Toxic effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal on the reproduction of female mice.
Cigarette smoke can affect female reproductive health by causing follicle destruction and oocyte dysfunction. Third-hand smoke has received increasing attention as a public health issue. However, the effects of third-hand smoke on the female reproductive system, particularly the ovaries, remain unclear. 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA) can be used as a biomarker of third-hand smoke. We studied the in vivo toxic effects of NNA on mice ovaries and offspring development. Three-week-old premature female mice were exposed to NNA at two different concentrations (0.075 μg/kg and 0.15 μg/kg body weight) and tap water (blank control) and diluted dimethylsulfoxide (solvent control) for 30 days. We found that oral administration of NNA (0.075 μg/kg and 0.15 μg/kg) significantly reduced ovary weight (the 0.15 μg/kg group was reduced to 18.69% ± 0.89%) and ovarian follicle number (reduced by about 30%) (p < 0.05). Consumption of 0.15 μg/kg NNA reduced the survival rate of superovulated oocytes from 91.36% to 60.55% (p < 0.05). In addition, treated female mice in each group were mated with normal male mice to observe the effects of NNA on the F1 offspring, and during mating and lactation, all groups were given tap water. Two different concentrations of NNA exposure also significantly reduced body weight and impaired ear opening, tooth eruption and eye opening in F1 offspring, especially those exposed to 0.15 μg/kg NNA (p < 0.05). Our study suggested that NNA exposure had toxic effects on the reproductive health of female mice and their offspring. The results obtained may help evaluate the risks of third-hand smoke to women's reproductive health and to the health of their offspring.


1,4-Difluoro-2,5-dimethoxybenzene as a precursor for iterative double benzyne-furan Diels-Alder reactions.
[reaction: see text] The use of 1,4-difluoro-2,5-dimethoxybenzene as a novel precursor for iterative two-directional benzyne-furan Diels-Alder reactions, using a range of 2- and 3-substituted furans, is reported. Substituted oxabenzonorbornadienes were synthesized following the initial Diels-Alder reaction, which upon ring opening under acidic conditions gave substituted naphthol derivatives. Highly substituted anthracenols were generated in the second benzyne-furan Diels-Alder reaction following acid-catalyzed isomerization of the cycloadducts.


In Arabidopsis, the spatial and dynamic organization of the endoplasmic reticulum and Golgi apparatus is influenced by the integrity of the C-terminal domain of RHD3, a non-essential GTPase.
The mechanisms underlying the organization and dynamics of plant endomembranes are largely unknown. Arabidopsis RHD3, a distant member of the dynamin superfamily, has recently been implicated in plant ER morphology and Golgi movement through analyses of dominant-negative mutants of the putative GTPase domain in a heterologous system. Whether RHD3 is indispensable for ER architecture and what role regions other than the putative GTPase domain play in RHD3 function are unanswered questions. Here we characterized an EMS mutant, gom8, with disrupted Golgi movement and positioning and compromised ER shape and dynamics. gom8 mapped to a missense mutation in the RHD3 hairpin loop domain, causing accumulation of the mutant protein into large structures, a markedly different distribution compared with wild-type RHD3 over the ER network. Despite the GOM8 distribution, tubules fused in the peripheral ER of the gom8 mutant. These data imply that integrity of the hairpin region is important for the subcellular distribution of RHD3, and that reduced availability of RHD3 over the ER can cause ER morphology defects, but does not prevent peripheral fusion between tubules. This was confirmed by evidence that gom8 was phenocopied in an RHD3 null background. Furthermore, we established that the region encompassing the RHD3 hairpin domain and the C-terminal cytosolic domain is necessary for RHD3 function. We conclude that RHD3 is important in ER morphology, but is dispensable for peripheral ER tubulation in an endogenous context, and that its activity relies on the C-terminal region in addition to the GTPase domain.


Mechanism of Rh prophylaxis: an experimental study on specificity of immunosuppression.
The mechanism by which Rh immunization is prevented by IgG anti-D was investigated by studying the specificity of immunosuppression. 62 D-negative Kell(K)-negative male volunteers were given two successive stimuli of 1 ml D-positive K-positive red cells. Thirty-one of the volunteers were also given 13-14 mug of IgG anti-K immediately after each stimulus, the others acting as controls. Anti-D developed in 11 of the 31 controls and in one of the 31 volunteers who had received anti-K. This marked suppression of the anti-D response by IgG anti-K was accompanied by the rapid clearance of the injected red cells to the spleen. This shows that the predominant mechanism that must be operating when IgG anti-D prevents Rh immunization is not antigen specific but is one that must involve the whole red cell, probably through destruction within splenic macrophages.


Metabolic syndrome in overweight or obese children and adolescents based on own material Abstract Key words.
Aim: To assess the prevalence of metabolic syndrome (MS) components in overweight or obese children and adolescents, as well as analyze the risk factors of its occurrence. Material and methods: The study was conducted in a group of 70 children and adolescents aged 5-18 hospitalized in the Department of Gastroenterology, Allergology and Pediatrics, Polish Mother's Memorial Hospital - Research Institute in Lodz (Poland) based on the results of medical histories, physical examination, biochemical investigation, and calculation of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Results: MS was diagnosed in 14 children (20%). The most common abnormalities besides obesity included: decreased High Density Lipoprotein Cholesterol (HDL-C) levels (n=13, 92.9%), increased triglycerides (TG) concentrations (n=10, 71.4%) and arterial hypertension (n=10, 71,4%). Among all the children, insulin resistance was diagnosed in 29 subjects (41.4%). The results of univariate logistic regression showed that the occurrence of lipid disorders, obesity, hypertension and diabetes in their parents, as well as the duration of pregnancy, birth weight, or breastfeeding were not associated with the risk of MS development in the subjects (p>0.05). However, in the study group, 92.9% of subjects had one or more particular risk factor for MS development. Conclusions: Besides visceral obesity, lipid disorders were the most frequently observed components of MS in the subjects analyzed, which may have prognostic significance. The occurrence of one or more MS risk factors in almost all of the children studied indicates the increased risk of cardiovascular diseases in the studied group in the future.


[A case of bone lipoma of the femur head].
A case of intra-osseous lipoma of the upper femur is reported. A review of the literature shows that this lesion is rare, only about 33 cases having been published. The radiological appearance is that of a fibroma. The diagnosis is made at the time of surgery which reveals the presence of fat in a large cavity. Curettage and bone graft resulted in healing.


Prediction of Preventive Behaviors of the Needlestick Injuries during Surgery among Operating Room Personnel: Application of the Health Belief Model.
Operating room personnel are at high risk of needlestick injuries (NSIs) and exposure to blood and body fluids. To investigate the predictors of NSIs preventive behaviors during surgery among operating room personnel based on a health belief model (HBM). This cross-sectional study was conducted on 128 operating room personnel in Hamadan, western Iran. Participants were selected, by census sampling, from teaching hospitals, completed a self-reported questionnaire including demographic characteristics, knowledge and HBM constructs. The levels of knowledge and perceived self-efficacy for the NSIs preventive behaviors among operating room personnel were not satisfactory. However, the levels of perceived benefits, susceptibility and severity were reported to be relatively good. The results showed that the perceived susceptibility (β ‑0.627) and cues to action (β 0.695) were the most important predictors of the NSIs preventive behaviors. The framework of the HBM is useful to predict the NSIs preventive behaviors among operating room personnel.


Pre-anthropocene mercury residues in North American freshwater fish.
Mercury (Hg) has been entering the environment from both natural and anthropogenic sources for millennia, and humans have been influencing its environmental transport and fate from well before the Industrial Revolution. Exposure to Hg (as neurotoxic monomethylmercury [MeHg]) occurs primarily through consumption of finfish, shellfish, and marine mammals, and regulatory limits for MeHg concentrations in fish tissue have steadily decreased as information on its health impacts has become available. These facts prompted us to consider 2 questions: 1) What might the MeHg levels in fish tissue have been in the pre-Anthropocene, before significant human impacts on the environment? and 2) How would these pre-Anthropocene levels have compared with current regulatory criteria for MeHg residues in fish tissue? We addressed the first question by estimating pre-Anthropocene concentrations of MeHg in the tissues of prey and predatory fish with an integrated Hg speciation, transport, fate, and food web model (SERAFM), using estimated Hg concentrations in soil, sediment, and atmospheric deposition before the onset of significant human activity (i.e., ≤2000 BCE). Model results show MeHg residues in fish varying depending on the characteristics of the modeled water body, which suggests that Hg in fish tissue is best considered at the scale of individual watersheds or water bodies. We addressed the second question by comparing these model estimates with current regulatory criteria and found that MeHg residues in predatory (but not prey) fish could have approached or exceeded these criteria in some water bodies during the pre-Anthropocene. This suggests that the possibility of naturally occurring levels of Hg in fish below which it is not possible to descend, regardless of where those levels stand with respect to current regulatory limits. Risk management decisions made under these circumstances have the potential to be ineffectual, frustrating, and costly for decision makers and stakeholders alike, suggesting the need for regulatory flexibility when addressing the issue of Hg in fish.


Non-invasive monitoring of hydraulic surge propagation in a wounded tobacco plant.
When a plant is wounded, a rapid hydraulic surge, acting probably as a systemic signal, spreads from the site of injury throughout the plant and leads to small transient deformation of tissues. So far, the propagation of hydraulic surge has been monitored by contact and thus potentially invasive methods. Here we present a non-invasive optical method, which allows simultaneous monitoring of micrometric shift of two opposite stem margins. The usefulness of this method was demonstrated by the measurement of the hydraulic surge propagation in a tobacco (Nicotiana tabacum (L.) cv. Samsun) after burning of its upper leaf. We have observed transient narrowing the stem below the burned leaf, which started within a few minutes after local burning. The comparison of the shift of the stem margin following vascular trace of the burned leaf and the margin on the opposite side of the stem has revealed that the stem deformation is highly asymmetric. This optical method represents a novel tool to investigate the mechanism of systemic response of plants to local damage. Our results points out the complexity of the relationship between hydraulic surge propagation and stem deformation.


Blood Neurofilament Light Chain in Genetic Ataxia: A Meta-Analysis.
No comprehensive meta-analysis has ever been performed to assess the value of neurofilament light chain (NfL) as a biomarker in genetic ataxia. We conducted a meta-analysis to summarize NfL concentration and evaluate its utility as a biomarker in genetic ataxia. Studies were included if they reported NfL concentration of genetic ataxia. We used log (mean ± SD) NfL to describe mean raw value of NfL. The effect size of NfL between genetic ataxia and healthy controls (HC) was expressed by mean difference. Correlation between NfL and disease severity was calculated. We identified 11 studies of 624 HC and 1006 patients, here referred to as spinocerebellar ataxia (SCA1, 2, 3, 6, and 7), Friedreich ataxia (FRDA), and ataxia telangiectasia (A-T). The concentration of blood NfL (bNfL) elevated with proximity to expected onset, and progressively increased from asymptomatic to preclinical to clinical stage in SCA3. Compared with HC, bNfL levels were significantly higher in SCA1, 2, 3, and 7, FRDA, as well as A-T, and the difference increased with the advancing disease in SCA3. bNfL levels correlated with disease severity in SCA3. There was a significant correlation between bNfL and longitudinal progression in SCA3. Additionally, bNfL increased with age in HC, yet this is probably masked by higher disease-related effects on bNfL in genetic ataxia. bNfL can be used as a potential biomarker to predict disease onset, severity, and progression of genetic ataxia. Reference-value setting of bNfL should be divided according to age. © 2021 International Parkinson and Movement Disorder Society.


[Treatment of scalp psoriasis: review of the evidence and Delphi consensus of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology].
Scalp lesions are common in psoriasis and difficult to treat. Scientific evidence on the topic is scant and fragmentary, especially with respect to long-term treatment. This consensus statement is based on a critical assessment of the results of a MEDLINE search for clinical trials of the efficacy and safety of therapies used to treat scalp psoriasis. The recommendations were developed by an expert panel using the Delphi process to reach a consensus and then ratified by the members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. The recommended induction therapy for scalp psoriasis is either a topical corticosteroid or a topical treatment combining calcipotriol and betamethasone. The choice of an appropriate vehicle is crucial in improving effectiveness and patient adherence to treatment. The only formulations that have been studied in the long-term treatment of scalp psoriasis are a combination of calcipotriol and betamethasone in gel and calcipotriol alone in solution.


Immunosuppressive effects of Prevotella intermedia on in vitro human lymphocyte activation.
In this study, we have assessed four strains of Prevotella intermedia, isolated from periodontally involved lesions, for their ability to inhibit lymphocyte functions. All four strains were found to cause a dose-dependent inhibition of B- and T-cell proliferation in response to mitogens and antigens. This was reflected in altered DNA, RNA, and protein syntheses. Furthermore, P. intermedia appeared to affect the early stages of cell activation. This was ascertained by kinetic analysis in which it was determined that the extract had to be present during the first 24 h of incubation to cause suppression. Moreover, direct assessment of the early stages of cell activation indicated that release of cytokines and expression of the interleukin 2 receptor and CD69 on T cells were inhibited by P. intermedia sonic extracts. Finally, preliminary characterization of the immunosuppressive agent indicates that it has a molecular mass of approximately 50 kDa and is heat labile. It has been proposed that impaired host defense may play a pivotal role in the pathogenesis of many infections. The data presented in this paper suggest that microbially mediated immunosuppression may contribute to the pathogenesis of periodontal disease by altering the nature and consequences of host-parasite interactions.


Inhibition of spontaneous beta 2-adrenergic activation rescues beta 1-adrenergic contractile response in cardiomyocytes overexpressing beta 2-adrenoceptor.
Cardiac-specific overexpression of the human beta(2)-adrenergic receptor (AR) in transgenic mice (TG4) enhances basal cardiac function due to ligand-independent spontaneous beta(2)-AR activation. However, agonist-mediated stimulation of either beta(1)-AR or beta(2)-AR fails to further enhance contractility in TG4 ventricular myocytes. Although the lack of beta(2)-AR response has been ascribed to an efficient coupling of the receptor to pertussis toxin-sensitive G(i) proteins in addition to G(s), the contractile response to beta(1)-AR stimulation by norepinephrine and an alpha(1)-adrenergic antagonist prazosin is not restored by pertussis toxin treatment despite a G(i) protein elevation of 1.7-fold in TG4 hearts. Since beta-adrenergic receptor kinase, betaARK1, activity remains unaltered, the unresponsiveness of beta(1)-AR is not caused by betaARK1-mediated receptor desensitization. In contrast, pre-incubation of cells with anti-adrenergic reagents such as muscarinic receptor agonist, carbachol (10(-5)m), or a beta(2)-AR inverse agonist, ICI 118,551 (5 x 10(-7)m), to abolish spontaneous beta(2)-AR signaling, both reduce the base-line cAMP and contractility and, surprisingly, restore the beta(1)-AR contractile response. The "rescued" contractile response is completely reversed by a beta(1)-AR antagonist, CGP 20712A. Furthermore, these results from the transgenic animals are corroborated by in vitro acute gene manipulation in cultured wild type adult mouse ventricular myocytes. Adenovirus-directed overexpression of the human beta(2)-AR results in elevated base-line cAMP and contraction associated with a marked attenuation of beta(1)-AR response; carbachol pretreatment fully revives the diminished beta(1)-AR contractile response. Thus, we conclude that constitutive beta(2)-AR activation induces a heterologous desensitization of beta(1)-ARs independent of betaARK1 and G(i) proteins; suppression of the constitutive beta(2)-AR signaling by either a beta(2)-AR inverse agonist or stimulation of the muscarinic receptor rescues the beta(1)-ARs from desensitization, permitting agonist-induced contractile response.


Searching the schizophrenic brain for temporal lobe deficits: a systematic review and meta-analysis.
Several empirical studies have found temporal lobe impairments in many patients with schizophrenia. The strength and consistency of this evidence, however, has not been evaluated and synthesized quantitatively. Hence, we ask to what extent are temporal cortices really defective in schizophrenia? Meta-analytical methods were used to determine the magnitude of evidence in support of structural and physiological temporal-hippocampal system deficits in schizophrenia. We report effect sizes from studies since 1980 that used structural (CT, MRI) and functional (SPECT, PET) neuroimaging methods. Both structural and functional imaging literatures are distinguished by heterogeneity whereby most patients show normative temporal function and structure, a minority shows diminished values and some patients demonstrate augmented function and structure rather than a deficit. The findings are hard to incorporate within single disease models that propose major involvement of the temporal system in schizophrenia, at least at the degree of resolution obtained with current imaging technology.


A full genome scan for age-related maculopathy.
Age-related macular degeneration or age-related maculopathy (ARM) is a major public health issue, as it is the leading cause of irreversible vision loss in the elderly in the Western world. Using three diagnostic models, we have genotyped markers in 16 plausible candidate regions and have carried out a genome-wide screen for ARM susceptibility loci. A panel of 225 ARM families comprising up to 212 affected sib pairs was genotyped for 386 markers. Under our most stringent diagnostic model, the regions with the strongest evidence of linkage were on chromosome 9 near D9S301 and on 10 near D10S1230, with peak multipoint heterogeneity LOD scores (HLOD) of 1.87 and 1. 42 and peak GeneHunter-Plus non-parametric LOD scores (GHP LOD) of 1. 69 and 1.83. After expanding our initial set of families to 364 ARM families with up to 329 affected sib pairs, the linkage signal on chromosome 9 vanished, while the chromosome 10 signal decreased to a GHP LOD of about 1.0, with a SimIBD P -value of 0.008 under the broadest diagnostic model with marker D10S1236. After error filtration, the GHP LOD increased to 1.27 under our most stringent model and 1.42 under our broadest model, peaking near D10S1236. This peak was seen consistently across all three diagnostic models. Our analyses also excluded up to nine different candidate regions and identified a few other regions of potential linkage, suitable for further studies. Of particular interest was the region on chromosome 5 near D5S1480, where a reasonable candidate gene, glutathione peroxidase 3, resides.


Integrative biology for integrative medicine: A complete approach.
India's AYUSH systems of medicine, Ayurveda, Yoga and Naturopathy, Unani, Siddha and Sowa-Rigpa, and Homeopathy, use natural self-healing abilities of body and mind. Their ways to treat non-communicable diseases reduce use of modern drugs with their side-effects. Scientific acceptance requires them to be explained from a modern biological perspective. This paper indicates how to achieve such an integrative approach, using aspects of biology not yet taught in medical schools. A new, 'Sandwich Model' of biology is introduced that includes holistic epigenetic regulation; also, complexity biology's concept of self-organized criticality; a systems treatment of organism function from Ayurveda; and Ayurveda's six stages of etiology, Shadkriyakala. Molecular biology is upgraded by the sandwich model's layer of epigenetics, leading to a new, scientific definition of health as optimized regulation. Fractal Physiology then expands this to explain self-healing, used in all AYUSH systems. Ayurveda contributes in two ways: its systems approach yields a holistic understanding of organism functioning, while Shadkriyakala improves our understanding of pathophysiology. These additions create an integrative biology; modern biology expands to include AYUSH systems' concepts. It provides a scientific basis for India's plan for integrative medical education, with AYUSH systems treated as equal to modern medicine.


Passive properties and membrane currents of canine ventricular myocytes.
The membrane potential and membrane currents of single canine ventricular myocytes were studied using either single microelectrodes or suction pipettes. The myocytes displayed passive membrane properties and an action potential configuration similar to those described for multicellular dog ventricular tissue. As for other cardiac cells, in canine ventricular myocytes: (a) an inward rectifier current plays an important role in determining the resting membrane potential and repolarization rate; (b) a tetrodotoxin-sensitive Na current helps maintain the action potential plateau; and (c) the Ca current has fast kinetics and a large amplitude. Unexpected findings were the following: (a) in approximately half of the myocytes, there is a transient outward current composed of two components, one blocked by 4-aminopyridine and the other by Mn or caffeine; (b) there is clearly a time-dependent outward current (delayed rectifier current) that contributes to repolarization; and (c) the relationship of maximum upstroke velocity of phase 0 to membrane potential is more positive and steeper than that observed in cardiac tissues from Purkinje fibers.


Crohn's disease.
Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria. In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty.


A novel but frequent variant in LPA KIV-2 is associated with a pronounced Lp(a) and cardiovascular risk reduction.
Lp(a) concentrations represent a major cardiovascular risk factor and are almost entirely controlled by one single locus (LPA). However, many genetic factors in LPA governing the enormous variance of Lp(a) levels are still unknown. Since up to 70% of the LPA coding sequence are located in a difficult to access hypervariable copy number variation named KIV-2, we hypothesized that it may contain novel functional variants with pronounced effects on Lp(a) concentrations. We performed a large scale mutation analysis in the KIV-2 using an extreme phenotype approach. We compiled an discovery set of 123 samples showing discordance between LPA isoform phenotype and Lp(a) concentrations and controls. Using ultra-deep sequencing, we identified a splice site variant (G4925A) in preferential association with the smaller LPA isoforms. Follow-up in a European general population (n = 2892) revealed an exceptionally high carrier frequency of 22.1% in the general population. The variant explains 20.6% of the Lp(a) variance in carriers of low molecular weight (LMW) apo(a) isoforms (P = 5.75e-38) and reduces Lp(a) concentrations by 31.3 mg/dL. Accordingly the odds ratio for cardiovascular disease was reduced from 1.39 [95% confidence interval (CI): 1.17-1.66, P = 1.89e-04] for wildtype LMW individuals to 1.19 [95%CI: 0.92; 1.56, P = 0.19] in LMW individuals who were additionally positive for G4925A. Functional studies point towards a reduction of splicing efficiency by this novel variant. A highly frequent but until now undetected variant in the LPA KIV-2 region is strongly associated with reduced Lp(a) concentrations and reduced cardiovascular risk in LMW individuals.


Quality of life lost due to non-fatal road traffic injuries.
The objective of this paper is to evaluate the effect of a non-fatal road crash on the health-related quality of life of injured people. A new approach based on the cardinalization of categorical Self-Assessed Health valuations is suggested. Health losses have been estimated by using different Time Trade-off and Visual Analogue Scale tariffs, in order to assess the robustness of the results. The methodology is based on the existing literature about treatment effects. Our main contribution focuses on evaluating the loss of health up to 1 year after the non-fatal accident, for those who are non-institutionalized, which aids the appropriate estimation of the aggregated health losses in quality-of-life terms.


Vitamin D, parathyroid hormone, and bone mineral density status in kidney transplant recipients.
Bone disease and bone fractures are common among kidney transplant recipients. The aim of this study was to investigate the prevalence of vitamin D deficiency, hyperparathyroidism, and osteoporosis kidney transplant patients. A total of 113 kidney transplant recipients (58 women and 55 men) were selected consecutively from the transplant clinic between January and April 2010. A serum sample from each patient was analyzed for creatinine, calcium, phosphorus, 25-hydroxyvitamin D, and intact parathyroid hormone levels. Bone mineral density was measured by the dual energy x-ray absorptiometry method and classified according to the classification of the World Health Organization. Risk factors of bone mineral density outcomes were evaluated in univariable and multivariable analyses. Forty-five percent of the patients had vitamin D deficiency and 76.2% had hyperparathyroidism. There was a significant correlation between vitamin D deficiency and high serum parathyroid hormone (P = .04) and serum creatinine levels (P = .001). However, there were no significant associations of serum calcium and phosphorus with vitamin D or parathyroid hormone levels. The osteoporosis and osteopenia were reported in 12.4% and 52.2% of the recipients in the lumbar spine and 45.1% and 36.3% of the patients in the femoral neck, respectively. Multivariable analyses showed that there were significant correlations between patients' age and body mass index and femoral neck osteoporosis. Risk factors for lumbar spine osteoporosis were end-stage renal disease duration, serum calcium, and body mass index. Vitamin D deficiency, hyperparathyroidism, and osteoporosis are very common in our kidney transplant recipients. Early diagnosis and treatment of these abnormalities should be included in the posttransplant follow-up of patients in order to prevent severe bone diseases and bone fractures.


Modification of endoscopic retrograde cholangiopancreatography (ERCP) septic complications by the addition of an antibiotic to the contrast media. Randomized controlled investigation.
We studied the efficacy of gentamicin or placebo to decrease the incidence of septic complications after ERCP in 61 inpatients with possible pancreatic or biliary tract disease. The antibiotic or placebo was added to the Renograffin-60 contrast media and the study was conducted in a randomized controlled fashion. There were 29 patients who received gentamicin and 32 patients who were in the placebo group. No patient received parenteral antibiotic prior to, during, or after the ERCP unless a septic complication developed and each was followed daily with complete blood counts and oral temperatures. The incidence of febrile episodes in the gentamicin group was one (3%). All blood cultures were negative. One patient (3%) in the placebo group developed a febrile episode with subsequent blood cultures growing Escherichia coli. There was no statistical difference in the incidence of septic episodes between the two study groups. The results of this study demonstrate that the incidence of septic complications during ERCP is not modified by the addition of gentamicin to the contrast media.


The Bariatric Quality of Life index: a measure of well-being in obesity surgery patients.
Quality of life (QoL) is considered to be the true measure for the effectiveness of a surgical procedure, but there are only a few validated instruments available for bariatric surgery. Therefore, a new diseasespecific 30-item instrument was created, which was called Bariatric Quality of Life (BQL) questionnaire. To validate the BQL, we studied 133 patients after 4 different types of bariatric surgery. Initially, mean body mass index (BMI) was 47.2 +/-7.6 kg/m2 and mean age was 38.8 +/-11.0 years. At baseline, and 1, 6, and 12 months after surgery, patients filled in the BQL, the SF-12 (Short Form of SF-36 Health Survey), the GIQLI (Gastrointestinal Quality of Life Index), and the BAROS (Bariatric Analysis and Reporting Outcome System). Internal consistency of the BQL was found to be good, with Cronbach's alpha ranging between 0.71 and 0.86. Factor analyses suggested that the BQL included a highly consistent set of QoL items and a second part on co-morbidities and gastrointestinal symptoms. At the 12 months follow-up, the BQL was closely correlated to SF 12 (Pearson's r = 0.86), GIQLI (0.68), BAROS (0.71), and excess weight loss (0.55). Standardized effect sizes over time were larger for the BQL (1.39 and 1.58) than for the other instruments. The BQL questionnaire is a validated instrument ready for clinical use.


Ethnic differences in atrial fibrillation identified using implanted cardiac devices.
Atrial fibrillation (AF) is suggested to be less common among black and Asian individuals, which could reflect bias in symptom reporting and access to care. In the Asymptomatic AF and Stroke Evaluation in Pacemaker Patients and the AF Reduction Atrial Pacing Trial (ASSERT), patients with hypertension but no history of AF had AF recorded via an implanted pacemaker or defibrillator, thus allowing both symptomatic and asymptomatic AF incidence to be determined without ascertainment bias. The ASSERT enrolled 2,580 patients in 23 countries in North America, Europe, and Asia. AF was defined as device-recorded AF episodes >190/min, lasting either for >6 minutes or >6 hours in duration. All ethnic groups with >50 patients were enrolled. Ethnic groups studied include Europeans (n = 1900), black Africans (n = 73), Chinese (n = 89), and Japanese (n = 105) patients. Compared to Europeans, black Africans had more risk factors for AF such as heart failure (27.8 vs 14.6%) and diabetes (41.7 vs 26.3%). At 2.5 years follow-up, all 3 non-European races had a lower incidence of AF (8.3%, 10.1%, and 9.5% vs 18.0%, respectively, for AF>6 minutes, P < 0.006). When adjusted for baseline difference, Chinese had a lower incidence of AF > 6 minutes (P < 0.007), and Japanese and black Africans had a lower incidence of AF > 6 hours (P < 0.04 and P = 0.057, respectively). Black Africans, Chinese, and Japanese had lower incidence of AF compared to Europeans. In the case of black Africans, this is despite an increased prevalence of AF risk factors.


Ultrastructure of adenoid cystic carcinoma arising in the salivary gland of a child.
A case of adenoid cystic carcinoma which developed in the left parotid gland of an 11-year-old girl was studied by electron microscopy. Islands of tumor cells, showing glandular and cribriform appearances, infiltrated the surrounding tissue and nerves. True lumina and pseudocysts were present in the islands of tumor cells. Electron microscopic examination revealed two types of tumor cells; clear cells (secretory epithelial cells) and dark cells myoepitheium-like cells). Some of the tumor cells, showing a transitional form between the two types, formed a part of the luminal wall. There were many crystalline spicules, cellular debris, and fine stellate granules in the lumina. Pseudocysts were composed of replicated basal laminae, fine stellate granules, and a central core of microfilaments. Rarely, a capillary was noted in the center of the pseudocysts. It is speculated that ultrastrutural features of adenoid cystic carcinoma in chidren may differ from the adult cases in the following ways; they contain numerous crystalline spicules in the lumina, dark cells with microvilli forming the luminal wall, and fine capillaries in the pseudocysts.


Occupational exposure to pesticides during pregnancy and neurobehavioral development of infants and toddlers.
Few studies have examined the effects of in utero exposure to organophosphate and carbamate pesticides on neurobehavioral development in infants and young children. This study considers the potential effects of maternal occupation in the cut-flower industry during pregnancy on neurobehavioral development in Ecuadorian children. Data were collected during 2003-2004 for 121 children aged 3-23 months and living in the rural highland region of Cayambe, Ecuador. Children were administered the Ages and Stages Questionnaire and were given specific developmental tests including prehension (reach-and-grasp) and visual skills. Information was gathered on maternal health and work characteristics, the home environment, and child health status. Growth measurements and a hemoglobin finger-prick blood test were obtained. We conducted multiple linear and logistic regression analyses. Children whose mothers worked in the flower industry during pregnancy scored lower on communication (8% decrease in score, 95% confidence interval [CI]: -16% to 0.5%) and fine motor skills (13% decrease, 95% CI: -22% to -5), and had a higher odds of having poor visual acuity (odds ratio = 4.7 [CI =1.1-20]), compared with children whose mothers did not work in the flower industry during pregnancy, after adjusting for potential confounders. Maternal occupation in the cut-flower industry during pregnancy may be associated with delayed neurobehavioral development of children aged 3-23 months. Possible hazards associated with working in the flower industry during pregnancy include pesticide exposure, exhaustion, and job stress.


Insulin sensitivity in newly detected hypertensive patients: influence of captopril and other antihypertensive agents on insulin sensitivity and related biological parameters.
In a recent study in which metabolic characteristics of newly detected obese and nonobese hypertensive subjects were compared with those of normotensive subjects, insulin sensitivity was decreased, fasting insulin values and insulin values after an intravenous glucose tolerance test (IVGTT) were increased, and fasting and IVGTT glucose values were increased in both hypertensive groups. Furthermore, adverse alterations in lipid profile variables were found in the hypertensive groups when compared with the normotensive group. The effects of various antihypertensive agents on these metabolic variables have been assessed in prospective trials. Treatment with the beta 1-selective blocking agents metoprolol and atenolol was associated with decreased insulin sensitivity and increased fasting values of insulin and glucose. There were also indications of a suppressive effect on insulin secretion during IVGTT, as well as an increase in serum triglycerides and a decrease in serum high-density lipoprotein cholesterol. Hydrochlorothiazide treatment was associated with a decrease in insulin sensitivity and an increase in blood glucose concentrations. In addition, hydrochlorothiazide increased total cholesterol, particularly the low-density lipoprotein fraction. The calcium channel blocker diltiazem did not appear to produce any negative metabolic effects. Treatment with the angiotensin converting enzyme inhibitor captopril resulted in increased insulin sensitivity with no adverse effects on lipids. All of the agents reduced blood pressure to a similar degree. These findings, and those of other studies, suggest that captopril and diltiazem offer advantages over the other agents with regard to effects on risk factors for coronary artery disease other than hypertension. Unlike diltiazem, captopril improves insulin sensitivity and this may prove to be important.


A linear optical trap with active medium for experiments with high power laser pulses.
A linear optical trap for circulating high power laser pulses and tuning these pulses to high repetition frequency of several tens of MHz has been developed. A ns excimer pumped dye laser pulse has been injected with help of a Wollaston prism and a synchronized Pockels cell into an optical trap formed by two highly reflecting mirrors in a linear configuration. The test was done at λ = 580 nm, but the optical trap can be used without limitations in a broad band of optical wavelengths (400-700 nm). Power considerations give an increase of the efficiency of the optical trap of about 7 times compared to single passage of the laser pulse through the experimental section. The time structure of the trapped laser pulses can be controlled by changing the distance between the two high reflecting mirrors. The efficiency of the optical trap strongly depends upon optical losses. To compensate the optical losses, an amplifying cell was introduced, and the efficiency was about 60 times higher than that by single passage of the laser pulse through the experimental section.


Simulations of the Biodegradation of Citrate-Based Polymers for Artificial Scaffolds Using Accelerated Reactive Molecular Dynamics.
In this study, we investigate the reactivity and mechanical properties of poly(1,6-hexanediol-co-citric acid) via ReaxFF molecular dynamics simulations. We implement an accelerated scheme within the ReaxFF framework to study the hydrolysis reaction of the polymer which is provided with a sufficient amount of energy known as the restrain energy after a suitable pretransition-state configuration is obtained to overcome the activation energy barrier and the desired product is obtained. The validity of the ReaxFF force field is established by comparing the ReaxFF energy barriers of ester and ether hydrolysis with benchmark DFT values in the literature. We perform chemical and mechanical degradation of polymer chain bundles at 300 K. We find that ester hydrolyzes faster than ether because of the lower activation energy barrier of the reaction. The selectivity of the bond-boost scheme has been demonstrated by lowering the boost parameters of the accelerated simulation, which almost stops the ether hydrolysis. Mechanical degradation of prehydrolyzed and intermittent hydrolyzed polymer bundles is performed along the longitudinal direction at two different strain rates. We find that the tensile modulus of the polymers increases with increase in strain rates, which shows that polymers show a strain-dependent behavior. The tensile modulus of the polyester-ether is higher than polyester but reaches yield stress faster than polyester. This makes polyester more ductile than polyester-ether.


RRR-alpha-tocopheryl succinate enhances TGF-beta 1, -beta 2, and -beta 3 and TGF-beta R-II expression by human MDA-MB-435 breast cancer cells.
The proliferation of MDA-MB-435 human breast cancer cells was inhibited by RRR-alpha-tocopheryl succinate (vitamin E succinate, VES). Conditioned media (CM) from VES growth-inhibited cells contained potent antiproliferative activity, part of which is contributed by transforming growth factor-beta (TGF-beta) isoforms. Antibody neutralization analysis, employing TGF-beta isoform-specific antibody reagents, showed that TGF-beta 1, -beta 2, and -beta 3 were present in the CM from VES-treated cells. Culturing MDA-MB-435 cells with VES did not alter the levels of constitutively expressed 2.4-kb TGF-beta 1, 3.0- and 4.0-kb TGF-beta 2, or 1.2- and 3.5-kb TGF-beta 3 mRNA transcripts. Inhibition of DNA synthesis by MDA-MB-435 cells was increased by combinations of suboptimal levels of VES and purified TGF-beta 1. VES-treated MDA-MB-435 cells exhibited enhanced binding of radiolabeled TGF-beta 1, and Western immunoblotting analyses showed that VES treatment enhanced TGF-beta type II receptor protein expression. TGF-beta type I receptor protein levels were not modified by VES treatments. Although the mRNA transcript for the 5.5-kb TGF-beta type II receptor was upregulated after four hours of treatment with VES, this treatment did not modify the 6.5-kb TGF-beta type I or the 6.5-kb TGF-beta type II receptor mRNAs. Results demonstrate that biologically active TGF-beta 1, -beta 2, -beta 3 and levels of TGF-beta type II receptor expressed by human breast cancer cells are enhanced by VES treatment.


Primary sclerosing cholangitis and pregnancy.
Primary sclerosing cholangitis is a progressive disease, and coincidentally in pregnancy it is rare. It is characterized by progressive inflammation and destruction of bile ducts finally resulting in liver failure. A rare case of primary sclerosing cholangitis in pregnancy is presented. The course of the pregnancy was marked by threatened preterm delivery and exacerbation of cholestasis. She was successfully treated with ursodeoxycholic acid (UDCA). Although, primary sclerosing cholangitis has both maternal and fetal effects on pregnancy, the overall outcome is favorable. Only few cases have been reported using high dose ursodeoxycholic acid for primary sclerosing cholangitis in pregnancy, it often improves pruritus but has no protection against stillbirth. Data on the safety to the fetus or neonate and long-term outcome are scarce.


Non-fragile guaranteed cost control of microbial fuel cells.
A microbial fuel cell (MFC), which is a new type of energy source, utilises electrogenic bacteria in sewage or soil to convert chemical energy into electrical energy. MFCs typically require an external controller to provide a stable output voltage to the external load. This study develops a non-fragile guaranteed cost (NFGC) controller to suppress the interference of the controller of an MFC and ensure that the quadratic cost function of the system satisfies certain performance indexes. First, for the convenience of controller design, a Takagi-Sugeno fuzzy model is established to approximate a single-chamber single-population MFC model. Subsequently, the linear matrix inequality method is used to design the NFGC controller. This control scheme can reduce the influence of controller disturbances on the system and ensure asymptotic stability of the closed-loop system under the specified upper bound of the provided cost function. The simulation results demonstrate that the developed control method has a shorter adjustment time and smaller steady-state error than traditional control methods such as sliding mode control (SMC), backstepping control, and fuzzy SMC.


Gender differences in colorectal polyps and tumors.
To use a national endoscopy database (CORI) to determine 1) whether gender differences are noted in the prevalence and location of polyps and tumors; 2) whether women have a higher rate of right-sided polyps or tumors; and 3) whether age influences these results. CORI database from April 1, 1997 to February 19, 1999, captured in a computer-generated report, was analyzed. Polyps for this study were defined as sessile or pedunculated and as >9 mm. Tumors were defined as lesions characteristic of adenocarcinoma (mass, apple-core). Pure right-sided colon (PRS) was defined as cecum, ascending, hepatic flexure; right-sided as PRS plus the transverse colon; and left-sided as the splenic flexure, descending, sigmoid and rectum. Men have a greater risk of polyps [odds ratio (OR), 1.5] and tumors (OR, 1.4) than women. The risk of finding polyps and tumors at colonoscopy increases with age, with the highest risk noted in those >69 yr of age relative to patients <50 yr of age (polyps, OR = 2.7; tumors, OR = 4.0). Right-side polyps and pure right-sided polyps as defined by the study design were noted to be more frequent than left-sided polyps in patients >60 yr of age. Women have a greater risk of developing pure right-sided polyps (OR, 1.2), tumors (OR, 1.6) and right-sided tumors (OR, 1.5) than men. Men have a higher prevalence of colon polyps and tumors than women. A progressive risk of polyp or tumor formation is noted with aging. Women had a greater number of pure right-sided polyps and tumor development. Colonoscopy is needed to correctly diagnose an increasing prevalence of right-sided pathology in the elderly.


[Arthroscopic repair of subscapularis tendon tear].
In this study the arthroscopic reconstruction of a rupture of the subscapularis tendon is described and the results of the technique are evaluated, with the aim to show the advantages and effectiveness of this surgical procedure. Between 2006 and 2008, arthroscopic repair of the subscapularis tendon was carried out in 23 patients, 16 men and seven women, with an average age of 55 (range, 37-74) years. The dominant arm was treated more often (15x). All 23 patients treated by this diagnostic arthroscopic technique were included in the evaluation. With the patient in a lateral recumbent position, the arthroscope was introduced from a dorsal port, and the procedure was carried out through working ventral and anterosuperolateral ports. Following its identification, the subscapularis tendon was mobilised and an insertion site was prepared. Subsequently, a Fastin anchor (Mitek) was inserted. The tendon was stitched through using the mattress suture technique and firmly reinserted to the lesser tuberosity. If necessary, a coracoplasty was performed and the biceps long head tendon was managed.When more tendons of the rotator cuff were torn, the subscapularis tendon was treated first. A complete tear was treated with two anchors and a partial rupture with one Fastin anchor. Post-operative immobilisation lasted 6 weeks and was followed by a six-month rehabilitation therapy. The tears were assessed according to the system proposed by Lafosse et al. The outcomes were evaluated using the University of California at Los Angeles (UCLA) and Constant scoring systems at a minimum of 1 year after surgery. The 23 patients undergoing arthroscopic repair of the subscapularis tendon were evaluated. The average follow-up was 24 months. The average pre-operative values for the Constant and UCLA scores were 44.4% (25-72%) and 13.8 points (8-24), respectively. Post-operatively, they improved to 84.75% (50-100%) for the Constant score and 28.6 points (17-35) for the UCLA score. The only post-operative complication involving persistent purulent secretion from the posterior port was successfully managed. All patients reported improvement as against the pre-operative condition, all were satisfied with the outcome and expressed their willingness to undergo the same surgery on the other shoulder, if need be. Rupture of the subscapularis tendon is an infrequent injury to the rotator cuff and an isolated tear is rare. An exact clinical diagnosis of a subscapularis tendon tear is difficult. However, subscapularis tendon tears can be reliably diagnosed as well as treated by arthroscopy, including partial ruptures that are often misdiagnosed. Our results compare well with those reported in the international literature and are rated as very good. Arthroscopy is the most suitable method to diagnose as well as manage ruptures of the subscapularis tendon classified as Lafosse grades I to IV. Arthroscopic tear repair results in a significant improvement in function of the shoulder joint and pain relief. Based on these results, the arthroscopic treatment of all Lafosse grade I-IV ruptures in our institution is recommended.


Retinal injury induced by near-ultraviolet radiation in aphakic and pseudophakic monkey eyes. A preliminary report.
The effect of repeated exposures to low-intensity, near-ultraviolet (UV) radiation on the retinas of phakic, aphakic, and pseudophakic monkey eyes was studied. Ten eyes (4 aphakic eyes, 3 pseudophakic eyes, and 3 normal phakic eyes) of five rhesus monkeys were used. The near-UV radiation was generated by a high-pressure mercury vapor lamp with a total radiance of 14.43 mW/cm2/sr. Exposure regimens were 5 minutes a day for 10 days, 15 minutes a day for 5 days, or 60 minutes a day for 5 days. The retinas of aphakic and pseudophakic eyes were exposed to a daily dose of more than 0.97 J/cm2, or a total dose of more than 4.9 J/cm2 in 5 days at a retinal irradiance of more than 1.0 mW/cm2. Three of four aphakic eyes and one of three pseudophakic eyes showed clinical and pathologic retinal lesions after radiation. None of the three phakic eyes was damaged. The retinal lesions showed mild opalescent thickening ophthalmoscopically and retinal pigment epithelial staining by fluorescein angiography. Histopathologically, the retinal pigment epithelium was the site of primary injury by near-UV radiation.


Membrane glycoproteins associated with breast tumor cell progression identified by a lectin affinity approach.
The membrane glycoprotein component of the cellular proteome represents a promising source for potential disease biomarkers and therapeutic targets. Here we describe the development of a method that facilitates the analysis of membrane glycoproteins and apply it to the differential analysis of breast tumor cells with distinct malignant phenotypes. The approach combines two membrane extraction procedures, and enrichment using ConA and WGA lectin affinity columns, prior to digestion and analysis by LC-MS/MS. The glycoproteins are identified and quantified by spectral counting. Although the distribution of glycoprotein expression as a function of MW and p I was very similar between the two related cell lines tested, the approach enabled the identification of several distinct membrane glycoproteins with an expression index correlated with either a precancerous (MCF10AT1), or a malignant, metastatic cellular phenotype (MCF10CA1a). Among the proteins associated with the malignant phenotype, Gamma-glutamyl hydrolase, CD44, Galectin-3-binding protein, and Syndecan-1 protein have been reported as potential biomarkers of breast cancer.


A prospective comparison of capsule endoscopy and push enteroscopy in patients with GI bleeding of obscure origin.
Capsule endoscopy is used to investigate the small bowel in patients with GI bleeding of obscure etiology. Capsule endoscopy was compared prospectively with push enteroscopy in 20 patients with GI hemorrhage. Twenty patients (8 men, 12 women; mean age 65.5 years, range 38-80 years) were enrolled in the study. All had undergone non-diagnostic EGD, colonoscopy, and barium contrast radiography of the small bowel. All patients underwent capsule endoscopy followed by push enteroscopy. The physician performing the enteroscopy (senior endoscopist) interpreted the capsule endoscopy in an unblinded manner, while a second blinded reviewer (endoscopy fellow) interpreted the capsule endoscopy to establish interinterpreter reliability. There was complete agreement between the blinded and the unblinded physicians in 18 of 20 cases; minor disparities were noted in the remaining two cases. In the small bowel, capsule endoscopy identified positive findings in 14 (70%) patients, whereas, push enteroscopy identified positive findings in 5 (25%) patients. Despite these results, the findings were definitive in only 6 of the 20 patients by using capsule endoscopy, and in two of 20 patients with push enteroscopy. When strict standards of interpretation were used, capsule endoscopy resulted in more positive findings than push enteroscopy, but the number of definitive findings for both imaging methods was low. There was a high degree of reliability between a novice and an experienced endoscopist with respect to the interpretation of capsule endoscopy.


Joint effects of social class and community occupational structure on coronary mortality among black men and white men, upstate New York, 1988-92.
Occupational structure represents the unequal geographical distribution of more desirable jobs among communities (for example, white collar jobs). This study examines joint effects of social class, race, and county occupational structure on coronary mortality rates for men, ages 35-64 years, 1988-92, in upstate New York. Upstate New York's 57 counties were classified into three occupational structure categories; counties with the lowest percentages of the labour force in managerial, professional, and technical occupations were classified in category I, counties with the highest percentages were in category III. Age adjusted coronary heart disease (CHD) mortality rates, 35-64 years, (from vital statistics and census data) were calculated for each occupational structure category. An inverse association between CHD mortality and occupational structure was observed among blue collar and white collar workers, among black men and white men, with the lowest CHD mortality observed among white collar, white men in category III (135/100,00). About two times higher mortality was observed among blue collar than white collar workers. Among blue collar workers, mortality was 1.3-1.8 times higher among black compared with white workers, and the highest rates were observed among black, blue collar workers (689/100,00). Also, high residential race segregation was shown in all areas. Results suggest the importance of community conditions in coronary health of local populations; however, differential impact on subpopulations was shown. Blue collar and black workers may especially lack economic and other resources to use available community services and/or may experience worse working and living conditions compared with white collar and white workers in the same communities.


Diversity and Spatial-Temporal Distribution of Soil Macrofauna Communities Along Elevation in the Changbai Mountain, China.
The understanding of patterns of vertical variation and diversity of flora and fauna along elevational change has been well established over the past century. However, it is unclear whether there is an elevational distribution pattern for soil fauna. This study revealed the diversity and spatial-temporal distribution of soil macrofauna communities in different vegetation zones from forest to alpine tundra along elevation of the Changbai Mountain, China. The abundance, richness, and Shannon-Wiener diversity index of soil macrofauna communities were compared in four distinguished vegetation zones including the coniferous and broadleaved mixed forest zone, the coniferous forest zone, the subalpine dwarf birch (Betula ermanii) forest zone, and the alpine tundra zone. Soil macrofauna were extracted in May, July, and September of 2009. In each season, the abundance and richness of the soil macrofauna decreased with the ascending elevation. The Shannon-Wiener diversity indices of the soil macrofauna were higher in the vegetation zones of lower elevation than of higher elevation. Significant differences were observed in the abundance, richness, and Shannon-Wiener diversity index for the studied vegetation zones. Soil macrofauna congregated mainly to the litter layer in the low-elevation areas and in the 0-5 cm soil layer of the higher elevation areas. The results emphasized that the diversity of soil macrofauna communities decreased as the elevation increased and possess the distinct characteristics of zonation in the mountain ecosystem. The diversity and distribution of soil macrofauna communities were influenced by mean annual precipitation, altitude, annual radiation quantity, and mean annual temperature.


STB5 is a negative regulator of azole resistance in Candida glabrata.
The opportunistic yeast pathogen Candida glabrata is recognized for its ability to acquire resistance during prolonged treatment with azole antifungals (J. E. Bennett, K. Izumikawa, and K. A. Marr. Antimicrob. Agents Chemother. 48:1773-1777, 2004). Resistance to azoles is largely mediated by the transcription factor PDR1, resulting in the upregulation of ATP-binding cassette (ABC) transporter proteins and drug efflux. Studies in the related yeast Saccharomyces cerevisiae have shown that Pdr1p forms a heterodimer with another transcription factor, Stb5p. In C. glabrata, the open reading frame (ORF) designated CAGL0I02552g has 38.8% amino acid identity with STB5 (YHR178w) and shares an N-terminal Zn(2)Cys(6) binuclear cluster domain and a fungus-specific transcriptional factor domain, prompting us to test for homologous function and a possible role in azole resistance. Complementation of a Δyhr178w (Δstb5) mutant with CAGL0I02552g resolved the increased sensitivity to cold, hydrogen peroxide, and caffeine of the mutant, for which reason we designated CAGl0I02552g CgSTB5. Overexpression of CgSTB5 in C. glabrata repressed azole resistance, whereas deletion of CgSTB5 caused a modest increase in resistance. Expression analysis found that CgSTB5 shares many transcriptional targets with CgPDR1 but, unlike the latter, is a negative regulator of pleiotropic drug resistance, including the ABC transporter genes CDR1, PDH1, and YOR1.


The role of social and cognitive factors in individual gambling: An empirical study on college students.
Most of the studies on the determinants of individual gambling behaviour rely on cognitive theories. In our study, we argue that, besides cognitive factors, several social factors might play an important role as well. We analyse data from an ad hoc webmail survey conducted on about 2000 undergraduate students enrolled in a large public university in the Northern Italy in the academic year 2012-13. Using a variety of statistical techniques (standard regression models, boosted regression trees and structural equations models), we show that social variables affect both participation in gambling in the past year and latent gambling propensity. In particular, controlling for several proxies for individual cognitive ability and understanding of probability, gambling propensity is positively affected by the degree of gambling in the social surrounding (parents, peers, neighbourhood) and the acceptability of gambling activities to the individual. Moreover, in our sample of college students the role of social factors appears to be larger than that of cognitive factors, and this is consistent across different types of models and specifications.


Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors.
To determine if interindividual genetic variation in single-nucleotide polymorphisms (SNPs) related to age at natural menopause is associated with risk of ovarian failure in breast cancer survivors. A prospective cohort of 169 premenopausal breast cancer survivors recruited at diagnosis with stages 0 to III disease were followed longitudinally for menstrual pattern via self-reported daily menstrual diaries. Participants were genotyped for 13 SNPs previously found to be associated with age at natural menopause: EXO1, TLK1, HELQ, UIMC1, PRIM1, POLG, TMEM224, BRSK1, and MCM8. A risk variable summed the total number of risk alleles in each participant. The association between individual genotypes, and also the risk variable, and time to ovarian failure (>12 months of amenorrhea) was tested using time-to-event methods. Median age at enrollment was 40.5 years (range 20.6-46.1). The majority of participants were white (69%) and underwent chemotherapy (76%). Thirty-eight participants (22%) experienced ovarian failure. None of the candidate SNPs or the summary risk variable was significantly associated with time to ovarian failure. Sensitivity analysis restricted to whites or only to participants receiving chemotherapy yielded similar findings. Older age, chemotherapy exposure, and lower body mass index were related to shorter time to ovarian failure. Thirteen previously identified genetic variants associated with time to natural menopause were not related to timing of ovarian failure in breast cancer survivors.


Sumner's "On testing the sense of smell" revisited.
The routine test of olfaction need not lead to an ambiguous outcome, a rather widely held notion. A multiple-choice test of odor identification that avoided the difficulty of retrieving odor names yielded excellent resolution among the categories normosmic, hyposmic, and anosmic. The outcome agreed almost perfectly with a more complicated test of threshold and offered much encouragement for the use of odor identification in rapid screening of olfaction.


Avascular necrosis of the femoral head after allogenic bone-marrow transplantation. A retrospective study of 27 consecutive THAs with a minimal two-year follow-up.
After an allogenic bone-marrow transplant, avascular necrosis of the femoral head may affect young adults, producing destructive lesions which require hip replacement. We have reviewed 27 consecutive such total hip arthroplasties (THA) at a minimal follow-up of two years. Of these, 20 were primary operations for Ficat (1985) stage-III and stage-IV lesions, and seven were revisions after the failure of previous surgery. The median age at operation was 30 years (17.5 to 44). The prostheses had a cemented, collared titanium-alloy stem, an alumina-alumina joint, and a press-fit socket. Seven had a titanium-alloy metal back and 20 had all-alumina cups of which six had to be cemented. At an average follow-up of five years, no patient had been lost to follow-up. One had died from septicaemia after two years and another with chronic graft-versus-host disease developed a deep infection 2.5 years postoperatively and had a successful revision. There were no revisions for aseptic loosening. The clinical results on the Merle d'Aubigné++ and Postel (1954) scale were very good or excellent in 23 hips (88%), good in one and fair in two. Ten hips showed incomplete acetabular radiolucencies less than 1 mm thick, but there were no radiolucent lines around the stems. We conclude that for these difficult patients THA with ceramic joints and careful technique provides the best short- and medium-term option after the failure of medical treatment.


The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated from the epidermal growth factor receptor.
Insulin-like growth factor I (IGF-I)/somatomedin C is an important mediator of keratinocyte growth in vitro, and the expression of IGF-I receptors in the basal layer of normal epidermis suggests that this growth pathway may function in the regulation of keratinocyte growth in vivo as well. The pattern of IGF-I receptor expression in normal skin is distinct from that of the epidermal growth factor (EGF) receptor, suggesting that these receptors might be differentially regulated. The purpose of this study was to obtain a better understanding of IGF-I receptor function in the skin by examining IGF-I receptor expression in psoriatic epidermis and in cultured human keratinocytes. Our findings indicate that IGF-I receptor expression is increased in psoriasis as measured by protein tyrosine kinase assays of biopsy extracts and by immunohistochemical staining with an IGF-I receptor-specific monoclonal antibody. Unlike EGF receptor expression, which is also increased in psoriatic epidermis, the pattern of IGF-I receptor expression corresponds closely with the increased size of the keratinocyte proliferative compartment in psoriasis. Biochemical agents that diminish EGF receptor ligand binding (phorbol ester or calcium ionophore treatment) produce opposite effects on the IGF-I receptor. These results suggest that cellular expression and differential regulation of both growth factor receptor systems may control critical aspects of epidermal proliferation or function.


A comparison of the metabolic effects of captopril and atenolol on glucose, insulin and lipoproteins in patients with mild-to-moderate essential hypertension.
The metabolic effects of captopril 25 mg twice daily and atenolol 50 mg daily on glucose, insulin and lipids were compared in 83 otherwise healthy mild-to-moderate hypertensive between the ages of 25 and 60 years in a randomised double-blind trial. Hourly glucose and insulin levels were measured during a 2-hour 75 g oral glucose tolerance test at baseline and after 12 weeks of treatment. Lipid profiles including total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2, HDL3, triglycerides, apoprotein (Apo)A1, ApoB, and Apo(a) were obtained before and after the treatment period. Blood pressure decreased significantly and equivalently in both treatment groups. The glucose and insulin levels and glucose x insulin product at 2 hours after the glucose load increased after 12 weeks of treatment with atenolol compared with the baseline values, but these parameters all decreased after the treatment period with captopril compared with their baseline values. These results indicate an improvement in insulin sensitivity with captopril and a deterioration with atenolol. HDL-cholesterol and HDL3 decreased in the atenolol group but increased in the captopril group. We conclude that captopril has more favourable effects than atenolol on glucose, insulin and lipid metabolism in the treatment of mild-to-moderate hypertension.


A comparison of the PTH-dependent cAMP responses in osteoclastic and osteoblastic bone cells.
Isolated bone cells enriched for either osteoclastic (OC) or osteoblastic (OB) characteristics have been previously described. Only OC cells respond to calcitonin (sCT), but both types of cell populations demonstrate adenosine 3':5'-cyclic phosphate (cAMP) increases with parathyroid hormone (PTH), suggesting a common PTH-responsive cell in both. In view of this, the cAMP responses to PTH were compared in terms of turnover time, induction of dose-dependent desensitization, recovery from desensitization and inhibition by trifluoperazine (TFP). In the absence of new protein synthesis, OC cell cAMP response to PTH declined more slowly than that of OB cells (t/2 of approximately 24 h vs. 8 h for OB cells). The relative stability of PTH responsiveness in OC cells was unique in that the same was not seen for sCT or prostaglandin E1 (PGE1) responsiveness which declined with a t/2 of 8 and 6 h, respectively. In comparison to OB cells, OC cells also demonstrated (1) a more rapid recovery from autologous desensitization with PTH, regaining responsiveness with a t/2 of approximately 6 h vs. 14 h for OB cells; (2) greater resistance to desensitization by submaximal doses of PTH (4 X 10(-10) -4 X 10(-9) M), and (3) resistance to inhibition by low doses of TFP (less than 5 microM). These results suggest that the PTH-responsive cells in OC populations are metabolically different from those in OB populations.


"Darwin's butterflies"? DNA barcoding and the radiation of the endemic Caribbean butterfly genus Calisto (Lepidoptera, Nymphalidae, Satyrinae).
The genus Calisto Hübner, 1823 is the only member of the diverse, global subfamily Satyrinae found in the West Indies, and by far the richest endemic Caribbean butterfly radiation. Calisto species occupy an extremely diverse array of habitats, suggestive of adaptive radiation on the scale of other classic examples such as the Galápagos or Darwin's finches. However, a reliable species classification is a key requisite before further evolutionary or ecological research. An analysis of 111 DNA 'barcodes' (655 bp of the mitochondrial gene COI) from 29 putative Calisto species represented by 31 putative taxa was therefore conducted to elucidate taxonomic relationships among these often highly cryptic and confusing taxa. The sympatric, morphologically and ecologically similar taxa Calisto confusa Lathy, 1899 and Calisto confusa debarriera Clench, 1943 proved to be extremely divergent, and we therefore recognize Calisto debarriera stat. n. as a distinct species, with Calisto neiba Schwartz & Gali, 1984 as a junior synonym syn. n. Species status of certain allopatric, morphologically similar sister species has been confirmed: Calisto hysius (Godart, 1824) (including its subspecies Calisto hysius aleucosticha Correa et Schwartz, 1986, stat. n.), and its former subspecies Calisto batesi Michener, 1943 showed a high degree of divergence (above 6%) and should be considered separate species. Calisto lyceius Bates, 1935/Calisto crypta Gali, 1985/Calisto franciscoi Gali, 1985 complex, also showed a high degree of divergence (above 6%), confirming the species status of these taxa. In contrast, our data suggest that the Calisto grannus Bates, 1939 species complex (including Calisto grannus dilemma González, 1987, Calisto grannus amazona González, 1987, stat. n., Calisto grannus micrommata Schwartz & Gali, 1984, stat. n., Calisto grannus dystacta González, 1987, stat. n., Calisto grannus phoinix González, 1987, stat. n., Calisto grannus sommeri Schwartz & Gali, 1984, stat. n., and Calisto grannus micheneri Clench, 1944, stat. n.) should be treated as a single polytypic species, as genetic divergence among sampled populations representing these taxa is low (and stable morphological apomorphies are absent). A widely-distributed pest of sugar cane, Calisto pulchella Lathy, 1899 showed higher diversification among isolated populations (3.5%) than expected, hence supporting former separation of this species into two taxa (pulchella and darlingtoni Clench, 1943), of which the latter might prove to be a separate species rather than subspecies. The taxonomic revisions presented here result in Calisto now containing 34 species and 17 subspecies. Three species endemic to islands other than Hispaniola appear to be derived lineages of various Hispaniolan clades, indicating ancient dispersal events from Hispaniola to Puerto Rico, Cuba, and Jamaica. Overall, the degree of intrageneric and intraspecific divergence within Calisto suggests a long and continuous diversification period of 4-8 Myr. The maximum divergence within the genus (ca. 13.3%) is almost equivalent to the maximum divergence of Calisto from the distant pronophiline relative Auca Hayward, 1953 from the southern Andes (14.1%) and from the presumed closest relative Eretris Thieme, 1905 (14.4%), suggesting that the genus began to diversify soon after its split from its continental sister taxon. In general, this 'barcode' divergence corresponds to the high degree of morphological and ecological variation found among major lineages within the genus.


Developing an efficient phase-matched attenuation correction method for quiescent period PET in abdominal PET/MRI.
Respiratory motion causes misalignments between positron emission tomography (PET) and magnetic resonance (MR)-derived attenuation maps (µ-maps) in addition to artifacts on both PET and MR images in simultaneous PET/MRI for organs such as liver that can experience motion of several centimeters. To address this problem, we developed an efficient MR-based attenuation correction (MRAC) method to generate phase-matched µ-maps for quiescent period PET (PETQ) in abdominal PET/MRI. MRAC data was acquired with CIRcular Cartesian UnderSampling (CIRCUS) sampling during 100 s in free-breathing as an accelerated data acquisition strategy for phase-matched MRAC (MRACPM-CIRCUS). For comparison, MRAC data with raster (Default) k-space sampling was also acquired during 100 s in free-breathing (MRACPM-Default), and used to evaluate MRACPM-CIRCUS as well as un-matched MRAC (MRACUM) that was un-gated. We purposefully oversampled the MRACPM data to ensure we had enough information to capture all respiratory phases to make this comparison as robust as possible. The proposed MRACPM-CIRCUS was evaluated in 17 patients with 68Ga-DOTA-TOC PET/MRI exams, suspected of having neuroendocrine tumors or liver metastases. Effects of CIRCUS sampling for accelerating a data acquisition were evaluated by simulating the data acquisition time retrospectively in increments of 5 s. Effects of MRACPM-CIRCUS on PETQ were evaluated using uptake differences in the liver lesions (n = 35), compared to PETQ with MRACPM-Default and MRACUM. A Wilcoxon signed-rank test was performed to compare lesion uptakes between the MRAC methods. MRACPM-CIRCUS showed higher image quality compared to MRACPM-Default for the same acquisition times, demonstrating that a data acquisition time of 30 s was reasonable to achieve phase-matched µ-maps. Lesion update differences between MRACPM-CIRCUS (30 s) versus MRACPM-Default (reference, 100 s) were 0.1% ± 1.4% (range of -2.7% to 3.2%) and not significant (P > .05); while, the differences between MRACUM versus MRACPM-Default were 0.6% ± 11.4% with a large variation (range of -37% to 20%) and significant (P < .05). In conclusion, we demonstrated that a data acquisition of 30 s achieved phase-matched µ-maps when using specialized CIRCUS data sampling and phase-matched µ-maps improved PETQ quantification significantly.


Apneic oxygen insufflation decreases the incidence of hypoxemia during one-lung ventilation in open and thoracoscopic pulmonary lobectomy: A randomized controlled trial.
Hypoxemia is common during one-lung ventilation (OLV) for thoracic surgery. When hypoxemia occurs, surgery is interrupted for rescue ventilation. Apneic oxygen insufflation (AOI), which provides O2 without applying pressure, may prevent hypoxemia and does not interrupt surgery. The aim of this study was to determine the effectiveness of the AOI technique for preventing hypoxemia during OLV in thoracic surgery. Patients undergoing open or thoracoscopic pulmonary lobectomy from September to December 2015 were included. Patients were assigned randomly to a non-AOI group or an AOI group (n = 45 each). OLV was initiated and at the 15-minute mark (OLV15), patients in the AOI group received oxygen insufflation at 3 L/min to the nonventilated lung for 30 minutes (OLV45). The primary endpoint was the occurrence of hypoxemia (SaO2 <90%) during OLV. The demographic and operative data were similar between the 2 groups. The incidence of hypoxemia was greater in the non-AOI than the AOI group (18% vs 0%; P = .009). ΔPaO2 (the difference in partial pressure of oxygen in arterial blood between OLV 45 and 15 minutes) was smaller in the AOI than the non-AOI group (-29 mm Hg vs -69 mm Hg; P = .005). Duration of surgery and incidence of complications did not vary between groups. AOI decreases the incidence of hypoxemia and improves arterial oxygenation during OLV for open and thoracoscopic surgery. AOI may be a valuable option to prevent hypoxemia. It can be used before relying on continuous positive airway pressure or intermittent two-lung ventilation and result in fewer interruptions in surgery.


Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren's syndrome.
Sjögren's syndrome (SS) is an autoimmune disorder characterized by dry eyes and mouth (sicca syndrome) and lymphocytic infiltration of the lacrimal and salivary glands. Abnormalities of parasympathetic neurotransmission may contribute to the glandular dysfunction. In this study, we used a functional assay to investigate autoantibody-mediated effects on parasympathetic neurotransmission and smooth muscle contraction. Serum and purified IgG were obtained from patients with primary and secondary SS and from control subjects. Contraction of isolated bladder strips in response to stimulation of M3-muscarinic receptors by a muscarinic receptor agonist, carbachol, or by endogenous acetylcholine released from postganglionic parasympathetic nerves was measured before and after the addition of patient serum or IgG. Sera from 5 of 9 patients with primary SS and from 6 of 6 patients with secondary SS inhibited carbachol-evoked bladder contraction by approximately 50%. Sera from these patients also inhibited the action of neuronally released acetylcholine at M3-muscarinic receptors. Sera from 7 of 8 healthy individuals, from patients with rheumatoid arthritis without sicca symptoms, and from patients with systemic lupus erythematosus had no effect. The anti-muscarinic receptor activity was localized in the IgG fraction, since purified IgG from patients with SS also inhibited agonist- and nerve-evoked contractions. In this preliminary study, the autoantibodies seemed to be associated with the presence of bladder symptoms and other autonomic features. Autoantibodies that act as antagonists at M3-muscarinic receptors on smooth muscle occur in a subset of patients with primary and secondary SS. Their presence in secondary SS was unexpected and provides new evidence for a common pathogenetic link between primary and secondary SS. These autoantibodies appear to contribute to sicca symptoms and may explain associated features of autonomic dysfunction in some patients.


Analgesic comparison of systemic lidocaine, morphine or lidocaine plus morphine infusion in dogs undergoing fracture repair.
To compare the postoperative analgesic effects of lidocaine, morphine and lidocaine plus morphine administered by constant rate infusion (CRI) and analyzing their effects on opioid requirements after orthopedic surgery in dogs. Twenty-four dogs underwent fracture repairs were premedicated with IM acepromazine (0.05 mg/kg) combined with morphine (0.3mg/kg). Anesthesia was induced with IV propofol (4 to 5 mg/ kg) and maintained with isoflurane. The dogs were randomly assigned to 3 groups and administered a CRI IV of lidocaine (T-L), morphine (T-M) or lidocaine plus morphine (T-LM) at the same doses. Postoperative analgesia was assessed for 24 hours using a Visual Analog Scale (VAS) and the Glasgow Composite Pain Scale (GCPS). Rescue analgesia was performed if the evaluation score exceeded 50% of the VAS and/or 33% of the GCPS. The pain score and postoperative opioid requirements did not differ among the treatments. Rescue analgesia was administered to 1/8 dogs in the T-M and T-LM, and to 3/8 dogs in the T-L. Lidocaine, morphine or lidocaine/morphine CRI may be efficacious techniques for pain management in the first 24 hours post-surgery. However, the two drugs administered together did not reduce the postoperative opioid requirement in dogs undergoing fracture repair. Key words: Anesthesia. Analgesics. Analgesics, Opioid. Lidocaine. Morphine. Dogs.


Rapid 1α,25(OH)₂D ₃ membrane-mediated activation of Ca²⁺/calmodulin-dependent protein kinase II in growth plate chondrocytes requires Pdia3, PLAA and caveolae.
1α,25-Dihydroxy vitamin D3 [1α,25(OH)2D3] regulates growth zone chondrocytes (GC) via classical steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-mediated signaling pathways. 1α,25(OH)2D3 initiates its membrane effects via its specific membrane-associated receptor (Pdia3) in caveolae. 1α,25(OH)2D3 binding to Pdia3 leads to phospholipase-A2 (PLA2)-activating protein (PLAA) activation, stimulating PLA2, resulting in prostaglandin E2 (PGE2) release and protein kinase C activation. Recently, we reported that 1α,25(OH)2D3 rapidly activates Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in GC cells. However, the roles of Pdia3, PLAA and caveolae in 1α,25(OH)2D3-dependent rapid activation of CaMKII are not clear. The aim of the present study was to evaluate the roles of Pdia3, PLAA and caveolae in 1α,25(OH)2D3 membrane-stimulated CaMKII activation. Pre-treating chondrocytes from the growth zone of the rat costochondral cartilage with antibodies against PLAA or Pdia3 blocked activation of CaMKII by 1α,25(OH)2D3. PLAA peptide rapidly activated CaMKII in GC cells. Caveolae disruption abolished CaMKII activation in response to 1α,25(OH)2D3 or PLAA peptide treatment. Immunoprecipitation studies showed increased CaM binding to PLAA in response to 1α,25(OH)2D3. The results indicated that Pdia3, PLAA and caveolae are required for rapid 1α,25(OH)2D3 membrane-mediated activation of CaMKII. 1α,25(OH)2D3 signaling via Pdia3 receptor triggered the interaction between PLAA and CaM suggesting that CaM may play a major role linking PLAA to CaMKII in membrane-mediated actions of 1α,25(OH)2D3.


Antimicrobial Peptide-Loaded Nanoparticles as Inhalation Therapy for Pseudomonas aeruginosa Infections.
Antibiotic-resistant bacteria kill 25,000 people every year in the EU. Patients subject to recurrent lung infections are the most vulnerable to severe or even lethal infections. For these patients, pulmonary delivery of antibiotics would be advantageous, since inhalation can achieve higher concentration in the lungs than iv administration and can provide a faster onset of action. This would allow for the delivery of higher doses and hence reduce the number of treatments required. We report here about a new nanosystem (M33-NS) obtained by capturing SET-M33 peptide on single-chain dextran nanoparticles. SET-M33 is a non-natural antimicrobial peptide synthesized in branched form. This form gives the peptide resistance to degradation in biological fluids. SET-M33 has previously shown efficacy in vitro against about one hundred of Gram-negative multidrug and extensively drug-resistant clinical isolates and was also active in preclinical infection models of pneumonia, sepsis and skin infections. The new nanosystem was evaluated for its efficacy in bacteria cells and in a mouse model of pneumonia. Toxicity and genotoxicity were also tested in vitro. Biodistribution and pharmacokinetic studies in healthy rats were carried out using a radiolabeled derivative of the nanosystem. The M33-nanosystem, studied here, showed to be effective against Pseudomonas aeruginosa in time-kill kinetic experiments. Cytotoxicity towards different animal cell lines was acceptable. Lung residence time of the antimicrobial peptide, administered via aerosol in healthy rats, was markedly improved by capturing SET-M33 on dextran nanoparticles. M33-NS was also efficient in eradicating pulmonary infection in a BALB/c mouse model of pneumonia caused by P. aeruginosa. This study revealed that the encapsulation of the antimicrobial peptide in dextran nanoparticles markedly improved lung residence time of the peptide administered via aerosol. The result has to be considered among the aims of the development of a new therapeutic option for patients suffering recurrent infections, that will benefit from high local doses of persistent antimicrobials.


Albatrellus citrinus sp. nov., connected to Picea abies on lime rich soils.
Field observations indicated that a morphotype of Albatrellus subrubescens seemed connected to Picea abies and lime rich soils, while the original morphotype seemed connected with Pinus sylvestris and indifferent to lime. We conducted a molecular study (ITS sequencing of 22 Albatrellus specimens) to test the hypothesis that we in fact had discovered a new species. Our results confirmed the hypothesis, i.e. the Picea taxon (604 bp ITS) had little intraspecific variation in spite of 1600 km distance between samples, but compared with the Pinus taxon (598 bp ITS) the sequence difference was constantly 5.6% regardless of close distance (75 km). We describe the new species A. citrinus, which apart from ecology and ITS sequence, is different from A. subrubescens by a distinct yellowing with age, lack of dark spots of the cap, a mild taste and somewhat narrower spores. A. citrinus seems to be more related to A. ovinus than to A. subrubescens, and A. syringae may not even be a true Albatrellus.


Chick embryo extract demethylates tumor suppressor genes in osteosarcoma cells.
Epigenetics is the study of changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. It is widely accepted that cancer has genetic and epigenetic origins. The idea of epigenetic reprogramming of cancer cells by an embryonic microenvironment possesses potential interest from the prospect of both basic science and potential therapeutic strategies. Chick embryo extract (CEE) has been used for the successful expansion of many specific stem cells and has demonstrated the ability to facilitate DNA demethylation. The current study was conducted to compare the status of DNA methylation in highly metastatic and less metastatic osteosarcoma cells and to investigate whether CEE may affect the epigenetic regulation of tumor suppressor genes and thus change the metastatic phenotypes of highly metastatic osteosarcoma cells. K7M2 murine OS cells were treated with CEE to determine its potential effect on DNA methylation, cell apoptosis, and invasion capacity. Our current results suggest that the methylation status of tumor suppressor genes (p16, p53, and E-cadherin) is significantly greater in highly metastatic mouse ostoesarcoma K7M2 cells in comparison with less metastatic mouse osteosarcoma K12 cells. CEE treatment of K7M2 cells caused demethylation of p16, p53, and E-cadherin genes, upregulated their expression, and resulted in the reversion of metastatic phenotypes in highly metastatic osteosarcoma cells. CEE may promote the reversion of metastatic phenotypes of osteosarcoma cells and can be a helpful tool to study osteosarcoma tumor reversion by epigenetic reprogramming. Demethylation of tumor suppressor genes in osteosarcoma may represent a novel strategy to diminish the metastatic potential of this neoplasm. Further studies, both in vitro and in vivo, are warranted to evaluate the clinical feasibility of this approach as an adjuvant to current therapy.


The importance of arginine codons AGA and AGG for the expression in E. coli of triosephosphate isomerase from seven different species.
Rare arginine codons AGA and AGG affect the heterologous expression of proteins in Eschericha coli. The tRNAs necessary for protein synthesis are scarce in E. coli strain BL21(DE3) pLysS and plentiful in strain BL21(DE3) CodonPlus -RIL. We evaluated in both bacterial strains the effect of these rare codons on the expression of triosephosphate isomerases from 7 different species, whose sequences had different dispositions of rare arginine codons. The ratio of expressed protein (CP/Bl21) correlated with the number of rare codons. Our study shows that the number, position and particularities of the combination of rare Arg codons in the natural non-optimized sequences of the triosephosphate isomerases influence the synthesis of heterologous proteins in E. coli and could have implications in the selection of better sequences for engineering enzymes for novel or manipulated metabolic pathways or for the expression levels of non enzymatic proteins..


Autoimmune hemolytic anemia and cold hemagglutinin disease: clinical disease and laboratory findings.
As is apparent from the length of this review, a multitude of laboratory investigations can be performed on the blood of patients with AIHA and CHD. Unfortunately, because of the considerable complexity of some of these tests, their significance is not always apparent to the physician who treats the patient. Communication gaps between the laboratory scientist and the physician at the bedside are bound to occur because of the high degree of specialization of both immunohematology and medical care. The purpose of this review has been to bridge the communication gap. The agents that cause AIHA and CHD are antibodies. Although they are often autoantibodies of complex specificity, usually reacting with all normal red cells, they nevertheless obey most of the rules explaining the action of alloantibodies that sometimes complicate transfusion therapy. By approaching AIHA and CHD as antibody-induced conditions, and by regarding autoantibodies as similar in their actions to alloantibodies, hopefully, physicians will appreciate the significance of the tests performed in the laboratory. For their part, the laboratory workers will be able not only to report test results but also to explain the findings. This review may aid in establishing the essential dialogue.


Identification of nodal metastases in melanoma using sox-10.
The presence of S100-positive dendritic cells hinders the identification of isolated melanoma tumor cells and micrometastases in sentinel lymph nodes. Sox-10, a transcription factor that plays an important role in schwannian and melanocytic cell development, is not expressed in dendritic cells. We investigated the diagnostic utility of Sox-10 in the identification of metastases in sentinel and nonsentinel lymph nodes for melanoma. We examined the expression pattern of Sox-10, as compared with S100, Melan-A, and HMB-45 in 93 lymph nodes (40 originally reported as positive and 53 originally reported as negative for metastasis) from 33 sentinel lymph node biopsies and regional lymphadenectomies. Sox-10 and S100 both highlighted metastases in 43 of 43 (100%) positive lymph nodes identified in this study; however, Sox-10 immunohistochemical staining significantly improved the detection of nodal metastases. The nuclear staining of Sox-10 promoted improved distinction between heavily pigmented melanophages and melanocytic metastases in 3 positive lymph nodes. In 2 lymph nodes, Sox-10 was critical in distinguishing S100-positive atypical nodal dendritic cells from tumor cells. Also, Sox-10 significantly improved the identification of micrometastases and isolated tumor cells as compared with S100 in 10 positive lymph nodes. Most importantly, Sox-10 identified micrometastases in 2 lymph nodes, originally reported as negative on S100, Melan-A, and HMB-45 immunostains. Therefore, Sox-10 is a comparable marker to S100 in identifying nodal metastases in melanoma and is especially useful in the setting of lymph nodes with heavily pigmented metastases, numerous S100-positive nodal dendritic cells, micrometastases, and isolated tumor cells.


[Bronchiectasis in patients with situs inversus viscerum (Kartagener syndrome) (author's transl)].
The case records of 23 patients with Kartagener Syndrome in the past 10 years were reviewed. For diagnostics bronchoscopy, bilateral bronchography, lung function investigations and angiopulmonography were done. Their immunologic and genetic aspects were studied. Lung resections were performed in 17 patients, 5 of them underwent bilateral pulmonary resections. The lung specimens were investigated morphologically. As top clinico-morphologic features bronchiectasis in patients with situs inversus viscerum did not differ significantly from that without accompanying diseases. Unfavourable hereditary, dyskinesia of bronchial tree, paranasal sinus underdevelopment provoked inflammatory processes of bronchi and development of bronchiectasis.


Exploring the relationship between chronic undernutrition and asymptomatic malaria in Ghanaian children.
A moderate association has been found between asymptomatic parasitaemia and undernutrition. However, additional investigation using the gold standard for asymptomatic parasitaemia confirmation, polymerase chain reaction (PCR), is needed to validate this association. Anthropometric measurements and blood samples from children less than five years of age in a rural Ghanaian community were used to determine if an association exists between chronic undernutrition and PCR-confirmed cases of asymptomatic malaria. This was a descriptive cross-sectional study of 214 children less than five years of age from a community near Kumasi, Ghana. Blood samples and anthropometric measurements from these children were collected during physical examinations conducted in January 2007 by partners of the Barekuma Collaborative Community Development Programme. Findings from the logistic model predicting the odds of asymptomatic malaria indicate that children who experienced mild, moderate or severe stunting were not more likely to have asymptomatic malaria than children who were not stunted. Children experiencing anaemia had an increased likelihood (OR = 4.15; 95% CI: 1.92, 8.98) of asymptomatic malaria. Similarly, increased spleen size, which was measured by ultrasound, was also associated with asymptomatic malaria (OR = 2.17; 95% CI: 1.44, 3.28). Fast breathing, sex of the child, and age of the child were not significantly associated with the asymptomatic malaria. No significant association between chronic undernutrition and presence of asymptomatic malaria was found. Children who experience anaemia and children who have splenomegaly are more likely to present asymptomatic malaria. Programmes aimed at addressing malaria should continue to include nutritional components, especially components that address anaemia.


Room-temperature ferroelectricity in strained SrTiO3.
Systems with a ferroelectric to paraelectric transition in the vicinity of room temperature are useful for devices. Adjusting the ferroelectric transition temperature (T(c)) is traditionally accomplished by chemical substitution-as in Ba(x)Sr(1-x)TiO(3), the material widely investigated for microwave devices in which the dielectric constant (epsilon(r)) at GHz frequencies is tuned by applying a quasi-static electric field. Heterogeneity associated with chemical substitution in such films, however, can broaden this phase transition by hundreds of degrees, which is detrimental to tunability and microwave device performance. An alternative way to adjust T(c) in ferroelectric films is strain. Here we show that epitaxial strain from a newly developed substrate can be harnessed to increase T(c) by hundreds of degrees and produce room-temperature ferroelectricity in strontium titanate, a material that is not normally ferroelectric at any temperature. This strain-induced enhancement in T(c) is the largest ever reported. Spatially resolved images of the local polarization state reveal a uniformity that far exceeds films tailored by chemical substitution. The high epsilon(r) at room temperature in these films (nearly 7,000 at 10 GHz) and its sharp dependence on electric field are promising for device applications.


Superoxide dismutase, catalase and glutathione peroxidase in the human cataractous lens.
The activities of the protective enzymes, superoxide dismutase, catalase and glutathione peroxidase have been measured in the cortical and nuclear sections of 76 human cataractous lenses as well as in calf, rabbit and rat lenses. No changes was observed in the activity of catalase with the progressive development of cataract. However, a precipitous decrease (70%) in both superoxide dismutase and glutathione peroxidase in the nuclear region of the lens was found at the onset of nuclear cataract. Further decreases accompanied the progression of the cataract and similar, but less marked, decreases were observed in the cortical region of the lens. It is suggested that the inactivation of these enzymes may result in an elevation of the H2O2 and O2.- levels in the lens and that this may be responsible for the oxidative modification of lens proteins observed in nuclear cataracts.