examined 10-year survival by site, stage, p16, and treatment using Kaplan-Meier and Cox proportional hazard models. Cases were compared to age-matched, noncancer controls with stratification by p16 and smoking status. Ten-year OS for HNSCC is less than controls. In 581 cases, OS differed between sites with p16+ oropharynx having the most favorable prognosis (87%), followed by oral cavity (69%), larynx (67%), p16- oropharynx (56%), and hypopharynx (51%). Initial stage, but not treatment, also impacted OS. When compared to controls matched on smoking status, the hazard ratio (HR) for death in p16+ oropharynx cases was 1.5 (95% confidence interval [CI]: 0.7-3.1) for smokers and 2.4 (95% CI: 0.7-8.8) for nonsmokers. Similarly, HR for death in non-HPV-associated HNSCC was 2.2 (95% CI: 1.7-3.0) for smokers and 2.4 (95% CI: 1.4-4.9) for nonsmokers. OS for HNSCC cases continues to decrease 5 years posttreatment, even after stratification by p16 and smoking status. Site, stage, smoking, and p16 status are significant factors. These data provide important prognostic information for HNSCC. 2 Laryngoscope, 129:2506-2513, 2019.


Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: multi-target compounds with dual antimicrobial and anti-inflammatory activities.
Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were assessed for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA, E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii, respectively, with safe therapeutic dose. Compounds 7a-k, 8a-c, and 9a-c showed good anti-inflammatory activity with excessive selectivity towards COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site was correlated with the results of in vitro COX-2 inhibition assays.


[Preliminary proteome analysis for Saccharomyces cerevisiae under different culturing conditions].
For the investigation of the metabolic regulation of Saccharomyces cerevisiae under different culture conditions, the proteins of cell utilizing various carbon sources were separated by two-dimensional electrophoresis with immobilized pH gradients as the first dimension and SDS-PAGE as the second. Samples were taken in the log phase of batch culture using glucose or lactic acid as carbon source, while another sample was taken from the broth when glucose was consumed up and ethanol accumulated in the previous phase was further metabolized. After electrophoresis, the protein spots were detected by silver-stain in a Hoefer Automated Gel Stainer with a protein silver staining kit. Silver-stained gels were scanned and digitized to create computer images. About 500 protein spots were detected by employing the 2D proteome image analysis system Image Master 2D Elite and SWISS-2DPAGE proteome database. Most of the protein expressed and involved in the glycolysis, pentose phosphate (PP) pathway, anaplerotic pathway, as well as TCA cycle were analyzed. The metabolism regulation of protein level for Saccharomyces cerevisiae under various carbon sources, as well as during different phase of growth, was studied. The expression of several glycolytic enzymes (glk, pgi, pgk, eno, pyk) was up-regulated while the expression of enzymes in oxidative pentose phosphate pathway (zwf, gnd) was down-regulated when ethanol and lactic acid were taken as carbon source. Simultaneously, frucotose 1,6-biphosphatase was found to be up-regulated due to the gluconeogenic requirement. Citrate synthase and Malate dehydrogenase do not exhibit significant difference, indicating TCA cycle is necessary when utilizing glucose, ethanol or lactic acid as carbon source. Thus, the NADPH loss due to the repressed pentose phosphate pathway could be compensated by TCA cycle in cases of ethanol and lactic acid. The expression of malic enzyme and isocitrate lyase are activated to a large extent when metabolizing ethanol, indicating glyoxylate shunt is essential in transferring ethanol to generate four carbon precursors for the biosynthesis and the NADP-dependent malic enzyme could also serve as compensation mechanism for NADPH loss in this case.


Optical Screening of Female Breast Cancer from Whole Blood Using Raman Spectroscopy.
This study is intended to develop a screening method for female breast cancer (BRC) from whole blood using Raman spectroscopy. A multivariate partial least squares (PLS) regression model is developed which is based upon Raman spectra of BRC-positive and healthy participants. It yields coefficients of regression at the corresponding Raman shifts. These coefficients represent the changes in molecular structures which are associated with the progress of disease. The present study pointed out some specific molecules which differentiated BRC-positive and healthy groups. In the BRC-positive group, a rising trend of calcium oxalate, calcium hydroxyapatite, phosphatidylserine and qunoid ring, and a lowering trend of tryptophan, tyrosine, and proline were observed in PLS-based coefficients of regression. The R-square value of the model was found to be 0.987, which is accepted clinically. The model was tested for the prediction of 50 randomly collected samples at a cutoff value of 0.5 with the gray region defined in the range of 0.4-0.6. Goodness of fit was estimated using accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curve, and area under ROC curve. All of these parameters were found to be very promising.


Association of G-protein beta-3 subunit gene (GNB3) T825 allele with Type II diabetes.
To date, the human G-protein beta 3 subunit (GNB3) gene and some of its variants represent some of the best examples of genetic influences that are involved in the determination of hypertension and obesity, which make it a sensible candidate gene for type 2 diabetes. To assess the influence of GNB3 in type II diabetes mellitus (NIDDM), we carried out a retrospective, case-control study of variant GNB3 825C>T for putative correlations with NIDDM amongst nationals from the United Arab Emirates (Emirati) - an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 510 Emirati (257 men, 253 women) comprising two groups - 254 controls and 256 patients with clinical diagnoses of type 2 diabetes (cases). The GNB3 C825T dimorphism showed an association with NIDDM Chi2 =22.5, 2 df, P<0.001). Further analysis revealed that the GNB3 T/T 825 genotype was positively associated with NIDDM (Yates corrected Chi2=20.6, 2 df, P<0.001; odds ratio of 2.44 with a 95% confidence interval of 1.64 - 3.63) compared to pooled CC/CT genotypes. Our data shows that GNB3 T825 allele may be involved in the pathogenesis of DM through a pathway that is different from the one implicated in obesity.


Four terpene synthases contribute to the generation of chemotypes in tea tree (Melaleuca alternifolia).
Terpene rich leaves are a characteristic of Myrtaceae. There is significant qualitative variation in the terpene profile of plants within a single species, which is observable as "chemotypes". Understanding the molecular basis of chemotypic variation will help explain how such variation is maintained in natural populations as well as allowing focussed breeding for those terpenes sought by industry. The leaves of the medicinal tea tree, Melaleuca alternifolia, are used to produce terpinen-4-ol rich tea tree oil, but there are six naturally occurring chemotypes; three cardinal chemotypes (dominated by terpinen-4-ol, terpinolene and 1,8-cineole, respectively) and three intermediates. It has been predicted that three distinct terpene synthases could be responsible for the maintenance of chemotypic variation in this species. We isolated and characterised the most abundant terpene synthases (TPSs) from the three cardinal chemotypes of M. alternifolia. Functional characterisation of these enzymes shows that they produce the dominant compounds in the foliar terpene profile of all six chemotypes. Using RNA-Seq, we investigated the expression of these and 24 additional putative terpene synthases in young leaves of all six chemotypes of M. alternifolia. Despite contributing to the variation patterns observed, variation in gene expression of the three TPS genes is not enough to explain all variation for the maintenance of chemotypes. Other candidate terpene synthases as well as other levels of regulation must also be involved. The results of this study provide novel insights into the complexity of terpene biosynthesis in natural populations of a non-model organism.


[The collateral branching of the axons of efferent neurons in the cat parietal cortex].
Collateral branching of efferent neurons' axons in the cat parietal associative cortex was studied with intracellular recording of antidromic activity. Specific features of the axon collaterals projecting onto the sensorimotor cortex, pontine nuclei proper and red nucleus, were revealed and described. Information arriving from the parietal cortex simultaneously at the above two motor structures suggests their interrelationship to be actualized through the axon collaterals of efferent neurons. This kind of functional interrelationship of the structures via axon branching of efferent neurons of the parietal cortex provides synchronous arrival of signals at the structures participating in motor integration.


Combatting the rising costs of cancer drugs; interventions from a university hospital's perspective.
Rapid increase in cost continues to have negative impact on patients' accessibility to life-changing anticancer medications. Moreover, the rising cost does not equate to similar increase in medication effectiveness. We recognise our responsibility as a university hospital to tackle this imbalance and strive to provide high quality, sustainable, affordable and accessible care. An active approach in cost containment of expensive and innovative cancer drugs was adopted in our organisation to safeguard accessibility and improve quality of life for patients. In this article, we described four inverventions: 1) identify right patient and minimise overtreatment, 2) in-house medicine production for selected indications, 3) minimise medicine spillages and 4) effective procurement strategies. We call on other hospitals to take action and, favourably, to collaborate on a European level. Together, we will safeguard the current and future care of our patients.


[Movement-related brain potentials during the treatment of parkinsonism].
The authors studied motor associated brain potentials (MABP) in patients with disturbed motor function (hypertonia, tremor) due to affection of the basal ganglia (parkinsonism) and studied the changes of these potentials after stereotaxic operations conducted for the correction of the motor pathology. It was found that in a favourable effect of operative treatment manifested by decrease of the tonus and inhibition of tremor in patients with parkinsonism, there was a tendency towards normalization of MABP. Restoration of some of the components of the motor response and in certain cases of the MABP on the whole occurred on the 14-16th postoperative day. No clearly defined changes of motor associated potentials characteristic of different forms of parkinsonism were discovered.


The immunopathogenesis of cow's milk protein allergy (CMPA).
The most frequent symptoms among the manifestations of cow milk protein allergy (CMPA) are gastrointestinal. CMPA pathogenesis involves immunological mechanisms with participation of immunocompetent cells and production of immunoglobulin E (IgE). Nevertheless, recent studies have been focused on the description of other forms of CMPA, not-mediated by IgE reactions, mostly involving the T lymphocite immune system. Thus, in this field it is important to note how different kind of cells are involved in the immunopathogenesis of CMPA, such as antigen-specific T cells, T regulatory cells, cytokines secreted by the different T lymphocite subsets, B lymphocytes, antingen-presenting cells, mast cells, that together orchestrate the complex mechanism leading to the phenotipic expression of CMPA.The progress in the diagnosis of immunologic disorders allowed the recent literature to develop new models for immuno-mediate disorders, involving new cells (such as Treg cells) and thus allowing the acquisition of a new vision of the pathogenesis of atopic diseases.The aim of this review is to describe the immunopathogenetic aspects of CMPA in view of these new discoveries in the immunologic field, considering the immunologic pathway at the basis of both IgE- and not-IgE mediated CMPA.


Co-encapsulation of dexamethasone 21-acetate and SPIONs into biodegradable polymeric microparticles designed for intra-articular delivery.
Intra-articular drug delivery systems still suffer from too short-lasting effects. Magnetic particles retained in the joint using an external magnetic field might prolong the local release of an anti-inflammatory drug. For the purpose, superparamagnetic iron oxide nanoparticles (SPIONs) and dexamethasone 21-acetate (DXM) were co-encapsulated into biodegradable microparticles. Poly(D,L-lactide-co-glycolide) microparticles embedding both SPIONs and DXM were prepared by a double emulsion technique. The formulation was optimized in two steps, a screening design and a full factorial design, aiming at 10-microm particle diameter and high DXM encapsulation efficacy. The most significant parameters were the polymer concentration, the stirring speed during solvent extraction and the extractive volume. Increasing the polymer concentration from 200 to 300 mg ml(-1), both the microparticle mean diameter and the DXM encapsulation efficacy increased up to 12 microm and 90%, respectively. The microparticles could be retained with an external magnet of 0.8 T placed at 3 mm. Faster DXM release was obtained for smaller microparticles. The experimental set-up offered the tools for tailoring a formulation with magnetic retention properties and DXM release patterns corresponding to the required specifications for intra-articular administration.


The effects of stunning methods on product qualities in force-fed ducks and geese. 1. Carcass downgrading and meat quality.
This study investigated the effects of various stunning methods on the quality of carcass and meat in ducks and geese force-fed for the production of French 'foie gras'. The ducks (n = 30 per group) were stunned with one of the following techniques: electrical stunning in a water bath (50 Hz AC, 130 mA, 4 s), head-only electrical stunning (50 Hz AC, 600 mA, 4 s), mechanical stunning (captive bolt) and controlled atmosphere stunning (CAS: phase 1, CO2 (40%)-O2 (30%)-N2 (30%), for 2 min followed by phase 2, CO2 > 85% in air, for 2 min). The same methods (except head-only stunning which was not applied) were used in geese (n = 40 per group). During the first 5 min after slaughter, the stunning techniques that did not kill the animals were associated with a high incidence of head movements (mechanical and electrical head-only stunning), convulsions and convulsive wing flapping (mechanical stunning), in both species. Consequently, the rate of post-mortem pH fall in breast muscle was enhanced and the meat was paler when measured at 24 h or 6 days post mortem (L*, a*, b* coordinates). In ducks, the animals stunned in the water bath showed the lowest bleeding efficiency, compared to the three other procedures. In geese, the mechanical stunning allowed the highest recovery of blood compared to the CAS and the water-bath methods. Meat texture assessed instrumentally and fluid losses during storage and processing were not affected by the stunning method in any species. Sensory analysis showed a higher score for bloody appearance of raw meat in ducks stunned with the methods that kill before neck cutting (water-bath and CAS). This effect was, however, not linked to the rate of bleeding. The sensory properties of cooked meat were not affected by the stunning method. In both ducks and geese, CAS was associated with the lowest rate of fractures of humeral bone but CAS-stunned geese showed the most engorged wing veins. Overall, these results show the positive effect of CAS on the appearance defects of carcass and meat of ducks and geese, and, on the contrary, they confirm the detrimental effects of water-bath stunning on these criteria. However, the incidences on meat sensory qualities were scarce.


The safety of intranasal steroids.
The increasing use of intranasal steroids in the management of allergic rhinitis reflects their efficacy, tolerability, and safety. However, issues related to the safety of intranasal steroids continue to generate debate and confusion among clinicians. Consequently, there is often reluctance and uncertainty in prescribing these effective agents for the treatment of perennial and seasonal allergic rhinitis. Issues of particular concern are whether intranasal steroids adversely affect various homeostatic systems, influence growth and bone metabolism, and compromise ocular function. Furthermore, the expanding role of intranasal steroids in the pediatric, geriatric, and postmenopausal populations has raised concerns that these agents may result in a steroid burden that more readily causes adverse effects. An extensive review of the literature overwhelmingly supports the assertion that intranasal steroids are safe in prescribed doses and should allay the misconceptions regarding their appropriate use in the management of allergic rhinitis.


[Directed synthesis of 2',5'-oligoadenylates with increased stability towards phosphodiesterases].
Phosphodiesterase stability of synthetic analogs of 2',5'-oligoadenylates, the mediators of antiviral and antiproliferative action of interferons was analysed. The analogs with a 3'-terminal acyclic nucleoside residue were prepared. These analogs were treated with NIH3T3 cell lysate, mice liver homogenate and snake venom phosphodiesterase. All analogs have demonstrated a high stability as compared with the natural 2',5'-oligoadenylate and its 3'-deoxyderivative. The possible biological activity of these stable analogs of 2',5'-oligoadenylates is discussed.


In vivo robotic laparoscopy.
Laparoscopy reduces patient trauma but limits the surgeon's ability to view or touch the surgical environment directly. The surgeon's ability to visualize and manipulate target organs can be improved using currently available external robotic systems. However, tool tip orientation and optimal camera placement remain limited because the robot instruments and cameras are still constrained by the entry incisions. Placing a robot completely within the abdominal cavity would provide an unconstrained platform that could provide an enhanced field of view from arbitrary angles and dexterous manipulators not constrained by the abdominal wall fulcrum effect. Several in vivo robots have been developed and successfully tested in a porcine model. These in vivo robots have been used to observe trocar and tool insertions and placement, and to provide additional camera angles that improved surgical visualization. Equipped with a grasper, such robots will provide task assistance. These in vivo robots will be much less expensive than the current generation of large external robotic surgical systems and will ultimately allow a surgeon to be a remote first responder irrespective of the location of the patient.


The value of embedding: integrated palliative care for patients with metastatic breast cancer.
The American Society of Clinical Oncology recommends concurrent palliative care (PC) for patients with metastatic cancer. Recent data show benefits of early PC (at least 90 days before death). However, little is known about PC among patients who die from metastatic breast cancer. Patients with metastatic breast cancer at a comprehensive cancer center. Analysis of medical records and clinician and patient surveys. Assess referral patterns and value to patients at the end of life (EOL) of a specialty PC service embedded in a breast oncology program; compare to a prior period of stand-alone PC. In the 18-month study period, oncologists referred for palliative care 105 of their 515 (20.4%) patients; 59 (11.5%) patients were seen by the PC physician. Of the 38 referred patients who died, 23 (60.5%) were seen by embedded PC and all 23 received PC within 90 days of death; 0 of 18 decedents with data available for analysis had ICU stays within 30 days of death. In an earlier 24-month period of stand-alone PC, 43 patients died after receiving PC, but only 11 (25.5%) received PC within 90 days of death (p < 0.01) and 7 of 43 had ICU stays within 30 days of death (p = 0.074). Embedded PC was well-received by patients and oncologists, increased early PC referrals, and improved EOL care. Avoidable, unnecessary health care utilization at the end of life, such as ICU stays in the last month of life, represent an important potential reduction in patient suffering and system costs.


The effect of various pretreatment methods of the enamel in bonding procedures.
Thirty-eight pairs of premolars, extracted for orthodontic reasons, were tested for the effects of various pretreatment methods of the enamel in bonding procedures. Etched enamel surfaces and inner bracket surfaces facing the etched enamel were studied with the scanning electron microscope. The results were based on a pair-by-pair evaluation of 650 photographs. The degree of surface irregularities indicating the quality of microretentions was evaluated. A scale from 0 to 3 was used; 0 represented a smooth surface, and 3 represented optimum irregularities. Scores for bracket inner surfaces were always higher than those for corresponding etched enamel surfaces. Future SEM comparative investigations, therefore, ought to be based on replicas of etched enamel surfaces. One-minute etching with an acid gel had the same effect as etching with an acid liquid for the same time. Furthermore, mechanical pretreatment procedures, such as diamond grinding and aluminum oxide grinding, as opposed to pumicing did not improve the effect of the acid. Chemical pretreatment of the enamel with organic solvents such as 8 to 12 percent sodium hypochlorite did not improve the effect of the acid. Fluoride pretreatment with a fluoride varnish, Duraphat, did not have any negative effect on the etching results.


Development of a tool to assess oral health-related quality of life in patients hospitalised in critical care.
Oral health deteriorates following hospitalisation in critical care units (CCU) but there are no validated measures to assess effects on oral health-related quality of life (OHQoL). The objectives of this study were (i) to develop a tool (CCU-OHQoL) to assess OHQoL amongst patients admitted to CCU, (ii) to collect data to analyse the validity, reliability and acceptability of the CCU-OHQoL tool and (iii) to investigate patient-reported outcome measures of OHQoL in patients hospitalised in a CCU. The project included three phases: (1) the development of an initial questionnaire informed by a literature review and expert panel, (2) testing of the tool in CCU (n = 18) followed by semi-structured interviews to assess acceptability, face and content validity and (3) final tool modification and testing of CCU-OHQoL questionnaire to assess validity and reliability. The CCU-OHQoL showed good face and content validity and was quick to administer. Cronbach's alpha was 0.72 suggesting good internal consistency. For construct validity, the CCU-OHQoL was strongly and significantly correlated (correlation coefficients 0.71, 0.62 and 0.77, p < 0.01) with global OHQoL items. In the validation study, 37.8% of the participants reported a deterioration in self-reported oral health after CCU admission. Finally, 26.9% and 31% of the participants reported considerable negative impacts of oral health in their life overall and quality of life, respectively. The new CCU-OHQoL tool may be of use in the assessment of oral health-related quality of life in CCU patients. Deterioration of OHQoL seems to be common in CCU patients.


Hydrogen water reduces NSE, IL-6, and TNF-α levels in hypoxic-ischemic encephalopathy.
This study retrospectively analyzed the efficacy of hydrogen water in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE) and its effect on serum neuron-specific enolase (NSE), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. Forty newborns with HIE who received treatment from April 2014 to April 2015 were divided into a conventional care group and a hydrogen water group according to the different treatment methods applied. Twenty healthy full-term newborns comprised the control group. In the hydrogen water group, 5-mL/kg hydrogen water was orally administered two days after birth daily for 10 days in addition to conventional treatment. After 10 days, efficacy indicators were examined in the HIE groups. The NSE, IL-6, and TNF-α levels were compared among all three groups. The efficacy indicators were significantly lower in the hydrogen water group compared with the conventional group. Before treatment, the serum NSE, IL-6, and TNF-α levels in the HIE groups were higher than those in the control group. After treatment, these levels in the hydrogen water group were lower than those in the conventional group. Hydrogen water lowers serum NSE, IL-6, and TNF-α levels in HIE newborns, thereby exerting a protective effect.


Restricting youth suicide: behavioral health patients in an urban pediatric emergency department.
Suicide is the third leading cause of death among individuals age 10 years to 19 years in the United States. Adolescents with suicidal behaviors are often cared for in emergency departments (EDs)/trauma centers and are at an increased risk for subsequent suicide. Many institutions do not have standard procedures to prevent future self-harm. Lethal means restriction (LMR) counseling is an evidence-based suicide prevention strategy that informs families to restrict access to potentially fatal items and has demonstrated efficacy in preventing suicide. The objectives of this study were to examine suicidal behavior among behavioral health patients in a pediatric ED and to assess the use of LMR by hospital staff. A sample of 298 pediatric patients was randomly selected from the population of behavioral health patients treated at the ED from January 1 through December 31, 2012 (n = 2,294). Descriptive data include demographics (age, sex, race/ethnicity, etc,), chief complaint, current and past psychiatric history, primary diagnosis, disposition, alcohol/drug abuse, and documentation of any LMR counseling provided in the ED. Of the 298 patients, 52% were female, 47% were white, and 76% were in the custody of their parents. Behavior/out of control was the most common chief complaint (43%). The most common diagnoses were mood disorder (25%) and depression (20%). Thirty-four percent of the patients had suicidal ideation, 22% had a suicide plan, 32% had documented suicidal behavior, and 25% of the patients reported having access to lethal means. However, only 4% of the total patient population received any LMR counseling, and only 15% of those with access to lethal means had received LMR counseling. Providing a safe environment for adolescents at risk for suicidal behaviors should be a priority for all families/caretakers and should be encouraged by health care providers. The ED is a key point of entry into services for suicidal youth and presents an opportunity to implement effective secondary prevention strategies. The low rate of LMR counseling found in this study suggests a need for improved LMR counseling for all at-risk youth.


Your attention please: increasing ambient noise levels elicits a change in communication behaviour in humpback whales (Megaptera novaeangliae).
High background noise is an important obstacle in successful signal detection and perception of an intended acoustic signal. To overcome this problem, many animals modify their acoustic signal by increasing the repetition rate, duration, amplitude or frequency range of the signal. An alternative method to ensure successful signal reception, yet to be tested in animals, involves the use of two different types of signal, where one signal type may enhance the other in periods of high background noise. Humpback whale communication signals comprise two different types: vocal signals, and surface-generated signals such as 'breaching' or 'pectoral slapping'. We found that humpback whales gradually switched from primarily vocal to primarily surface-generated communication in increasing wind speeds and background noise levels, though kept both signal types in their repertoire. Vocal signals have the advantage of having higher information content but may have the disadvantage of loosing this information in a noisy environment. Surface-generated sounds have energy distributed over a greater frequency range and may be less likely to become confused in periods of high wind-generated noise but have less information content when compared with vocal sounds. Therefore, surface-generated sounds may improve detection or enhance the perception of vocal signals in a noisy environment.


Transnational gestational surrogacy: does it have to be exploitative?
This article explores the controversial practice of transnational gestational surrogacy and poses a provocative question: Does it have to be exploitative? Various existing models of exploitation are considered and a novel exploitation-evaluation heuristic is introduced to assist in the analysis of the potentially exploitative dimensions/elements of complex health-related practices. On the basis of application of the heuristic, I conclude that transnational gestational surrogacy, as currently practiced in low-income country settings (such as rural, western India), is exploitative of surrogate women. Arising out of consideration of the heuristic's exploitation conditions, a set of public education and enabled choice, enhanced protections, and empowerment reforms to transnational gestational surrogacy practice is proposed that, if incorporated into a national regulatory framework and actualized within a low income country, could possibly render such practice nonexploitative.


A zeolite family with expanding structural complexity and embedded isoreticular structures.
The prediction and synthesis of new crystal structures enable the targeted preparation of materials with desired properties. Among porous solids, this has been achieved for metal-organic frameworks, but not for the more widely applicable zeolites, where new materials are usually discovered using exploratory synthesis. Although millions of hypothetical zeolite structures have been proposed, not enough is known about their synthesis mechanism to allow any given structure to be prepared. Here we present an approach that combines structure solution with structure prediction, and inspires the targeted synthesis of new super-complex zeolites. We used electron diffraction to identify a family of related structures and to discover the structural 'coding' within them. This allowed us to determine the complex, and previously unknown, structure of zeolite ZSM-25 (ref. 8), which has the largest unit-cell volume of all known zeolites (91,554 cubic ångströms) and demonstrates selective CO2 adsorption. By extending our method, we were able to predict other members of a family of increasingly complex, but structurally related, zeolites and to synthesize two more-complex zeolites in the family, PST-20 and PST-25, with much larger cell volumes (166,988 and 275,178 cubic ångströms, respectively) and similar selective adsorption properties. Members of this family have the same symmetry, but an expanding unit cell, and are related by hitherto unrecognized structural principles; we call these family members embedded isoreticular zeolite structures.


Comparison of methods and sampling designs to test for association between rare variants and quantitative traits.
Genome-wide association studies succeeded in finding genetic variants associated with various phenotypes, but a large portion of the predicted genetic contribution to many traits remains unknown. One plausible explanation is that some missing variation is due to rare variants. Latest sequencing technology facilitates the investigation of such rare variants, but their statistical analysis remains challenging. For quantitative traits, a commonly used approach is to contrast the frequency of putatively functional rare variants between subjects in the two tails of the trait distribution. The contrast is usually performed by Fisher's exact or similar test. These tests are conservative as they discard trait rank information and are most useful under the unrealistic homogeneity assumption (i.e., variants have similar effects). We propose, and investigate via simulations, various designs for resequencing studies and statistical methods that incorporate information about rank, predicted function and allow for heterogeneity of effects. We propose designs which accommodate heterogeneity by sequencing both tails and the middle of the trait and novel statistical tests for trend, for heterogeneity and for a combination of the two. The conclusions of the simulations are four fold: (1) sequencing both tails and the middle of the trait distributions is desirable when heterogeneity is suspected, (2) trend and heterogeneity statistics should be used alongside other methods, (3) using rank information improves power over Fisher's exact test when the number of rare variants is not very large and (4) due to high misclassification rates, incorporating current predictions of a variant's function does not improve power.


Psychological correlates of COVID-19 conspiracy beliefs and preventive measures: Evidence from Turkey.
COVID-19 pandemic has led to popular conspiracy theories regarding its origins and widespread concern over the level of compliance with preventive measures. In the current preregistered research, we recruited 1088 Turkish participants and investigated (a) individual differences associated with COVID-19 conspiracy beliefs; (b) whether such conspiracy beliefs are related to the level of preventive measures; and (c) other individual differences that might be related to the preventive measures. Higher faith in intuition, uncertainty avoidance, impulsivity, generic conspiracy beliefs, religiosity, and right-wing ideology, and a lower level of cognitive reflection were associated with a higher level of belief in COVID-19 conspiracy theories. There was no association between COVID-19 conspiracy beliefs and preventive measures while perceived risk was positively and impulsivity negatively correlated with preventive measures. We discuss the implications and directions for future research.


Sequential studies of lymphocyte responsiveness and antibody formation in acute bacterial meningitis.
Lymphocyte transformation responses in vitro were studied in eight patients with acute bacterial meningitis (in five due to Neisseria meningitidis). Sequential studies were done from 24--48 hr after the first symptoms of infection to complete recovery. In all cases lymphocyte transformation was depressed during the acute phases of illness. The responses to microbial antigens were more affected than the responses to mitogens. The course of the lymphocyte responses to the causative micro-organism showed no difference from the responses to other microbial species. A moderate shift towards increased sensitivity of the lymphocytes to lower doses of the causative micro-organism was observed during the course of illness in three cases. In N. meningitidis infection, a rapid rise was seen in the serum titres of complement-fixing antibodies and in the number of precipitating antibodies, whereas the rise in immunoglobulin concentrations was more prolonged. Characteristic patterns of elevation and return towards normal were found in the serum concentrations of the acute-phase reactants alpha1-antitrypsin, haptoglobin, and orosomucoid. It is concluded that the lymphocyte transformation responses in vitro during severe bacterial infection are largely governed by non-specific factors, and that studies of lymphocyte responses to micro-organisms should always include other microbial species as controls.


Immunological mechanisms of survival and "rejection" of the fetal allograft.
Critical features of the trophoblast for immune protection in the mother are: 1) it is resistant to cytotoxic lymphocytes and antibodies; 2) it forms a physical barrier to immune effector cells, but not antibody, preventing them from reaching the fetus; 3) it signals the migration of suppressor and other functionally hyporesponsive lymphocytes into the uterine decidua and uterine lymphatics; 4) it promotes the production of maternal serum MLR blocking antibody with paternal antigen specificity. Some of these immunological features are lacking in women with recurrent abortions of immune etiology. Eleven women who aborted an additional time post immunization with paternal leukocytes were compared with 26 women who delivered infants at term post immunization. It was found that those who aborted: 1) shared more HLA D/DR and MT locus antigens with their spouses; 2) were more hyporesponsive in MLR to paternal antigens pre and post immunization; 3) failed to develop female serum MLR blocking factors post immunization; 4) failed to develop humoral antibodies to B cell alloantigens; and 5) had lymphocytes in the uterine decidua mantling the conceptus and in the uterine lymphatics that were reactive/cytotoxic to paternal stimulating alloantigens. These results are in sharp contrast with the immunodynamics of peripheral blood leukocytes and decidual leukocytes to paternal alloantigens in women who delivered infants at term post immunization.


Antitumor activity of Moringa oleifera (drumstick tree) flower trypsin inhibitor (MoFTI) in sarcoma 180-bearing mice.
The plant Moringa oleifera is used as food and medicine. M. oleifera flowers are source of protein, fiber, and antioxidants, and are used to treat inflammation and tumors. This work evaluated the antitumor activity of the M. oleifera flower trypsin inhibitor (MoFTI) in sarcoma 180-bearing mice. Swiss female mice were inoculated with sarcoma 180 cells. Seven days later, the animals were treated intraperitoneally for 1 week with daily doses of PBS (control) or MoFTI (15 or 30 mg/kg). For toxicity assessment, water and food consumption, body and organ weights, histological alterations, and blood hematological and biochemical parameters were measured. Treatment with MoFTI caused pronounced reduction (90.1%-97.9%) in tumor weight. The tumors of treated animals had a reduced number of secondary vessels and lower gauge of the primary vessels compared to the control. No significant changes were observed in water and food consumption or in body and organ weights. Histopathological analysis did not indicate damage to the liver, kidneys, and spleen. In conclusion, MoFTI showed antitumor potential, with no clear evidence of toxicity.


Gender difference in health expectancy trends in Greenland.
The population of Greenland comprises almost 31,000 Inuit Greenlanders aged 20-65. The purpose of this study was to estimate trends in expected life years between age 20 and 65 in good and poor health, and to compare changes between men and women since the mid-1990s. Partial life expectancy was calculated and combined with prevalence data on self-rated health, longstanding illness and musculoskeletal diseases derived from health surveys carried out in 1993-94, 1999-2001 and 2005-10. Trends for men and women were compared and changes were decomposed into contributions from changes in mortality and disability. Partial life expectancy increased by 2.2 years for men and 0.8 years for women during the entire period. However, expected lifetime in self-rated good health decreased by 3.3 years for men and by 4.6 years for women (p<0.01). For men, life expectancy without longstanding illness increased by 4.7 years (p<0.001). The increase for women by 1.4 years was non-significant (p=0.29). Expected lifetime without musculoskeletal diseases increased significantly by 4.5 years for men and by 1.9 years for women. The development of expected lifetime without longstanding illness supports the theory of compression of morbidity, but as the trend direction differs according to which measure for health is used, a definite conclusion cannot be drawn. The different rate of development of partial life expectancy and expected lifetime in good health between men and women is remarkable, and has reduced the gender gap. The results call for special concern about the women's health in Greenland.


Telomerase Activity in Articular Chondrocytes Is Lost after Puberty.
Telomere length and telomerase activity are important indicators of cellular senescence and replicative ability. Loss of telomerase is associated with ageing and the development of osteoarthritis. Implantation of telomerase-positive cells, chondrocytes, or stem cells expressing a normal chondrocyte phenotype is desired for cartilage repair procedures. The objective of this study was to identify at what age chondrocytes and at what passage bone marrow-derived mesenchymal stem cells (MSCs) become senescent based on telomerase activity. The effect of osteogenic protein-1 (OP-1) or interleukin-1α (IL-1α) treatment on telomerase activity in chondrocytes was also measured to determine the response to anabolic or catabolic stimuli. Articular cartilage was collected from horses (n = 12) aged 1 month to 18 years. Chondrocytes from prepubescent horses (<15 months) were treated with OP-1 or IL-1α. Bone marrow aspirate from adult horses was collected and cultured for up to 10 days to isolate MSCs. Telomerase activity was measured using the TeloTAGGG Telomerase PCR ELISA kit. Chondrocytes from prepubescent horses were positive for telomerase activity. Treatment with IL-1α resulted in a decrease in chondrocyte telomerase activity; however, treatment with OP-1 did not change telomerase activity. One MSC culture sample was positive for telomerase activity on day 2; all samples were negative for telomerase activity on day 10. These results suggest that chondrocytes from prepubescent donors are potentially more suitable for cartilage repair procedures and that telomerase activity is diminished by anabolic and catabolic cytokine stimulation. If MSCs are utilized in cartilage repair, minimal passaging should be performed prior to implantation.


Screening of some anti-androgenic endocrine disruptors using a recombinant cell-based in vitro bioassay.
The present work describes the development and optimization of a cell-based androgen reporter assay using the Chinese hamster ovarian cell line (CHO K1) in the 96-well format. The recent reports on increasing exposure of humans and wild-life to environmental endocrine disrupting chemicals (ED) prompt the need for high throughput screening systems for such compounds in environmental and biological samples. To this end, CHO cells were cotransfected with plasmids encoding mouse mammary tumour virus-neomycin-luciferase and human androgen receptor (hAR), and a stable cell line was established. After selection with neomycin, a highly active clone was obtained which stably expressed both the hAR and the androgen-responsive luciferase reporter. Stimulation of the cells with androgens for 24 h resulted in about 15-fold stimulation of luciferase activity, with the minimum effective dose of testosterone being 0.1 nmol/l. Potent steroidal and non-steroidal anti-androgens, such as hydroxyflutamide and cyproterone acetate, significantly inhibited the androgen-induced transactivation. Non-androgenic steroids like estradiol, progesterone, dexamethasone and cortisol showed weak activity at high concentrations. RT-PCR and western blot confirmed proper transcription and translation as well as stable expression of the AR gene in the cells. About 60 different chemicals (mostly pesticides or their metabolites, and common industrial chemicals) were screened with the cell line for their ability to stimulate luciferase activity or inhibit that evoked by 0.1 nmol/l R1881, used as a positive androgenic control. About 10 highly potent anti-androgenic chemicals were identified. The most potent anti-androgenic compounds identified in our assay included bisphenol A, alpha-hexachlorocyclohexane, vinclozolin and 4,4-DDE. These compounds had alone either no effect or were weak agonists (with cytotoxic effects at very high concentrations), but none showed any significant agonistic activity. In conclusion, we demonstrate that the bioassay based on this cell line provides a reliable test for detecting androgenic and anti-androgenic compounds. The 96-well plate format makes the assay suitable for high throughput screening.


Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary edema.
Ventilation-perfusion (VA/Q) mismatch has been shown to increase during exercise, especially in hypoxia. A possible explanation is subclinical interstitial edema due to high pulmonary capillary pressures. We hypothesized that this may be pathogenetically similar to high-altitude pulmonary edema (HAPE) so that HAPE-susceptible people with higher vascular pressures would develop more exercise-induced VA/Q mismatch. To examine this, seven healthy people with a history of HAPE and nine with similar altitude exposure but no HAPE history (control) were studied at rest and during exercise at 35, 65, and 85% of maximum 1) at sea level and then 2) after 2 days at altitude (3,810 m) breathing both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) gas at both locations. We measured cardiac output and respiratory and inert gas exchange. In both groups, VA/Q mismatch (assessed by log standard deviation of the perfusion distribution) increased with exercise. At sea level, log standard deviation of the perfusion distribution was slightly higher in the HAPE-susceptible group than in the control group during heavy exercise. At altitude, these differences disappeared. Because a history of HAPE was associated with greater exercise-induced VA/Q mismatch and higher pulmonary capillary pressures, our findings are consistent with the hypothesis that exercise-induced mismatch is due to a temporary extravascular fluid accumulation.


Modeling the relationship between descriptive norms and behaviors: a test and extension of the theory of normative social behavior (TNSB).
Informed by the theory of normative social behavior, this article sought to determine the underlying mediating and moderating factors in the relationship between descriptive norms and behavioral intentions. Furthermore, the theory was extended by asking whether and what role behavioral identity played in normative influences. Simulating the central message of norms-based interventions to reduce college students' alcohol consumption, in this field experiment, descriptive norms were manipulated by informing half of the students (n = 665) that their peers consumed less alcohol than they might believe. Others (n = 672) were not provided any norms information. students' injunctive norms, outcome expectations, group identity, behavioral identity, and behavioral intention surrounding alcohol consumption were then measured. Exposure to the low-norms information resulted in a significant drop in estimates of the prevalence of consumption. Injunctive norms and outcome expectations partially mediated and also moderated the relationship between descriptive norms and behavioral intentions. Group identity and behavioral identity also moderated the relationship between descriptive norms and behavioral intentions, but the effect size was relatively small for group identity. Implications for health campaigns are also discussed.


In Vivo Validation of the Viral Barcoding of Simian Immunodeficiency Virus SIVmac239 and the Development of New Barcoded SIV and Subtype B and C Simian-Human Immunodeficiency Viruses.
Genetically barcoded viral populations are powerful tools for evaluating the overall viral population structure as well as assessing the dynamics and evolution of individual lineages in vivo over time. Barcoded viruses are generated by inserting a small, genetically unique tag into the viral genome, which is retained in progeny virus. We recently reported barcoding the well-characterized molecular clone simian immunodeficiency virus (SIV) SIVmac239, resulting in a synthetic swarm (SIVmac239M) containing approximately 10,000 distinct viral clonotypes for which all genetic differences were within a 34-base barcode that could be tracked using next-generation deep sequencing. Here, we assessed the population size, distribution, and authenticity of individual viral clonotypes within this synthetic swarm using samples from 120 rhesus macaques infected intravenously. The number of replicating barcodes in plasma correlated with the infectious inoculum dose, and the primary viral growth rate was similar in all infected animals regardless of the inoculum size. Overall, 97% of detectable clonotypes in the viral stock were identified in the plasma of at least one infected animal. Additionally, we prepared a second-generation barcoded SIVmac239 stock (SIVmac239M2) with over 16 times the number of barcoded variants of the original stock and an additional barcoded stock with suboptimal nucleotides corrected (SIVmac239Opt5M). We also generated four barcoded stocks from subtype B and C simian-human immunodeficiency virus (SHIV) clones. These new SHIV clones may be particularly valuable models to evaluate Env-targeting approaches to study viral transmission or viral reservoir clearance. Overall, this work further establishes the reliability of the barcoded virus approach and highlights the feasibility of adapting this technique to other viral clones.IMPORTANCE We recently developed and published a description of a barcoded simian immunodeficiency virus that has a short random sequence inserted directly into the viral genome. This allows for the tracking of individual viral lineages with high fidelity and ultradeep sensitivity. This virus was used to infect 120 rhesus macaques, and we report here the analysis of the barcodes of these animals during primary infection. We found that the vast majority of barcodes were functional in vivo We then expanded the barcoding approach in a second-generation SIVmac239 stock (SIVmac239M2) with over 16 times the number of barcoded variants of the original stock and a barcoded stock of SIVmac239Opt5M whose sequence had 5 changes from the wild-type SIVmac239 sequence. We also generated 4 barcoded stocks from subtype B and C SHIV clones each containing a human immunodeficiency virus (HIV) type 1 envelope. These virus models are functional and can be useful for studying viral transmission and HIV cure/reservoir research.


The anxiolytic effect of chronic inositol depends on the baseline level of anxiety.
Inositol, a precursor for membrane phosphoinositides involved in signal transduction, has been found to be clinically effective in a number of psychiatric disorders and to reverse behavioural effects of lithium. To gain insight into the mechanism of action of inositol, it is critical to establish its efficacy in animal models. Following the initial report by Cohen et al. (1997b) that inositol was anxiolytic in the elevated plus maze model of anxiety, the effect of chronic intraperitoneal and chronic dietary inositol administration in rats was tested in four experiments. There was a significant increase in closed arm and total arm entries following chronic injection of inositol, but no effect of inositol when it was given chronically in rat chow. Because the first 2 experiments suggested that the mode of drug administration affected the control levels of anxiety (open arm entries and time in open arms) in control groups, the effect of chronic dietary inositol was tested in rats that were exposed to a mild and a more severe form of stress. Chronic saline injections elevated anxiety in the plus maze, which was only marginally affected by chronic dietary inositol. Following 3 weeks administration of 5% dietary inositol rats were pre-exposed to a cat. There was a clear increase in number of entries into open arms, suggesting an anxiolytic effect of inositol.


Long-term surgical and functional outcomes of the intact canal wall technique for middle ear cholesteatoma in the paediatric population.
In this paper, we report the postoperative outcomes in canal wall up procedures with second stage surgery in 40 children undergoing intervention for cholesteatoma of the middle ear. The residuals, recurrences and the hearing results were analysed. All 40 patients had a follow-up of at least five years. Of the 39 patients who underwent two staged surgery, 18 (46.1%) had a residual lesion that was identified and excised during the second surgery. Over a five year follow-up period, there were five (12.5%) patients with recurrences, all belonging to the group in whom a residual cholesteatoma was identified during the second staged surgery. The rate of residual cholesteatoma tends to decrease as age increases. The type of cholesteatoma, acquired or congenital middle ear, were not statistically related to the incidence of residual cholesteatoma. Hearing analysis showed that hearing recovery was excellent with canal wall up procedures and remained stable over five years.


Current Use of Cigarettes in the United States: The Joint Role of Race/Ethnicity and Health Insurance Coverage.
The goal of this study was to assess the joint role of race/ethnicity and a health insurance coverage type (private, Medicare, Medicaid) in current cigarette use among adults in the U.S. Data from the 2019 Tobacco Use Supplement and the 2019 Annual Social and Economic Supplement of the Current Population Survey were merged (n = 39,882). Bivariate associations between each coverage type and smoking prevalence were examined within each of six racial/ethnic groups. A multiple logistic regression model (for the odds of current cigarette use) was estimated to explore the interactions between race/ethnicity and an indicator of each type of coverage among Hispanic, non-Hispanic (NH) Black/African American, and NH White adults. All analyses included survey weights. Results of bivariate analyses indicated that private and Medicare coverage were associated with significantly lower smoking prevalence (compared to no such coverage), while Medicaid coverage was associated with significantly higher smoking prevalence (all p ≤ 0.05). Some of these associations were significant among NH Black/African American and NH White adults (all p ≤ 0.05). The model indicated that the interaction between race/ethnicity and the indicator of private coverage was significant (p = 0.044): private coverage was significantly associated with lower prevalence among NH White adults only (AOR = 0.59, 98.3%, CI = 0.46:0.76). In addition, Medicaid coverage was significantly associated with higher smoking prevalence (overall). The study points to possible racial/ethnic disparities in the quality of smoking-related health care that people with the same type of coverage receive and possible underutilization of health care services even among adults with health insurance coverage, especially among communities of color and Medicaid enrollees.


Application of quantitative real-time PCR for quantification of Rhodococcus sp. EH831 in a polyurethane biofilter.
Rhodococcus sp. EH831 is a microbial species that can degrade volatile organic compounds. We optimized a method for monitoring quantitative real-time PCR (qRT-PCR) of EH831 that was incorporated into a polyurethane (PU) biofilter. When the genomic DNA of EH831 was directly extracted from a PU sample with immobilized EH831, the recovery efficiency was very low due to DNA absorption into the PU. DNA amplification during PCR was also inhibited by PU impurities. Therefore, a pre-treatment step was necessary. We successfully recovered cells from the PU by squeezing the matrix, adding sterilized water, and vortexing. The recovery efficiency ranged from 105 to 144%, and there was no statistically significant difference. We designed a novel TaqMan probe for EH831 and demonstrated its high specificity for EH831. The detection range for EH831 was 10(5)-10(11) CFU ml(-1). The method described in this study can be used to investigate the relationship between quantitative analysis of Rhodococcus sp. EH831 and PU biofilter performance.


Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): III. Emotional dysfunction superspectrum.
The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and across clinicians. This paper reviews evidence on the validity and utility of the internalizing and somatoform spectra of HiTOP, which together provide support for an emotional dysfunction superspectrum. These spectra are composed of homogeneous symptom and maladaptive trait dimensions currently subsumed within multiple diagnostic classes, including depressive, anxiety, trauma-related, eating, bipolar, and somatic symptom disorders, as well as sexual dysfunction and aspects of personality disorders. Dimensions falling within the emotional dysfunction superspectrum are broadly linked to individual differences in negative affect/neuroticism. Extensive evidence establishes that dimensions falling within the superspectrum share genetic diatheses, environmental risk factors, cognitive and affective difficulties, neural substrates and biomarkers, childhood temperamental antecedents, and treatment response. The structure of these validators mirrors the quantitative structure of the superspectrum, with some correlates more specific to internalizing or somatoform conditions, and others common to both, thereby underlining the hierarchical structure of the domain. Compared to traditional diagnoses, the internalizing and somatoform spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and greater clinical applicability. Validated measures are currently available to implement the HiTOP system in practice, which can make diagnostic classification more useful, both in research and in the clinic.


Modelling the experimental electron density: only the synergy of various approaches can tackle the new challenges.
Electron density is a fundamental quantity that enables understanding of the chemical bonding in a molecule or in a solid and the chemical/physical property of a material. Because electrons have a charge and a spin, two kinds of electron densities are available. Moreover, because electron distribution can be described in momentum or in position space, charge and spin density have two definitions and they can be observed through Bragg (for the position space) or Compton (for the momentum space) diffraction experiments, using X-rays (charge density) or polarized neutrons (spin density). In recent years, we have witnessed many advances in this field, stimulated by the increased power of experimental techniques. However, an accurate modelling is still necessary to determine the desired functions from the acquired data. The improved accuracy of measurements and the possibility to combine information from different experimental techniques require even more flexibility of the models. In this short review, we analyse some of the most important topics that have emerged in the recent literature, especially the most thought-provoking at the recent IUCr general meeting in Montreal.


Human DAZL1 encodes a candidate fertility factor in women that localizes to the prenatal and postnatal germ cells.
The human DAZ (Deleted in AZoospermia) gene family contains a cluster of DAZ genes on the Y chromosome and a single autosomal homologue, DAZL1 (DAZ-Like) that maps to chromosome 3p24. Although the role of the Y chromosome gene family in determining fertility and the expression of the gene family has been well explored in men, little is known of the role of the DAZL1 gene in determining the fertility of women. In mice, loss of function of the homologue of DAZL1 results in the loss of male and female germ cells. In mice, Dazl1 protein is localized to prenatal and postnatal follicles. Here we demonstrate using two antisera that recognize human DAZL1 that the protein is expressed embryonically in germ cells of girls and in mature oocytes. This pattern of expression suggests that the DAZL1 gene is a candidate fertility factor in women and that it would be appropriate to search for mutations in the DAZL1 gene in peripheral blood DNA from women with primary amenorrhoea or premature ovarian failure.


N-truncated Abeta starting with position four: early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody.
The amyloid hypothesis in Alzheimer disease (AD) considers amyloid β peptide (Aβ) deposition causative in triggering down-stream events like neurofibrillary tangles, cell loss, vascular damage and memory decline. In the past years N-truncated Aβ peptides especially N-truncated pyroglutamate AβpE3-42 have been extensively studied. Together with full-length Aβ1-42 and Aβ1-40, N-truncated AβpE3-42 and Aβ4-42 are major variants in AD brain. Although Aβ4-42 has been known for a much longer time, there is a lack of studies addressing the question whether AβpE3-42 or Aβ4-42 may precede the other in Alzheimer's disease pathology. Using different Aβ antibodies specific for the different N-termini of N-truncated Aβ, we discovered that Aβ4-x preceded AβpE3-x intraneuronal accumulation in a transgenic mouse model for AD prior to plaque formation. The novel Aβ4-x immunoreactive antibody NT4X-167 detected high molecular weight aggregates derived from N-truncated Aβ species. While NT4X-167 significantly rescued Aβ4-42 toxicity in vitro no beneficial effect was observed against Aβ1-42 or AβpE3-42 toxicity. Phenylalanine at position four of Aβ was imperative for antibody binding, because its replacement with alanine or proline completely prevented binding. Although amyloid plaques were observed using NT4X-167 in 5XFAD transgenic mice, it barely reacted with plaques in the brain of sporadic AD patients and familial cases with the Arctic, Swedish and the presenilin-1 PS1Δ9 mutation. A consistent staining was observed in blood vessels in all AD cases with cerebral amyloid angiopathy. There was no cross-reactivity with other aggregates typical for other common neurodegenerative diseases showing that NT4X-167 staining is specific for AD. Aβ4-x precedes AβpE3-x in the well accepted 5XFAD AD mouse model underlining the significance of N-truncated species in AD pathology. NT4X-167 therefore is the first antibody reacting with Aβ4-x and represents a novel tool in Alzheimer research.


Micropatterning of poly(dimethylsiloxane) using a photoresist lift-off technique for selective electrical insulation of microelectrode arrays.
A poly(dimethylsiloxane) (PDMS) patterning method based on a photoresist lift-off technique to make an electrical insulation layer with selective openings is presented. The method enables creating PDMS patterns with small features and various thicknesses without any limitation in the designs and without the need for complicated processes or expensive equipments. Patterned PDMS layers were created by spin-coating liquid phase PDMS on top of a substrate having sacrificial photoresist patterns, followed by a photoresist lift-off process. The thickness of the patterned PDMS layers could be accurately controlled (6.5-24 µm) by adjusting processing parameters such as PDMS spin-coating speeds, PDMS dilution ratios, and sacrificial photoresist thicknesses. PDMS features as small as 15 µm were successfully patterned and the effects of each processing parameter on the final patterns were investigated. Electrical resistance tests between adjacent electrodes with and without the insulation layer showed that the patterned PDMS layer functions properly as an electrical insulation layer. Biocompatibility of the patterned PDMS layer was confirmed by culturing primary neuron cells on top of the layer for up to two weeks. An extensive neuronal network was successfully formed, showing that this PDMS patterning method can be applied to various biosensing microdevices. The utility of this fabrication method was further demonstrated by successfully creating a patterned electrical insulation layer on flexible substrates containing multi-electrode arrays.


A Constitutively Active Cytokinin Receptor Variant Increases Cambial Activity and Stem Growth in Poplar.
The cambial meristem is responsible for bark and wood formation in woody plants. The activity of the cambial meristem is controlled by various factors; one of them is the plant hormone cytokinin. Here, we have explored different approaches to genetically engineering cambial activity in poplar plants by the ectopic expression of a cytokinin biosynthesis gene with enhanced activity (named ROCK4) or of a gene encoding a constitutively active cytokinin receptor variant (ROCK3). Both genes are derived from Arabidopsis thaliana and were expressed in poplar trees under the control of their own promoter or the cambium-specific pHB8 promoter. pIPT3:ROCK4- and pHB8:ROCK4-expressing plants were smaller than wild-type plants and formed more lateral branches; pHB8:ROCK4 transgenic plants additionally showed an increased stem diameter. In contrast, pAHK3:ROCK3- and pHB8:ROCK3-expressing plants grew taller than wild type without an altered branching pattern and formed more cambial cells, leading to increased radial stem growth. The effectivity of ROCK3 when expressed in either secondary phloem cells or in cambial cells is consistent with a dual, tissue-autonomous and non-autonomous activity of cytokinin in regulating cambial activity. We propose ROCK3 as a novel gene to enhance biomass formation in woody plants.


Mass spectrometric determination of selenenylsulfide linkages in rat selenoprotein P.
The reversible formation of a selenenylsulfide linkage in mammalian thioredoxin reductase was identified as having a key role in its activity. Identification of selenenylsulfide and/or diselenide linkages is therefore critical to the determination of the structure and function of selenoproteins. A selenopeptide, (298)SGSAITUQCAENLPSLCSUQGLFAEEK(324) (U=selenocysteine), was isolated from a tryptic digest of rat selenoprotein P. Its two cysteine residues and two selenocysteine (Sec) residues were determined to be present in oxidized form by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The selenopeptide was subjected to partial reduction by dithiothreitol with immediate alkylation by iodoacetamide. This process was monitored by MALDI-TOFMS to determine the number of alkylations that had taken place. The partially reduced and alkylated peptides were then analyzed by nano-electrospray ionization tandem mass spectrometry and the results indicated that selenenylsulfide linkages Sec304-Cys314 and Cys306-Sec316 were present. It is concluded that selenoprotein P contains these two selenenylsulfide bonds.


Ribonucleotides embedded in template DNA impair mitochondrial RNA polymerase progression.
Human mitochondria lack ribonucleotide excision repair pathways, causing misincorporated ribonucleotides (rNMPs) to remain embedded in the mitochondrial genome. Previous studies have demonstrated that human mitochondrial DNA polymerase γ can bypass a single rNMP, but that longer stretches of rNMPs present an obstacle to mitochondrial DNA replication. Whether embedded rNMPs also affect mitochondrial transcription has not been addressed. Here we demonstrate that mitochondrial RNA polymerase elongation activity is affected by a single, embedded rNMP in the template strand. The effect is aggravated at stretches with two or more consecutive rNMPs in a row and cannot be overcome by addition of the mitochondrial transcription elongation factor TEFM. Our findings lead us to suggest that impaired transcription may be of functional relevance in genetic disorders associated with imbalanced nucleotide pools and higher levels of embedded rNMPs.


Co-administration of calcium gluconate and magnesium acetate effectively blocks the signs of morphine withdrawal in mice.
The present study was conducted to investigate the effect of oral administration of calcium gluconate and magnesium acetate on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of increasing doses of morphine. Mice were observed for 30 minutes for the withdrawal signs (jumping or standing events, diarrhea, piloerection, tremor and ptosis). Separate oral administration of magnesium (50, 75 and 100 mg/kg) and calcium (500, 750 and 1,000 mg/kg) significantly decreased the jumping, without affecting standing in animals withdrawn from morphine. Co-administration of magnesium (at a fixed dose of 100 mg/kg) and calcium (at a range of doses from 250 to 1,000 mg/kg) resulted in a significant reduction in jumping and standing events (P<0.05). In a similar fashion, the qualitative signs of withdrawal were also reduced when the above combination of calcium and magnesium was administered. Co-administration of calcium/magnesium at 500/50, 750/75 and 1,000/100 mg/kg significantly reduced the number of jumps in morphine-dependent animals without affecting the number of standing events. This study demonstrates the potential activity of the co-administration calcium and magnesium in preventing the signs associated with morphine withdrawal syndrome.


Fast Water Relaxation through One-Dimensional Channels by Rapid Energy Transfer.
Water in carbon nanotubes is surrounded by hydrophobic carbon surfaces and shows anomalous structural and fast transport properties. However, the dynamics of water in hydrophobic nanospaces is only phenomenologically understood. In this study, water dynamics in hydrophobic carbon nanotubes is evaluated based on water relaxation using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Extremely fast relaxation (0.001 s) of water confined in carbon nanotubes of 1 nm in diameter on average is observed; the relaxation times of water confined in carbon nanotubes with an average diameter of 2 nm (0.40 s) is similar to that of bulk water (0.44 s). The extremely fast relaxation time of water confined in carbon nanotubes with an average diameter of 1 nm is a result of frequent energy transfer between water and carbon surfaces. Water relaxation in carbon nanotubes of average diameter 2 nm is slow because of the limited number of collisions between water molecules. The dynamics of interfacial water can therefore be controlled by varying the size of the hydrophobic nanospace.


Fetomodulin: marker surface protein of fetal development which is modulatable by cyclic AMP.
A novel cell surface marker of fetal development was identified in both in vivo and in vitro systems of the mouse using monoclonal antibodies against a glycoprotein of an apparent size of 133,000 Da. Two independent clones of hybridomas were isolated by fusing murine myeloma cells, NS-1, with spleen cells of a rat which was immunized with murine 3T3 fibroblast. The analysis of molecular size and tryptic peptides of the immunoprecipitate indicated that fibroblast and putative parietal endoderm cells, which were derived by induced differentiation of F9 embryonal carcinoma cells with retinoic acid and cyclic AMP, expressed apparently the same protein. Undifferentiated F9 cells and F9 cells which were treated with retinoic acid or cyclic AMP alone had little or no immunoprecipitable proteins. Analogously, parietal endoderm of in vivo embryos tested positive for this protein but visceral endoderm and embryonic ectoderm did not. The amount of this surface protein was increased in fibroblast and differentiated F9 cells by elevation of intracellular cyclic AMP concentrations. These results are consonant with a hypothesis that this surface protein plays a role in fetal development via a quantitative modulation by cyclic AMP.


Evolution, selection and isolation: a genomic view of speciation in fungal plant pathogens.
895 I. 895 II. 896 III. 898 IV. 900 V. 902 VI. 904 VII. 905 905 References 905 SUMMARY: Speciation of fungal plant pathogens has been associated with host jumps, host domestication, clonal divergence, and hybridization. Although we have substantial insight into the speciation histories of several important plant pathogens, we still know very little about the underlying genetics of reproductive isolation. Studies in Saccharomyces cerevisiae, Neurospora crassa, and nonfungal model systems illustrate that reproductive barriers can evolve by different mechanisms, including genetic incompatibilities between neutral and adaptive substitutions, reinforcement selection, and chromosomal rearrangements. Advances in genome sequencing and sequence analyses provide a new framework to identify those traits that have driven the divergence of populations or caused reproductive isolation between species of fungal plant pathogens. These traits can be recognized based on signatures of strong divergent selection between species or through the association of allelic combination conferring hybrid inferiority. Comparative genome analyses also provide information about the contribution of genome rearrangements to speciation. This is particularly relevant for species of fungal pathogens with extreme levels of genomic rearrangements and within-species genome plasticity.


Use of the pulsed infrared diode laser (904 nm) in the treatment of alopecia areata.
Alopecia areata is a rapid and complete loss of hair in one or several patches, usually on the scalp, affecting both males and females equally. It is thought to be an autoimmune disease which is treated with different modalities with variable success. Laser treatment of different wavelengths has been used in the management of this problem. To study the effect of the pulsed infrared diode laser (904 nm) in the treatment of alopecia areata.Methods. Sixteen patients with 34 resistant patches that had not responded to different treatment modalities for alopecia areata were enrolled in this study. In patients with multiple patches, one patch was left as a control for comparison. Patients were treated on a four-session basis, once a week, with a pulsed diode laser (904 nm) at a pulse rate of 40/s. A photograph was taken of each patient before and after treatment. The treated patients were 11 males (68.75%) and five females (31.25%). Their ages ranged between 4 and 50 years with a mean of 26.6+/-SD of +/-13.8, and the durations of their disease were between 12 months and 6 years with a mean of 13.43+/-SD of +/-18.34. Regrowth of hair was observed in 32 patches (94%), while only two patches (6%) failed to show any response. No regrowth of hair was observed in the control patches. The regrowth of hair appeared as terminal hair with its original color in 29 patches (90.6%), while three patches (9.4%) appeared as a white villous hair. In patients who showed response, the response was detected as early as 1 week after the first session in 24 patches (75%), while eight patients (25%) started to show response from the second session. The pulsed infrared diode laser is an effective mode of therapy with a high success rate for resistant patches of alopecia areata.


Tree growth and water-use in hyper-arid Acacia occurs during the hottest and driest season.
Drought-induced tree mortality has been recently increasing and is expected to increase further under warming climate. Conversely, tree species that survive under arid conditions might provide vital information on successful drought resistance strategies. Although Acacia (Vachellia) species dominate many of the globe's deserts, little is known about their growth dynamics and water-use in situ. Stem diameter dynamics, leaf phenology, and sap flow were monitored during 3 consecutive years in five Acacia raddiana trees and five Acacia tortilis trees in the Arid Arava Valley, southern Israel (annual precipitation 20-70 mm, restricted to October-May). We hypothesized that stem growth and other tree activities are synchronized with, and limited to single rainfall or flashflood events. Unexpectedly, cambial growth of both Acacia species was arrested during the wet season, and occurred during most of the dry season, coinciding with maximum daily temperatures as high as 45 °C and vapor pressure deficit of up to 9 kPa. Summer growth was correlated with peak sap flow in June, with almost year-round activity and foliage cover. To the best of our knowledge, these are the harshest drought conditions ever documented permitting cambial growth. These findings point to the possibility that summer cambial growth in Acacia under hyper-arid conditions relies on concurrent leaf gas exchange, which is in turn permitted by access to deep soil water. Soil water can support low-density tree populations despite heat and drought, as long as recharge is kept above a minimum threshold.