Red raspberry (Rubus idaeus L.) intake decreases oxidative stress in obese diabetic (db/db) mice.
Red raspberry fruit intake was investigated on obese diabetic (db/db) mice for 8weeks. Animals fed isocaloric diets (5.3% freeze-dried raspberry, or control) were assessed for obesity-diabetes-disease risk biomarkers. Results showed that raspberry intake improved antioxidant status and lessened plasma interleukin (IL)-6 (0.3-fold of control, p<0.1); most likely through enhancing glutathione peroxidase (GPx) activity in liver (4.3-fold of control), and in blood (2.1-fold of control). Other disease-risk biomarkers were similar between groups (p>0.05). Plasma levels of total cholesterol (T-CHL), low density lipoprotein-cholesterol (LDL-CHL), and resistin were higher in the raspberry group. Overall, the enhanced detoxifying cell defenses exerted by raspberry intake might be due to its polyphenolics and fibre. This study demonstrates in vivo that raspberry intake, at a dose that can be achieved by human consumption, might protect against diabetes-induced oxidative stress.


[Clinical significance of sentinel lymph node micrometastases in invasive breast carcinoma].
Axillary lymph node status is one of the most important prognostic factors in patients with invasive breast carcinoma. Sentinel lymph node biopsy leads to more accurate examination of the lymph nodes and has resulted in an increased detection rate of small cancer deposits. Patients with micrometastatic foci can have nonsentinel lymph node involvement, including macrometastatic foci. Sentinel lymph node micrometastases are associated with an adverse impact on disease recurrence or survival. Axillary clearance offers no advantage in reducing the incidence of disease recurrence and survival. However, the long-term outcomes can be improved with the use of adjuvant systemic therapy, and it would be reasonable to consider systemic treatment in these patients.


Value of purinic compounds in assessing sinus node dysfunction in man: a new diagnostic method.
The purpose of this paper is to investigate whether the inhibitory action of purinic compounds (striadyne: STR) on the sinus node is quantitatively different on a pathological sinus node in comparison to a normal one and thus whether it is possible, as suggested by other authors, to use STR as a pharmacological test in the diagnosis of sick sinus syndrome (SSS). With this aim we investigated 55 patients, divided into 3 groups according to ECG and sinus function evaluation tests: 1--normal; 2--SSS (2a: flagrant SSS; 2b: latent SSS); 3--excess vagotonia and/or abnormal response to vagal stimulation. In all patients after a prophylactic insertion of a temporary pacemaker, 30 mg of STR were rapidly injected i.v. and the surface and intracavitary ECG continuously recorded until the basal state was regained; the following parameters were evaluated: average baseline sinus cycle (SC), minimum and maximum SC after the drug. In all patients STR caused first a slowing, then an acceleration of the sinus rate. SC lengthening was moderate in groups 1 and 3 [max SC was respectively 740-1820 ms (1198 +/- 290.9 ms) and 720-1440 ms (1157.5 +/- 223.3 ms)], but it was severe in patients with SSS [max SC in group 2a 2500-11880 ms (5398.3 +/- 2687.4 ms) in group 2b 1620-11140 ms. (4470.7 +/- 3660.6 ms)]. The difference between the max post STR SC of SSS patients, and the control group was highly significant P less than 0.001). Assuming as upper limit of the normal a value of 2071 ms. (corresponding to the mean + 3 standard deviations of the response of the control group) we recorded abnormal responses in 100% in group 2a and in 85.7% in group 2b, whereas there were no abnormal responses in group 3. In addition, nodal atrioventricular block occurred frequently. The authors believe this test could be useful in the diagnosis of SSS, but it is essential to insert a ventricular pacing catheter prophylactically if this test is used.


Association of serum lactate with outcome after out-of-hospital cardiac arrest treated with therapeutic hypothermia.
Lactate reflects hypoxic insult in many conditions and is considered as a prognosis factor. But, after cardiac arrest, its interest is still debated. Our study aimed to assess the prognosis value of lactate in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. This retrospective observational study included out-of-hospital cardiac arrest patients treated with therapeutic hypothermia in four ICUs. Lactate levels were compared at different times during the first 24 hours according to outcome at ICU discharge and to the type of death (multiorgan or neurologic failure). Two hundred and seventy-two patients were included, 89 good outcome and 183 poor outcome. In the latter group, 171 patients died, from multiorgan failure in 30% and neurologic failure in 70%. Lactate levels were higher in the poor compared to the good outcome patients at admission (5.4 (3.3-9.4) vs. 2.2 (1.5-3.6) mmol/L; p<0.01), 12 hours (2.5 (1.6-4.7) vs. 1.4 (1.0-2.2) mmol/L; p<0.01) and 24 hours (1.8 (1.1-2.8) vs. 1.3 (0.9-2.1) mmol/L; p<0.01). Patients succumbing from multiorgan failure exhibited higher lactate levels compared to those dying from neurologic failure at admission (7.9 (3.9-12.0) vs. 5.2 (3.3-8.8) mmol/L; p<0.01), H12 (4.9 (2.1-8.9) vs. 2.2 (1.4-3.4) mmol/L; p<0.01) and H24 (3.3 (1.8-5.5) vs. 1.4 (1.1-2.5) mmol/L; p<0.01). Initial lactate levels showed an increasing proportion of poor outcome from the first to fourth quartile. After out-of-hospital cardiac arrest treated with therapeutic hypothermia, lactate levels during the first 24 hours seem linked with ICU outcome. Patients dying from multiorgan failure exhibit higher initial lactate concentrations than patients succumbing from neurological failure.


PCR Based Cloning and Sequence Analysis of the Pichia pastoris Cystathionine beta-Synthase Gene.
The cystathionine beta-Synthase (CBS) gene of Pichia pastoris has been cloned by homology to the CBS gene of Saccharomyces cerevisiae. First, based on the homology alignment of CBS genes from different sources, a pair of degenerate PCR primers were designed to amplify a conservative fragment of Pichia pastoris CBS gene. After the sequence was revealed, 5' RACE and 3' RACE were performed separately. The whole sequence of Pichia pasotris CBS gene was assembled. This gene encodes a polypeptide of 501 residues. Comparison of deduced amino acid sequence of this new gene with that of S. cerevisiae CBS showed 54% identity. Disruption of CBS gene resulted in a Cys(-) auxotrophy in Pichia pastoris. Thesequence was submitted to GenBank/EMBL/DDBJ under Accession No.AF367364.


Studies on the induction and phosphorylation of xanthine dehydrogenase in cultured chick embryo hepatocytes.
Chick embryo hepatocytes, cultured in a chemically defined medium, were used to investigate hormonal requirements for xanthine-dehydrogenase induction and to determine whether the enzyme is phosphorylated. Triiodothyronine is found to be required to induce the synthesis of active enzyme. Inclusion of sodium tungstate in the medium resulted in the complete loss of enzyme activity but no decrease of immunochemically detectable levels of enzyme. Immunoprecipitated xanthine dehydrogenase from cell extracts migrates with enzyme purified from adult chicken liver on SDS/PAGE. Both the native 150-kDa subunit and the 130-kDa form of the enzyme is observed. N-terminal sequence analysis of the 150-kDa subunit shows the following; Ala-Pro-Pro-Glu-Thr-Gly-Asp-Glu-Leu-Val-Phe-Phe-Val-Asn-Gly-Lys-Lys-Val- Val which is similar to the published N-terminal sequences of rat, mouse and insect xanthine dehydrogenases. Autoradiography of denaturing gels of xanthine dehydrogenase isolated from 32P(i)-labeled hepatocytes demonstrates that the 150-kDa and the 130-kDa forms of the enzyme are phosphorylated. Chemical phosphate analysis of acid-precipitated, electrophoretically pure chicken liver xanthine dehydrogenase also shows the presence of covalently bound phosphate. Phosphoamino acid analysis of both 32P-labeled forms of the enzyme demonstrates the presence of phosphoserine. Thus, chicken liver xanthine dehydrogenase contains a phosphoserine residue as found previously in bovine milk xanthine oxidase [Davis, M. D., Edmondson, D. E. & Müller, F. (1984) Eur. J. Biochem. 145, 237-250].


A photographic technique for teaching topographical anatomy from whole body transverse sections.
A photographic technique is described which enables the production of a series of 35 mm transparencies for teaching topographical anatomy from whole body transverse sections. It shows the sequential build-up of a section from an easily identifiable individual structure to the whole, therefore allowing the viewer to identify important areas and key structures within a section more readily.


The UCSF screening exam effectively screens cognitive and behavioral impairment in patients with ALS.
The University of California San Francisco (UCSF) Screening Battery provides clinicians with a uniquely tailored tool to measure ALS patients' cognitive and behavioral changes, adjusting for dysarthria and hand weakness. The battery consists of the ALS-CBS ( 1 ), Written Fluency Test ( 2 ), and a new revision of the Frontal Behavior Inventory (FBI-ALS) ( 3 ). The validity of each component was tested by comparing results with a gold standard neuropsychological exam (GNE). Consensus criteria-based GNE diagnoses ( 4 ) were assigned (n = 24) and concurrent validity was tested for each screening exam component. Results showed that each of the four cognitive and behavioral screening test components were significantly associated with diagnoses confirmed by GNE. GNE diagnoses were significantly associated with FBI-ALS negative score, written S-words score, and ALS-CBS cognitive score. The total FBI-ALS score and C-words tests were less predictive of GNE-diagnosed impairment. In conclusion, the UCSF Cognitive Screening Battery demonstrates good external validity compared with GNE in this modest sample, encouraging its use in larger investigations. These data suggest that this battery may provide an effective screen to identify ALS patients who will then benefit from a full examination to confirm their diagnosis.


Diagnostic dilemma in a patient with nasopharyngeal tuberculosis: A case report and literature review.
Tuberculosis remains a major cause of morbidity and mortality globally, with a global total of about 10 million people falling ill with it in 2020. Until the coronavirus (COVID-19) pandemic, tuberculosis was the leading cause of death from a single infectious agent. Nasopharyngeal tuberculosis is a rare type of extrapulmonary tuberculosis that may be either primary or secondary to pulmonary tuberculosis. Nasopharyngeal tuberculosis may be mistaken for nasopharyngeal carcinoma as both conditions may present with a nasopharyngeal mass and cervical lymph node enlargement. We present a case of nasopharyngeal tuberculosis secondary to pulmonary tuberculosis who presented without any nasal or respiratory symptoms. The patient presented with a cervical lymph node enlargement and a nasopharyngeal mass was detected on nasal endoscopy. Fine needle cytology from the cervical node and the initial biopsy report from the nasopharyngeal mass were not confirmatory, causing a diagnostic dilemma. A repeat biopsy from the nasopharyngeal mass with the demonstration of caseating granuloma and acid-fast bacilli in the specimen pointed to the diagnosis of nasopharyngeal tuberculosis. The patient responded well to the standard 6-month anti-tubercular regimen. Nasopharyngeal tuberculosis may mimic nasopharyngeal carcinoma and a repeat biopsy may be necessary to confirm the diagnosis.


Three Switchable Orthogonal Dynamic Covalent Reactions and Complex Networks Based on the Control of Dual Reactivity.
Achieving complexity is central to the creation of chemical systems, inspired by natural systems. Herein we introduce a strategy of switchable orthogonal dynamic covalent chemistry (DCC) toward the regulation of complex dynamic networks. The control of dual reactivity of tautomers and resulting pathways allowed reversible covalent bonding of a large scope of primary amines, secondary amines, alcohols, and thiols with high efficiency. The selection of reaction pathways next enabled the realization of orthogonal but switchable dynamic covalent reactions (DCRs) with nucleophile pairs of amine/alcohol, alcohol/thiol, and amine/thiol by varying protonation and oxidation states. Control experiments confirmed the crucial role of dual reactivity on the stability and switchability of DCRs. The specificity toward amines, alcohols, and thiols, as well as interconversion between their corresponding assemblies, was further accomplished in one vessel, thus creating tunable communicating networks with three types of DCRs. Moreover, the switchable orthogonality combined with differential reactivity of multiple sulfonamides and nucleophiles enhanced the complexity within dynamic libraries. The generality and versatility of our approaches should facilitate their incorporation into many aspects of chemistry endeavors.


Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights into mechanisms and management.
Angiotensin-converting enzyme inhibitors are widely prescribed for hypertension and heart failure. These drugs are commonly associated with cough, and are less commonly associated with angioedema, which may be potentially life threatening. This review describes data that extend our understanding of the mechanisms of these reactions, and provides guidance about clinical management. For patients who develop angioedema from angiotensin-converting enzyme inhibitors, recent data are reassuring that the majority of such patients can tolerate angiotensin-II receptor blockers. These data support earlier conclusions that most patients with angiotensin-converting enzyme inhibitor-induced cough can tolerate angiotensin-II receptor blockers. Limited case reports suggest that in acute angioedema induced by angiotensin-converting enzyme inhibitors, patients refractory to standard treatment may benefit from the infusion of fresh frozen plasma. Although data are incomplete, it appears that angiotensin-converting enzyme inhibitors cause cough and angioedema through a cascade of effects that begins with the accumulation of kinins, and then involves arachidonic acid metabolism and nitric oxide generation. Most patients who develop either cough or angioedema from angiotensin-converting enzyme inhibitors can tolerate angiotensin-II receptor blocking agents.


Multi-omics integration in the age of million single-cell data.
An explosion in single-cell technologies has revealed a previously underappreciated heterogeneity of cell types and novel cell-state associations with sex, disease, development and other processes. Starting with transcriptome analyses, single-cell techniques have extended to multi-omics approaches and now enable the simultaneous measurement of data modalities and spatial cellular context. Data are now available for millions of cells, for whole-genome measurements and for multiple modalities. Although analyses of such multimodal datasets have the potential to provide new insights into biological processes that cannot be inferred with a single mode of assay, the integration of very large, complex, multimodal data into biological models and mechanisms represents a considerable challenge. An understanding of the principles of data integration and visualization methods is required to determine what methods are best applied to a particular single-cell dataset. Each class of method has advantages and pitfalls in terms of its ability to achieve various biological goals, including cell-type classification, regulatory network modelling and biological process inference. In choosing a data integration strategy, consideration must be given to whether the multi-omics data are matched (that is, measured on the same cell) or unmatched (that is, measured on different cells) and, more importantly, the overall modelling and visualization goals of the integrated analysis.


The puzzle of chloroplast vesicle transport - involvement of GTPases.
In the cytosol of plant cells vesicle transport occurs via secretory pathways among the endoplasmic reticulum network, Golgi bodies, secretory granules, endosome, and plasma membrane. Three systems transfer lipids, proteins and other important molecules through aqueous spaces to membrane-enclosed compartments, via vesicles that bud from donor membranes, being coated and uncoated before tethered and fused with acceptor membranes. In addition, molecular, biochemical and ultrastructural evidence indicates presence of a vesicle transport system in chloroplasts. Little is known about the protein components of this system. However, as chloroplasts harbor the photosynthetic apparatus that ultimately supports most organisms on the planet, close attention to their pathways is warranted. This may also reveal novel diversification and/or distinct solutions to the problems posed by the targeted intra-cellular trafficking of important molecules. To date two homologs to well-known yeast cytosolic vesicle transport proteins, CPSAR1 and CPRabA5e (CP, chloroplast localized), have been shown to have roles in chloroplast vesicle transport, both being GTPases. Bioinformatic data indicate that several homologs of cytosolic vesicle transport system components are putatively chloroplast-localized and in addition other proteins have been implicated to participate in chloroplast vesicle transport, including vesicle-inducing protein in plastids 1, thylakoid formation 1, snowy cotyledon 2/cotyledon chloroplast biogenesis factor, curvature thylakoid 1 proteins, and a dynamin like GTPase FZO-like protein. Several putative potential cargo proteins have also been identified, including building blocks of the photosynthetic apparatus. Here we discuss details of the largely unknown putative chloroplast vesicle transport system, focusing on GTPase-related components.


Non-canonical functions of EZH2 in cancer.
Mutations in chromatin modifying genes frequently occur in many kinds of cancer. Most mechanistic studies focus on their canonical functions, while therapeutic approaches target their enzymatic activity. Recent studies, however, demonstrate that non-canonical functions of chromatin modifiers may be equally important and therapeutically actionable in different types of cancer. One epigenetic regulator that demonstrates such a dual role in cancer is the histone methyltransferase EZH2. EZH2 is a core component of the polycomb repressive complex 2 (PRC2), which plays a crucial role in cell identity, differentiation, proliferation, stemness and plasticity. While much of the regulatory functions and oncogenic activity of EZH2 have been attributed to its canonical, enzymatic activity of methylating lysine 27 on histone 3 (H3K27me3), a repressive chromatin mark, recent studies suggest that non-canonical functions that are independent of H3K27me3 also contribute towards the oncogenic activity of EZH2. Contrary to PRC2's canonical repressive activity, mediated by H3K27me3, outside of the complex EZH2 can directly interact with transcription factors and oncogenes to activate gene expression. A more focused investigation into these non-canonical interactions of EZH2 and other epigenetic/chromatin regulators may uncover new and more effective therapeutic strategies. Here, we summarize major findings on the non-canonical functions of EZH2 and how they are related to different aspects of carcinogenesis.


Analysis of inter-(simple sequence repeat) PCR products from human colorectal cancers.
Genomic instability is a fundamental characteristic of solid tumors, and understanding genomic instability should significantly clarify the process of tumorigenesis. We adapted the sampling technique of inter-(simple sequence repeat) PCR [inter-(SSR) PCR] to measure genetic alterations between simple sequence repeats in colorectal tumors. It becomes important to precisely define both normal and altered inter-(SSR) PCR products. BLAT searches of 131 cloned inter-(SSR) PCR sequences reveal that inter-(SSR) PCR products are located on almost all the chromosomes except chromosome Y, indicating that inter-(SSR) PCR samples a representative diverse range of the genome. We confirm that a change in the pattern of the inter-(SSR) PCR products as seen on gel electrophoresis reflects a true alteration within the genome.


Effect of aerosolized isoproterenol on resting myogenic tone in normals.
The effects of aerosolized isoproterenol on expiratory (exp) and inspiratory (insp) conductance (Gaw), maximal exp and insp flow (VEmax and VImax), and static elastic recoil pressure (Pst) were measured in 12 normals. Both exp and insp Gaw increased throughout the vital capacity (37% at 50% VC; P less than 0.01). VEmax increased only at 50% VC (9%; P less than 0.01). VImax and Pst did not change. Accordingly, a dichotomy existed between the Gaw and Vmax changes during both exp and insp. We do not attribute this dichotomy to loss of driving pressure or to volume-time-dependent behavior of airway tone. We interpret the increased exp and insp Gaw to indicate isoproterenol deposition within and bronchodilatation of larger central airways (trachea, main stem, lobar, segmental). Since insp Gaw increased and VImax did not, we conclude that the caliber of these central airways is not the exclusive deteminant of VImax, that the caliber of some more distal airways (subsegmental and beyond) did not change, and that these airways are important determinants of VImax. We conclude that non-uniform distribution of isoproterenol could account for the Gaw-Vmax dichotomy during inspiration, and that such non-uniform distribution coupled with resultant increased compliance and compressibility of the downstream segment could account for the Faw-Vmax dichotomy during expiration.


Making it safer: a health centre's strategy for suicide prevention.
Developing and implementing consistent methodology for suicide assessment and intervention is challenging, particularly in a large community hospital which provides both inpatient care and a wide range of ambulatory and community based mental health programs. Patients, families, staff, and ongoing evaluation contributed to the development of an initiative to determine what is best practice and in effecting changes in clinical and organizational practices. The Suicide Assessment project resulted in improved clinical outcomes for patients and clients. Staff report that they feel more supported in probing for suicidal ideation and have the skills required to effectively intervene with the 'suicidal' patient/client. This project advanced our knowledge of suicide assessment and risk management and provided new insights to assist professionals in the aftermath of a client's suicide when, as Valente describes, clinicians report 'feeling overwhelmed with feelings of guilt, self-blame, and responsibility (Valente S: Journal of Psychosocial Nursing 40:7 22-23, 2002).


The impact of work-related and personal resources on older workers' fatigue, work enjoyment and retirement intentions over time.
This study aims to examine the impact of work-related and personal resources on older workers' retirement intentions by studying the pathways (fatigue and work enjoyment) from resources to retirement intentions, the buffering role of resources for psychological job demands, in a cross-sectional and longitudinal timeframe. Longitudinal results on a subsample of full-time, older workers (n = 1642) from the Maastricht Cohort Study suggest that over four years of follow-up personal resources like personal mastery and perceived health related to less (prolonged) fatigue and more work enjoyment. Personal mastery also related to later retirement intentions. A work-related resource like decision authority related to less prolonged fatigue. (Prolonged) fatigue related to earlier retirement intentions, suggesting that fatigue may be a pathway to early retirement. Finally, little evidence was found for effect modification by resources. This prospective study indicates that work-related and personal resources may be useful for prolonging working careers. Practitioner Summary: To date, the impact of work-related and personal resources on older workers' retirement intentions is rarely studied. As this prospective study shows that resources may impact older workers' (prolonged) fatigue, work enjoyment and retirement intentions, the monitoring and fostering of resources is of importance for prolonging their working careers.


Attenuation by prostaglandins of adrenergically induced renal vasoconstriction in anesthetized rats.
We have investigated the role of prostaglandins (PG) in the modulation of adrenergic neuroeffector events by examining the effect of PGI2 and PGE2 and their precursor, arachidonic acid, on the decrease in renal blood flow elicited by renal nerve stimulation or by injected norepinephrine in pentobarbital-anesthetized rats, with or without pretreatment with the cyclooxygenase inhibitor, sodium meclofenamate. Administration of PGI2 or PGE2 (0.4 micrograms X kg-1 X min-1) or arachidonic acid (5 micrograms X kg-1 X min-1) into the renal artery reduced vascular resistance and inhibited the vasoconstrictor response elicited by renal nerve stimulation or by injected norepinephrine. In contrast, administration of sodium meclofenamate (10 mg/kg iv + 30 micrograms X kg-1 X min-1) into the renal artery increased renal vascular resistance and enhanced the renal vasoconstrictor response to both adrenergic stimuli. In animals pretreated with the cyclooxygenase inhibitor, the ability of arachidonic acid, but not that of either PGE2 or PGI2, to reduce renal vascular resistance and the vasoconstrictor response to either nerve stimulation or injected norepinephrine was abolished. These data indicate that one or more prostaglandins, probably PGE2 or PGI2, formed in the kidney reduce renal vascular tone by their direct action on the vascular smooth muscle and by attenuating the influence of adrenergic stimuli on renal vasculature.


"Where is the relationship" revisited: Using actor-partner interdependence modeling and common fate model in examining dyadic working alliance and session quality.
Building on previous studies (e.g., Kivlighan, 2007), we explored the application of actor-partner interdependence modeling (APIM) and the common fate model (CFM) in a multilevel framework to examine the dyadic multilevel associations between therapists' and clients' perceptions of working alliance and session quality. Forty-four therapists and their 284 adult community clients completed measures of working alliance and session quality after every session (a total of 8,188 sessions included in this study). We used APIM to unravel the mutual interdependence between therapist and client perceptions and used CFM to model both the shared and individual perceptions of the therapists and clients. APIM analyses showed that, at the between-session level, therapist and client perception of the session quality each was significantly predicted by the other's perception of the working alliance. At the between-client level, only therapist perception of the session quality was significantly predicted by the client's perception of the working alliance. There were no significant partner effects at the between-therapist level. CFM analyses showed that therapist-client shared perceptions of working alliance significantly predicted their shared perception of session quality at all three levels. In contrast, individual perceptions of working alliance correlated with individual perceptions of session quality for therapists only at the between-therapist and between-session levels, and for clients only at the between-client and between-session levels. Theoretical, methodological, and practical implications are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Inflammation-based prognostic scores as indicators to select candidates for primary site resection followed by multimodal therapy among colorectal cancer patients with multiple metastases.
Although patients with metastatic colorectal cancer (CRC) are often unable to undergo treatment after resection of primary tumors, identifying such patients before surgery is not easy. In this study, we evaluated the association among clinicopathological findings, survival outcomes, and ability to undergo multimodal therapy after primary tumor resection in patients with Stage IV CRC. We collected clinicopathological findings and preoperative laboratory data, including carcinoembryonic antigen (CEA) and systemic inflammatory response markers for 92 patients who were treated for Stage IV CRC between 2005 and 2014. We used multivariate analysis on factors that affect prognosis and ability to undergo postoperative treatment. Postoperative multimodal therapy improved overall survival (OS) significantly. Among serum markers, elevated CEA, neutrophil-to-lymphocyte ratio, and modified Glasgow prognosis score (mGPS) were significant indicators of shorter OS. In multivariate analysis, low performance status (P = 0.003), undifferentiated histology type (P = 0.019), and elevated mGPS (P = 0.042) were independent predictors of worse prognosis; and older age (P = 0.016), right-sided colon cancer (P = 0.043), and elevated mGPS (P = 0.031) were independent risk factors for difficulty of introducing postoperative multimodal therapy. Preoperative mGPS is a useful objective indicator for CRC patients with multiple metastases who are able to undergo primary site resection followed by postoperative multimodal therapy.


Diversity of ground arthropod community at organic and chemically intensive tea plantation of Darjeeling terai.
Tea in Darjeeling foothills and terai are grown conventionally, with application of chemical fertilizers and pesticides, as well as organically without these inputs. Ground level arthropod community was collected from the above two types of tea plots using pitfall traps. Catches from these environments showed variation in the arthropod faunal structure with numerically and taxonomically greater abundance in the organic than that of the conventional plot. Coleopterans were more diverse with largest number of families and Recognizable Taxonomic Units (or morphospecies) in the organic tea plot. The diversity and similarity indices for coleopterans were comparable, in organic and conventional tea plots at species and family levels. The close relationship of the indices suggested that diversity study at family level could be used as surrogate for species level diversity; thus alleviating the laborious and expertise job of taxonomic identification of arthropod species. Faunal diversity study at ground level gave the clue that soil of the organic plantation was healthier than that of the conventional tea plot.


Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.
Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.


Is GRO J1744-28 a strange star?
The unusual hard x-ray burster GRO J1744-28 recently discovered by the Compton Gamma-Ray Observatory can be modeled as a strange star with a dipolar magnetic field of </=10(11) gauss. According to this model, when the accreted mass of the star exceeds some critical mass, its crust breaks, resulting in the conversion of the accreted matter into strange matter and a release of energy. Subsequently, a fireball forms and expands relativistically outward. The expanding fireball interacts with the surrounding interstellar medium, causing its kinetic energy to be radiated in shock waves and producing a burst of x-ray radiation. The burst energy, duration, interval, and spectrum derived from such a model are consistent with the observations of GRO J1744-28.


Kex2 protease converts the endoplasmic reticulum alpha1,2-mannosidase of Candida albicans into a soluble cytosolic form.
Cytosolic alpha-mannosidases are glycosyl hydrolases that participate in the catabolism of cytosolic free N-oligosaccharides. Two soluble alpha-mannosidases (E-I and E-II) belonging to glycosyl hydrolases family 47 have been described in Candida albicans. We demonstrate that addition of pepstatin A during the preparation of cell homogenates enriched alpha-mannosidase E-I at the expense of E-II, indicating that the latter is generated by proteolysis during cell disruption. E-I corresponded to a polypeptide of 52 kDa that was associated with mannosidase activity and was recognized by an anti-alpha1,2-mannosidase antibody. The N-mannan core trimming properties of the purified enzyme E-I were consistent with its classification as a family 47 alpha1,2-mannosidase. Differential density-gradient centrifugation of homogenates revealed that alpha1,2-mannosidase E-I was localized to the cytosolic fraction and Golgi-derived vesicles, and that a 65 kDa membrane-bound alpha1,2-mannosidase was present in endoplasmic reticulum and Golgi-derived vesicles. Distribution of alpha-mannosidase activity in a kex2Delta null mutant or in wild-type protoplasts treated with monensin demonstrated that the membrane-bound alpha1,2-mannosidase is processed by Kex2 protease into E-I, recognizing an atypical cleavage site of the precursor. Analysis of cytosolic free N-oligosaccharides revealed that cytosolic alpha1,2-mannosidase E-I trims free Man8GlcNAc2 isomer B into Man7GlcNAc2 isomer B. This is believed to be the first report demonstrating the presence of soluble alpha1,2-mannosidase from the glycosyl hydrolases family 47 in a cytosolic compartment of the cell.


Application of Peleg's equation to describe creep responses of potatoes under constant and variable storage conditions.
The application of Peleg's equation to characterize creep behavior of potatoes during storage was investigated. Potatoes were stored at 25, 15, 5C, and variable (fluctuating) temperature for 16 or 26 weeks. The Peleg equation adequately described the creep response of potatoes during storage at all storage conditions (R2 = .97to .99). Peleg constant k1 exhibited a significant (p < .05) decreasing trend with storage time (ts ) for samples stored under the experimental conditions whereas the constant k2 appeared to be unaffected much by ts except for samples stored at 25C. Under constant temperature storage, k1 was found to be a linear function of ts (R2 = .87 to .97). Also, the rate of change of k1 appeared to be temperature dependent described by a linear relationship between the degradation rate constant for k1 (α) and storage temperature (T). For the variable storage condition, a bulk mean temperature (Tbm ) was calculated to account for a series combination of storage time and temperature which the potatoes were subjected to. It was possible to describe the changes in k1 due to variable storage temperature in terms of Tbm and ts using stepwise multiple regression (R2 = . 94). Precise description of the changes in the rheological properties of raw potatoes during storage could help predict the associated effect on the texture of cooked potatoes. Easy and simple methods of describing creep responses during storage or processing will be potentially helpful to better understand the phenomenon. The model parameters from such model could be used to relate rheological properties of raw and cooked potatoes. Moreover, the model parameters could be used to establish relationship between instrumental and sensory attributes which will help in the prediction of sensory attributes from instrumental data.


Advances in In Vitro and In Vivo Bioreactor-Based Bone Generation for Craniofacial Tissue Engineering.
Craniofacial reconstruction requires robust bone of specified geometry for the repair to be both functional and aesthetic. While native bone from elsewhere in the body can be harvested, shaped, and implanted within a defect, using either an in vitro or in vivo bioreactors eliminates donor site morbidity while increasing the customizability of the generated tissue. In vitro bioreactors utilize cells harvested from the patient, a scaffold, and a device to increase mass transfer of nutrients, oxygen, and waste, allowing for generation of larger viable tissues. In vivo bioreactors utilize the patient's own body as a source of cells and of nutrient transfer and involve the implantation of a scaffold with or without growth factors adjacent to vasculature, followed by the eventual transfer of vascularized, mineralized tissue to the defect site. Several different models of in vitro bioreactors exist, and several different implantation sites have been successfully utilized for in vivo tissue generation and defect repair in humans. In this review, we discuss the specifics of each bioreactor strategy, as well as the advantages and disadvantages of each and the future directions for the engineering of bony tissues for craniofacial defect repair.


Prevalence of Opisthorchis viverrini infection among villagers harboring Opisthorchis-like eggs.
The precise occurrence of Opisthochis viverrini infection in humans, who were positive for Opisthorchis-like eggs in a stool examination, was determined using the potassium permanganate staining method. In the 68 specimens examined, there were more individual O. viverrini eggs (38.24%) than singular Haplorchis taichui eggs (29.41%). One-fourth of the total specimens contained a mixed infection of O. viverrini and H. taichi eggs. The median ratio of O. viverrini: H. taichui eggs in mixed infection cases was 2.29 (min = 1, max = 17.5). It is suggested that chemotherapy with praziquentel treatment should be given to patients who are positive for O. viverrini-like eggs.


Experimental evaluation of tissue revascularization using a transferred muscular-vascular pedicle.
Skin and cartilage can be revascularized from a transferred muscular-vascular pedicle. Muscle vessels appear to connect with existing vessels in the subdermal plexus or perichondrium and determine the ultimate distribution of the skin or cartilage revascularized. The ideal timing for flap elevation following revascularization in this model is 21 to 28 days following transfer. Isolation of the muscular-vascular pedicle from underlying tissue by a silicone sheet does not appear to augment tissue revascularization. Delay procedures do not improve surviving flap length. Composite flaps of cartilage and skin can be revascularized using this technique.


Attempting the Impossible: Keeping a Jail COVID-Free.
AbstractPrior to the COVID-19 pandemic, the United States housed 2.3 million inmates in 7,147 incarceration structures that, because of age, overcrowding, and poor ventilation, exacerbated the spread of airborne infections. The flow of individuals into and out of correctional facilities compounded the challenges in keeping them COVID-free. This article focuses on the work of the health and administrative leadership, in partnership with judicial and police personnel, to prevent COVID-19 inside the Albemarle-Charlottesville Regional Jail and to mitigate its spread when the jail population and/or its staff became infected. From the onset, implementing science-based policies and upholding the human right to health and healthcare for all were priorities.


Differential growth of U and M type infectious haematopoietic necrosis virus in a rainbow trout-derived cell line, RTG-2.
Infectious haematopoietic necrosis virus (IHNV) is one of the most important viral pathogens of salmonids. In rainbow trout, IHNV isolates in the M genogroup are highly pathogenic, while U genogroup isolates are significantly less pathogenic. We show here that, at a multiplicity of infection (MOI) of 1, a representative U type strain yielded 42-fold less infectious virus than an M type strain in the rainbow trout-derived RTG-2 cell line at 24 h post-infection (p.i.). However, at an MOI of 10, there was only fivefold difference in the yield of infectious virus between the U and M strains. Quantification of extracellular viral genomic RNA suggested that the number of virus particles released from cells infected with the U strain at a MOI of 1 was 47-fold lower than from M-infected cells, but U and M virions were equally infectious by particle to infectivity ratios. At an MOI of 1, U strain intracellular viral genome accumulation and transcription were 37- and 12-fold lower, respectively, than those of the M strain at 24 h p.i. Viral nucleocapsid (N) protein accumulation in U strain infections was fivefold lower than in M strain infections. These results suggest that the block in U type strain growth in RTG-2 cells was because of the effects of reduced genome replication and transcription. The reduced growth of the U strain does not seem to be caused by defective genes, because the U and M strains grew equally well in the permissive epithelioma papulosum cyprini cell line at an MOI of 1. This suggests that host-specific factors in RTG-2 cells control the growth of the IHNV U and M strains differently, leading to growth restriction of the U type virus during the RNA synthesis step.


Surgical management of idiopathic normal-pressure hydrocephalus.
To develop evidence-based guidelines for surgical management of idiopathic normal-pressure hydrocephalus (INPH). Compared with the diagnostic phase, the surgical management of INPH has received less scientific attention. The quality of much of the literature concerning the surgical management has been limited by many factors. These include retrospective analysis, small patient numbers, analysis of a mixed NPH population, and sometimes a lack of detail as to what type of shunt system was used. Many earlier studies predated our current understanding of the hydrodynamics of cerebrospinal fluid shunts, and therefore, the conclusions drawn may no longer be valid. A MEDLINE and PubMed search from 1966 to the present was conducted using the following key terms: normal-pressure hydrocephalus and idiopathic adult-onset hydrocephalus. Only English-language literature in peer-reviewed journals was reviewed. The search was further limited to articles that described the method of treatment and outcome selectively for INPH patients. Finally, only studies that included 20 or more INPH patients were considered with respect to formulating the recommendations in these Guidelines (27 articles). For practical reasons, it is important to identify probable shunt responders diagnosed with INPH. If the patient is an acceptable candidate for anesthesia, then an INPH-specific risk-benefit analysis should be determined. In general, patients exhibiting negligible symptoms may not be suitable candidates for surgical management, given the known risks and complications associated with shunting INPH. The choice of valve type and setting should be based on empirical reasoning and a basic understanding of shunt hydrodynamics. The most conservative choice is a valve incorporating an antisiphon device, with the understanding that underdrainage (despite a low opening pressure) may occur in a small percentage of patients because of the antisiphon device. On the basis of retrospective studies, the use of an adjustable valve seems to be beneficial in the management of INPH. The treatment of INPH should not be considered lightly, given the seriousness of the potential complications. Within these limitations and the available evidence, guidelines for surgical management were developed.


[Hypercholesterolemia and hypertension in Mexico: urban conjunctive consolidation with obesity, diabetes and smoking].
To know the prevalence and the interaction among the principal cardiovascular risk factors such as hypercholesterolemia (HCL), hypertension (HTA), overweight, carbohydrates metabolism disturbances, and smoking, an urban survey was performed in the six Mexican Republic states, where the national population is more concentrated. This survey was transversally designed using the WHO type-III model in 120,005 adults from 6 highly populated urban centers (Mexico City, Guadalajara, León, Puebla, Monterrey andTijuana) were included. A blood sample from each person was obtained to quantify fasting glucose and cholesterol. Blood pressure, height and weight were measured using daily validated systems. Data were analyzed by a multicategorical conjunctive consolidation model and by multiple regression models. HCL global prevalence showed to be 43.3% for a population with an average age of 44.1 years. Female gender showed a slightly but statistically significant greater prevalence of HCL than male gender (44% vs 42.2%). From whole women population 33.2% declared to be in menopause, and 59.7% of them had HCL. In addition, HCL was directly related to body mass index (BMI). Thus, in those subjects with BMI < 25 showed a HCL prevalence 34.1%; while those with BMI was between 25 and 29.9, the HCL prevalence was 45.9%, and in those subjects with BMI > or = 30 Kg/m2, ranked a HCL prevalence of 47.3%. The prevalence of hypertension was 30.2% and 52.5% of them had HCL prevalence. Type-2 diabetes mellitus prevalence (DM-2) was 10.7%, 55.2% of them had HCL. In the group aged between 20 to 34 years old, the obesity was the principal determinant for higher HCL prevalence. The HCL prevalence showed to be quite similar in population with and without smoking. In conclusion, HCL prevalence shows 4 progressively increasing gradients associated with age, HTA, DM-2 and BMI.


Current Status and Major Challenges to the Safety and Efficacy Presented by Chinese Herbal Medicine.
Traditional Chinese medicine (TCM) is not only used prevalently in Asian countries but has also gained a stable market globally. As a principal form of TCM, Chinese herbal medicine (CHM) is comprised of treatments using multiple Chinese herbs which have complex chemical profiles. Due to a lack of understanding of its modality and a lack of standardization, there are significant challenges associated with regulating CHM's safety for practice and understanding its mechanisms of efficacy. Currently, there are many issues that need to be overcome in regard to the safety and efficacy of CHM for the further development of evidence-based practices. There is a need to better understand the mechanisms behind the efficacy of CHM, and develop proper quality standards and regulations to ensure a similar safety standard as Western drugs. This paper outlines the status of CHM in terms of its safety and efficacy and attempts to provide approaches to address these issues.


Impact of Systemic Normobaric Short-Term Hypoxia on Pro-Inflammatory and Anti-Inflammatory Cytokines in Healthy Volunteers.
Hypoxia has been shown to induce a microvascular inflammation, affect the cell count of different types of immune cells, and influence cytokine production in blood. In the present study, serum levels of different cytokines were investigated to achieve insights into the effect of hypoxia on the balance of inflammation and anti-inflammation. Pro- (IL-8) and anti-inflammatory (IL-10) cytokines were measured in an experiment exposing 12 healthy subjects (35 ± 9 yr, 176 ± 7 cm, 73 ± 16 kg, BMI 23 ± 4 kg/m2) to systemic, normobaric hypoxia in a hypoxic chamber. In this chamber oxygen was replaced by nitrogen to reach an oxygen content of 9.9% that is equivalent to an altitude of 5500 m during 7 hours. Serum cytokine concentrations were analyzed using ELISA. As expected, a significant decrease in peripheral oxygen saturation accompanied by a significant increase in breathing frequency and heart rate were observed in the subjects during hypoxia compared to baseline (BL). Blood leukocytes increased slightly, but significantly in the course of hypoxia. A statistically significant increase was measured for IL-8 serum level during hypoxia compared to the baseline measurements (BL 12.0 ± 1.1 pg/mL, hypoxia 16.2 ± 1.6 pg/mL, p = 0.006). For IL-10 a statistically significant decrease was measured upon hypoxia compared to baseline (BL 11.6 [6.2 - 43.31 pg/mL, hypoxia 8.3 [4.4 - 26.6] pg/mL, p = 0.016). Additionally, a significant inverse correlation was found comparing the anti-inflammatory cytokine IL-10 with the pro-inflammatory cytokine IL-8 (r = -0.69, p < 0.001). The results of this study demonstrate a hypoxia-induced increase in pro- and decrease in anti-inflammatory cytokines reflecting an increased pro-inflammatory status during hypoxia.


Cysteine Prevents Menopausal Syndromes in Ovariectomized Mouse.
Cysteine (Cys) is well known to be involved in oxidation-reduction reactions, serving as a source of sulfides in the body. Amino acids are known to improve menopausal symptoms and significantly reduce morbidity. This study aims to find an unrevealed effect of Cys with estrogenic and osteogenic actions. Ovariectomized (OVX) mice were treated with Cys daily for 8 weeks. Estrogen-related and osteoporosis-related factors were analyzed in the vagina, serum, and tibia. Cys was treated in estrogen receptor (ER)-positive human osteoblast-like MG-63 cells and ER-positive human breast cancer Michigan Cancer Foundation-7 (MCF-7) cells. Cysteine administration ameliorated overweightness of the body and vaginal atrophy in the OVX mice. Cysteine increased the levels of alkaline phosphatase (ALP) and 17β-estradiol in the serum of the OVX mice and improved the bone mineral density in the OVX mice. In MG-63 cells, Cys increased the proliferation, ERβ messenger RNA (mRNA) expression, and estrogen response element (ERE) activity. Cysteine increased the ALP activity and the phosphorylation of extracellular signal-regulated kinase. In MCF-7 cells, Cys also increased the proliferation, ERβ mRNA expression, and ERE activity. Taken together, these results demonstrated that Cys has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells. The novel insights gained here strongly imply the potential use of Cys as a new agent for postmenopausal women.


Entropic effects and slow kinetics revealed in titrations of D2O-H2O solutions with different D/H ratios.
There is much renewed interest in the arrangement and kinetic of hydrogen bonds in water and heavy water. D(2)O forms a higher average number of hydrogen bonds per molecule (10% more) compared to the case for H(2)O, which cause a larger entropic cost for solvating molecules in D(2)O. Here we used isothermal titration calorimetry (ITC) to investigate the enthalpy of titration of D(2)O-H(2)O solutions with different D/H isotope ratios. We found significant enthalpy deviations (exothermic contributions) relative to the computed enthalpy for the limit of ideal mixing both for dilution titration and for concentration titration (injection of solutions with lower D/H ratios into solutions with higher ratios and vice versa). We propose that the observed exothermic deviations might be connected to entropic effects associated with differences in the H and D arrangements that depend on the D/H ratio of the solutions. This ratio varies during the titration processes, leading to the entropy production beyond that of ideal mixing. We also used the ITC in the nonstirring mode to measure the titration kinetics and found long relaxation times of up to tens of minutes for the concentration titrations (but not for the dilution titrations). These observations are consistent with slow propagation of the reaction H(2)O + D(2)O <--> 2HDO that involves hopping of deuterium and rearrangements of the H and D bonding.


An audit of letters of referral to a prosthodontic department in a dental teaching hospital.
The purpose of this study was to investigate the quality and number of letters of referral for new patients received in the Prosthodontics Department of a Dental Teaching Hospital. Letters received during the month of May 2006 were included. Each letter of referral was tested against five criteria which might be expected in an appropriate letter of referral. These were information on the following: relevant dental history, relevant medical history, teeth present, diagnosis, and treatment plan. The results showed that only 8% of letters met all five criteria and 11% met none of them. Letters requesting better information were sent to referring practitioner as a result of this audit. However a re-audit in May 2007 showed that 9% of letters met all five criteria and 15% met none of them. A need has been identifiedfor better referral letters and ways of achieving this were discussed.


Influence of mutation bias and hydrophobicity on the substitution rates and sequence entropies of protein evolution.
The number of amino acids that occupy a given protein site during evolution reflects the selective constraints operating on the site. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, while the sequence entropy only depends on the equilibrium frequencies of the amino acids, the substitution rate also depends on the exchangeability matrix that describes mutations in the mathematical model of the substitution process. Here we apply two variants of a mathematical model of protein evolution with selection for protein stability, both against unfolding and against misfolding. Exploiting the approximation of independent sites, these models allow computing site-specific substitution processes that satisfy global constraints on folding stability. We find that site-specific substitution rates do not depend only on the selective constraints acting on the site, quantified through its sequence entropy. In fact, polar sites evolve faster than hydrophobic sites even for equal sequence entropy, as a consequence of the fact that polar amino acids are characterized by higher mutational exchangeability than hydrophobic ones. Accordingly, the model predicts that more polar proteins tend to evolve faster. Nevertheless, these results change if we compare proteins that evolve under different mutation biases, such as orthologous proteins in different bacterial genomes. In this case, the substitution rates are faster in genomes that evolve under mutational bias that favor hydrophobic amino acids by preferentially incorporating the nucleotide Thymine that is more frequent in hydrophobic codons. This appearingly contradictory result arises because buried sites occupied by hydrophobic amino acids are characterized by larger selective factors that largely amplify the substitution rate between hydrophobic amino acids, while the selective factors of exposed sites have a weaker effect. Thus, changes in the mutational bias produce deep effects on the biophysical properties of the protein (hydrophobicity) and on its evolutionary properties (sequence entropy and substitution rate) at the same time. The program Prot_evol that implements the two site-specific substitution processes is freely available at https://ub.cbm.uam.es/prot_fold_evol/prot_fold_evol_soft_main.php#Prot_Evol.


Regio- and stereoselective oxidation of linoleic acid bound to serum albumin: identification by ESI-mass spectrometry and NMR of the oxidation products.
An efficient RP-HPLC method was developed for the detection of the oxidation products derived from the AAPH-initiated peroxidation of linoleic acid bound to human serum albumin. Diode array UV-detection allowed the quantification at 234 nm of four regioisomeric hydroperoxyoctadecadienoic acids (HPODE) and four hydroxyoctadecadienoic acids (HODE) while at 280 nm four oxooctadecadienoic acid isomers (KODE) were detected. Full identification of the different underivatized HODE, HPODE and KODE isomers was achieved by negative ESI-mass spectrometry outlining common fragmentation pathways for 9- and 13-regioisomers. Chemical synthesis of 9-(E,Z)-, 9-(E,E)-, 13-(Z,E)- and 13-(E,E)-KODE helped to their structural characterization by 1H NMR. Lipid peroxidation in the presence of albumin proved to be regioselective with a larger accumulation of 13-HPODE and 9-KODE isomers. Thermodynamically more stable E,E-stereoisomers were also favored by albumin for both HPODE and KODE.


Beneficence, respect for autonomy, and justice: principles in practice.
The principles of beneficence, respect for autonomy, and justice have been debated in various ways in a number of disciplines including philosophy ( 1 , 2 ) and medical ethics ( 3 - 7 ). The scope of debate is broad and encompasses critiques of orthodox perspectives on ethical theories, for example, McIntyre ( 8 , 9 ), and Nunner-Winkler ( 10 ); critiques of the ethics of scientific research, for example, Faulder ( 11 ); and social scientific interest in examining the moral component of research processes ( 12 , 13 ).


Community centrality and social science research.
Community centrality is a growing requirement of social science. The field's research practices are increasingly expected to conform to prescribed relationships with the people studied. Expectations about community centrality influence scholarly activities. These expectations can pressure social scientists to adhere to models of community involvement that are immediate and that include community-based co-investigators, advisory boards, and liaisons. In this context, disregarding community centrality can be interpreted as failure. This paper considers evolving norms about the centrality of community in social science. It problematises community inclusion and discusses concerns about the impact of community centrality on incremental theory development, academic integrity, freedom of speech, and the value of liberal versus communitarian knowledge. Through the application of a constructivist approach, this paper argues that social science in which community is omitted or on the periphery is not failed science, because not all social science requires a community base to make a genuine and valuable contribution. The utility of community centrality is not necessarily universal across all social science pursuits. The practices of knowing within social science disciplines may be difficult to transfer to a community. These practices of knowing require degrees of specialisation and interest that not all communities may want or have.


Magnesium deficiency, requirement and toxicity in the young Japanese quail.
Studies of magnesium deficiency, requirement and toxicity in the young Japanese quail (Coturnix coturnix japonica) were conducted. Day-old birds were fed an adequate purified diet containing 35% soy protein to 2 weeks of age. Residual magnesium in the diet without any added magnesium salts was 21 p.p.m. magnesium was supplied by graded amounts of MgSO4 to a total of 11 levels ranging from 125 to 2,000 p.p.m. Deficiency signs included poor growth, and occasionally excitability, gasping and convulsions. Most mortality occurred during the first 7 days. The maximum dietary magnesium concentrations that produced the minimal significant deviation from normal values for mortality, body weight, hemoglobin and tibia ash was 225, 200, 250 and 250 p.p.m., respectively. Based on these measurements, 300 p.p.m. magnesium is considered adequate to meet the young quail's requirement under the conditions of these experiments. With 2,000 p.p.m. magnesium, the only adverse effect was an increase in mortality. Between 200 and 1,000 p.p.m. magnesium there was a linear relationship between concentration of magnesium in the tibia and the log of the concentration of dietary magnesium. This suggests that tibia magnesium concentration might be useful for bioassay of magnesium in foodstuffs.


[Risks of 360 degree suture trabeculotomy].
In 1995, Beck and Lynch reported a method to perform a 360 degrees trabeculotomy by prolene suture introduced into Schlemm's canal. Because this type of surgery has proved to have perils and can lead to extreme hypotony, even a small series of cases must be reported. Suture trabeculotomy was planned in five eyes of four patients, 5 and 7 months old and 6 and 51 years old, with primary congenital glaucoma, but completed in only two eyes. In one child, suture trabeculotomy could be accomplished easily in both eyes. In the first eye a 360 degrees-tomy was performed, in the second eye only a 180 degrees-tomy was done. Both eyes remained extremely hypotonic (4 mm Hg). In one eye Schlemm's canal could not be disrupted by the suture; in another eye, Schlemm's canal could be probed only for a short distance, and in one eye the suture went the wrong way. Because a suture trabeculotomy can be transformed into a normal trabeculotomy any time, the main problems of the 360 degrees-suture trabeculotomy are not the possible technical difficulties, but that a successful suture trabeculotomy is followed by extreme hypotony.


Acetylsalicylic acid in a trial to diminish thromboembolic complications after elective hip surgery.
Fifty-one patients were investigated concerning thromboembolic complications in the operated leg after elective surgery of the hip. Suspicion of clinical deep venous thrombosis (DVT) arose in 11 patients, i.e. 21 per cent. Thirty-five patients were investigated with phlebography. The incidence of DVT among those patients was 15 cases, i.e. 43 per cent. It is concluded that acetylsalicylic acid, a drug which inhibits the platelet release reaction and thereby blocks the platelet aggregation, given orally in a dose of 2 gram per day from the first postoperative day, is not effective in diminishing the incidence of postoperative deep venous thrombosis.


Regional refractoriness within the ventricular conduction system. An evaluation of the "gate" hypothesis.
We studied the refractoriness of Purkinje fibers with the intent of localizing critical sites of block of premature impulses. To preserve the ventricular conducting system (VCS) nearly intact in vitro, we used a modification of the Elizari preparation. This was superfused with a physiologic salt solution. Action potential durations increased progressively from the His bundle to the distal Purkinje fibers along three pathways: (1) the main right bundle branch and moderator band; (2) the anterior border fibers of the left bundle and anterior false tendons; (3) the posterior border fibers of the left bundle and posterior false tendons. The action potential durations near the terminations of the false tendons were the longest ones found. The interior fibers of the left bundle branch had action potentials of shorter duration and greater variability than those of simultaneously activated fibers in the right bundle branch or the border fibers of the left bundle branch. Similarly, on the right side, the septal branches of the right bundle had action potentials of shorter duration than those of the moderator band. We also found that the fibers with short action potential durations provided the quickest pathways to septal myocardium. When extrastimuli were applied to the His bundle, block in a bundle branch always occurred in the proximal 1 or 2 cm of the main bundle branch. Experiments performed in vivo in which extrastimuli were delivered to the atrium or His bundle and recordings made from the terminations of false tendons and the distal ends of the main right bundle branch confirmed the finding that the critical sites of block were located in the proximal main bundle branches.


Searching for the mechanism of signalling by plant photoreceptor cryptochrome.
Even though the plant photoreceptors cryptochromes were discovered more than 20 years ago, the mechanism through which they transduce light signals to their partner molecules such as COP1 (Constitutive Photomorphogenic 1) or SPA1 (Suppressor of Phytochrome A) still remains to be established. We propose that a negative charge induced by light in the vicinity of the flavin chromophore initiates cryptochrome 1 signalling. This negative charge might expel the protein-bound ATP from the binding pocket, thereby pushing off the C-terminus that covers the ATP pocket in the dark state of the protein. This conformational change should allow for phosphorylation of previously inaccessible amino acids. A partially phosphorylated 'ESSSSGRR-VPE' fragment of the C-terminus could mimic the sequence of the transcription factor HY5 that is essential for binding to the negative regulator of photomorphogenesis COP1. HY5 release through competition for the COP1 binding site could represent the long-sought connection between light activation of cryptochrome and modulation of photomorphogenesis.


Increased Oxygen Vacancies in CeO2 for Improved Electrocatalytic Nitrogen Reduction Performance.
Electrochemical nitrogen fixation is a sustainable and economical strategy to produce ammonia. However, fabricating efficient electrocatalysts for nitrogen fixation is still challenging. Theoretical predictions prove that the oxygen vacancy is able to modulate the electronic state of CeO2 and enhance its electrical conductivity, thus promoting the electrochemical nitrogen reduction reaction (NRR) process. Herein, CeO2 with high oxygen vacancy concentration was prepared via a two-step pyrolysis strategy of Ce metal-organic frameworks (MOFs, denoted H-CeO2). Compared to CeO2 with low oxygen vacancy concentration synthesized via one-step pyrolysis of Ce-MOFs (denoted L-CeO2), H-CeO2 exhibits a large NH3 yield rate (25.64 μg h-1 mgcat-1 at -0.5 V vs reversible hydrogen electrode, RHE) and high faradaic efficiency (FE, 6.3% at -0.4 V vs RHE).


Knowledge, Practice Behaviors, and Perceived Barriers to Fertility Care Among Providers of Transgender Healthcare.
Transgender individuals may experience impaired fertility due to gender-affirming hormonal interventions (e.g., pubertal suppression treatment and/or exogenous hormones). Clinical practice guidelines recommend providers discuss fertility implications and options for fertility preservation. The goal of this study was to examine fertility knowledge, practice behaviors, and perceived barriers to fertility care among multidisciplinary providers who care for transgender pediatric and/or adult patients. A 46-item survey was distributed to relevant listservs and at conferences with a focus on transgender health. Two hundred two providers completed the survey: (1) physicians (n = 87), (2) psychologists (n = 51), (3) Master (MA)-level mental health providers (n = 39), and (4) nonphysician healthcare providers, comprising advanced practice nurses, registered nurses, and physician assistants (n = 25). Overall knowledge was high (M = 3.64, SD = 1.61). Significant differences were identified in knowledge by provider type (p <.001) but not patient age group (p = .693). Physicians had significantly greater knowledge than MA-level mental health providers (p = .005). Variables associated with fertility discussion included provider-related barriers [b = -.42, p < .001], and perceived patient-related barriers, including perceptions that patients are unwilling to delay treatment [b = .12, p = .011] or are unable to afford fertility preservation (FP) [b = .12, p = .029]. While overall fertility-related knowledge was high, there was variability in domains of knowledge, as well as provider practice behaviors related to fertility counseling and referral for FP. Findings related to perceived barriers to fertility counseling and fertility preservation warrant further investigation; qualitative studies may be particularly helpful in understanding how specific provider- and patient-related barriers impact counseling and referral for fertility-related care.


Polymorphisms of Platelet Glycoprotein Receptors and Cell Adhesion Molecules in Fetuses with Fetal Growth Restriction and Their Mothers As Detected with Pyrosequencing.
Vascular thrombotic tendency may lead to fetal growth restriction (FGR). Altered platelet function and genetic heterogeneity may play a role in this procedure. We investigated whether maternal or fetal genotypic frequencies of genes polymorphisms for certain platelet receptor and cell adhesion molecules are altered in FGR. We compared the maternal and fetal genotypic frequencies of single nucleotide polymorphisms (SNPs) in four genes coding for platelet receptors and cell adhesion molecules [integrin alpha subunit 2 (ITGA2)C807T, integrin subunit beta 3(ITGB3) T1565C, platelet cell adhesion protein 1 (PECAM1) CTG-GTG and selectin P(SELP)A/C]. A total of 32 fetuses with fetal growth restriction and their mothers were matched with 18 normal controls. Using maternal venous blood and umbilical cord blood samples, nucleotide sequences were determined from pyrograms. Genotypic frequencies were calculated and analyzed using appropriate tests and logistic regression. There was no statistical difference in the proportion of heterozygotes or homozygotes for any of the genotypic frequencies between FGR and control groups in mothers or fetuses. Our study demonstrated no association of maternal or fetal ITGA2 C807T SNP, ITGB3 T1565C SNP, PECAM1 CTG - GTG and SELP A/C polymorphisms with FGR.


Bismuth: effects on gastritis and peptic ulcer.
The healing properties of colloidal bismuth subcitrate (CBS) on peptic ulcer are well established and several studies have shown that healing with CBS is associated with a lower relapse rate than that produced by H2-receptor antagonists. The recent observation that CBS is effective against Campylobacter pylori has shed light on this because recent studies have shown that eradication of C. pylori by CBS leads to resolution of the associated gastritis and this may explain the low relapse rates. CBS is also effective in C. pylori positive patients with non ulcer dyspepsia (NUD) in whom clearance of these organisms from the stomach is associated with significant improvement of the associated gastritis and symptoms.


Body composition of animals treated with partitioning agents: implications for human health.
Excess fat in meat products has been identified as a dietary problem by public health officials. The meat animal industry has responded during the last 25 years to concerns about excess fat intake from animal products by implementing strategies to depress fat deposition and increase lean (protein) tissue gain in meat animals. The most successful strategy to date is the use of large, late-maturing animals for meat production. At desired market weights, these animals are much leaner than smaller, early-maturing animals. In addition, exogenous agents such as anabolic steroids (FDA approved for cattle) have been used to increase lean gain and depress fat deposition in cattle. Growth hormone (GH) and beta-adrenergic agonists (beta AA) are not yet approved by the FDA, but if/when approved would also markedly increase lean gain and depress fat deposition. Both GH and beta AA are called partitioning agents because they partition nutrients and energy toward lean (protein) accretion and dramatically lower fat deposition. Contingent on approval by the FDA and subsequent adoption of partitioning agents by the animal industry would result in meat products containing less and 30% of total calories from fat.


Interactions Between Temperature Variability and Reproductive Physiology Across Traits in an Intertidal Crab.
Thermal extremes alter population processes, which can result in part from temperature-induced movement at different spatial and temporal scales. Thermal thresholds for animal movement likely change based on underlying thermal physiology and life-history stage, a topic that requires greater study. The intertidal porcelain crab Petrolisthes cinctipes currently experiences temperatures that can reach near-lethal levels in the high-intertidal zone at low tide. However, the thermal thresholds that trigger migration to cooler microhabitats, and the extent to which crabs move in response to temperature, remain unknown. Moreover, the influence of reproductive status on these thresholds is rarely investigated. We integrated demographic, molecular, behavioral, and physiological measurements to determine if behavioral thermal limits varied due to reproductive state. Demographic data showed a trend for gravid, egg bearing, crabs to appear more often under rocks in the cooler intertidal zone where crab density is highest. In situ expression of 31 genes related to stress, metabolism, and growth in the field differed significantly based on intertidal elevation, with mid-intertidal crabs expressing the gene for the reproductive yolk protein vitellogenin (vg) earlier in the season. Furthermore, VG protein levels were shown to increase with density for female hemolymph. Testing for temperatures that elicit movement revealed that gravid females engage in heat avoidance behavior at lower temperatures (i.e., have a lower voluntary thermal maximum, VTmax) than non-gravid females. VTmax was positively correlated with the temperature of peak firing rate for distal afferent nerve fibers in the walking leg, a physiological relationship that could correspond to the mechanistic underpinning for temperature dependent movement. The vulnerability of marine organisms to global change is predicated by their ability to utilize and integrate physiological and behavioral strategies in response to temperature to maximize survival and reproduction. Interactions between fine-scale temperature variation and reproductive biology can have important consequences for the ecology of species, and is likely to influence how populations respond to ongoing climate change.


Fluorescent antibody method for the detection of Salmonella: development, evaluation, and collaborative study.
In preliminary studies, several commercial polyvalent fluorescent antibody (FA) preparations were evaluated for specificity and crossreactivity and an FA method was developed for the screening of Salmonella in products. Approximately 4000 product samples were tested by the FA method and the results were compared to those from the official final action AOAC method, 46.013-46.026. Only 4 FA false-negatives were found for a total of 619 confirmed positive Salmonella samples. The FA false-positive rate was 7%. The method was then subjected to a 2-phase collaborative study. In Phase I, 22 analysts tested 5 inoculated and 5 uninoculated samples of dried milk. In Phase II, 5 naturally contaminated and 5 presumably uncontaminated foods were analyzed. The study was designed to compare results from 11 analysts experienced in FA methodology with those from 11 analysts with little or no experience. Selenite cystine (SC) and tetrathionate (TT) broths were used for enrichment and both were inoculated into SC for post-enrichment. All 4 combinations (SC, TT, SC-SC, and TT-SC) were used with the FA method to determine the best technique. Results were compared to the analysis with TT and SC by the AOAC culture method. In all studies, FA analysis with SC-SC gave the highest correlation with the AOAC method. In a total of 200 samples, the experienced group found 125 AOAC positives and 127 FA positives; no FA false-negatives and only 2 false-positives were reported. The inexperienced group reported 9 FA false-negatives and 5 FA false-positives. All false-negatives occurred in only 3 of the inexperienced laboratories. These studies showed that enrichment and post-enrichment in SC gave the best FA results and that training in FA methodology is required for correlation with existing AOAC methodology. The FA method for the detection of Salmonella has been adopted as official first action.


Non-Destructive Classification of Organic and Conventional Hens' Eggs Using Near-Infrared Hyperspectral Imaging.
Eggs that are produced using organic methods retail at higher prices than those produced using conventional methods, but they cannot be differentiated reliably using visual methods. Eggs can therefore be fraudulently mislabeled in order to increase their wholesale and retail prices. The objective of this research was therefore to test near-infrared hyperspectral imaging (NIR-HSI) to identify whether an egg has been produced using organic or conventional methods. A total of 210 organic and 210 conventional fresh eggs were individually scanned using NIR-HSI to obtain absorbance spectra for discrimination analysis. The physical properties of each egg were also measured non-destructively in order to analyze the performance of discrimination compared with those of the NIR-HSI spectral data. Principal component analysis (PCA) showed variation for PC1 and PC2 of 57% and 23% and 94% and 4% based on physical properties and the spectral data, respectively. The best results of the classification using NIR-HSI spectral data obtained an accuracy of 96.03% and an error rate of 3.97% via partial least squares-discriminant analysis (PLS-DA), indicating the possibility that NIR-HSI could be successfully used to rapidly, reliably, and non-destructively differentiate between eggs that had been produced using organic methods from eggs that had been produced using conventional methods.


Coadministration of Allopurinol To Increase Antimycobacterial Efficacy of Pyrazinamide as Evaluated in a Whole-Blood Bactericidal Activity Model.
Coadministering pyrazinamide (PZA) with the xanthine oxidase inhibitor allopurinol increases systemic levels of the active metabolite, pyrazinoic acid (POA), but the effects on bactericidal activity against tuberculosis are unknown. We randomized healthy volunteers to take a single dose of PZA (either 10 or 25 mg/kg of body weight) at the first visit and the same dose 7 days later, coadministered with allopurinol (100 mg daily; 2 days before to 1 day after the PZA dose). Blood was drawn at intervals until 48 h after each PZA dose, and drug levels were measured using liquid chromatography-tandem mass spectrometry. Whole-blood bactericidal activity (WBA) was measured by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial CFU after 72 h of incubation. Allopurinol increased the POA area under the concentration-time curve from 0 to 8 h (AUC0-8) (18.32 h · μg/ml versus 24.63 h · μg/ml for PZA alone versus PZA plus allopurinol) (P < 0.001) and its peak plasma concentration (Cmax) (2.81 μg/ml versus 4.00 μg/ml) (P < 0.001). There was no effect of allopurinol on mean cumulative WBA (0.01 ± 0.02 ΔlogCFU versus 0.00 ± 0.02 ΔlogCFU for PZA alone versus PZA plus allopurinol) (P = 0.49). Higher systemic POA levels were associated with greater WBA levels (P < 0.001), but the relationship was evident only at low POA concentrations. The lack of an effect of allopurinol on WBA despite a significant increase in blood POA levels suggests that host-generated POA may be less effective than POA generated inside bacteria. Coadministration of allopurinol does not appear to be a useful strategy for increasing the efficacy of PZA in clinical practice. (This study has been registered at ClinicalTrials.gov under registration no. NCT02700347.).


[Use of human albumin and dextran-70 in extracorporeal circulation. Postoperative function of blood platelets (author's transl)].
Human albumin and dextran 70 were used as volume expanders in extracorporeal circulation in two homogeneous series of patients. Comparative results were statistically processed. No significant differences were observed either to early postoperative bleeding or needed volume of transfused blood. Postoperative complications neither developed in the two groups of patients. The total number of platelets showed a 50 percent decrease in relation to basal extraction figures and those after immediate heparin neutralization. Results of platelet function tests were similar in both series, except for a statistical significant decrease in ADP-induced platelet aggregation in the group with dextran 70. Such decrease, however, was not followed by an increase of postoperative bleeding. Thus, dextran 70 has showed to be a valuable substitute for human albumin in extracorporeal circulation.


Electrochemical survey: the effect of the cage size and structure on the electronic structures of a series of ytterbium metallofullerenes.
The electrochemical properties of a series of metallofullerenes with different cages, namely, Yb@C74(II), Yb@C76(I, II), Yb@C78, Yb@C80, Yb@C82(I, II, III), and Yb@C84(II, III, IV), have been systematically investigated by cyclic and differential pulse voltammetry experiments for the first time. This article discusses the electronic structures of these metallofullerenes based on the results from these experiments. From previous electrochemical work and the above discussion, it is concluded that the nondegenerate LUMO is a common characteristic of the electronic structures of the higher fullerenes and monometallofullerenes. In addition, the effect of the cage on the electronic structure and properties of the metallofullerene is estimated from the plot of the reduction potential versus the carbon number of the metallofullerene. This estimation shows that usually the electronic structure and properties of the metallofullerene vary with cage size and structure. The cage structure is of particular importance for determining the electronic structure and properties. Moreover, an explanation concerning the abundance and stability of C82-based trivalent monometallofullerenes is given from an electronic structural standpoint.


Examination of shared risk and protective factors for overweight and disordered eating among adolescents.
To identify shared risk and protective factors for purging, binge eating, and overweight. Prospective cohort study. Population-based questionnaires of children and adolescents residing across the United States. Girls (n = 6022) and boys (n = 4518), aged 11 to 17 years in 1998, in the ongoing Growing Up Today Study. Putative risk and protective factors within the psychological, behavioral, and socioenvironmental domains. Overweight, use of laxatives or purging (vomiting), and binge eating. Because of the low prevalence of purging, we did not examine shared factors for this behavior among boys. In 1998, a total of 219 girls (3.7%) and 30 boys (0.7%) reported purging behaviors, 426 girls (7.1%) and 90 boys (2.0%) reported binge eating, and 1019 girls (17.4%) and 1040 boys (24.6%) were overweight. From 1999 through 2001, 331 girls (7.8%) initiated purging behaviors, 503 girls (11.8%) and 132 boys (4.5%) initiated binge eating behaviors, and 424 girls (10.0%) and 382 boys (13.6%) became overweight. Concern for weight was directly associated with all 3 weight-related problems among boys and girls. Among girls, dieting, parental weight-related teasing, and family meal frequency had a shared effect on the weight-related problems examined. Factors within the psychological, behavioral, and socioenvironmental domains may have a shared effect on purging, binge eating, and overweight. Further research is needed to determine if an intervention designed to address these shared risk and protective factors is effective in simultaneously reducing these weight-related problems.


Two functional assays employed to detect an unusual mutation in the oligomerisation domain of p53 in a Li-Fraumeni like family.
Previous investigations of a Li - Fraumeni like family (Barnes et al., 1992) demonstrated that both the proband and her mother had elevated p53 protein levels in both tumour tissue and normal tissue at sites distant from the tumour, although no mutation was found in the p53 gene. In the present study two recently described functional assays for p53, an apoptotic assay and the functional assay for the separation of alleles in yeast (FASAY), have been employed to study the functional activity of p53 from this patient. The results of the apoptotic assay demonstrated that this patient had a p53 functional defect and the FASAY result suggested that this defect was in fact a germline mutation of the p53 gene. A point mutation of codon 337, which results in an amino acid substitution of a cysteine for an arginine, was demonstrated initially in cDNA and was confirmed by sequencing of genomic DNA. This is an unusual mutation as it is in the oligomerisation domain of p53, in contrast to the majority of p53 mutations which are in the core DNA binding domain. This mutation results in a protein which still retains partial transactivational activity in the FASAY. The mutation of codon 337 is only the second reported case of a germline missense mutation occurring in the oligomerisation domain of p53.


Misregulation of cell adhesion molecules in the Ciona neural tube closure mutant bugeye.
Neural tube closure (NTC) is a complex multi-step morphogenetic process that transforms the flat neural plate found on the surface of the post-gastrulation embryo into the hollow and subsurface central nervous system (CNS). Errors in this process underlie some of the most prevalent human birth defects, and occur in about 1 out of every 1000 births. Previously, we discovered a mutant in the basal chordate Ciona savignyi (named bugeye) that revealed a novel role for a T-Type Calcium Channel (Cav3) in this process. Moreover, the requirement for CAV3s in Xenopus NTC suggests a conserved function among the chordates. Loss of CAV3 leads to defects restricted to anterior NTC, with the brain apparently fully developed, but protruding from the head. Here we report first on a new Cav3 mutant in the related species C. robusta. RNAseq analysis of both C. robusta and C. savignyi bugeye mutants reveals misregulation of a number of transcripts including ones that are involved in cell-cell recognition and adhesion. Two in particular, Selectin and Fibronectin leucine-rich repeat transmembrane, which are aberrantly upregulated in the mutant, are expressed in the closing neural tube, and when disrupted by CRISPR gene editing lead to the open brain phenotype displayed in bugeye mutants. We speculate that these molecules play a transient role in tissue separation and adhesion during NTC and failure to downregulate them leads to an open neural tube.


[3H]Digoxin in the optic tract in digoxin intoxication.
Normal and chronically hypokalemic dogs were infused with [3H]digoxin until ventricular tachycardia occurred, at which point the concentration of digoxin was measured in all tissues involved in vision. The highest concentration was found in the choroid-retina of the eye, and this was considered the most likely site for the various visual changes seen in digitalis intoxication in man. Chronic hypokalemia did not influence the concentration or distribution of digoxin in the optic tract. It is speculated that the increased digoxin level in the extracranial part of the optic nerve is due to a weakness in the blood-retina barrier where the optic nerve fibers pass through the retina. One eye was left in situ for 3 days after death to study post-mortem changes in digoxin distribution. Vitreous humor analysis is being used to study the cause of death in man, but we found an increase in the vitreous humor digoxin level after death due to loss from its primary binding site in the choroid-retina. A similar effect would be expected with any drug bound to the retina and would have to be taken into account when considering the cause of death forensic pathology.


Distribution of serotypes, IS901 and a 40 kDa protein in Mycobacterium avium complex strains isolated from man and animals in Denmark.
The aim of the present study was to characterize all strains of the Mycobacterium avium complex isolated in Denmark in 1993. A total of 141 M. avium complex strains (86 from man, 38 from animals, and 17 from peat) were analysed by serotyping, ELISA specific for a 40 kDa protein, and IS901-specific PCR. Serotype analysis showed that the most frequent serotypes among human strains were serotype 4 (27%) and serotype 6 (19%), which differs from an earlier survey where serotype 1 was most prevalent. The most frequent serotypes in animals were serotype 2 (53%) and serotype 6 (13%), whereas the most prevalent serotypes among strains isolated from peat were serotype 4 (29%) and serotype 9 (18%). There was a concurrent appearance of IS901 and p40 in all strains. Only M. avium complex strains isolated from animals, and belonging to serotype 1 or serotype 2, contained the IS901/p40 markers. The different distribution of serotypes of M. avium complex strains in animals and man, and the presence of IS901/p40 exclusively in animal strains, suggests that transmission of M. avium from animals to man is not of significance in Denmark.


[The application of noninvasive urodynamics in early detection of diabetic cystopathy].
To evaluate the early detection of diabetic cystopathy (DCP) with the technology of noninvasive urodynamics. 70 patients with type 2 diabetes mellitus (DM) and 30 normal control subjects were checked with the technology of noninvasive urodynamics. Based on their disease course of less or more than 5 years, the DM patients were divided into two groups. Maximal flow rate, average flow rate, the volume leading to first bladder sensation and residual urine volume were measured by using noninvasive urodynamic technology. Among the 70 DM patients, 34 were detected to have bladder residual urine, so the DCP detection rate was 48.6%. In the patients with DCP, the average residual urine volume was 7-139 ml (30.1 +/- 27.1) ml, while there was no residual urine in the normal control group. As compared with the normal control group, maximal flow rate and average flow rate were decreased in all the patients with DM and those with DCP (P < 0.01). After follow up of the disease, the patients with a course of more than five years of disease control had even lower maximal flow rate and average flow rate. Maximal flow rate decrease and bladder residual urine detected with the technology of noninvasive urodynamics may be widely used in early detection and early diagnosis of DCP.


Population Genetics, Genetic Structure, and Inbreeding of Commiphora gileadensis (L.) C. Chr Inferred from SSR Markers in Some Mountainous Sites of Makkah Province.
Commiphora gileadensis (L.) C. Chr is a perennial plant existing mainly in the southern and western mountains of the Arabian Peninsula. In the Makkah province, the remaining populations are threatened by many factors such as overcutting, overgrazing, and urban developments. These dangers are expected to be aggravated by the progression of aridification factors arising from climate change. To overcome the decline in remaining populations of this valuable species, a timely evaluation of the population's genetic variables and genetic structure is vital for the conservation of existing C. gileadensis populations. In this study, we used 61 SSR primers to achieve this objective. Only 50 loci showed polymorphisms, which led to further analysis of the population genetics for 600 genotypes that were collected from 50 populations of C. gileadensis found in 10 different sites in the Makkah region: Gebel Al Muliesaa, Wadi Albathna, Wadi Houra, Wadi Albaidaa, Wadi Elebiedia, Gebel Kniethl, Wadi Sayaa, Wadi Elbarasa, Wadi Alfawara, and Wadi Alkharar. The results showed an obvious decrease in genetic diversity variables in all studied populations. The range of PPL was between 8 and 40; additionally, the low HT value of 0.804 and the high value of inbreeding, Fis = 0.238, reflected a severe lack of heterozygotes. High levels of FST and GST and low gene flow indicate considerable segregation among the C. gileadensis populations, which creates a barrier to gene migration. Our data suggest the need for conservation planning for C. gileadensis in order to avoid the species' forthcoming extinction. Efforts should be largely oriented around managing water consumption, prohibiting overcutting and overgrazing, and establishing appropriate seed banks.


Multifunctional Pristine Chemically Modified Graphene Films as Strong as Stainless Steel.
Pristine chemically modified graphene films with light weights and excellent mechanical properties can be prepared by chemically engineering the structure of the graphene oxide sheets and the microstructures of the films. Particularly, these reduced graphene oxide films are as strong as stainless steel, ultra-tough, and have high electrical and thermal conductivities.


Factors That Explain Differences in Abstinence Between Black and White Smokers: A Prospective Intervention Study.
Black-white differences in smoking abstinence are not well understood. This trial sought to confirm previously reported differences in quitting between blacks and whites and to identify factors underlying this difference. During enrollment, 224 black and 225 white low-income smokers were stratified on race and within race on age and sex to ensure balance on these factors known to impact abstinence. The intervention included varenicline for 12 weeks and six guideline-based smoking cessation counseling sessions. The primary endpoint was cotinine-verified 7-day point prevalence smoking abstinence at week 26. A priori socioeconomic, smoking, treatment process (eg, treatment utilization, side effects, withdrawal relief), psychosocial, and biological factors were assessed to investigate race differences in abstinence. Unadjusted odds ratios (OR) were used to compare abstinence between blacks and whites. Adjusted odds ratios from logistic regression models were used to examine predictors of abstinence. All statistical tests were two-sided. Blacks were less likely to achieve abstinence at week 26 (14.3% vs 24.4%, OR = 0.51, 95% confidence interval [CI] = 0.32 to 0.83, P = .007). Utilizing best subsets logistic regression, five factors associated with race jointly predicted abstinence: home ownership (yes/no, OR = 3.03, 95% CI = 1.72 to 5.35, P < .001), study visits completed (range = 0-6, OR = 2.81, 95% CI = 1.88 to 4.20, P < .001), income (household member/$1000, OR = 1.03, 95% CI = 1.01 to 1.06, P = .02), plasma cotinine (per 1 ng/mL, OR = 0.997, 95% CI = 0.994 to 0.999, P = .002), and neighborhood problems (range = 10-30, OR = 0.88, 95% CI = 0.81 to 0.96, P = .003). The race difference in abstinence was fully explained by lack of home ownership, lower income, greater neighborhood problems, higher baseline cotinine, and higher visit completion, which were disproportionately represented among blacks. Findings illuminate factors that make it harder for blacks in the United States to quit smoking relative to whites and provide important areas for future studies to reduce tobacco-related health disparities.


Meiotic induction in cumulus cell-enclosed mouse oocytes: involvement of the pentose phosphate pathway.
In this study we tested the hypothesis that the pentose phosphate pathway (PPP) participates in the meiotic induction of mouse oocytes. The electron acceptors methylene blue, phenazine ethosulfate (PES), and pyrroline-5-carboxylate (P5C) oxidize NADPH to NADP and activate the NADP-dependent enzymes of the PPP. Each of these compounds triggered a dose-dependent increase in meiotic maturation in hypoxanthine-arrested cumulus cell-enclosed oocytes during 17- to 18-h cultures. More than 96% of the oocytes underwent germinal vesicle breakdown (GVB) at the highest concentrations of P5C and PES tested (250 and 1 microM, respectively) as compared to only 45-52% of control oocytes. P5C was also stimulatory to denuded oocytes. Analysis of energy substrates in microdrop cultures revealed a 3.6-fold increase in glucose consumption by PES-treated oocyte-cumulus cell complexes that was associated with stimulation of GVB. On the other hand, 2-deoxyglucose, which interferes with glucose utilization, prevented the induction of maturation brought about by P5C. Apocynin and diphenyleneiodonium, inhibitors of NADPH oxidase, prevented meiotic maturation in the presence or absence of FSH. Gonadotropin-induced maturation was also prevented by 6-aminonicotinamide (6-AN) and dehydroepiandrosterone (DHEA), inhibitors of the two NADP-dependent enzymes of the PPP, and this was accompanied by suppression of glucose consumption. Phosphoribosyl-pyrophosphate (PRPP) is an important compound required in purine metabolism and can be formed from the end product of the oxidative arm of the PPP, ribose-5-phosphate. Ribose, which can be metabolized to PRPP, increased PRPP synthesis in complexes and induced meiotic maturation when added to hypoxanthine-arrested cumulus cell-enclosed oocytes in glucose-free medium in both the presence and absence of FSH. PRPP levels within complexes were also increased by glucose and FSH, but were reduced by hypoxanthine, 6-AN, and DHEA. In addition, exogenous PRPP stimulated maturation in hypoxanthine-arrested oocytes. These results support the proposition that glucose metabolism through the PPP is important in the meiotic induction mechanism and may involve the generation of PRPP that acts, at least in part, through the purine metabolizing pathways.


Acute generalized exanthematous pustulosis associated with azathioprine hypersensitivity.
Acute generalized exanthematous pustulosis (AGEP) is identified by several characteristic features. We present a patient showing AGEP associated with azathioprine hypersensitivity. To our knowledge, this is the first reported case of this association.