Molecular cloning of complementary DNA for the alpha subunit of the G protein that stimulates adenylate cyclase.
A complementary DNA clone encoding the alpha subunit of the adenylate cyclase stimulatory G protein (Gs) was isolated and identified. A bovine brain complementary DNA library was screened with an oligonucleotide probe derived from amino acid sequence common to known G proteins. The only clone that was obtained with this probe has a complementary DNA insert of approximately 1670 base pairs. An antibody to a peptide synthesized according to deduced amino acid sequence reacts specifically with the alpha subunit of Gs. In addition, RNA that hybridizes with probes made from the clone is detected in wild-type S49 cells; however, cyc- S49 cells, which are deficient in Gs alpha activity, are devoid of this messenger RNA.


No evidence for left superior temporal dysfunction in asymptomatic schizophrenia and bipolar disorder. PET study of verbal fluency.
Positron emission tomography (PET) studies have revealed functional left superior temporal gyrus (STG) abnormalities in symptomatic schizophrenia during word generation. To discover if this dysfunction is present in asymptomatic schizophrenia. To determine whether, without concurrent symptomatology, schizophrenia and bipolar affective disorder (BPD) are distinguishable by differing regional cerebral blood flow (rCBF) patterns during word generation. A PET verbal fluency protocol was applied to six patients with BPD in remission and six patients with asymptomatic schizophrenia. Analysis included 10 control subjects from a contemporaneous study. All groups showed relative reduction of rCBF in both superior temporal cortices. There were no quantitative differences in any group comparison. All groups exhibited negative covariation between rCBF in left prefrontal and right (but not left) temporal regions. Abnormal patterns of left STG function cannot be regarded as a trait marker for schizophrenia. Functional abnormalities may reflect aspects of mental state.


Bisphosphonate remains highly localized after elution from porous implants.
Local elution of zoledronic acid from a porous implant reportedly enhances periimplant bone formation and implant fixation. However, there is no information in the literature on the extent to which eluted bisphosphonate remains localized around the implant or becomes systemically distributed. We ascertained to what extent eluted zoledronic acid remains local and whether there is systemic exposure after local elution from porous implants. A hydroxyapatite-coated porous tantalum implant dosed with 100 μg (14)C-labeled zoledronic acid was implanted into the left femoral intramedullary canal of six dogs. Bone samples near to and distant from the implant were harvested from three dogs at 6 weeks and three dogs at 52 weeks. The concentration of radiolabeled bisphosphonate in each sample was quantified using liquid scintillation spectrophotometry and its distribution in periimplant bone was revealed by exposing histologic sections to autoradiography film. In all six dogs, the concentration of zoledronic acid in immediate periimplant bone was two orders of magnitude higher than in any other sampled tissue, averaging 732.6 ng/g at 6 weeks and 377.2 ng/g at 52 weeks. Minute amounts of zoledronic acid (≤ 7.2 ng/g) were detected throughout the skeleton, indicating some escape into the circulation after local elution. Autoradiographs revealed the greatest concentration of zoledronic acid on and within the implant, with rapid decrease short distances away and no uptake within the femoral cortex. Zoledronic acid eluted from an implant remains mainly localized with minimal systemic distribution. Local bisphosphonate elution reduces the risk of systemic side effects and skeletal bisphosphonate exposure.


Influence of dissolved oxygen concentration on intracellular pH for regulation of Aspergillus niger growth rate during citric acid fermentation in a stirred tank bioreactor.
In this paper we report the regulation of Aspergillus niger growth rate during citric acid fermentation in a stirred tank bioreactor. For this, the influence of dissolved oxygen concentration in a medium on intracellular pH values and consequently on overall microbial metabolism was emphasized. Intracellular pH of mycelium grown under different concentrations of dissolved oxygen in the medium was determined. Sensitivity of proteins toward proton concentration is well recognized, therefore pH influences on the activities of key regulatory enzymes of Aspergillus niger were determined at pH values similar to those detected in the cells grown under lower dissolved oxygen concentrations. The results have shown significantly reduced specific activities of hexokinase, 6-phosphofructokinase and glucose-6-phosphate dehydrogenase in more acidic environment, while pyruvate kinase was found to be relatively insensitive towards higher proton concentration. As expected, due to the reduced specific activities of regulatory enzymes under more acidic conditions, overall metabolism should be hindered in the medium with lower dissolved oxygen concentration which was confirmed by detecting the reduced specific growth rates. From the studies, we conclude that dissolved oxygen concentration affects the intracellular pH and thus growth rate of Aspergillus niger during the fermentation process.


Intraventricular metastatic clear cell renal carcinoma.
Intraventricular tumors represent a diagnostic problem, due to a wide range of differential diagnosis, with an important variability of tumoral histological types in adult and pediatric population. Patient, Our case is represented by a patient, aged 48 years, without any history of significant personal pathology, accusing nausea, vomiting, and intensive headache. In the morning, he became confused, having hallucinations for a short period of time, and has accused drowsiness for several weeks. Imaging (CT and MRI) shows a neoformation in the third ventricle, accompanied by bilateral lateral ventricles dilatation, with predominantly annular enhancement. During surgery, through the middle third transcallosal interhemispheric approach, it was revealed a reddish, well-demarcated intraventricular mass, well vascularized and with a firm consistency. Final pathologic diagnosis was metastatic clear cell renal carcinoma. Initial postoperative evolution was good, and then neurological and respiratory condition worsened as a bronchopneumonia lead to patient's death in 12 days after surgery. Clear cell carcinoma metastasis located in the third ventricle should be taken into consideration for patients presenting a single intraventricular lesion even they have no documented primary malignancy.


Study and application of coupling relationship between water-salt-resistivity-soil structure in saline soils in arid and semi-arid areas of northwest China.
Widespread saline soils in Northwest China pose a serious threat to the region's ability to use infrastructure safely because they are prone to soil structure damage when subjected to external environmental fluctuations, which in turn affects the stability of the foundations for buildings. The non-destructive approach of measuring resistivity can be used to swiftly reflect the subsoil body's state and make assumptions about its safety. However, the electrical resistivity of the underground soil body can be used to quickly identify unstable areas because the resistivity is influenced by the water content, salt content, and structural characteristics of the soil body. To do this, it is necessary to understand the coupling relationship between various factors. In this study, we first constructed samples with various water, salt, and soil structure characteristics, and then used indoor tests, such as soil resistivity measurement and thermogravimetric analysis, to analyze the multiple factors affecting the resistivity characteristics of the soil. The relationship between soil resistivity and actual saline soil diseases in Northwest China was then further discussed in conjunction with the results of the indoor tests and analyses. subsequently, the resistivity and soil properties have been measured in the field at specific locations in Northwest China where railway roadbeds are diseased. The study's findings can theoretically support a deeper comprehension of the law and mechanism of soil resistivity change, as well as provide assistance for building infrastructure in Northwest China.


Stochastic dynamics of hematopoietic tumor stem cells.
Many tumors derive from the transformation of normal stem cells into cancer stem cells that retain their self-renewal capacity. This modern view of cancer has provided a natural explanation for the striking parallels which exist between these two different types of self-renewing cells. Here we develop a simple mathematical model to investigate the implications of this concept regarding the evolution of tumors in the hematopoietic system. Our results unequivocally demonstrate that stochastic effects related to the finite size of the active stem cell population have a profound influence on the dynamics of cancer evolution. For input parameters compatible with both the natural history of human cancer and mouse models, our results show how stochastic dynamics alone may lead to both remission in some cases and rapid expansion in others.


Mammary Carcinoma Arising in Microglandular Adenosis: A Report of Five Cases.
Mammary carcinoma arising in microglandular adenosis (MGA) is extremely rare, and MGA is regarded as a non-obligate precursor of triple-negative breast cancer. We report five cases of carcinoma arising in MGA of the breast. All cases showed a spectrum of proliferative lesions ranging from MGA to atypical MGA, ductal carcinoma in situ or invasive carcinoma. Immunohistochemically, all cases were triple-negative and expression of S-100 protein gradually decreased as the lesions progressed from MGA to atypical MGA and carcinoma. Three cases showed acinic cell differentiation with reactivity to α1-antitrypsin, and one case was metaplastic carcinoma. During clinical follow-up, one patient developed local recurrence. Carcinoma arising in MGA is a rare but distinct subset of triple-negative breast cancer with characteristic histologic and immunohistochemical findings.


NKp44 and Natural Cytotoxicity Receptors as Damage-Associated Molecular Pattern Recognition Receptors.
Natural killer (NK) cells are a key constituent of the innate immune system, protecting against bacteria, virally infected cells, and cancer. Recognition and protective function against such cells are dictated by activating and inhibitory receptors on the surface of the NK cell, which bind to specific ligands on the surface of target cells. Among the activating receptors is a small class of specialized receptors termed the natural cytotoxicity receptors (NCRs) comprised of NKp30, NKp46, and NKp44. The NCRs are key receptors in the recognition and termination of virally infected and tumor cells. Since their discovery over 10 years ago, ligands corresponding to the NCRs have largely remained elusive. Recent identification of the cellular ligands for NKp44 and NKp30 as exosomal proliferating cell nuclear antigen (PCNA) and HLA-B-associated transcript 3 (BAT3), respectively, implicate that NCRs may function as receptors for damage-associated molecular pattern (DAMP) molecules. In this review, we focus on NKp44, which surprisingly recognizes two distinct ligands resulting in either activation or inhibition of NK cell effector responses in response to tumor cells. The inhibitory function of NKp44 requires further study as it may play a pivotal role in placentation in addition to being exploited by tumors as a mechanism to escape NK cell killing. Finally, we suggest that the NCRs are a class of pattern recognition receptors, which recognize signals of genomic instability and cellular stress via interaction with the c-terminus of DAMP molecules localized to the surface of target cells by various co-ligands.


Uncontrolled asthma in a commercially insured population from 2002 to 2007: trends, predictors, and costs.
Uncontrolled asthma leads to preventable morbidity and increased health care utilization. The authors examined trends, predictors, and costs of uncontrolled asthma over 5 years in a large health plan population. The authors retrospectively examined administrative health claims data from mid-2000 to mid-2007 on patients with asthma aged 1 to 56 years (n = 54,653 patient-years, 28,595 unique patients). Uncontrolled asthma events were defined as > or =2 oral steroid fills or > or =5 short-acting beta(2)-agonist (SABA) fills over 12 months, or an asthma-related hospitalization or emergency department (ED) visit. Multivariate generalized mixed regression models determined patient- and neighborhood-level predictors for uncontrolled asthma events. The authors compared asthma-related costs for patients with and without uncontrolled asthma events. In 2002-2003, 39% of patients had > or =1 uncontrolled asthma event. Most frequent were high use of rescue asthma medications. Asthma-related hospitalizations and ED visits were infrequent. The percentage having uncontrolled asthma events decreased significantly over time to 27% in 2006-2007, due to a decreased rate of frequent SABA fills. Males and adults > or =24 years had higher odds of medication-based uncontrolled asthma events, whereas residence in neighborhoods with more minorities and lower educational attainment was associated with ED visits or hospitalizations. Patients with uncontrolled asthma events had significantly higher asthma-related costs. In this population, the proportion of patients with uncontrolled asthma, particularly as indicated by high SABA fills, decreased over a 5-year period. Several individual- and neighborhood-level characteristics were associated with uncontrolled asthma events. Clinicians and health plans can identify higher-risk patients in order to target asthma management strategies and reduce asthma-related morbidity and its associated costs.


The 190 kDa centrosome-associated protein of Drosophila melanogaster contains four zinc finger motifs and binds to specific sites on polytene chromosomes.
Microinjection of a bacterially expressed, TRITC labelled fragment of the centrosome-associated protein CP190 of Drosophila melanogaster, into syncytial Drosophila embryos, shows it to associate with the centrosomes during mitosis, and to relocate to chromatin during interphase. Indirect immunofluorescence staining of salivary gland chromosomes of third instar Drosophila larvae, with antibodies specific to CP190, indicate that the protein is associated with a large number of loci on these interphase polytene chromosomes. The 190 kDa CP190 protein is encoded by a 4.1 kb transcript with a single, long open reading frame specifying a polypeptide of 1,096 amino acids, with a molecular mass of 120 kDa, and an isoelectric point of 4.5. The central region of the predicted amino acid sequence of the CP190 protein contains four CysX2CysX12HisX4His zinc-finger motifs which are similar to those described for several well characterised DNA binding proteins. The data suggest that the function of CP190 involves cell cycle dependent associations with both the centrosome, and with specific chromosomal loci.


Nourishing the Cognition with Millets: A Comprehensive Review of Their Nutritional Impact and Potential as Cognitive Enhancers.
Cognition is the mental processes and abilities involved in acquiring, storing, retrieving and using it for decision making. Cognitive decline due to aging, lifestyle factor, chronic health conditions, genetic, and environmental factors are rising global concern and propose a potential threat to the cognitive health. The nutritional imbalance has led to increase in cognitive disorders around the world. Millets can be a nutritional intervention for promoting cognitive health and preventing cognitive decline. Millets has abundant phenolic compounds, flavonoids, and antioxidants to protect against oxidative stress-induced cognitive impairment. Millets exert neuroprotective effects by modulating pathways involved in neuronal-survival, synaptic-plasticity, and release of brain-derived neurotrophic factor. Millets demonstrates anti-inflammatory properties by regulating inflammatory-pathways and suppressing cytokines associated with cognitive impairment. Millets maintain healthy gut microbiota by producing metabolites such as short-chain fatty acids, which influence brain function and cognition. However, further research is needed to elucidate the underlying mechanisms and on optimizing the proportion do exploit its potential. Implementing millet-based dietary strategies through public health initiatives and educational programs can be a practical approach to support cognitive health across populations. Harnessing the potential of millets as a nutritional intervention offers a promising avenue for promoting cognitive health and improving the quality of life.


Spatial pattern formation during aggregation of the slime mould Dictyostelium discoideum.
Stream formation and spiral wave behaviour during the aggregation of Dictyostelium discoideum (Dd) are studied in a model based on the Martiel-Goldbeter equations for cAMP relay, combined with chemotactic motion of Dd cells. The results show that stream formation occurs if the turnover rate of intracellular cAMP is increased. This increase in the turnover rate of cAMP[in] leads to a dependence of the speed of the cAMP wave on the cell density. We propose that this dependence of wave speed on cell density is the underlying mechanism for stream formation. Besides stream formation, increasing the turnover rate of cAMP[in] also results in a spiral wave period that decreases during aggregation, a phenomenon that is commonly observed in situ. Furthermore, the dependence of wave speed on cell density is measured empirically. The speed of the cAMP wave is found to decrease as the wave travels from high to low cell density. This indicates that in situ, wave speed does depend on cell density.


Your note, your way: how to write an inpatient progress note accurately and efficiently as an intern.
A physician's progress note is an essential piece of documentation regarding key events and the daily status of patients during their hospital stay. It serves not only as a communication tool between care team members, but also chronicles clinical status and pertinent updates to their medical care. Despite the importance of these documents, little literature exists on how to help residents to improve the quality of their daily progress notes. A narrative literature review of English language literature was performed and summated to provide recommendations on how to write an inpatient progress note more accurately and efficiently. In addition, the authors will also introduce a method to build a personal template with the goal of extracting relevant data automatically to reduce clicks for an inpatient progress note in the electronic medical record system.


A stereoselective synthesis of anti-gamma,delta-alkynyl- and -alkenyl-beta-hydroxy-alpha-amino esters from tin(II) enolates of glycinate.
Condensations between the tin(II) enolate 11 of ethyl N-tosylglycinate and conjugated ynals 12 and ynones 14 are highly diastereoselective, in favour of the anti-isomers 13 and 15; similar reactions of enals and enones 17 show lower but still useful levels of anti-stereoselectivity.


Heat stress destabilizes symbiotic nutrient cycling in corals.
Recurrent mass bleaching events are pushing coral reefs worldwide to the brink of ecological collapse. While the symptoms and consequences of this breakdown of the coral-algal symbiosis have been extensively characterized, our understanding of the underlying causes remains incomplete. Here, we investigated the nutrient fluxes and the physiological as well as molecular responses of the widespread coral Stylophora pistillata to heat stress prior to the onset of bleaching to identify processes involved in the breakdown of the coral-algal symbiosis. We show that altered nutrient cycling during heat stress is a primary driver of the functional breakdown of the symbiosis. Heat stress increased the metabolic energy demand of the coral host, which was compensated by the catabolic degradation of amino acids. The resulting shift from net uptake to release of ammonium by the coral holobiont subsequently promoted the growth of algal symbionts and retention of photosynthates. Together, these processes form a feedback loop that will gradually lead to the decoupling of carbon translocation from the symbiont to the host. Energy limitation and altered symbiotic nutrient cycling are thus key factors in the early heat stress response, directly contributing to the breakdown of the coral-algal symbiosis. Interpreting the stability of the coral holobiont in light of its metabolic interactions provides a missing link in our understanding of the environmental drivers of bleaching and may ultimately help uncover fundamental processes underpinning the functioning of endosymbioses in general.


Pharmacological characterization of the human 5-HT(4(d)) receptor splice variant stably expressed in Chinese hamster ovary cells.
The recently identified C-terminal splice variant of the human 5-HT(4) receptor, the h5-HT(4(d)) receptor, was stably expressed in a CHO cell line at 493+/-25 fmol mg(-1) protein. We analysed its pharmacological properties by measuring binding affinities and 5-HT(4) ligand-induced cyclic AMP production. The pharmacological binding profile determined in competition studies with the specific antagonist [(3)H]-GR113808 revealed a rank order of affinity of 5-HT(4) ligands for the h5-HT(4(d)) receptor that was consistent with those previously reported for other 5-HT(4) receptor isoforms. In adenylyl cyclase functional assays, the h5-HT(4(d)) receptor displayed equipotent coupling for all 5-HT(4) agonists tested (EC(50) in the range of 1 - 6 nM). EC(50) values were lower than those previously obtained with the 5-HT(4(e)) receptor stably expressed in CHO cells indicating that the 5-HT(4(d)) receptor was more efficiently coupled to its effector than the 5-HT(4(e)) receptor isoform. Moreover, in terms of agonist efficacy (E(max)), the benzamide derivative, renzapride displayed full agonist properties at the h5-HT(4(d)) receptor (same E(max) as 5-HT) whereas it was previously shown to be a partial agonist at the h5-HT(4(e)) receptor. A constitutive activity of the h5-HT(4(d)) receptor was observed in CHO cells in the absence of any 5-HT(4) ligand. Surprisingly, two 5-HT(4) ligands, SB204070 and RS39604 which are described as highly potent antagonists in various biological models, revealed partial agonist properties at the h5-HT(4(d)) receptor. We conclude that C-terminal tails of 5-HT(4) receptor isoforms may directly influence their functional properties.


Quality of cardiovascular disease care in Ontario's primary care practices: a cross sectional study examining differences in guideline adherence by patient sex.
Women are disproportionately affected by cardiovascular disease, often experiencing poorer outcomes following a cardiovascular event. Evidence points to inequities in processes of care as a potential contributing factor. This study sought to determine whether any sex differences exist in adherence to process of care guidelines for cardiovascular disease within primary care practices in Ontario, Canada. This is a secondary analysis of pooled cross-sectional baseline data collected through a larger quality improvement initiative known as the Improved Delivery of Cardiovascular Care (IDOCC). Chart abstraction was performed for 4,931 patients from 84 primary care practices in Eastern Ontario who had, or were at high risk of, cardiovascular disease. Measures examining adherence to guidelines associated with nine areas of cardiovascular care (coronary artery disease, peripheral vascular disease (PVD), stroke/transient ischemic attack, chronic kidney disease, diabetes, dyslipidemia, hypertension, smoking cessation, and weight management) were collected. Multivariable logistic regression analysis was performed to evaluate sex differences, adjusting for age, physician remuneration, and rurality. Women were significantly less likely to have their lipid profiles taken (OR=1.17, 95% CI 1.03-1.33), be prescribed lipid lowering medication for dyslipidemia (OR=1.54, 95% CI 1.20-1.97), and to be prescribed ASA following stroke (OR=1.56, 95% CI 1.39-1.75). Women with PVD were significantly less likely to be prescribed ACE inhibitors and/or angiotensin receptor blockers (OR=1.74, 95% CI 1.25-2.41) and lipid lowering medications (OR=1.95, 95% CI 1.46-2.62) or ASA (OR=1.59, 95% CI 1.43-1.78). However, women were more likely to have two blood pressure measurements taken and to be referred to a dietician or weight loss program. Male patients with diabetes were less likely to be prescribed glycemic control medication (OR=0.84, 95% CI 0.74-0.86). Sex disparities exist in the quality of cardiovascular care in Canadian primary care practices, which tend to favour men. Women with PVD have a particularly high risk of not receiving appropriate medications. Our findings indicate that improvements in care delivery should be made to address these issues, particularly with regard to the prescribing of recommended medications for women, and preventive measures for men.


Asymmetrical distribution of cardiolipin in yeast inner mitochondrial membrane triggered by carbon catabolite repression.
Transmembrane asymmetry of cardiolipin in yeast was monitored during the switch from fermentative to gluconeogenic growth and the reverse. As soon as cells used ethanol as an electron donor to produce ATP by oxidative phosphorylation, rapid and abundant cardiolipin synthesis was observed on the matrix side of the inner mitochondrial membrane followed by a transverse rearrangement between the two leaflets. The cardiolipin distribution changed from about 20:80 (in/out) to 70:30 (in/out), and after translocation towards the outer leaflet it finally became 37:63 (in/out). At the same time, cytochrome c oxidase activity remained stable, then increased as a possible result of the topographical rearrangement. During the reverse process from gluconeogenic to fermentative growth, the amount of cardiolipin rapidly decreased by half, its bilayer distribution apparently changing to a monolayer organization before the 20:80 (in/out) asymmetry of repressed cells was re-established. Experimental impairment of cardiolipin topography by antibiotic inhibition of gene expression or in situ dissipation of mitochondrial membrane potential produced data that prove that the amount and transmembrane distribution of the phospholipid are two specific parameters of the mitochondrial inner membrane organization in both fermentative (2.2 fmol/cell and 20:80, in/out) and gluconeogenic (4.2 fmol/cell and 37:63, in/out) growing yeast cells. Finally, the inner mitochondrial membrane topography of cardiolipin appeared to be closely associated with the transmembrane redox potential.


A new highly effective short-term therapy schedule for Helicobacter pylori eradication.
Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (< 80%). To evaluate the efficacy of a new short-term treatment sequence on H. pylori eradication. A total of 52 patients with H. pylori infection and either non-ulcer dyspepsia (34 patients) or peptic ulcer (18 patients) were enrolled to receive a 10-day therapy: omeprazole 20 mg b.d. plus amoxycillin 1 g b.d. for the first 5 days, followed by omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Bacterial eradication was assessed by endoscopy (peptic ulcer patients) or 13C urea breath test (non-ulcer dyspepsia patients) 4-6 weeks after therapy had ended. All patients completed the study. H. pylori eradication was achieved in all but one patient, with an eradication rate of 98% (95% CI: 94.3-100) with intention-to-treat analysis. Patient compliance was good (consumption of prescribed drugs > 95%) for all but one patient, who took the triple therapy regimen for 4 days instead of 5 days. No major side-effects were reported but three (6%) patients complained of mild side-effects. The use of this 'five plus five' therapy schedule as an initial treatment for H. pylori deserves further investigation.


Selective determination of tobacco-specific nitrosamines in mainstream cigarette smoke by GC coupled to positive chemical ionization triple quadrupole MS.
A rapid method for the selective determination of four kinds of tobacco-specific nitrosamines, N-nitrosonornicotine, N-nitrosoanatabine, N-nitrosoanabasine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, in mainstream cigarette smoke was developed by GC coupled to positive chemical ionization triple-quadrupole MS. After mainstream cigarette smoke was collected on a cambridge filter pad, the particulate matter was extracted with 0.1 M HCL aqueous solution, cleaned by positive cation-exchange solid extraction, and finally injected into GC-MS/MS using isotopically labeled analogues as internal standards. Excellent linearity was obtained over the concentration range of 0.5-200.0 ng mL(-1) for all tobacco-specific nitrosamines with values for correlation coefficient between 0.9996-0.9999. Limits of detection of each tobacco specific nitrosamine varied from 0.023-0.028 ng cig(-1), and lower limits of quantification varied from 0.077-0.093 ng cig(-1). The recovery of each tobacco specific nitrosamine was from 90.0-109.0%. The relative standard deviations of the intra-day and inter-day precisions were 3.1-5.8 and 3.9-6.6, respectively. This method was applied to reference and domestic cigarettes. The result showed that the method was consistent with traditional methods and can be used as an effective approach for the routine analysis of tobacco-specific nitrosamines.


Disease-causing cystathionine β-synthase linker mutations impair allosteric regulation.
Cystathionine β-synthase (CBS) catalyzes the committing step in the transsulfuration pathway, which is important for clearing homocysteine and furnishing cysteine. The transsulfuration pathway also generates H2S, a signaling molecule. CBS is a modular protein with a heme and pyridoxal phosphate-binding catalytic core, which is separated by a linker region from the C-terminal regulatory domain that binds S-adenosylmethionine (AdoMet), an allosteric activator. Recent cryo-EM structures reveal that CBS exists in a fibrillar form and undergoes a dramatic architectural rearrangement between the basal and AdoMet-bound states. CBS is the single most common locus of mutations associated with homocystinuria, and, in this study, we have characterized three clinical variants (K384E/N and M391I), which reside in the linker region. The native fibrillar form is destabilized in the variants, and differences in their limited proteolytic fingerprints also reveal conformational alterations. The crystal structure of the truncated K384N variant, lacking the regulatory domain, reveals that the overall fold of the catalytic core is unperturbed. M391I CBS exhibits a modest (1.4-fold) decrease while the K384E/N variants exhibit a significant (∼8-fold) decrease in basal activity, which is either unresponsive to or inhibited by AdoMet. Pre-steady state kinetic analyses reveal that the K384E/N substitutions exhibit pleiotropic effects and that the differences between them are expressed in the second half reaction, that is, homocysteine binding and reaction with the aminoacrylate intermediate. Together, these studies point to an important role for the linker in stabilizing the higher-order oligomeric structure of CBS and enabling AdoMet-dependent regulation.


[Functional and aesthetic significance of the uvula in cleft palate repair].
To investigate functional and aesthetic role of uvula in cleft palate repair. Forty-one patients aged from 1 year 2 months to 7 years were included in this study with congenital cleft lip and/or palate. The morphological investigation of the resected hemi- uvula was done. Palatoplasty was performed in all cases. According to morphological results, most of the resected hemi-uvula consisted of vascularized fibrous tissue, covered with epithelium. In three groups of patients (with unilateral, bilateral and isolated cleft palate), the duration of the surgery and intraoperative blood loss did not exceed similar values for conventional methods. The volume of infusion therapy revealed a deficit of fluid intake of no more than 30%, which indicates early restoration of swallowing function. The technique of preserving one of the «hemi-uvulas» lead to excellent aesthetic results and increasing functionality. Resection of one of the «hemi-uvulas» is safe and physiological.


Expression of viral early functions in rat 3Y1 cells infected with human papovavirus BK.
A plaque morphology mutant (pm-522) of BK virus (BKV) with a small deletion at map unit 0.72 can readily transform rat 3Y1 cells, but wild-type BKV (wt-501) cannot. We examined the expression of the viral early functions in BKV (wt-501 or pm-522)-infected 3Y1 cells within a 2-week period after infection, before foci of transformed cells became detectable, to know how the difference between the two BKVs occurs. After a high-multiplicity infection, comparable amounts of free viral DNA (forms I and II) were found by Southern blotting analyses to persist in the nuclei of the cells infected with wt and pm BKVs. Whereas the proportion of T antigen-positive cells, as revealed by the indirect immunofluorescence method with complement, remained at a level of 60% in pm BKV infection, the level of T antigen-positive cells in wt BKV infection decreased from the initial 45% to 1% on day 9. The results obtained by the immunoprecipitation analyses of radiolabeled proteins from the infected cells were consistent with the immunofluorescence data. Viral early mRNA was detectable on day 2 and increased on day 9 in pm BKV infection, but in wt BKV infection, the low level of early mRNA detected on day 2 disappeared on day 9. Cell DNA synthesis and cell growth were enhanced more in pm BKV infection than in wt BKV infection. The low level of viral DNA synthesis that occurred in the infected rat cells was more prominent in pm BKV infection than in wt BKV infection. These data indicate that the expression of viral early functions continued much longer in pm BKV-infected rat cells than in wt BKV-infected rat cells, where the expression was probably repressed soon after infection. Continued T antigen production directed by the unintegrated viral genomes appears to be required for efficient transformation of rat cells by BKV.


Cross-sectional community-based study of the socio-demographic factors associated with the prevalence of dengue in the eastern part of Sudan in 2011.
Dengue is caused by an arthropod-borne flavivirus. Infection can be either primary or secondary based on serology, with each stage of the disease characterized by specific serological conversion and antibody formation. Further study is needed to fully identify the factors associated with and predisposing to dengue infection. The objective of this study was to identify socio-demographic factors associated with the prevalence of dengue serotypes in Kassala State in the eastern part of Sudan in 2011. This was a cross-sectional community-based study with 530 participants who were randomly selected through multi-stage cluster sampling. Dengue serotype prevalence was determined using capture Enzyme-linked immunosorbent assay (ELISA). ELISA IgG. A multivariate logistic regression model was designed to measure the strength of associations between socio-demographic factors and dengue serotype prevalence. All participants who tested negative for dengue were used as the statistical reference group. From this study, the prevalence of dengue in Kassala was estimated to be 9.4% (95% CI: 7.1-12.3). Lack of knowledge about dengue fever disease (OR 2.8, 95% CI: 1.24-6.53) and a household density of more than 3 people per room (OR 2.1, 95% CI: 1.06-4.09) were the most important factors associated with dengue infection among the study population. Community-oriented interventions are needed to modify existing social behaviors to reduce the risk of dengue in the eastern part of Sudan. Additional studies are also required in this field.


Uncoupling protein 2 impacts endothelial phenotype via p53-mediated control of mitochondrial dynamics.
Mitochondria, although required for cellular ATP production, are also known to have other important functions that may include modulating cellular responses to environmental stimuli. However, the mechanisms whereby mitochondria impact cellular phenotype are not yet clear. To determine how mitochondria impact endothelial cell function. We report here that stimuli for endothelial cell proliferation evoke strong upregulation of mitochondrial uncoupling protein 2 (UCP2). Analysis in silico indicated increased UCP2 expression is common in highly proliferative cell types, including cancer cells. Upregulation of UCP2 was critical for controlling mitochondrial membrane potential (Δψ) and superoxide production. In the absence of UCP2, endothelial growth stimulation provoked mitochondrial network fragmentation and premature senescence via a mechanism involving superoxide-mediated p53 activation. Mitochondrial network fragmentation was both necessary and sufficient for the impact of UCP2 on endothelial cell phenotype. These data identify a novel mechanism whereby mitochondria preserve normal network integrity and impact cell phenotype via dynamic regulation of UCP2.


Extrastriatal uptake related to dopaminergic dysfunction on 99mTc-TRODAT-1 brain SPECT in patient with atypical meningioma.
Extrastriatal accumulation on technetium-99m-([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]- ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)])(99mTc)-TRODAT-1 is unexpected during nuclear medicine nigrostriatal pathway examinations on 99mTc-TRODAT-1 brain single photon emission computed tomography (SPECT). An 86-year-old female with a history of right hemiparesis, speech expressive difficulties, unstable gait, and bradykinesia on right side was reported. Technetium-99m -TRODAT-1 dopamine transporter SPECT revealed an incidental extrastriatal accumulation of radiotracer in the left anterior frontal region, accompanied by a photopenic area which resulted in the displacement of the left striatum with decreased dopaminergic neuronal function. The brain magnetic resonance imaging (MRI) revealed an invasive meningioma corresponding to the extrastriatal uptake on SPECT, accompanied by edema and mass effect. The patient received surgery and the histopathological results confirmed the diagnosis of atypical meningioma.This study emphasizes the importance of understanding the underlying causes of extrastriatal uptake from 99mTc-TRODAT-1 brain SPECT, which may indicate an invasive brain tumor.


Impact of particle size, oxidation state and capping agent of different cerium dioxide nanoparticles on the phosphate-induced transformations at different pH and concentration.
The potential hazard posed by nanomaterials can be significantly influenced by transformations which these materials undergo during their lifecycle, from manufacturing through to disposal. The transformations may depend on the nanomaterials' own physicochemical properties as well as the environment they are exposed to. This study focuses on the mechanisms of transformation of cerium oxide nanoparticles (CeO2 NPs) in laboratory experiments which simulate potential scenarios in which the NPs are exposed to phosphate-bearing media. We have experimented with the transformation of four different kinds of CeO2 NPs, in order to investigate the effects of nanoparticle size, capping agent (three were uncapped and one was PVP capped) and oxidation state (two consisted mostly of Ce4+ and two were a mix of Ce3+/Ce4+). They were exposed to a reaction solution containing KH2PO4, citric acid and ascorbic acid at pH values of 2.3, 5.5 and 12.3, and concentrations of 1mM and 5mM. The transformations were followed by UV-vis, zeta potential and XRD measurements, which were taken after 7 and 21 days, and by transmission electron microscopy after 21 days. X-ray photoelectron spectroscopy was measured at 5mM concentration after 21 days for some samples. Results show that for pH 5 and 5mM phosphate concentration, CePO4 NPs were formed. Nanoparticles that were mostly Ce4+ did not dissolve at 1mM reagent concentration, and did not produce CePO4 NPs. When PVP was present as a capping agent it proved to be an extra reducing agent, and CePO4 was found under all conditions used. This is the first paper where the transformation of CeO2 NPs in the presence of phosphate has been studied for particles with different size, shapes and capping agents, in a range of different conditions and using many different characterisation methods.


Gravitational waves and electrodynamics: new perspectives.
Given the recent direct measurement of gravitational waves (GWs) by the LIGO-VIRGO collaboration, the coupling between electromagnetic fields and gravity have a special relevance since it opens new perspectives for future GW detectors and also potentially provides information on the physics of highly energetic GW sources. We explore such couplings using the field equations of electrodynamics on (pseudo) Riemann manifolds and apply it to the background of a GW, seen as a linear perturbation of Minkowski geometry. Electric and magnetic oscillations are induced that propagate as electromagnetic waves and contain information as regards the GW which generates them. The most relevant results are the presence of longitudinal modes and dynamical polarization patterns of electromagnetic radiation induced by GWs. These effects might be amplified using appropriate resonators, effectively improving the signal to noise ratio around a specific frequency. We also briefly address the generation of charge density fluctuations induced by GWs and the implications for astrophysics.


Growth hormone-dependent potentiation of gonadotropin-stimulated steroid production by ovarian follicles of the goldfish.
The possible involvement of growth hormone (GH) in the regulation of ovarian function in the goldfish was investigated by determining the effects of common carp GH on steroid production by vitellogenic and preovulatory ovarian follicles incubated in vitro. Carp GH acts in a dose-dependent manner to potentiate the actions of common carp gonadotropin (GtH) on the production of 17 beta-estradiol and testosterone by vitellogenic ovarian follicles and the actions of human chorionic gonadotropin (hCG) on testosterone production by preovulatory ovarian follicles. Carp GH alone had no effect on basal steroid secretion by either class of ovarian follicles. Chum salmon GH but not bovine GH also enhanced carp GtH-induced production of 17 beta-estradiol by vitellogenic ovarian follicles. Common carp prolactin had no effects on basal or GtH-stimulated steroid production by vitellogenic or preovulatory ovarian follicles. The actions of carp GH on preovulatory follicles were not apparent when tested with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, suggesting that GH may act to enhance either the formation or actions of cAMP. In summary, these data demonstrate that GH has a direct modulatory effect on GtH-stimulated steroid production and suggest that GH may be an important regulator of follicular development in the goldfish.


The seventh annual Gordon K. Moe Lecture. Atrial fibrillation: from cell t bedside.
Atrial fibrillation is the most common sustained tachyarrhythmia and, as such, has become the recent focus of intense clinical and experimental interest. Because of its associated morbidity and mortality, there is a multidisciplinary effort to understand the pathophysiology that may ultimately lead to improved therapeutic options. This review concentrates on three aspects of atrial fibrillation that influence contemporary choices for treatment: an electrophysiologic basis for initiation of atrial fibrillation, anatomic and electrophysiologic remodeling, and concepts regarding its termination or prevention.


Genetic variation of root angle distribution in rice (Oryza sativa L.) seedlings.
We developed a new method of using seedling trays to evaluate root angle distribution in rice (Oryza sativa. L), and found a wide genetic variation among cultivars. The seedling tray method can be used to evaluate in detail the growth angles of rice crown roots at the seedling stage by allocating nine scores (10° to 90°). Unlike basket methods, it can handle large plant populations over a short growth period (only 14 days). By using the method, we characterized the root angle distributions of 97 accessions into two cluster groups: A and B. The numbers of accessions in group A were limited, and these were categorized as shallow rooting types including soil-surface root. Group B included from shallow to deep rooting types; both included Indica and Japonica Group cultivars, lowland and upland cultivars, and landraces and improved types. No relationship between variation in root vertical angle and total root number was found. The variation in root angle distribution was not related to differentiation between the Japonica and Indica Groups, among ecosystems used for rice cultivation, or among degrees of genetic improvement. The new evaluation method and associated information on genetic variation of rice accessions will be useful in root architecture breeding of rice.


Single-particle imaging of macromolecules by cryo-electron microscopy.
Cryo-electron microscopy (cryo-EM) of biological molecules in single-particle (i.e., unordered, nonaggregated) form is a new approach to the study of molecular assemblies, which are often too large and flexible to be amenable to X-ray crystallography. New insights into biological function on the molecular level are expected from cryo-EM applied to the study of such complexes "trapped" at different stages of their conformational changes and dynamical interactions. Important molecular machines involved in the fundamental processes of transcription, mRNA splicing, and translation are examples for successful applications of the new technique, combined with structural knowledge gained by conventional techniques of structure determination, such as X-ray crystallography and NMR.


Immunogenetics of dermatitis herpetiformis.
Dermatitis herpetiformis (DH) is a pruritic, papulovesicular skin disease characterized in part by the presence of granular deposits of IgA at the dermal-epidermal junction, an associated gluten sensitive enteropathy (GSE), and a strong association with specific human histocompatibility leukocyte antigens (HLA). Initial investigations revealed that 60% to 70% of patients with DH expressed the HLA antigen B8 (normal subjects = 21%). Further investigation of the HLA associations seen in patients with DH has revealed an even higher frequency of the HLA class II antigens HLA-DR3 (DH = 95%; normal = 23%), HLA-DQw2 (DH = 100%; normal = 40%), and HLA-DPw1 (DH = 42%; normal = 11%). Analysis of the genetic linkage of HLA antigens has revealed that the strongest HLA association in patients with DH is with the HLA class II antigens DR3 and DQw2. This article will discuss current studies regarding the role of HLA associations and DH and the role this strong HLA association may play in the pathophysiology of DH.


Population-based laboratory surveillance for Escherichia coli-producing extended-spectrum beta-lactamases: importance of community isolates with blaCTX-M genes.
A prospective, population-based laboratory surveillance study was conducted to define the epidemiology of extended-spectrum beta -lactamase-producing Escherichia coli infections in the Calgary Health Region during the years 2000-2002. The incidence was 5.5 cases per 100,000 population per year. The annualized incidence of 3.9 cases per 100,000 population for January through March was significantly lower than the incidence for the other quarters of the year (6.0 per 100,000 population; P<.01). Seventy-one percent of subjects had community-onset disease. Patients aged > or =65 years (22.0 vs. 3.8 cases per 100,000 population per year; P<.0001) and women (9.2 vs. 1.7 cases per 100,000 population per year; P<.0001) had significantly higher rates of infection. Polymerase chain reaction identified 23 (15%) of 157 isolates as positive for blaCTX-M genes from the CTX-M-I subgroup and 87 (55%) from the CTX-M-III subgroup. Ciprofloxacin resistance was independently associated with CTX-M- beta -lactamases (odds ratio, 14.2; 95% confidence interval, 3.69-54.84). Strains of E. coli with blaCTX-M genes commonly cause community-onset infections, and women and older patients are at highest risk.


[THE INDIVIDUAL AND SOCIAL FACTORS EFFECTING REFUSAL FROM VACCINATION OF CHILDREN IN THE TOWN OF SEMEII OF THE REPUBLIC OF KAZAKHSTAN].
The number of cases of refusal from vaccination increases all over the world. In the Republic of Kazakhstan many studies are devoted to epidemiology of propagation of vaccine-controllable infections, medical aspects ofimmunization, analysis of immunological status and complications of immunization. The issues of awareness of population of the Republic of Kazakhstan about vaccination and refusal of it are investigated insufficiently. This occurrence became a cause of studying the given problem. The study was carried out to investigate attitude ofpopulation to vaccination and main factors of risk of refusal from vaccination of children residing in the city of Semeii and rural districts of the Eastern Kazakhstan oblast. The single-stage longitudinal study was carried out in the Centers of primary medical social care ofpopulation ofcity of Semeii and in polyclinic of the Abaiiskii district of the Eastern Kazakhstan oblast. The period of study continued from April 7 2015 to May 31 2015. The criteria of inclusion were conditionally healthy children. The questionnaire survey included 1184 respondents (mothers) with average age of 27.2 years. The sampling predominantly consisted ofKazakhs (805), Russians (307), representatives ofother nationalities (72). Among mothers, most of them had specialized secondary education (43.7%), the higher education had 30.5%, undergraduate higher education - 1.4%, secondary education - 21.6% and basic school education --2.8%. The results of study demonstrated that families refused from vaccination have negative attitude to vaccination in general though they are satisfied with functioning of vaccination room. The refusal of vaccination is more characterized to urban full families with satisfied income and having girls as children. The respondents consider that information about vaccination received by themfrom medical personnel contains surplus data concerning complications. They are not enouzh for activities in case of deterioration of health of child after vaccination.


Vividness of positive mental imagery predicts positive emotional response to visually presented Project Soothe pictures.
Lang's bioinformational theory of mental imagery proposes that mental imagery and external stimuli engage emotional information-processing systems in similar ways. However, the positive and negative systems are thought to be distinct, so this similarity is likely to show a valence-specific effect. Therefore, we hypothesized that an individual's ability to construct vivid positive, but not negative, mental imagery would predict positive emotional responding to positive visual stimuli, independently of depressive symptoms. Our stimuli were pictures collected through Project Soothe for possible use in psychotherapy (www.projectsoothe.com); as these pictures were intended to induce soothing emotion, we hypothesized that theoretically linked variables Self-compassion and Self-criticism would also predict positive responding to the stimuli. A total of 214 participants completed an online study including validated questionnaire measures, mental imagery tasks, and a picture-rating exercise. Only Positive Imagery Vividness and Self-compassion were significant predictors of positive responding to the soothing pictures, even controlling for depressive symptoms, and Negative and General Imagery Vividness. These findings support Lang's theory and provide evidence for individual differences in a positive processing tendency shared across mental imagery-based and perceptual representations. As this relationship is distinct from depressive symptoms, future imagery-based psychotherapies might aim to influence this positive processing tendency.


Abberant chemotaxis and differentiation in Dictyostelium mutant fgdC with a defective regulation of receptor-stimulated phosphoinositidase C.
Dictyostelium cells use extracellular cyclic AMP both as a chemoattractant and as a morphogen inducing cell-type-specific gene expression. Cyclic AMP binds to surface receptors, activates one or more G-proteins, and stimulates adenylate cyclase, guanylate cyclase and phosphoinositidase C. Mutant fgdC showed aberrant chemotaxis, and was devoid of cyclic AMP-induced gene expression and differentiation. Both the receptor- and G-protein-mediated stimulation of adenylate cyclase and guanylate cyclase were unaltered in mutant fgdC as compared to wild-type cells. In wild-type cells phosphoinositidase C was activated about twofold by the cyclic AMP receptor. In mutant fgdC cells, however, the enzyme was inhibited by about 60%. These results suggest that phosphoinositidase C is regulated by a receptor-operated activation/inhibition switch that is defective in mutant fgdC. We conclude that activation of phosphoinositidase C is essential for Dictyostelium development.


Chronic Liver Disease in the Older Patient-Evaluation and Management.
As our population ages, the number of elderly patients with advanced chronic liver disease (ACLD) will increase. In this review we explore risk factors for liver injury, noninvasive assessment of liver disease, complications of cirrhosis, and management of frailty and sarcopenia in the older patient with ACLD. Multiple guidelines regarding ACLD have been updated over the past few years. New cutoffs for FIB-4 and NAFLD (MASLD - Metabolic Dysfunction Associated Steatotic Liver Disease) fibrosis scores for elderly patients are being validated. Older patients with MASLD benefit from caloric restriction, exercise programs, and GLP-1 agonists. Patients with ACLD need to be screened for alcohol use disorder with modified scoring systems, and if positive, benefit from referral to chemical dependency programs. Carvedilol and diuretics may safely be used in the elderly for portal hypertension and ascites, respectively, with careful monitoring. Malnutrition, frailty, sarcopenia, and bone mineral disease are common in older patients with ACLD, and early intervention may improve outcomes. Early identification of ACLD in elderly patients allows us to manage risk factors for liver injury, screen for complications, and implement lifestyle and pharmacological therapy to reduce decompensation and death. Future studies may clarify the role of noninvasive imaging in assessing liver fibrosis in the elderly and optimal interventions for nutrition, frailty, sarcopenia, bone health in addition to reevaluation of antibiotic prophylaxis for liver conditions with rising antibiotic resistance.


A multicentre, randomised trial examining the effect of test procedures measuring emergence from post-traumatic amnesia.
Post-traumatic amnesia (PTA) tests that record different PTA durations in the same patient, thereby raising measurement accuracy issues, have been reported previously. A major problem lies in determining the end point of PTA. To delineate areas of discrepancy in PTA tests and to provide independent verification for a criterion signalling emergence from PTA. In a randomised design, two related PTA procedures were compared, one purportedly more difficult (Westmead PTA Scale, WPTAS) than the other (Modified Oxford PTA Scale, MOPTAS). Eighty two patients in the early stages of PTA were examined daily until emergence, by using the Galveston Orientation and Amnesia Test (GOAT) and the WPTAS/MOPTAS. A short battery of cognitive and behavioural measurements was made on three occasions: at the early stage of PTA (time 1), towards the end of PTA when the maximum score (12/12) was first obtained (time 2) and at the traditional criterion for emergence (scoring 12/12 for 3 consecutive days; time 3). No significant difference was recorded in PTA duration between the MOPTAS and WPTAS. Both scales recorded longer PTA durations than the GOAT. By using Kaplan-Meier survival analyses, the WPTAS was found to show a more protracted pattern of emergence at the end stage of PTA than the MOPTAS. A time lag of > or = 1 week in the resolution of disorientation as compared with amnesia was observed in 59% cases. Significant improvements occurred on all independent measurements between time 1 and time 2, but on only 2 of 5 cognitive measurements between time 2 and time 3. Although no significant differences in the duration of PTA on the MOPTAS/WPTAS were recorded, emergence from the late stages of PTA occurred more promptly with the MOPTAS. The need for inclusion of both orientation and memory items in PTA tests is highlighted by the frequency of disorientation-amnesia dissociations. The patterns of results on the independent measures suggest that patients who are in PTA for > 4 weeks have probably emerged from PTA when they first score 12/12 on the MOPTAS/WPTAS, and this criterion can replace the traditional criterion.


Dose-Response Association Between Bilirubin and Cardiovascular Disease: A Systematic Review and Meta-analysis.
The association between bilirubin (BIL) and cardiovascular disease (CVD) remains controversial. We performed a meta-analysis of prospective studies to evaluate this association in the general population. We searched PubMed, EMBASE, Web of Science, Cochrane, and Scopus databases through to September 2021. The Newcastle-Ottawa Quality Assessment Scale was used to assess study quality. The pooled effect estimate was calculated by the fixed-effect model or random-effect model. We included 12 prospective studies (368 567 participants). The pooled risk ratio of CVD for the lowest vs highest groups of BIL levels was .75 (95% CI: .58-.97) with high heterogeneity (I2 = 87.5%, P < .001). Similar associations were observed for coronary heart disease and stroke. We further performed a "dose-response" meta-analysis, and a significant U-shaped relationship between circulating (most values were serum bilirubin, but a few were plasma bilirubin) BIL and CVD (P < .01) was observed. The lowest risk of CVD events was observed in participants with a BIL of 17-20 µmol/L in serum and/or plasma. In conclusion, there was a U-shaped dose-response relationship between BIL and CVD, especially for men. Further studies are needed to confirm our findings and identify the mechanisms involved as well as any prognostic or therapeutic potential.


Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome.
This technical report describes the procedures involved in developing the recommendations of the Subcommittee on Obstructive Sleep Apnea Syndrome in children. The group of primary interest for this report was otherwise healthy children older than 1 year who might have adenotonsillar hypertrophy or obesity as underlying risk factors of obstructive sleep apnea syndrome (OSAS). The goals of the committee were to enhance the primary care clinician's ability to recognize OSAS, identify the most appropriate procedure for diagnosis of OSAS, identify risks associated with pediatric OSAS, and evaluate management options for OSAS. A literature search was initially conducted for the years 1966-1999 and then updated to include 2000. The search was limited to English language literature concerning children older than 2 and younger than 18 years. Titles and abstracts were reviewed for relevance, and committee members reviewed in detail any possibly appropriate articles to determine eligibility for inclusion. Additional articles were obtained by a review of literature and committee members' files. Committee members compiled evidence tables and met to review and discuss the literature that was collected. A total of 2115 titles were reviewed, of which 113 provided relevant original data for analysis. These articles were mainly case series and cross-sectional studies; overall, very few methodologically strong cohort studies or randomized, controlled trials concerning OSAS have been published. In addition, a minority of studies satisfactorily differentiated primary snoring from true OSAS. Reports of the prevalence of habitual snoring in children ranged from 3.2% to 12.1%, and estimates of OSAS ranged from 0.7% to 10.3%; these studies were too heterogeneous for data pooling. Children with sleep-disordered breathing are at increased risk for hyperactivity and learning problems. The combined odds ratio for neurobehavioral abnormalities in snoring children compared with controls is 2.93 (95% confidence interval: 2.23-3.83). A number of case series have documented decreased somatic growth in children with OSAS; right ventricular dysfunction and systemic hypertension also have been reported in children with OSAS. However, the risk growth and cardiovascular problems cannot be quantified from the published literature. Overnight polysomnography (PSG) is recognized as the gold standard for diagnosis of OSAS, and there are currently no satisfactory alternatives. The diagnostic accuracy of symptom questionnaires and other purely clinical approaches is low. Pulse oximetry appears to be specific but insensitive. Other methods, including audiotaping or videotaping and nap or home overnight PSG, remain investigational. Adenotonsillectomy is curative in 75% to 100% of children with OSAS, including those who are obese. Up to 27% of children undergoing adenotonsillectomy for OSAS have postoperative respiratory complications, but estimates are varied. Risk factors for persistent OSAS after adenotonsillectomy include continued snoring and a high apnea-hypopnea index on the preoperative PSG. OSAS is common in children and is associated with significant sequelae. Overnight PSG is currently the only reliable diagnostic modality that can differentiate OSAS from primary snoring. However, the PSG criteria for OSAS have not been definitively validated, and it is not clear that primary snoring without PSG-defined OSAS is benign. Adenotonsillectomy is the first-line treatment for OSAS but requires careful postoperative monitoring because of the high risk of respiratory complications. Adenotonsillectomy is usually curative, but children with persistent snoring (and perhaps with severely abnormal preoperative PSG results) should have PSG repeated postoperatively.


Risk Factors for Postoperative Delirium in Abdominal Surgery: A Proposal of a Postoperative Delirium Risk Score in Abdominal Surgery.
Despite the presence of several diagnosis scales for delirium, no prediction scale that is specific for postoperative delirium after abdominal surgery is available. We sought to create a novel delirium prediction system that is specific for abdominal surgery. This study included 213 consecutive patients who required management in the surgical ICU following abdominal surgery. The Neelon and Champagne (NEECHAM) Confusion score was monitored throughout the postoperative course and patients with low NEECHAM score (≤26) were diagnosed as having delirium. Seventy-three patients (34%) were categorized in the delirium group. Multivariate analyses indicated that an age >70 years, hypertension, those undergoing hepatopancreatobiliary or upper gastrointestinal surgeries, a serum albumin level <2.5 g/dl on postoperative day (POD) 3 or 5 and a ≥6 mEq/l gap in the serum sodium level between the preoperative value and that on POD 3 were independently associated with a low NEECHAM score (≤26). When the presence of each risk was counted as 1 point, 21 patients had ≥4 points and 15 of them (71%) had low NEECHAM score. The scoring system combining multiple risk factors may be useful for predicting patients with an elevated risk for postoperative delirium after abdominal surgery.


Gram-negative endotoxins and staphylococcal toxic shock syndrome.
Strains of Staphylococcus aureus isolated from toxic shock syndrome (TSS) produce toxic shock syndrome toxin 1 (TSST1) which causes a shock-like illness in rabbits with many features similar to TSS in humans. TSST1 is lethal per se in rabbits and also acts synergistically with endotoxin to potentiate lethality. The mode of action of TSST1 is as yet unknown; it has been suggested that it may act by inhibiting the reticuloendothelial system thus allowing endotoxic shock to occur. Rabbits pretreated with polymyxin-B, which prevents the effect of endotoxin, were found to be protected from death by TSST1 indicating that endotoxin is indeed implicated in the pathogenesis of TSS. Specific pathogen-free rabbits which presumably have negligible levels of circulating LPS were susceptible to TSST1 suggesting that very small amounts of endotoxin are sufficient to potentiate lethality. The ways in which TSST1 may allow shock to occur is discussed.


Exceptional photoconductivity of poly(3-hexylthiophene) fibers through in situ encapsulation of molybdenum disulfide quantum dots.
Photo-responsive, electrically conductive nanostructures are highly desirable for wide-ranging applications in energy harvesting, nanophotonic and optoelectronic devices. To this end, we realize self-assembled, photoconductive hybrids of poly(3-hexylthiophene) (P3HT) micro- and nano-fibers integrated with MoS2 quantum dots (QDs). We present an innovative strategy to impregnate QDs within the walls of the P3HT fibers resulting in the emergence of the controllable photoconductivity of the QD-P3HT hybrid. The maximum photoconductivity (>80% higher than pristine P3HT) is observed at 360 nm and originates from a synergistic combination of (a) defect healing and quenching of surface trap states in QDs by P3HT and (b) efficient generation and transfer of photo-excited charges from P3HT to QDs. This mechanism is substantiated by a concomitant decrease in the excited-state lifetime of the QD-P3HT hybrid. Furthermore, a linear correlation between the enhancement in the emission of QDs and the emission quenching of P3HT supports the proposed mechanism of excited-state charge transfer. Finally, the hybrid of MoS2 nanosheets (NS) with P3HT fibers (NS-P3HT) does not exhibit any photo-conductivity and instead exhibits ground state charge transfer, underlying the critical role of quantum confinement effects operating in the QD-P3HT hybrid. Thus, we demonstrate a synergistic, self-assembled QD-P3HT hybrid exhibiting optically controllable electrical conductivity in the solid state as novel functional materials for optoelectronic applications.


Associations Between Disruptive Behavior Problems, Parenting Factors, and Sleep Problems Among Young Children.
To examine within an at-risk/clinical sample of preschool-aged children with externalizing problems: (1) which disruptive behavior and attention disorder symptoms (i.e., inattention, hyperactivity/impulsivity, and oppositionality/aggression) and (2) what aspects of parenting (e.g., discipline practices or stress) are related to children's sleep problems (e.g., sleep habit and night waking problems). The sample consisted of 148 children (meanage = 5.06 years, 82% male) with at-risk/clinically elevated levels of externalizing behavior problems and their primary caregiver. As part of a larger study, parents reported on their stress and parenting practices and their children's behavioral and sleep functioning. Positive and negative parenting behaviors ("do" and "don't" skills, respectively) were also observed during a 15-minute parent-child interaction during play. Oppositionality/aggression was the only disruptive behavior and attention disorder symptom associated with more sleep habit problems. Higher levels of inconsistent discipline and "don't" skills were also associated with more sleep habit problems. Within a combined model, an interaction emerged such that the association between "don't" skills and elevated sleep habit problems was only evident at low levels of inconsistent discipline. In terms of night waking problems, there was only an association with parenting stress, whereas the other parenting factors and disruptive behavior and attention disorder symptoms were unrelated. Although the directionality of our associations cannot be ascertained because of the cross-sectional nature of our study, these findings, nevertheless, highlight the importance of parenting factors (e.g., inconsistent discipline and parenting stress) when considering sleep difficulties in young children with disruptive behavior and attention disorders.


Regulation of glycolytic flux in the heart of the fetal guinea pig.
Functional glycolytic capacity and its regulation have been studied in the fetal guinea-pig heart during O2 deprivation in situ and in the Langendorff perfused heart. Anaerobic glycolytic flux, at 2 mumol/min per g wet wt. was similar in the 48-50 and 60-65 days fetal and adult guinea-pig heart, despite lower fetal phosphofructokinase activity. During O2 deprivation in situ and in the perfused heart glucose was the major substrate, with glycogen making a smaller contribution. Glycolytic capacity became more tightly regulated during fetal heart development. Thus at 48-50 days glycolysis was increased during O2 deprivation by substrate supply, but at 60-65 days activation of phosphofructokinase was required also. Low malate/aspartate cycle activity in the fetal heart was suggested by the absence of an increase in malate and alanine at the expense of aspartate. The large proportion of aerobic glycolytic flux converted to lactate concurred with this. Because of the low O2 consumption and relatively high aerobic glycolytic flux, the proportion of glycolytically-derived ATP was 3-4 fold higher in the fetal than adult heart, and may explain its functional resistance to O2 deprivation.


Enzymatic strategies for (near) clinical development of antibody-drug conjugates.
Target-specific killing of tumor cells with antibody-drug conjugates (ADCs) is an elegant concept in the continued fight against cancer. However, despite more than 20 years of clinical development, only four ADC have reached market approval, while at least 50 clinical programs were terminated early. The high attrition rate of ADCs may, at least in part, be attributed to heterogeneity and instability of conventional technologies. At present, various (chemo)enzymatic approaches for site-specific and stable conjugation of toxic payloads are making their way to the clinic, thereby potentially providing ADCs with increased therapeutic window.


Effects of bicalutamide and 4OH-tamoxifen on androgen-regulated gene expression in the LNCaP cell line.
Bicalutamide (BIC) is an alternative treatment to castration for advanced prostate cancer. Breast events are common adverse effects which can be effectively prevented by the concurrent administration of tamoxifen, a selective estrogen receptor modulator. We investigated the effects of BIC, 4-hydroxy Tamoxifen (4OHT), the active metabolite of tamoxifen, and their combination on the expression of a panel of genes implicated in prostate cancer development and progression in LNCaP cells stimulated with dihydrotestosterone. Our findings confirm the anti-proliferative activity of BIC on LNCaP cell growth but also show the down-regulating function of this anti-androgen on the expression of genes involved in tumor proliferation and invasion [cyclins, caspases, epidermal growth factor (EGF)]. The combination with 4OHT exerts a synergistic effect on the downregulation of some genes involved in prostate cancer progression. The observation that the expression of several genes [such as B-cell lymphoma-2 (BCL2), myelocytomatosis oncogene (MYC), caspases] is modulated midly-to-moderately, after 4OHT addition suggests that this combined approach in the clinical setting should be further investigated through appropriate trials.


Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer.
The pattern of exhaled breath volatile organic compounds represents a metabolic biosignature with the potential to identify and characterize lung cancer. Breath biosignature-based classification of homogeneous subgroups of lung cancer may be more accurate than a global breath signature. Combining breath biosignatures with clinical risk factors may improve the accuracy of the signature. To develop an exhaled breath biosignature of lung cancer using a colorimetric sensor array and to determine the accuracy of breath biosignatures of lung cancer characteristics with and without the inclusion of clinical risk factors. The exhaled breath of 229 study subjects, 92 with lung cancer and 137 controls, was drawn across a colorimetric sensor array. Logistic prediction models were developed and statistically validated based on the color changes of the sensor. Age, sex, smoking history, and chronic obstructive pulmonary disease were incorporated in the prediction models. The validated prediction model of the combined breath and clinical biosignature was moderately accurate at distinguishing lung cancer from control subjects (C-statistic 0.811). The accuracy improved when the model focused on only one histology (C-statistic 0.825-0.890). Individuals with different histologies could be accurately distinguished from one another (C-statistic 0.864 for adenocarcinoma versus squamous cell carcinoma). Moderate accuracies were noted for validated breath biosignatures of stage and survival (C-statistic 0.785 and 0.693, respectively). A colorimetric sensor array is capable of identifying exhaled breath biosignatures of lung cancer. The accuracy of breath biosignatures can be optimized by evaluating specific histologies and incorporating clinical risk factors.


Effects of morphine/CP55940 mixtures on an impulsive choice task in rhesus monkeys.
µ-Opioid receptor agonists are commonly used to treat pain despite their adverse effects. In preclinical studies, cannabinoid receptor agonists increase the potency of opioids for producing antinociceptive but not reinforcing effects. It is unknown whether other adverse effects of these drugs, such as impairment of complex behavior, are enhanced by their co-administration. This study characterized the effects of morphine (µ-opioid receptor agonist; 0.32-5.6 mg/kg, subcutaneously) and CP55940 (CB1/CB2 cannabinoid receptor agonist; 0.0032-0.32 mg/kg, subcutaneously), alone and in mixtures, in monkeys (n=3) choosing between one pellet delivered immediately and two pellets delivered after a delay. Two consecutive choices of the immediate or delayed reward decreased or increased, respectively, the delay. The median adjusted delay, indicating indifference between the immediate and delayed reinforcers, was increased by morphine (3.2 mg/kg) and CP55940 (0.01-0.032 mg/kg). Performance after administration of morphine (0.32 and 1 mg/kg)/CP55940 (0.0032-0.032 mg/kg) mixtures was not different from performance after CP55940 alone. Neither morphine, CP55940, nor mixtures decreased the median adjusted delay (i.e. increased impulsivity). These findings failed to confirm previous studies showing that morphine increases impulsivity, perhaps because of procedural differences among studies. Treatment of pain often requires repeated drug administration; thus, it remains to be determined whether the present findings predict the effects of chronically administered morphine/CP5540 mixtures on impulsive choice.


The synthesis and biological evaluation of mycobacterial p-hydroxybenzoic acid derivatives (p-HBADs).
Mycobacterium tuberculosis establishes chronic infection and causes disease through manipulation of the host's innate and adaptive immune response. The bacterial cell wall is highly complex and contains a rich variety of glycosylated compounds that are secreted during infection and have been proposed as immunomodulatory molecules. Amongst the most important of these are the p-hydroxybenzoic acid derivatives (p-HBADs). Here we report the synthesis of this important class of biomolecules and the first in vitro study of the immunomodulatory effects of these compounds in isolation from the host bacterium. The compounds do not have stimulatory properties but, in contrast, can inhibit the production of inflammatory cytokines, particularly interferon-γ (IFN-γ), by T-cells. This study offers a fundamental insight into the effect of these glycans on the immune response.


Routing Physarum with repellents.
Plasmodium of Physarum polycephalum is a single cell with many nuclei. Plasmodium is an easy-to-experiment-with biological substrate, a multi-functional bio-material used to implement novel and future computing architectures. The plasmodium exhibits typical features of excitable chemical systems and capable for distributed sensing, parallel information processing and decentralized actuation. Plasmodium of P. polycephalum is proved to be a universal storage modification machine. Actively growing zones of the plasmodium are considered to be elementary processors of the growing computing machine, as well as messages traveling in the spatially extended non-linear medium. Controlling propagation of the messages and computing processes is a prerequisite for a successful implementation of working prototypes of plasmodium machines. In laboratory experiments and computer simulation we show that active growing zones of plasmodium can be precisely routed using repelling diffusion gradients generated by crystals of sodium chloride. We demonstrate how to achieve controllable reflection, splitting/multiplication and merging of plasmodium's active zones.


Moiré contour-sum contour-difference, and vibration analysis of arbitrary objects.
A grid is projected onto an object and focused into a viewing camera which is offset from the angle of illumination. When the image is superimposed by double exposure or by filtering with the image of another object, contour-difference moiré fringes appear. By the use of two offset projectors, measurements of contour sums or contour doubling may be accomplished. The properties, limitations, sensitivity, and procedures are analyzed and discussed. The method lends itself to image enhancement and is extended to the study of vibration analysis in real time. In the latter application, time-average moiré fringes appear according to the zeroth-order Bessel function, which contains the modal amplitude function in its argument.


Response of von Willebrand factor parameters to desmopressin in patients with type 1 and type 2 congenital von Willebrand disease: diagnostic and therapeutic implications.
In the present study, we prospectively evaluated the contribution of the von Willebrand factor collagen-binding activity (vWF:CBA) assay, vWF multimeric analysis, and the response to intravenous desmopressin (DDAVP) to correctly diagnose and classify congenital von Willebrand disease (CvWD) in 24 probands with mild to moderate type 1 vWD, 6 probands with severe CvWD type 1, and 12 probands with type 2 CvWD. CvWD type 1 of mild to moderate severity is featured by proportionally decreased levels of vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCof), and vWF:CBA between 0.20 and 0.60 u/mL and a normal response to DDAVP of factor (F) VIIIc and all vWF parameters. Severe type 1 CvWD with vWF parameters below 0.10 or 0.20 u/mL is associated with a decreased response to DDAVP of all vWF parameters, indicating a defective synthesis or secretion vWF by endothelial cells, or both. CvWD 2M may present as severe type 1 CvWD, as type 1 "platelet-discordant" CvWD, or with the combination of a discrepant vWF:RCof/Ag ratio and the presence of all vWF multimers. Ristocetin-induced platelet aggregation (RIPA) is normal in type 1 CvWD. CvWD 2M is typically featured by decreased RIPA, normal or near normal vWF multimers, and no or only a poor response to DDAVP of vWF:RCof as compared with a fairly good response to DDAVP of vWF:Ag and vWF:CBA. CvWD Vicenza is characterized by unusually large vWF multimers and very low levels of FVIIIc, vWF:Ag, and vWF:RCof. CvWD Vicenza differs from CvWD 2M because the vWF:RCof/Ag ratios are completely normal before and after DDAVP; the response to DDAVP is equally good for FVIIIc, vWF:Ag, vWF:RCof, and vWF:CBA and is followed by very short half-life times for FVIIIc and all vWF parameters. Pertinent findings in type 2A and 2B CvWD included prolonged Ivy bleeding time (BT), low vWF:RCof/Ag and vWF:CBA ratios, absence of the high vWF multimers, and, depending on the severity of the absence of intermediate vWF multimers, pronounced increase of low vWF multimers and vWF degradation products because of increased proteolysis of the high and intermediate vWF multimers. RIPA is normal in CvWD 2A and increased in CvWD 2B. The response to DDAVP in CvWD 2A is normal for FVIIIc and vWF:Ag but is transient with partial correction and short half-life times of vWF:CBA and vWF:RCof. DDAVP does not correct BT and multimeric patterns in CvWD type 2B, despite significant increase of vWF parameters. CvWD types 2C, 2D, and 2E are featured by very low functional vWF parameters, the presence of typically abnormal vWF multimers, a very poor response of vWF:CBA, a decreased response of vWF:RCof, and a fairly good response of vWF:Ag to DDAVP with no correction of prolonged Ivy BT and no correction of the vWF multimeric pattern as the consequence of a multimerization or dimerization defect of the vWF molecules. CvWD type 2N usually presents with much lower levels for FVIIIc as compared with vWF, normal Ivy BT, and normal vWF multimeric pattern. The response to DDAVP is normal for all vWF parameters but is decreased for FVIIIc with shortened half-life times.


Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis.
Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED ∼ 71 %; FPF ∼ 49 %) compared to formulations containing MAN and NAC (ED ∼ 64 % and 44 %; FPF ∼ 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.


MPC1, a key gene in cancer metabolism, is regulated by COUPTFII in human prostate cancer.
Mitochondrial pyruvate carrier 1 (MPC1) and MPC 2 form a transporter complex in cells to control pyruvate transportation into mitochondria. Reduced expression of MPC1 disrupts the transporter function, induces metabolic shift to increase glycolysis, and thus plays important roles in several diseases, including cancer. However, the role of MPC1 in prostate cancer and the underlying mechanism causing the down-regulation of MPC1 in tumor cells remain to be defined. Here, we show that MPC1 serves as a critical regulator of glycolysis in prostate cancer cells, which in turn controls cancer cell growth, invasion, and the tumorigenic capability. More importantly, we identified that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), a steroid receptor superfamily member, transcriptionally regulates the expression of MPC1. We further demonstrate that COUP-TFII, which is upregulated in the prostate cancer patient, regulates MPC1 and glycolysis to promote tumor growth and metastasis. Our findings reveal that COUP-TFII represses MPC1 expression in prostate cancer cells to facilitate a metabolism switch to increase glycolysis and promote cancer progression. This observation raises an intriguing possibility of targeting COUP-TFII to modulate cancer cell metabolism for prostate cancer intervention.


Confusion, Urea, Respiratory Rate and Shock Index or Adjusted Shock Index (CURSI or CURASI) criteria predict mortality in community-acquired pneumonia.
Community-acquired pneumonia (CAP) is common and associated with a significant mortality. Shock index, heart rate divided by systolic blood pressure, has been shown to be associated with outcome in sepsis. To examine the usefulness of two new criteria CURSI (confusion, urea, respiratory rate and shock index), and CURASI where shock index is replaced by temperature adjusted shock index in mortality assessment of CAP. A prospective study was conducted in Norfolk and Suffolk, UK. We explored the usefulness of CURSI and CURASI which we derived and performed mapping exercise using a different cohort. In this study we compared these new indices with the CURB-65 criteria in correctly predicting mortality in CAP. A total of 190 patients were included (males=53%). The age range was 18-101 years (median=76 years). There were a total of 54 deaths during a six-week follow-up. All died within 30-days. Sixty-five (34%) had severe pneumonia by CURB-65. Using CURSI and CURASI, 71(37%) and 69(36%) had severe pneumonia, respectively. The sensitivity, specificity, positive and negative predictive values in predicting death during six-week follow-up were comparable among three indices examined. The Receiver Operating Characteristic curve values (95%CI) for the criteria were 0.67(0.60-0.75) for CURB-65, 0.67(0.59-0.74) for CURSI and 0.66(0.58-0.74) for CURASI (p>0.05). There were strong agreements between these three indices (Kappa values > or =0.75 for all). Repeating analyses in those who were aged 65years and over (n=135) did not alter the results. Both CURSI and CURASI are similarly useful to CURB-65 in predicting deaths associated with CAP including older patients.


Effect of intrarenal angiotensin II infusion on the renal escape from mineralocorticoid.
This study examined the hypothesis that suppression of the antinatriuretic action of angiotensin II (ANG II) is an important determinant of the escape from the sodium-retaining effects of mineralocorticoid. In five uninephrectomized dogs aldosterone (ALDO) infusion (10 ng X kg-1 X min-1) produced a fall in sodium excretion (UNaV) on the first day that returned to control on the fourth day of ALDO infusion. Mean arterial pressure (MAP) increased from 89 +/- 1 to 100 +/- 1 mmHg, and glomerular filtration rate (GFR) increased from 38 +/- 3 to 45 +/- 3 ml/min during ALDO infusion. After recovery, intrarenal infusion of ANG II (1.5 ng X kg-1 X min-1) was initiated to maintain a constant level of ANG II during the subsequent aldosterone administration. The intrarenal ANG II infusion produced a sustained increase in MAP (12 +/- 4 mmHg) and a sustained decrease in GFR (11 +/- 5 ml/min) and effective renal plasma flow (42 +/- 17 ml/min). With intrarenal ANG II levels fixed, ALDO infusion again produced a marked decrease in UNaV on the first day followed by a return to control levels on the third day. Again, MAP and GFR increased significantly during ALDO infusion (from 101 +/- 2 to 119 +/- 2 mmHg and from 27 +/- 6 to 35 +/- 4 ml/min, respectively). The absolute increase in MAP was significantly greater during ALDO infusion with intrarenal ANG II infusion as compared with ALDO infusion with intrarenal vehicle infusion alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Patient-Reported Outcomes of Aesthetics and Satisfaction in Immediate Breast Reconstruction After Nipple-Sparing Mastectomy With Implants and Fat Grafting.
Direct-to-implant (DTI) and tissue expander/implant (TE/I) reconstructions are the most common implant-based reconstructions after nipple-sparing mastectomy (NSM). However, there are little data beyond complication rates comparing these options. Fat grafting has emerged as an adjunct in NSM reconstructions to improve aesthetic results; however, its impact on patient perceptions of aesthetic outcomes remain unknown. To improve patient-centered care, aesthetic outcomes must be considered from the patients' perspective. To evaluate patient-reported outcomes of aesthetic satisfaction and quality of life in patients undergoing immediate DTI vs TE/I reconstruction after NSM and to assess the role of fat grafting on these outcomes. This is a prospective cohort study comparing NSM patients undergoing DTI or TE/I reconstruction. Patient-reported outcomes were evaluated using the BREAST-Q. Continuous and categorical variables were analyzed using t test and Fisher's exact test, respectively. Fifty-nine patients underwent 113 reconstructions with either DTI (n = 41) or TE/I (n = 18). Mean follow up was 12.1 months. DTI and TE/I patients had comparable satisfaction with outcome, though TE/I patients had significantly larger final implant sizes. TE/I who underwent fat grafting also had significantly higher satisfaction with outcome and psychosocial wellbeing. Patient-reported outcomes are comparable between DTI and TE/I reconstructions after NSM. In order for TE/I patients to achieve a similar level of satisfaction, they may require a larger final implant and additional operations compared to DTI patients. Additionally, fat grafting improves overall satisfaction. TE/I patients may have different aesthetic expectations than DTI patients, emphasizing patient-centered discussions are essential to optimizing outcomes after NSM. 3.


Indirect immunofluorescence microscopy for direct detection of Xylella fastidiosa in xylem sap.
The plant pathogen Xylella fastidiosa is the causative agent of a number of diseases of economically important crops, including Pierce's disease that affects grapevines. Using a commercially available antibody specific for X. fastidiosa, we have established a protocol for microscopic identification of the bacterium by indirect immunofluorescence. This antibody clearly labels an uncharacterized antigen concentrated at a single pole of X. fastidiosa cells, but does not react with a non- Xylella control. This technique was also performed successfully on xylem exudates from several different plant genera and correlated well with standard enzyme-linked immunosorbent assay tests. These results establish a novel method for in situ assessment of X. fastidiosa infection from host plants.


Missing female patients: an observational analysis of sex ratio among outpatients in a referral tertiary care public hospital in India.
To investigate gender discrimination in access to healthcare and its relationship with the patient's age and distance from the healthcare facility. An observational study based on outpatient data from a large referral public hospital in Delhi, India. Confirmed clinical appointments. Estimates from the logistic regression are used to compute sex ratios (male/female) of patient visits with respect to distance from the hospital and age. Missing female patients for each state-a measure of the extent of gender discrimination-is computed as the difference in the actual number of female patients who came from each state and the number of female patients that should have visited the hospital had male and female patients come in the same proportion as the sex ratio of the overall population from the 2011 census. Of 2377028 outpatient visits, excluding obstetrics and gynaecology patients, the overall sex ratio was 1.69 male to one female visit. Sex ratios, adjusted for age and hospital department, increased with distance. The ratio was 1.41 for Delhi, where the facility is located; 1.70 for Haryana, an adjoining state; 1.98 for Uttar Pradesh, a state further away; and 2.37 for Bihar, the state furthest from Delhi. The sex ratios had a U-shaped relationship with age: 1.93 for 0-18 years, 2.01 for 19-30 years, and 1.75 for 60 years or over compared with 1.43 and 1.40 for the age groups 31-44 and 45-59 years, respectively. We estimate there were 402 722 missing female outpatient visits from these four states, which is 49% of the total female outpatient visits for these four states. We found gender discrimination in access to healthcare, which was worse for female patients who were in the younger and older age groups, and for those who lived at increasing distances from the hospital.


Exposure of petrol station attendants and auto mechanics to premium motor sprit fumes in Calabar, Nigeria.
A population-based-cross-sectional survey was carried out to investigate the potential risk of exposure to premium motor spirit (PMS) fumes in Calabar, Nigeria, among Automobile Mechanics (AM), Petrol Station Attendants (PSA) and the general population. Structured questionnaire was administered on the randomly chosen subjects to elicit information on their exposure to PMS. Duration of exposure was taken as the length of work in their various occupations. Venous blood was taken for methaemoglobin (MetHb) and packed cells volume (PCV). Mean MetHb value was higher in AM (7.3%) and PSA (5.8%) than in the subjects from the general population (2.7%). PCV was lower in PSA (30.8%), than AM (33.3%) and the subjects from the general population (40.8%). MetHb level was directly proportional, and PCV inversely related, to the duration of exposure. The study suggested increased exposure to petrol fumes among AM, PSA, and MetHb as a useful biomarker in determining the level of exposure to benzene in petrol vapour.


Reflections on Alzheimer's disease.
As longevity increases, society will face a silent epidemic of idiopathic dementias. The concept, Alzheimer's disease, reflects a cumbersome and vaguely-defined cluster of signs, symptoms and other variables which might more appropriately be labelled as the idiopathic dementias, Alzheimer-type or IDAT. Diagnosis, which is made by exclusion and treatment, primarily custodial, demonstrates the complex nature and unfortunate prognosis of the problem. Dramatic progress, nevertheless, has been made in various scientific aspects of the issue, namely, in histology, genetics and neurochemistry. The resulting evidence warrants further speculation on the role of central cholinergic neurotransmission in cognitive functioning.


[From gene to disease; Charcot-Marie-Tooth disease or the hereditary motor and sensory neuropathies].
Charcot-Marie-Tooth disease is a clinically and genetically heterogeneous group of inherited neuropathies. The common clinical symptoms include distal muscle weakness, wasting and impaired distal sensation, more in the legs than in the arms, and reduced or absent reflexes. Moreover, foot and hand deformities are often encountered. A distinction between a primarily demyelinating or axonal neuropathy is often possible by means of nerve conduction studies. The major groups of inheritance are the autosomal dominant CMT1 (demyelinating), CMT2 (axonal) and the X-linked type (CMTX), but there are also autosomal recessive demyelinating (CMT4) and axonal (AR-CMT2) forms. The number of genes and loci is steadily increasing, with genes encoding proteins involved in myelin maintenance and axonal function, but also with genes encoding proteins, the function of which in peripheral nerve maintenance is notyet clear. Despite the increase in the number of known genes, especially for CMT2, there are many patients in whom no mutation can yet be found.


Photonic bandgap fiber bundle spectrometer.
By using a photonic bandgap (PBG) fiber bundle and a monochrome CCD camera, we experimentally demonstrate an all-fiber spectrometer. A total of 100 Bragg fibers that have complementary and overlapping bandgaps are chosen to compose the fiber bundle. A monochrome CCD is then used to capture the binned image. To reconstruct the test spectrum from a single CCD image, we develop an algorithm based on pseudoinversion of the spectrometer transmission matrix. We demonstrate that the peak center wavelength can always be reconstructed within several percent of its true value regardless of the peak width or position, and that, although the widths of the individual Bragg fiber bandgaps are quite large (60-180nm), the spectroscopic system has a resolution limit of approximately 30nm. Moreover, we conclude that, by minimizing system errors, the resolution can be further improved down to several nanometers in width. Finally, we report fabrication of PBG fiber bundles containing hundreds of fibers using a two-stage drawing technique. This method constitutes a very promising approach toward industrial-strength fabrication of all-fiber spectrometers.