[Improving the diagnostic potentials of isotope nephrography with 131I-hippuran].
In order to eliminate the false positive and the false negative results in the control isotopic nephrographic examinations due to the minute diuresis determination of the difference between the time of appearance of T-maximum of both kidneys is recommended. When the earlier (respectively the later) appearance of T max. is due to improved (or deteriorated) renal function the difference between the two T max. increases (or decreases). When the change in the time of appearance of the two T max. is due to the minute diuresis the difference between them remains unchanged.


α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates DSS-induced intestinal colitis by improving intestinal mucosal barrier function.
Cholinergic output, which could modulate innate immune responses through stimulation of α7 nicotinic acetylcholine receptor (α7nAChR), might be a target to minimize tissue damage in autoimmune disease. GTS-21, a selective α7nAChR agonist, has previously demonstrated to inhibit synovium inflammation in rheumatoid arthritis. In this study, we investigated the effect of GTS-21 on dextran sulfate sodium (DSS)-induced colitis model and its potential mechanism. Male BABL/c mice (n = 32) were randomly divided into four groups: normal control group, DSS-induced colitis group, GTS-21 treatment with or without α7nAChR antagonist α-BGT treatment group. Disease activity index (DAI), histological activity index (HAI) and colonic macroscopic damage were evaluated. Fluorescein isothiocyanate (FITC)-dextran assay was applied to measure intestinal permeability. The expressions of tight junction (TJ) proteins and NF-κB associated proteins were detected by Western blot. GTS-21 could decrease DAI scores, HAI scores, intestinal permeability and reduce the intestinal bacterial translocation in DSS-induced colitis group, whereas α7nAChR antagonist α-BGT could impair this protective influence. The expressions of TJ proteins were increased with administration of GTS-21 both in vivo and in vitro. Furthermore, GTS-21 also inhibited the NF-қB activation in intestinal epithelial cells and colitis model, while α-BGT reversed the inhibitory effect. The α7nAChR agonist GTS-21 attenuated DSS-induced colitis through increasing expressions of TJ proteins in colon tissues and improved intestinal barrier function, which might be due to modulating NF-қB activation in intestinal epithelial cells.


[Detection and follow up of inflammatory lesions of the central nervous system by means of cytological study of the cerebrospinal fluid (author's transl)].
Cytocentrifugation gives an excellent quantitative and qualitative preservation of the cerebrospinal fluid cells. This method permits the study various types of meningeal or ventricular inflammatory changes (acute inflammatory changes with granulocytes, immunitary type or macrophagic changes) and causal diagnosis. During meningitis following bleeding or neurosurgical operation, repeated cytological examinations allow a simple but useful follow up of the evolution during the treatment.


Mechanisms for reaching the differentiated state: Insights from neural crest-derived melanocytes.
Black pigment cells, or melanocytes, are the major contributing cells to pigmentation in vertebrate organisms. Although the function of these cells is distinct depending on the organism, the events involved in their development are remarkably similar. Here, we review the mechanisms involved in the early development of melanocytes from neural crest, many of which are conserved in organisms as diverse as zebrafish, birds and humans. We also discuss recent studies that provide further insight into how melanocyte differentiation is achieved and maintained.


New Interventional Treatment Model for Pancreatic Neoplasms Using Gemcitabine-Eluting Hydrogel Devices: In Vitro and In Vivo Results.
In vitro and in vivo evaluation of fast- and slow-release gemcitabine-eluting hydrogel (GEH) devices. For in vitro elution, the GEH devices were placed in phosphate-buffered saline at 37 °C. Periodically, the solution was analyzed for gemcitabine. The devices consisting of fast release (n = 8), slow release (n = 6), or bland (n = 4) were delivered through a 5-Fr catheter into the gastroduodenal artery of a pig. Additionally, four pigs were treated with intravenous (IV) injection of gemcitabine. Pigs were killed at day 1 (n = 9), day 7 (n = 11), or day 21 (n = 2). Gemcitabine concentrations in the plasma and tissues were determined. In vitro, gemcitabine was completely eluted within 6 h or 30 days for the fast- and slow-release devices, respectively. All 22 pigs were treated without morbidity or mortality. Gemcitabine plasma concentrations peaked at about 105,000 ± 30,000, 252 ± 101, 22 ± 29, and 0 ± 0 ppb for the IV, fast-release, slow-release, and bland treatments, respectively. At days 1 and 7, gemcitabine concentrations were higher in the pancreas for the GEH devices than IV. Gemcitabine delivery to the pancreas was sustained over 21 days in the slow-release group. Treatment with GEH devices resulted in at least equivalent gemcitabine concentration in the pancreas and reduced concentration in the plasma, heart, liver, and duodenum, at least equivalent to IV injection and reduced concentrations elsewhere. These results show the potential of sustained local delivery of gemcitabine to treat pancreatic neoplasms with reduced side effects.


MEDINFO--a medical information system.
The MEDINFO (MEDical INFOrmation) system is a general purpose computer-based information storage, retrieval, and analysis system. It is designed for a time sharing, on-line computer system for the rapid and easy creation, maintenance, and analysis of general data files. A wide variety of types of information may be used. These include numeric, categoric, text, date, and multiple-response. The file structure allows several sets of data, including date-orientated data, to be used. MEDINFO permits a study to be created, a description of the data made, data to be entered and updated into records, and for the data to be displayed or analyzed by the investigator without programmer intervention.


Associations between weight-adjusted waist index and bone mineral density: results of a nationwide survey.
The weight-adjusted waist circumference index (WWI) is a novel obesity indicator that offers improved accuracy in assessing both muscle and fat mass compared to traditional measures. This study aimed to investigate the association between WWI and bone mineral density (BMD) in adults. Weighted multivariate logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) curves were used to explore the relationship between WWI and BMD based on data from the National Health and Nutrition Examination Survey (NHANES). This study had 40,568 individuals in total. At all four measurement sites, we detected a negative linear correlation between WWI and BMD. Even when quartile factors for WWI were created, this unfavorable connection maintained. In comparison to those in the lowest quartile, those in the highest percentile of WWI showed declines in lumbar BMD of 0.08 g/cm2 and femoral neck BMD of 0.03 g/cm2, respectively. This adverse correlation, nevertheless, differed among several categories. Our findings suggest an adverse correlation between WWI and BMD among US adults. Employing WWI as a tool for osteoporosis prevention in the general population may enhance interventions.


Synthesis and P2Y₂ receptor agonist activities of uridine 5'-phosphonate analogues.
We explored the influence of modifications of uridine 5'-methylenephosphonate on biological activity at the human P2Y(2) receptor. Key steps in the synthesis of a series of 5-substituted uridine 5'-methylenephosphonates were the reaction of a suitably protected uridine 5'-aldehyde with [(diethoxyphosphinyl)methylidene]triphenylphosphorane, C-5 bromination and a Suzuki-Miyaura coupling. These analogues behaved as selective agonists at the P2Y(2) receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y(2) receptor.


Excess noise in modified conductance states following the interaction of ryanoids with cardiac ryanodine receptor channels.
The interaction of ryanodine with the ryanodine receptor (RyR) produces profound changes in channel function. Open probability increases dramatically and conductance is reduced. In this report we describe differences in the properties of reduced conductance states produced by the interaction of ryanodine derivatives with RyR channels. Some reduced conductance states are considerably noisier than the normal open state of the RyR channel. Inspection and analysis of these events reveals that the excess noise arises from transitions between two conductance states. Following the interaction of certain ryanodine derivatives, RyR channels undergo transitions between two conformations with slightly different ion-handling properties.


Purification and characterization of two glycopeptide hydrolases from jack beans.
Two glycopeptide hydrolases, an endo-beta-N-acetylglucosaminidase and peptide:N-glycanase (amidase), have been isolated from defatted jack bean meal by standard procedures involving differential solubility and column chromatography. The purified products appear to be free of contaminating proteases and exoglycosidases, and their substrate specificity has been explored with regard to both glycan and peptide structure of the substrates. The endoglycosidase appears to be specific for high mannose glycans; no hydrolysis of either hybrid or complex glycans has been observed. It shows limited activity with two intact glycoproteins, ribonuclease B and yeast invertase, and gives optimal rate with glycopeptides. Free glycan-Asn derivatives are poor substrates in comparison with glycopeptides or glycan-Asn derivatives where the alpha-amino group has been dansylated. The amidase will liberate both high mannose, hybrid, and asialo-complex glycans from both proteins and peptides, but many glycans in intact proteins or in long peptides are resistant to the amidase and become active as substrates only after further proteolytic cleavage. The best substrates appear to be those with the glycosylated asparagine no more than 4-5 residues in from either the NH2- or COOH-terminal end of the peptide. Sialylated glycans do not appear to be released by the amidase.


The sclera and myopia.
Myopia is a very common ocular problem, affecting perhaps one billion people worldwide. Most myopia is produced by lengthening of the vitreous chamber of the ocular globe. High myopia is characterized by scleral thinning and localized ectasia of the posterior sclera. The sclera is a dense, fibrous, viscoelastic connective tissue that forms the outer coat of the eye and consists of irregularly arranged lamellae of collagen fibrils interspersed with proteoglycans and non-collagenous glycoproteins. Scleral fibroblasts are located between scleral lamellae, and are responsible for synthesizing the extracellular matrix in which they reside. Research highlighted in this review clearly demonstrates that the sclera is not a static container of the eye, but rather is a dynamic tissue, capable of altering extracellular matrix composition and its biomechanical properties in response to changes in the visual environment to regulate ocular size and refraction. Based on these studies, a strategy directed at reversing myopia-associated scleral extracellular matrix remodeling events would be warranted, particularly in cases of high myopia in humans.


Viability of a random pattern dorsal skin flap, in diabetic rats.
Evaluation of the viability of a random pattern dorsal skin flap, in rats with experimentally induced diabetes mellitus. Thirty adult, male, Wistar EPM rats were distributed, at random, in two groups: I--Control (flap elevation) and II--Experimental (flap elevation ten days after alloxan induced diabetes). The mean areas of necrosis in the different groups were 36.4% (Control) and 52.1% (Experimental). The random pattern dorsal skin flap was less viable in the diabetic rats.


Short Peptides Protect Oral Stem Cells from Ageing.
Primary stem cells, after several cell divisions, enter into a senescence state, that is characterized by alterations to spindle-shape typical morphology. This concern is one of the main problems in the use of human mesenchymal stem cells (hMSCs) in clinical applications which demand cells in large numbers. Short peptides had geroprotective properties and stimulated stem cell differentiation. The aim of the study is to demonstrate the role of AEDG and KED peptides in maintaining oral hMSCs morphology and functions over long-term expansion. 2 types of hMSCs were investigated: human periodontal ligament stem cells (hPLSCs) and human gingival mesenchymal stem cells (hGMSCs). Cells at the 25th passage were divided into 3 groups: 1 - control (without adding peptide), 2 - treated with AEDG peptide, 3 - treated with KED peptide. Cell cultures were analyzed by an immunofluorescence method and RT-PCR on the p16 and p21 senescence markers expression. AEDG peptide decreased p16 and p21 mRNA expression by 1.56-2.44 times in comparison with the control group. KED peptide decreased p16 and p21 mRNA expression by 1.82-3.23 times in comparison with the control group. These results were confirmed by immunofluorescent visualization. AEDG and KED peptides could be used as supplementary substances in a culture medium to delay the expression of senescence markers in long term stem cell cultivation in order to promote the large-scale in vitro expansion necessarily required for stem cell therapy clinical application. The data obtained confirm the geroprotective effect of AEDG and KED peptide, which was shown early in animal and cells models.


High concordance of 70-gene recurrence risk signature and 80-gene molecular subtyping signature between core needle biopsy and surgical resection specimens in early-stage breast cancer.
With increased neoadjuvant therapy recommendations for early-stage breast cancer patients due to the COVID-19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens. Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient. We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance of BluePrint subtyping in matched samples was also excellent (98.3%). CNB samples demonstrated high concordance with paired SR samples for MammaPrint risk classification and BluePrint molecular subtyping, suggesting that physicians are provided with accurate prognostic information that can be used to guide therapy decisions.


High-performance analytical applications of immobilized metal ion affinity chromatography.
The separation of three sets of standard protein mixtures on a high-performance immobilized metal ion affinity chromatography (HP-IMAC) column by elution with linear gradients of imidazole is described. The affinity of the test proteins for the immobilized metal ions follows the order Cu2+ greater than Ni2+ greater than Zn2+. The iminodiacetic acid-Cu2+ column gives the best resolution of all three protein mixtures and is the only immobilized metal ion column that can be used for elution of absorbed proteins with a decreasing pH gradient. An application of HP-IMAC for the separation of monoclonal IgG from mouse ascites fluid is also outlined. This versatile separation method is thus suitable for both analytical and preparative separations of proteins and peptides resulting in high recoveries and good reproducibility. The leakage of immobilized metal ions from the TSK gel chelate-5PW is apparent if the column is eluted by buffers containing low concentrations of (i) glycine or (ii) primary amines at round neutral pH. Considerable amounts of immobilized Zn2+ and Ni2+ ions also leak from the column by washing with buffers of pH 4.5 or lower. However, all three immobilized metal ions are stable toward exposure to low concentrations of imidazole (up to 50 mM) in phosphate buffers between pH 6.5 and 8.0. Adsorbed proteins could thus be eluted conveniently by using linear gradients of imidazole to give reproducible results. Moreover, this elution procedure made it possible to use the IMAC columns for repeated runs without the need for regeneration and recharging of the columns with fresh metal ions after each use.


Transitioning the child fed by gastrostomy into school.
Young children dependent on gastrostomy feeding are examples of special-needs children now eligible for expanded nutrition services in schools through Public Law 99-457. With the implementation of this law, nutritionists have an opportunity to expand their roles as consultants to special education teachers. A team approach involving nutrition, nursing, and special education was used to prepare a gastrostomy-fed preschool child and his family for school. The family of the multihandicapped child had been isolated by the child's feeding problems and viewed the problems as barriers to his entering school. Components of a nutrition care plan for an interdisciplinary team included oral feeding readiness, nutritional adequacy and timing of meals, and mechanical aspects of gastrostomy feeding in the classroom. Nutrition interventions were adjusted for the classroom from those used in the home or clinical setting. The major activity in the transition program was behavioral management of the child's rumination, which affected nutritional status and feeding. The major outcome of the transition program was enrollment of the child in school, with gastrostomy feeding as a routine activity. A transition program for a gastrostomy-fed child is an appropriate mechanism for expanding the role of the nutritionist into the classroom.


[Double deficiency of sulfite and xanthine oxidase causing encephalopathy and due to a hereditary anomaly in the metabolism of molybdenum].
The clinical features and biological results in a second patient with a metabolic defect of the molybdenum cofactor are described. The first case was reported in 1978 by Duran et al. Their clinical description was similar with early encephalopathy and myoclonial and dislocation of the lens. Biologically, this condition is characterised by secondary hypo-uricemia and hypo-uricuria due to xanthine oxidase deficiency and by sulphituria, resulting from sulphite oxidase deficiency. These two enzymes have a common hepatic molybdenum cofactor, the structure and metabolism of which are only partially known.


SIMplyBee: an R package to simulate honeybee populations and breeding programs.
The Western honeybee is an economically important species globally, but has been experiencing colony losses that lead to economical damage and decreased genetic variability. This situation is spurring additional interest in honeybee breeding and conservation programs. Stochastic simulators are essential tools for rapid and low-cost testing of breeding programs and methods, yet no existing simulator allows for a detailed simulation of honeybee populations. Here we describe SIMplyBee, a holistic simulator of honeybee populations and breeding programs. SIMplyBee is an R package and hence freely available for installation from CRAN http://cran.r-project.org/package=SIMplyBee . SIMplyBee builds upon the stochastic simulator AlphaSimR that simulates individuals with their corresponding genomes and quantitative genetic values. To enable honeybee-specific simulations, we extended AlphaSimR by developing classes for global simulation parameters, SimParamBee, for a honeybee colony, Colony, and multiple colonies, MultiColony. We also developed functions to address major honeybee specificities: honeybee genome, haplodiploid inheritance, social organisation, complementary sex determination, polyandry, colony events, and quantitative genetics at the individual- and colony-levels. We describe its implementation for simulating a honeybee genome, creating a honeybee colony and its members, addressing haplodiploid inheritance and complementary sex determination, simulating colony events, creating and managing multiple colonies at the same time, and obtaining genomic data and honeybee quantitative genetics. Further documentation, available at http://www.SIMplyBee.info , provides details on these operations and describes additional operations related to genomics, quantitative genetics, and other functionalities. SIMplyBee is a holistic simulator of honeybee populations and breeding programs. It simulates individual honeybees with their genomes, colonies with colony events, and individual- and colony-level genetic and breeding values. Regarding the latter, SIMplyBee takes a user-defined function to combine individual- into colony-level values and hence allows for modeling any type of interaction within a colony. SIMplyBee provides a research platform for testing breeding and conservation strategies and their effect on future genetic gain and genetic variability. Future developments of SIMplyBee will focus on improving the simulation of honeybee genomes, optimizing the simulator's performance, and including spatial awareness in mating functions and phenotype simulation. We invite the honeybee genetics and breeding community to join us in the future development of SIMplyBee.


beta-Blockade in noncardiac surgery: outcome at all levels of cardiac risk.
We hypothesized that the relationship among beta-blocker use, heart rate control, and perioperative cardiovascular outcome would be similar in patients at all levels of cardiac risk. Retrospective cohort study. Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. Among all patients who underwent various noncardiac surgical procedures in 2000, those who received perioperative beta-blockers were matched and compared with a control group from the same patient population. Thirty-day stroke, cardiac arrest, myocardial infarction, and mortality, as well as mortality at 1 year. Patients at all levels of cardiac risk who received beta-blockers had lower preoperative and intraoperative heart rates. The beta-blocker group had higher rates of 30-day myocardial infarction (2.94% vs 0.74%, P =.03) and 30-day mortality (2.52% vs 0.25%, P =.007) compared with the control group. In the beta-blocker group, patients who died perioperatively had significantly higher preoperative heart rate (86 vs 70 beats/min, P =.03). None of the deaths occurred among the patients at high cardiac risk. Among patients at all levels of cardiac risk undergoing noncardiac surgery, administration of beta-blockers should achieve adequate heart rate control and should be carefully monitored in patients who are not at high cardiac risk.


A district-level vulnerability assessment of next COVID-19 variant (Omicron BA.2) in Uttarakhand using quantitative SWOT analysis.
COVID-19 has had an impact on the entire humankind and has been proved to spread in deadly waves. As a result, preparedness and planning are required to better deal with the epidemic's upcoming waves. Effective planning, on the other hand, necessitates detailed vulnerability assessments at all levels, from the national to the state or regional. There are several issues at the regional level, and each region has its own features. As a result, each region needs its own COVID-19 vulnerability assessment. In terms of climate, terrain and demographics, the state of Uttarakhand differs significantly from the rest of India. As a result, a vulnerability assessment of the next COVID-19 variation (Omicron BA.2) is required for district-level planning to meet regional concerns. A total of 17 variables were chosen for this study, including demographic, socio-economic, infrastructure, epidemiological and tourism-related factors. AHP was used to compute their weights. After applying min-max normalisation to the data, a district-level quantitative SWOT is created to compare the performance of 13 Uttarakhand districts. A COVID-19 vulnerability index (normalised R i ) ranging between 0 and 1 was produced, and district-level vulnerabilities were mapped. Quantitative SWOT results depict that Dehradun is a best performing district followed by Haridwar, while Bageshwar, Rudra Prayag, Champawat and Pithoragarh are on the weaker side and the normalised Ri proves Dehradun, Nainital, Champawat, Bageshwar and Chamoli to be least vulnerable to COVID-19 (normalised R i ≤ 0.25) and Pithoragarh to be the most vulnerable district (normalised R i > 0.90). Pauri Garwal and Uttarkashi are moderately vulnerable (normalised R i 0.50 to 0.75).


The role of cancer stromal fibroblasts in mediating the effects of tobacco-induced cancer cell growth.
Tobacco products cause a variety of cancers, nicotine and carcinogens are two major factors to link the tobacco products and various cancers. The mechanism of tobacco inducing carcinogenesis and promoting cancer progression have been studied for a long time. However, mainstream studies just focus on the mutagenic characteristics of tobacco product and its properties to induce carcinogenesis of epithelial cells. In the past decades, people began to aware of the significant role of tumor stroma in cancer development and progression. Fibroblasts, which is associated with various cancer in all stage of disease progression, are the dominant cell type in the tumor microenvironment. While only a few studies explore the crosstalk between tobacco-induced fibroblasts and surrounding epithelial cells. Our purpose is to systematically review the effects of tobacco products on fibroblasts and further discuss how these effects affect the development of cancer cells.


Abnormal recrossing retinotectal projections after early lesions in Syrian hamsters: age-related effects.
If the superficial layers of the right superior colliculus (SC) of a newborn hamster are removed, fibers from the left eye not only terminate in the surviving deeper layers of the right SC, but also cross the tectal midline and terminate in the medial third of the left SC. If the right eye is also removed at birth, the abnormally recrossing fibers from the left eye will spread over the entire surface of the left SC31. In this series of experiments, we ablated the right SC of hamsters at birth, but enucleated the right eye on different days postnatally in order to examine the spreading of the axon terminal pattern as a function of age. When the animals were young adults, the pattern of retinofugal projection of the left eye was traced using the Fink-Heimer technique or with autoradiography. It was found that the projections from the left eye continue to spread over the entire left SC when the right eye was removed up until day 10, though their distribution was more sparse when the eye was removed on days 7-10 than when it was removed on days 0-6. When the removal of the right eye was delayed until day 12, the lateral spreading of recrossing axons was markedly reduced. When the right eye was removed on day 14, the distribution of the projections from the left eye was restricted to the medial third of the left SC, just as if no early eye removal had been performed. It appears that after a critical age is reached, even when terminal space is available the axons and axon terminals will not move, at least not over any appreciable distance.


X-Ray Crystallographic Analysis, EPR Studies, and Computational Calculations of a Cu(II) Tetramic Acid Complex.
In this work we present a structural and spectroscopic analysis of a copper(II) N-acetyl-5-arylidene tetramic acid by using both experimental and computational techniques. The crystal structure of the Cu(II) complex was determined by single crystal X-ray diffraction and shows that the copper ion lies on a centre of symmetry, with each ligand ion coordinated to two copper ions, forming a 2D sheet. Moreover, the EPR spectroscopic properties of the Cu(II) tetramic acid complex were also explored and discussed. Finally, a computational approach was performed in order to obtain a detailed and precise insight of product structures and properties. It is hoped that this study can enrich the field of functional supramolecular systems, giving place to the formation of coordination-driven self-assembly architectures.


The Incapacitated Surrogate: What is the Consultation-Liaison Psychiatrist's Role?
When a patient is found to be lacking capacity to make a medical decision, the medical team is advised to turn to the patient's most appropriate surrogate decision maker (hereafter, surrogate) to make a choice on behalf of the patient. The assumption made by the medical team is that the surrogate will have the capacity to make appropriate medical decisions on behalf of the patient. At times though, the capacity of the surrogate himself may be called into question, leading to uncertainty in terms of how best to proceed in the care of the patient. Consultation-liaison psychiatrists are commonly consulted to assess a patient's capacity to make a particular medical decision, but their role assisting in cases of incapacitated surrogates is less clear. In this article, we summarize the existing literature and current state laws regarding incapacitated surrogates and propose guidelines for the role the consultation-liaison psychiatrist can take when the surrogate may be incapacitated.


Application of SiO2-poly(dimethylsiloxane) hybrid material in the fabrication of amperometric biosensor.
Silica xerogel was widely used in the development of biosensors by coupling the desired biological components to various transducers. Unfortunately, the application of xerogels is limited due to their poor mechanical properties and poor structural maintenance of entrapped biomaterials. In this study, the availability of poly(dimethylsiloxane) (PDMS)-modified silica sol-gel (TEOS/PDMS Ormosil) glass in the immobilization of enzymes and its application in the fabrication of amperometric biosensor was investigated. We demonstrated that most of activity of encapsulated horseradish peroxidase can be preserved in PDMS-modified SiO2 glass compared with conventional silica xerogel. The synthesized monoliths exhibited high transparency and crack-free. The enzyme electrode based on glucose oxidase encapsulated TEOS/PDMS Ormosil glass on Pd electrode was fabricated and characterized electrochemically. The characteristics of the biosensor were studied by cyclic voltammetry and chronoamperometry. The biosensor exhibited a series of good properties: high sensitivity (1.63 microA mM(-1) analyte), short response time and high reproducibility. The results indicate that TEOS/PDMS Ormosil glass has great potential to the immobilization of biomaterials as well as the fabrication of biosensors.


Amide proton exchange rates of oxidized and reduced Saccharomyces cerevisiae iso-1-cytochrome c.
Proton NMR spectroscopy was used to determine the rate constant, kobs, for exchange of labile protons in both oxidized (Fe(III)) and reduced (Fe(II)) iso-1-cytochrome c. We find that slowly exchanging backbone amide protons tend to lack solvent-accessible surface area, possess backbone hydrogen bonds, and are present in regions of regular secondary structure as well as in omega-loops. Furthermore, there is no correlation between kobs and the distance from a backbone amide nitrogen to the nearest solvent-accessible atom. These observations are consistent with the local unfolding model. Comparisons of the free energy change for denaturation, delta Gd, at 298 K to the free energy change for local unfolding, delta Gop, at 298 K for the oxidized protein suggest that certain conformations possessing higher free energy than the denatured state are detected at equilibrium. Reduction of the protein results in a general increase in delta Gop. Comparisons of delta Gd to delta Gop for the reduced protein show that the most open states of the reduced protein possess more structure than its chemically denatured form. This persistent structure in high-energy conformations of the reduced form appears to involve the axially coordinated heme.


Assessing the reliability and responsiveness of 5 shoulder questionnaires.
The purpose of this study was to compare the test-retest reliability and responsiveness of 5 different shoulder questionnaires in a sample of patients with shoulder pain. Ninety-nine patients completed the following shoulder questionnaires on 2 occasions: Subjective Shoulder Rating Scale, Simple Shoulder Test, Modified-American Shoulder and Elbow Surgeons Form, Shoulder Severity Index, and the Shoulder Pain and Disability Index. The Short Form-36 was also included. Test-retest reliability was assessed with intraclass correlation coefficients. Standardized response means were calculated to assess responsiveness. This procedure was done on 33 subjects who underwent rotator cuff surgery or total shoulder arthroplasty and who believed that they had improved between testings. All questionnaires had acceptable reliability (coefficients > 0.75) except the Subjective Shoulder Rating Scale (coefficient = 0.71) and were more responsive (0.65 < Standardized response mean < 1.23) than the Short Form-36 (0.08 < Standardized response mean < 0.43) except for pain (0.91). In this longitudinal study a direct comparison of 5 shoulder questionnaires was carried out. We found the Subjective Shoulder Rating Scale to have lower reliability and responsiveness. The other 4 questionnaires including 1 developed to measure whole extremity function (Modified American Shoulder and Elbow Surgeons Form) rather than the shoulder only were comparable with good reliability and responsiveness. The results indicate that the shoulder questionnaires were more sensitive to change in patients with shoulder pain than the generic questionnaire (Short Form-36), and both types of questionnaires should be used in outcome evaluations.


Granulated metrial gland cells in 'minor' species.
Granulated metrial gland cells, also known as uterine natural killer cells or large granular lymphocytes, are pregnancy associated leucocytes of granular phenotype. They are well characterised in mice and humans in terms of their structure, origin and distribution although the function of these cells has yet to be determined. In this review, granulated metrial gland cells in 'minor' species of rodents, insectivores, primates and species with epitheliochorial placentae are described. Emphasis is given to the comparative structure and distribution of granulated metrial gland cells in these minor species and to their possible functional association with trophoblast. Comparative studies of granulated metrial gland cells in minor species complements other approaches such as can be provided using mutant mice.


Respiratory changes induced by activation of testicular afferents in dogs.
Reportedly, more than 90% of the testicular afferents of the dog are of the polymodal type. The possible involvement of these afferents in modulation of respiration was studied using anesthetized dogs, which had been vagotomized and with both common carotid arteries ligated. Electrical stimulation of the superior spermatic nerve at an intensity of 1/5 Tc (Tc: threshold intensity for C-fiber activation) induced no substantial changes in respiration, while above 1/2 Tc it induced an increase in minute expiratory volume (VE), or a decrease followed by an increase in VE. The pattern of respiratory change was converted from the former to the latter by increasing the stimulation frequency while maintaining the same intensity. Mechanical stimulation of the testis through a stimulator with a tip of 1 cm in diameter caused an increase of VE at 200 g and a decrease followed by an increase of VE above 500 g. Intra-arterial injection of bradykinin (3 x 10(-6) M), hypertonic saline (1.5 M) and high K+ solution (180 mM) to the spermatic artery induced similar respiratory changes. Pneumograms showed a shift in end-expiratory position even at stimulus intensities without significant VE changes. Phrenic nerve recordings from some artificially ventilated dogs, revealed an prolongation of the first expiratory phase followed by augmentation of phrenic activity, mostly an increase in respiratory rate. Comparison between afferent activities and reflex respiratory changes suggests that above described two types of respiratory changes are brought about by the activities of testicular polymodal receptors.


Long-term clinical and cost-effectiveness of collaborative care in people with uncontrolled type 2 diabetes mellitus and polypharmacy: A multicenter randomized controlled trial.
This study examined the effectiveness of a collaborative care model on clinical and humanistic outcomes, medical cost, productivity loss, and its cost-effectiveness in managing uncontrolled Type 2 Diabetes Mellitus (T2DM). A randomized controlled study was conducted in two outpatient health institutions in Singapore. Patients aged above 21 years with HbA1c > 7% and polypharmacy were included. Eligible patients were randomized into the intervention (collaborative care) and control (usual care) arms. A total of 255 patients were included in the analysis. Compared to the control arm, the intervention arm achieved significantly greater glycated hemoglobin (HbA1c) reduction (mean difference: 0.25, 95%CI: [0.001, 0.50], p = 0.049) and quality-adjusted life year (QALY) (+0.011, 95%CI: [0.003, 0.019], p = 0.011) at 12 months. The costs per additional HbA1c and QALY improvements over one year were $40.52 and $920.91 respectively. Activity impairment was lower in the intervention group both at 6 months (12.7% vs 19.0%; p = 0.022) and at 12 months (6.7% vs 14.0%; p = 0.008). The collaborative care model achieved earlier HbA1c reduction and reduced patients' activity impairment without decreasing work productivity or increasing medical costs. This intervention is cost-effective for improving glycemic control and quality of life in patients with T2DM.


The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats.
Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/h; METH Mean = 0.4 and Max = 1.15; MDPV Mean = 0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01-0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1-0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5-1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (∼1.5 mg/kg/h) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH.


Application of autoregressive modelling in magnetic resonance imaging to remove noise and truncation artifacts.
Magnetic resonance imaging data is conventionally reconstructed using two dimensional discrete Fourier transforms. However, there is growing interest in other types of spectral estimation which minimize noise and artifacts due to truncated data. This note presents preliminary results--showing the improvement obtainable using a modified autoregressive model, the Transient Error method.


Recurrent spontaneous oocyte activation causes female infertility.
Spontaneous oocyte activation (SOA) is a recently classified phenomenon characterized by the presence of a single pronucleus immediately following oocyte retrieval, without the apparent involvement of sperm. SOA currently remains poorly understood in humans, with no clear genetic or pathological factor(s). Herein, we report two separate cases of recurrent spontaneous oocyte activation, investigating potential avenues to identify causative etiology. Two patients with several cycles with SOA have undergone further genetic and embryologic investigation to reveal underlying causes for SOA and provide a treatment if possible. One case was a patient with recurrent pregnancy loss and the other was diagnosed as unexplained infertility. In the first case, 61 out of 69 oocytes retrieved exhibited SOA in five cycles while in the second case 44 out of 49 oocytes exhibited SOA in five cycles. Oocytes were injected with sperm; embryo development and presence of paternal contribution were investigated. No pregnancy is ensued following embryo transfer in both patients. Time-lapse imaging of embryogenesis from the second case did not reveal even momentary second pronucleus appearance. We also performed clinical whole exome sequencing for both patients but did not identify any disease-causing variant. Patients with SOA suffer from infertility. Our results indicate that more investigation is required to understand the etiology of SOA in humans concentrating on the molecular mechanisms that underpin regulation of oocyte activation and calcium dynamics need to be investigated to fully understand, and perhaps in the future rectify, recurrent SOA.


Effect of ovarian hormones on serum adiponectin and resistin concentrations.
To investigate the effect of ovarian hormones on adiponectin and resistin levels in women. Experimental study. University hospital. Thirteen normally cycling women (7 in group 1 and 6 in group 2) and 8 postmenopausal women (group 3). Women of group 1 were investigated in a control cycle and in a subsequent cycle in which total abdominal hysterectomy plus bilateral salpingooophorectomy (TAH+BSO) was performed on day 3. In both cycles, the women received increasing doses of E(2) from days 3 to 5. Women of group 2 underwent TAH+BSO on day 3 without receiving any hormonal treatment. Women of group 3 received increasing doses of E(2) for 15 days. Adiponectin, resistin, and E(2) concentrations. In group 1, serum adiponectin and resistin levels did not show any significant changes for the week following day 3 and were similar in the two cycles. In group 2, adiponectin and resistin levels were similar before and after TAH+BSO and remained stable during the first postoperative week. In group 3, no significant changes in adiponectin and resistin levels were seen during the 15 days of E(2) administration. Adiponectin and resistin values were not affected either by estrogen treatment or after ovariectomy in women. It is suggested that ovarian hormones are not involved in the regulation of adiponectin and resistin secretion in women.


Properties of anticancer agents relevant to in vitro determinations of human tumor cell sensitivity.
The physical properties of 59 anticancer agents have been examined with respect to solubility in tissue culture media, binding to ultrafiltration materials, and molecular absorbance and fluorescence behavior. Methods for dissolving these agents, which are compatible with in vitro sensitivity testing of human tumor cells to anticancer agents, are reported in this paper. The potential for anticancer agent binding to cellulose nitrate/cellulose acetate and teflon membrane ultrafilters was documented, and quantitation of these anticancer agents based upon absorbance and fluorescence spectroscopy was performed. Post-filtration quantitation of anticancer agents was found to be a reliable method for determining the actual drug concentrations available in tumor cell sensitivity testing in vitro. The properties documented herein are pharmacologically relevant parameters related to in vitro determinations of human tumor cell sensitivity to anticancer agents.


Influence of intracellular pH on the membrane potential of cultured carotid body glomus cells.
The influence of acidity on the resting potential (Em) of cultured rat glomus cells was studied within a narrow range (7.32-7.54) of extracellular pH (pH0). Under these conditions, the intracellular pH (pHi) ranged from 6.3 to 7.21. Resting potentials were most negative when pHi was lowest, and least negative when pHi was highest. These effects were determined by the equilibrium potential of H+ ions (EH) since Em linearly followed EH. However, EH was little affected by pH0. Therefore, intracellular, and not extracellular, acidity was most important in contributing to the Em of glomus cells.


[Accidents in children and adolescents. Analysis of the accident event].
Accidents are the most frequent cause of death in children and adolescents. The aim of this study was to determine factors, which affect injury severity and to compare the absolute number of accidents with exposition data. From 1 January 1999 to 31 December 2001 a school survey of 2325 pupils was carried out. The 3645 accidents sustained by children and adolescents aged between 6 and 17 years treated at the surgical emergency department of the University Hospital Dresden were analyzed. Of the 3645 patients, 620 (17%) were admitted to hospital and 3025 (83%) were treated as outpatients. The most frequent diagnosis of the hospitalized patients was commotio cerebri; 83% of 36 severely injured patients had a head injury. 55.5% (297 of 536) of children between 6 and 9 years were using a protective helmet. In contrast only 14% of adolescents carried a protective helmet. None of 50 injured bicycle drivers with helmet had an AIS for head injuries >2. Twenty-for of 233 injured bicycle drivers without helmet had an AIS for head injuries >2. Head injuries are the main cause of hospitalization in traumatized children and adolescents. However, the use of a protective helmet becomes significantly less frequent with increasing age.


Inhibitory effects of Cnidium officinale Makino and Tabanus fulvus Meigan on the high glucose-induced proliferation of glomerular mesangial cells.
This study describes a potent activity of Cnidium officinale Makino (Cnidii rhizoma) and Tabanus fulvus Meigan (Tabanus) as an inhibitor of high glucose-induced proliferation of glomerular mesangial cells (GMCs). Raising the ambient glucose concentration from 5.6 to 25 mM for 24 h caused a dramatic increase in [3H]thymidine incorporation, and these increases were attenuated by treatment of GMCs with the extracts of Cnidii rhizoma and Tabanus (2.5-20 microg/ml) in a dose-dependent manner. In contrast, extracts of Cnidii rhizoma or Tabanus (20 microg/ml) did not change the growth of GMCs cultured under normal glucose condition. To clarify the mechanism involved in anti-proliferative activity of these medicines, this study examined the effects of Cnidii rhizoma and Tabanus on high glucose-stimulated extracellular matrix (ECM) protein accumulation and transforming growth factor-beta1 (TGF-beta1) production. Exposure of GMCs to high glucose significantly stimulated the ECM protein, collagen and fibronectin, accumulation and TGF-beta1 secretion, and these changes were dramatically diminished by treatment of GMCs with extracts of Cnidii rhizoma or Tabanus (10 microg/ml). Taken together, these results indicate that Cnidii rhizoma and Tabanus inhibit the high glucose-induced GMC proliferation partially through suppressing the ECM accumulation and TGF-beta1 production, suggesting that these medicines may be a promising agent for treating the development and progression of diabetic glomerulopathy.


Association of C-reactive Protein and Partial Mayo Score With Response to Tofacitinib Induction Therapy: Results From the Ulcerative Colitis Clinical Program.
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). These post hoc analyses assessed associations between C-reactive protein (CRP), partial Mayo score (PMS), and efficacy outcomes during tofacitinib induction in UC. Patients received tofacitinib 10 mg twice daily (BID) in an 8-week, phase 2 induction study and 2 identical, 8-week, phase 3 induction studies (OCTAVE Induction 1&2); induction nonresponders (IndNR) received an additional 8 weeks of tofacitinib 10 mg BID in an open-label, long-term extension study. Associations between CRP and PMS, and efficacy outcomes (clinical response, clinical remission, endoscopic improvement, and endoscopic remission) were analyzed using univariate and multivariable logistic regression and receiver operating characteristic curves. Changes from baseline in the logarithm of CRP ([log]CRP) and PMS at week 4 were associated with clinical response at week 8 (univariate: per unit, odds ratio [OR], 0.55 [95% confidence interval (CI), 0.48-0.62]; and 0.42 [0.37-0.47], respectively). Among IndNR, change from baseline in PMS at week 8 was associated with clinical response at week 16 (univariate: per unit, OR, 0.59; 95% CI, 0.46-0.75). C-reactive protein at week 4 (area under the curve [AUC] > 0.6) and PMS at weeks 2 and 4 (AUC, > 0.7) generally exhibited predictive value for week 8 efficacy outcomes. Patients who achieved clinical response at week 8 had larger decreases in CRP and PMS at week 4 than patients who did not. IndNR who achieved clinical response at week 16 with extended tofacitinib induction had a larger decrease in PMS at week 8 vs those who did not. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01470612.


A true reflection of executive functioning or a representation of task-specific variance? Re-evaluating the unity/diversity framework.
The unity/diversity framework, originally published by Miyake et al. (2000) has become the most cited model of executive functioning. Consequently, when researchers operationalise executive function (EF) they often exclusively assess the three "core" EFs: updating, shifting, and inhibition. However, rather than core EFs representing domain general cognitive abilities, these three EFs may instead represent specific procedural skills from the overlapping methodologies of the tasks selected. In this study, we conducted a confirmatory factor analysis (CFA) which showed both the traditional three-factor and nested-factor model from the unity/diversity framework failed to reach satisfactory levels of fit. Subsequently, an exploratory factor analysis supported a three-factor model reflecting: an expanded working memory factor, a combined shifting/inhibition factor representing cognitive flexibility, and a factor comprised solely of the Stroop task. These results demonstrate that working memory remains the most robustly operationalised EF construct, whereas shifting and inhibition may represent task-specific mechanisms of a broader domain-general cognitive flexibility factor. Ultimately, there is little evidence to suggest that updating, shifting, and inhibition encapsulates all core EFs. Further research is needed to develop an ecologically valid model of executive functioning that captures the cognitive abilities associated with real world goal-directed behaviour.


Potential of herb-drug / herb interactions between substrates and inhibitors of UGTs derived from herbal medicines.
Herbal medicines are widely used as alternative or complementary therapies worldwide to treat and prevent chronic diseases. However, herbal medicines coadministration with therapeutic drugs may cause dramatic clinical herb-drug/herb interactions (HDIs/HHIs) that may result in low drug efficacy or serious toxic reactions. Phase II metabolism enzyme UDP-glucuronosyltransferases (UGTs) play a significant detoxification role in vivo. Most drugs and non-drug xenobiotics undergo phase II metabolic transformations to be more polar compounds that are more easily excreted. Herbal medicines are a mixed and chemically varied group that includes flavonoids, stilbenes, coumarins, quinones, and terpenes, which are potential substrates and inhibitors of UGTs. Although increasing studies about glucuronidation metabolism and the inhibition toward UGTs of many herbal medicines have been reported, it is still difficult to determine which compounds from herbal medicines are substrates or inhibitors of UGTs. This article gives an overview of UGTs studies, which mainly focuses on glucuronidation of herbal constituents as substrates catalyzed by UGTs, potential herbal inhibitors for UGTs. We summarize the negative effects of UGT1A polymorphism and single nucleotide polymorphisms (SNPs), relevant clinical situations of HDIs/HHIs induced by inhibition of UGTs, and propose establishing classification criteria for inhibitors. Finally, we also discuss future research and strategic directions to advance the understanding of the potential HDIs/HHIs and suggest some additional studies revealing more information on UGT-mediated HDIs/HHIs.


Partial lesion of the dopaminergic innervation of the ventral striatum induces "depressive-like" behavior of rats.
Depression is a frequent comorbid disorder in Parkinson's disease (PD) which may precede appearance of its motor symptoms by several years. Pathomechanisms underlying PD have been suggested to be responsible for the PD-related depression. The aim of the study was to examine the influence of a partial lesion of striatal dopaminergic terminals on the "depressive-like" behavior of rats in the forced swimming test (FS). 6-Hydroxydopamine (6-OHDA) was injected bilaterally into the ventro-lateral region of the caudate-putamen (CP) (3.75 μg/2.5 μl/side). The locomotor activity and behavior of rats in the FS were measured 2 and 4 weeks after the operation. The lesion extent was analyzed by biochemical and immunohistochemical methods. Two weeks after the operation, the 6-OHDA-treated rats displayed a prolonged immobility in the FS. This effect disappeared after 4 weeks. The locomotor activity was not influenced by 6-OHDA. Levels of dopamine, DOPAC and HVA were decreased in the nucleus accumbens (NAC) 2 weeks after 6-OHDA but were not changed in the CP, frontal cortex (FCX) and substantia nigra (SN). No significant effect of 6-OHDA on tyrosine hydroxylase-immunoreactivity in the CP and NAC were found. The present study indicates that a relatively small lesion of dopaminergic terminals in the ventral striatum, which does not produce any motor disturbances, may induce "depressive-like" symptoms.


Elucidation of the coping strategy in an OMP homozygous knockout mutant of Synechocystis 6803 defective in iron uptake.
The TonB-dependent outer membrane (OM) transporters import iron (Fe) under Fe-deficient growth conditions in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 (S. 6803 or WT). The present study characterises the mechanisms employed by a homozygous Δslr1908 (Slr1908, an OM protein) mutant of S. 6803 to adapt to intracellular iron deficiency imposed due to lack of Slr1908 when grown under Fe sufficient conditions for short (1 week) and long term (3 weeks). Although the homozygous Δslr1908 cells showed symptoms of stress such as slow growth, high ROS and altered ultrastructure, they were transcriptionally as well as translationally modulating their physiology to abrogate the Fe limitation. The mutant displayed only 20% of the Fe content in comparison to the WT after 1 week of growth, which increased to 50% by the end of the third week. The increase in intracellular Fe is ascribed to higher transcripts as well as corresponding protein of slr0042 which is the alternate OM route for Fe uptake. The mutant was also allocating its available Fe pools judiciously among Fe requiring proteins such as catalase, superoxide dismutase and cytochromes. The results elucidate the mechanism employed to tide over the Fe deficiency by Δslr1908 mutant and will be important in explaining the fine-tuning of Fe homeostasis in this model cyanobacterium.


Behavioral differences among rainbow trout clonal lines.
Salmonid fish show considerable geographical variation in morphology, physiology, and behavior. Understanding the genetic mechanisms underlying this variation could be useful for enhancing aquaculture stocks, identifying unique populations for conservation, and determining the genetic factors underlying natural adaptation and domestication. As a first step toward the genetic dissection of salmonid behavioral diversity, we examined variation in behavior patterns among four clonal lines of rainbow trout ( Oncorhynchus mykiss ) derived from geographically diverse source populations with different domestication histories. Clonal lines were crossed with two outbred (i.e., not homozygous) females, and the resulting progenies were reared and tested under identical conditions. Clonal line had significant genetic effects on mean swim level, hiding, foraging, startle response, and aggression level. Multiple comparisons suggest that domestication history of the source populations had a strong influence on these behavior patterns. Progeny of two clonal lines derived from populations reared in captivity for over 100 years exhibited reductions in predator avoidance behavior patterns and increases in aggression compared to progeny of two clonal lines from more recently domesticated populations. These results will facilitate future investigation of the genetic factors underlying population variation in these behavior patterns influenced by domestication.


Expression signature of miRNAs and the potential role of miR-195-5p in high-glucose-treated rat cardiomyocytes.
MicroRNAs are endogenous small noncoding RNAs that posttranscriptionally regulate the expression of target genes and play crucial roles in diverse physiopathologic processes. In the current study, we examined the microRNA (miRNA) expression profile of high-glucose-treated neonatal rat cardiomyocytes and the potential mechanisms. Differentially expressed miRNAs were analyzed by a miRNA microarray and validated by a quantitative real-time polymerase chain reaction in high-glucose-treated rat cardiomyocytes. Based on the results of our previous study and the bioinformatics prediction, we identified miR-195-5p/SGK1/Nedd4-2/hERG as the top-ranked signal pathway in diabetes cell model in vitro. In summary, our present study provides novel insights into the regulatory mechanism of miR-195-5p/SGK1/Nedd4-2/hERG in rat cardiomyocytes under high-glucose stress, which may provide a novel idea for the development of diagnostic and therapeutic strategies for diabetic cardiomyopathy in the future.


Metabolic Labeling of Mitochondrial Translation Products in Whole Cells and Isolated Organelles.
Mitochondria retain their own genome and translational apparatus that is highly specialized in the synthesis of a handful of proteins, essential components of the oxidative phosphorylation system. During evolution, the players and mechanisms involved in mitochondrial translation have acquired some unique features, which we have only partially disclosed. The study of the mitochondrial translation process has been historically hampered by the lack of an in vitro translational system and has largely relied on the analysis of the incorporation rate of radiolabeled amino acids into mitochondrial proteins in cellulo or in organello. In this chapter, we describe methods to monitor mitochondrial translation by labeling newly synthesized mitochondrial polypeptides with [S35]-methionine in either yeast or mammalian whole cells or isolated mitochondria.


Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease.
Psychotic symptoms in subjects with Alzheimer disease (AD with psychosis, AD+P) define a phenotype characterized by greater cognitive burden than in AD without psychosis. We have proposed that genes of small effect may contribute to the risk for expression of psychosis in multiple disorders, including AD. Recently, sex-differential association of a three-locus haplotype, including a G-->A transition at codon 108/158 of catechol-O-methyltransferase (COMT) resulting in a Val-->Met substitution, has been reported to confer an increased risk for schizophrenia. The main objective of the study was to determine if COMT genetic variation is associated with risk of psychosis in AD, and included a case-control study of 373 individuals diagnosed with AD with, or without, psychosis. All subjects were characterized for alleles at the three loci associated with schizophrenia, RS737865, COMT G-->A 108/158 (RS4680), and RS165599, and for a C/T transition adjacent to an estrogen response element (ERE6) in the COMT P2 promoter region. Both single locus and haplotype tests of association were conducted. Logit models were used to examine independent and interacting effects of alleles at the associated loci. All analyses were stratified by sex. In female subjects, RS4680 demonstrated a modest association with AD+P; RS737865 demonstrated a trend towards an association. There was a highly significant association of AD+P with the four-locus haplotype, which resulted from additive effects of alleles at RS4680 and ERE6 (or RS737865, as this locus was in almost absolute linkage disequilibrium (LD) with ERE6). In male subjects, no single locus test was significant, but there remained a strong association between AD+P and the four-locus haplotype. This association appeared to result from interaction of the ERE6/RS737865, RS4680, and RS165599 loci. Genetic variation in COMT is associated with AD+P, and thus appears to contribute to psychosis risk across disorders. Sex-differential associations of COMT with psychosis may result from variation at, or in LD with, ERE6. Examination of variation at ERE6 in subjects with schizophrenia, and further examination of the independent and additive effects of variations in COMT on gene expression, is warranted.


Retinal artery and vein thrombotic occlusion during pregnancy: markers for familial thrombophilia and adverse pregnancy outcomes.
Ocular vascular occlusion (OVO), first diagnosed during or immediately after giving birth, often reflects superposition of the physiologic thrombophilia of pregnancy on previously undiagnosed underlying familial or acquired thrombophilia associated with spontaneous abortion, eclampsia, or maternal thrombosis. We describe OVO, first diagnosed during pregnancy or immediately postpartum, in three young females (ages 32, 35, 40) associated with previously undiagnosed familial thrombophilia. Branch retinal artery occlusion (BRAO) occurred at 9 and 13 weeks gestation in two females, aged 32 and 35. Central retinal vein occlusion occurred immediately postpartum in a 40-year-old. One of the two females with BRAO subsequently developed eclampsia, and one had a history of unexplained first trimester spontaneous abortion. All three females were found to have previously unexplained familial thrombophilia. The two females with BRAO had low first trimester free protein S 42 (41%), lower normal limit (50%), and one of these two had high factor VIII (165%, upper normal limit 150%). The woman with central retinal vein occlusion had high factor XI (169%, upper normal limit 150%). Enoxaparin (40-60 mg/day) was started and continued throughout pregnancy in both females with BRAO to prevent maternal-placental thrombosis, and of these two females, one had an uncomplicated pregnancy course and term delivery, and the second was at gestational week 22 without complications at the time of this manuscript. There were no further OVO events in the two females treated with enoxaparin or in the untreated patient with postpartum eclampsia. OVO during pregnancy may be a marker for familial or acquired thrombophilia, which confers increased thrombotic risk to the mother and pregnancy, associated with spontaneous abortion or eclampsia. OVO during pregnancy, particularly when coupled with antecedent adverse pregnancy outcomes, should prompt urgent thrombophilia evaluation and institution of thromboprophylaxis to prevent adverse maternal and fetal-placental thrombotic events.


Laparoscopic treatment of a perinephric abscess.
A 21-year-old woman was operated laparoscopically for peritonitis due to penetrating perinephric abscess (PNA). Following correct diagnosis and drainage, a definitive treatment was carried out to drain the intrarenal abscess laparoscopically. Although not the preferred approach, when diagnosed during exploratory laparoscopy for peritonitis, PNA can be successfully treated laparoscopically.


Dopamine receptor blockade and the neuroleptics, a crystallographic study.
The X-ray structures of 12 drugs of the tricyclic class having varying pharmacological profiles have been examined in detail in an attempt to rationalize the known structure-activity relations of neuroleptic drugs with respect to their ability to block dopamine receptors in the brain. Further evidence is presented in support of the theory that the neuroleptics are able to block dopamine receptors because of a conformational complementarity between certain portions of these drugs and dopamine.


Effects of thermoablation with or without caffeine on giant cell tumour of bone.
To evaluate the effect of caffeine on the apoptosis rate of giant cell tumour of bone cells during thermoablation. Giant cell tumour of bone tissue (2 cm3) was collected from 10 patients. Cells were incubated at 37ºC, 40ºC, 45ºC, 50ºC, 52.5ºC, and 55ºC for 20 minutes (3 tubes for each temperature). Caffeine was added to the tubes in amounts of 0 μg/ml (control), 50 μg/ml, and 100 μg/ml. The apoptotic effect of thermoablation with or without caffeine was evaluated. In all test conditions, the apoptotic rate of tumour cells increased when the temperature increased. Compared with controls (no caffeine), adding 50 or 100 μg/ml of caffeine did not increase the apoptotic rate significantly at 40ºC to 52.5ºC. Caffeine had no enhancing effect at any temperature. Conversely, at 55ºC, the apoptotic rate was lower when 100 μg/ml of caffeine was added than when no or 50 μg/ml of caffeine added (p=0.045). Thermoablation at 40ºC to 52.5ºC for 20 minutes increased the apoptosis rate of giant cell tumour of bone cells. Caffeine had no enhancing effect at any temperature. Conversely, at 55ºC, caffeine had cytoprotective effects on the tumour cells against thermoablation.


Death after PEG: results of the National Confidential Enquiry into Patient Outcome and Death.
Percutaneous endoscopic gastrostomy (PEG) is an accepted method of placing a feeding tube to enable enteral feeding in patients with swallowing difficulties. However, the factors associated with complications and death after PEG have not been studied in detail. We describe the largest audit of deaths after PEG tube insertion. Our purpose was to determine the factors associated with death after PEG tube insertion. Deaths occurring within 30 days after PEG tube insertion in the United Kingdom between April 2002 and March 2003 were identified and a questionnaire was sent to the consultant endoscopist for completion. A total of 719 patients (391 male, median age 80 years, range 26-98 years) who died within 30 days after PEG insertion were identified for this study. United Kingdom hospitals. Cause of death. A total of 97% of the identified patients had coexistent neurologic disease. PEG tubes were inserted by specialized GI physicians in 522 cases (73%). Seventy-two patients (10%) required reversal agents after sedation. After PEG tube insertion, 309 patients (43%) died within 1 week. Death was due to cardiovascular disease (n = 175), respiratory disease (n = 508), central nervous system disease (n = 358), renal disease (n = 38), and hepatic failure (n = 11). In 136 cases (19%) the National Confidential Enquiry into Patient Outcome and Death expert panel regarded the procedure as futile. Retrospective review of case records. Mortality and morbidity rates after PEG tube insertion are not insignificant. Selection of patients is paramount to good patient outcomes. Multidisciplinary team assessment should be performed on all patients being referred for PEG tube insertion.


Preserved vocabulary acquisition in Down's syndrome: the role of phonological short-term memory.
We report the study of a 23-year-old Italian girl, FF, with Down's syndrome (trisomy 21). FF showed a remarkably good developmental acquisition of Italian language and vocabulary and was able to learn English and French, although the latter with less proficiency. FF showed an entirely preserved function of the phonological short-term store and articulatory rehearsal components of verbal short-term memory. By contrast, she was impaired in a wide range of tasks assessing verbal and non-verbal reasoning, visuo-spatial perception and memory, and verbal long-term memory. These findings, in line with evidence from brain-damaged patients, normal subjects and children, suggest that phonological short-term memory plays a crucial role in vocabulary acquisition, which may occur in the presence of substantial deficits of general intelligence and episodic memory.


Willingness to engage in post-discharge follow-up service conducted via video telemedicine: Cross-sectional study.
Leading influencing factors for telemedicine implementation remain unclear, affecting the focus of intervention strategies. Despite recent effectiveness evidence of video telemedicine visits, limited evidence exists regarding patients' willingness to use video follow-up. Moreover, patients' acceptance is crucial for implementing such services. We conducted a large-sample survey to analyze patient willingness and perceptions of post-discharge video follow-up and assessed the factors influencing their willingness during the COVID-19 outbreak. In February and March 2022, we conducted a face-to-face questionnaire survey involving inpatients in a tertiary care hospital in Longhua District, Shenzhen, China. We assessed demographics, health-related determinants, access to technology and literacy, preferences, willingness, and opinions toward video telemedicine follow-up. We implemented random forest and logistic regression analyses to obtain reliable results. In total, 1,017 inpatients completed the survey. Overall, as an initial choice, 44.9 % preferred telephone consultation for post-discharge follow-up, which was followed by video telemedicine (17.1 %), WeChat voice calls (11.6 %), SMS text messages (10.7 %), WeChat graphic messages (10.5 %), and in-person visits (4.5 %). Moreover, 54.9 % were willing to experience video visits. The results highlight the perceived benefits outweighing the risks (OR 2.64, 95 % CI 1.76, 3.95), patients' trust in the physician (OR 2.41, 95 % CI 1.45, 3.99), access to a private space (OR 2.18, 95 % CI 1.01, 2.96), medium geographical distance (compared to long distance, OR 0.72, 95 % CI 0.54, 0.98), moderate disease (compared to mild disease, OR 0.75, 95 % CI 0.57, 0.99), followed by the comfort with video technology (OR 1.73, 95 % CI 1.76, 3.95), broadband internet accessibility (OR 1.56, 95 % CI 1.07, 2.27), privacy concerns (OR 0.62, 95 % CI 0.43, 0.89), and prior telemedicine video experience (OR 1.77, 95 % CI 1.15, 2.72), as factors influencing the willingness to use video follow-up. A low percentage of patients chose video visits as their initial decisions; nevertheless, most had a positive attitude toward video follow-up visits. The willingness to choose video telemedicine post-discharge follow-up was influenced by geographical distance, disease severity, basic telemedicine requirements, physician-patient relationship, and perceptions of video communication.


Studying mitochondria and microtubule localization and dynamics in standardized cell shapes.
Mammalian cells show a large diversity in shape and are both shape-changing and mobile when cultured on conventional uniform substrates. The use of micropatterning techniques limits the number of variable parameters, by imposing shape and standardized adhesive areas on the cells, which facilitates analysis. By changing size or shape of the micropattern, for example, forcing a polar axis on the cell, it is possible to study how these parameters impact organelle organization, distribution, and dynamics inside the cell. To study the mitochondrial network, which is composed of dynamic tubular organelles dependent on the microtubule cytoskeleton for its distribution, it is important to be able to distinguish between distinct mitochondria. Here, we present a practical method with which we spread the cells on large patterns created with deep UV technique, which not only makes the cells uniform in size and shape as well as immobile, and therefore easier to compare and analyze, but also expands the mitochondrial network and allows for an easier tracking of appropriately labeled individual mitochondria.


Prolactin and calcitropic hormones in preterm premature rupture of membranes.
To investigate the role of prolactin and calcitropic hormones in preterm premature rupture of membranes (PPROM) with intrauterine infection. Amniotic fluid was retrieved by transabdominal amniocentesis from 40 patients with PPROM and 36 normal pregnant women of matched gestational age. Microbial state of amniotic cavity included culture for aerobic and anaerobic bacteria, mycoplasmas and ureaplasma. Maternal serum and fetal serum prolactin, parathyroid hormone mid-molecule PTH-M, 1,25-dihydroxyvitamin D3 and calcitonin were determined by the corresponding radioimmunoassay Maternal serum and fetal serum electrolytes were determined by ion-selective electrodes. Chlorides were assayed colorimetrically and osmolality was determined by osmometry. Microbiological evaluation of amniotic fluid PPROM revealed aerobic, anaerobic or mixed aerobic anaerobic infections PPROM was associated with significant elevation of both fetal serum and amniotic fluid prolactin concentrations, increased amniotic fluid osmolality, sodium, chlorides and calcium. Amniotic fluid potassium level was significantly decreased, compared with controls. Maternal serum and fetal serum PTH-M, 1,25-dehydroxyvitamin D3 were significantly higher in patients with PPROM than in controls. Increased amniotic fluid prolactin leads to impairment of structural integrity of fetal membranes through electrolytes disturbances. Moreover, increased amniotic fluid calcium induced by increased fetal calcitropic hormones evokes myometrial contraction through prostaglandin E2 release. Both mechanisms may combine to trigger the onset of PPROM associated with intrauterine infection.


Lipiodol versus diaphragm in 4D-CBCT-guided stereotactic radiotherapy of hepatocellular carcinomas.
The purpose of this work was to investigate the potential of lipiodol as a direct tumor surrogate alternative to the diaphragm surrogate on four-dimensional cone-beam computed tomography (4D-CBCT) image guidance for stereotactic radiotherapy of hepatocellular carcinomas. A total of 29 hepatocellular carcinomas (HCC) patients treated by stereotactic radiotherapy following transarterial chemoembolization (TACE) with homogeneous or partial defective lipiodol retention were included. In all, 4-7 pretreatment 4D-CBCT scans were selected for each patient. For each scan, either lipiodol or the diaphragm was used for 4D registration. Resulting lipiodol/diaphragm motion ranges and position errors relative to the reconstructed midventilation images were analyzed to obtain the motion variations, and group mean (ΔM), systematic (Σ), and random (σ) errors of the treatment setup. Of the lipiodolized tumors, 55 % qualified for direct localization on the 4D-CBCT. Significant correlations of lipiodol and diaphragm positions were found in the left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions. ΔM and σ obtained with lipiodol and diaphragm were similar, agreed to within 0.5 mm in the LR and AP, and 0.3 mm in the CC directions, and Σ differed by 1.4 (LR), 1.1 (CC), and 0.6 (AP) mm. Variations of diaphragm motion range > 5 mm were not observed with lipiodol and in one patient with diaphragm. The margin required for the tumor prediction error using the diaphragm surrogate was 6.7 (LR), 11.7 (CC), and 4.1 (AP) mm. Image-guidance combining lipiodol with 4D-CBCT enabled accurate localization of HCC and thus margin reduction. A major limitation was the degraded lipiodol contrast on 4D-CBCT.


An analysis of genetic variation across the MBL2 locus in Dutch Caucasians indicates that 3' haplotypes could modify circulating levels of mannose-binding lectin.
Mannose-binding protein (MBL) is a critical component of innate immunity and provides first-line protection against pathogens. Both circulating MBL serum levels and functional activity have been correlated with common genetic variants in the MBL2 gene. Associations between MBL deficiency and severe infections have been reported in immuno-incompetent patients and for autoimmune disorders; however, measured MBL serum levels do not fully correlate with the 'secretor haplotypes'. Previously, the MBL2 locus was resequenced and determined that a recombination hotspot divides MBL2 into two haplotype blocks. It was sought to investigate whether additional variants, in either block structure could associate with MBL serum levels. Therefore, 31 common variants were analysed across the locus in 212 DNA samples of healthy Caucasian individuals with known MBL serum concentrations. The additional 5' variants were in strong linkage to the elements of the 'secretor haplotypes'; functional alleles B, C and D also lie on restricted haplotypes. Four variants in the 3' block (Ex4-1483T>C, Ex4-1067G>A, Ex4-901G>A and Ex4-710G>A) are components of a distinct haplotype block. The results of this study suggest that additional 5' variants as well as markers of distinct 3' haplotype blocks in MBL2 may contribute to circulating protein levels, but further studies are required to confirm these observations. Last, there could be a selective advantage for diversification of the 3' region of the gene.


The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths.
The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24-36 months post-trauma. PTSD symptoms were assessed 4-5, 14-15 and 24-36 months following the trauma. We found that increased PTSD symptom severity 24-36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4-5 months and 24-36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.


Increased use of immunohistochemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance.
This paper outlines the changes which have occurred over the last 25 years in the methods employed for the measurement of oestrogen receptors to aid the management of women with breast cancer. Immunohistochemistry is now the method of choice and knowledge of oestrogen receptor status is being used with increasing frequency for the selection of adjuvant treatment as well as for the treatment of metastatic disease. It is essential that good quality assurance procedures are established so that results are reproducible and can be used with confidence in individual centres as well as being comparable with those produced elsewhere. A retrospective study of 170 women with metastatic breast cancer provides the basis for a discussion on the advantages and pitfalls of the immunohistochemical assay. Particular emphasis is paid to the choice of cut-off and how the results may be applied in patient management.


Predictive value of heart rate deceleration capacity on coronary artery lesion in acute phase of Kawasaki disease.
This study was to investigate the correlation of vagal activity with coronary artery lesion (CAL) in Kawasaki disease (KD) children, and assess the predictive value of heart rate deceleration capacity (DC) for CAL in acute phase of KD.50 KD children with CAL, 130 KD children without CAL, 30 children with acute upper respiratory infection and 100 healthy children were recruited and indicators reflecting vagal activity including DC were measstuogram. KD children with CAL showed decreased vagal activity with significantly lower values of DC. DC was negatively correlated with levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) in KD children. DC was a usable cardiac electrophysiological index to predict CAL in children with KD, with an area under the receiver operating characteristic curve (AUC) of 0.741. The cut-off value of DC for predicting CAL in KD children was 4.37 ms. DC was an independent predictor of CAL in children with KD, evaluated by multiple logistic regression analysis, KD children with DC ≤ 4.37 ms had an increased risk of CAL, with odds ratios (OR) of 5.94. Our study illustrates DC could be used to predict CAL in acute phase of KD.


A new focus of cutaneous leishmaniasis caused by Leishmania tropica in northern Jordan.
An endemic focus of cutaneous leishmaniasis caused by Leishmania tropica was identified in the district of Bani Kinana, northern Jordan. Fifty-five autochthonous cases were detected from February to September 1994 in a population of about 50,000. Most cases (74.5%) were from the villages of Malka and Um-Quais. The lesions were typically small, dry and mostly located on the face and extremities. Multiple lesions were common. Incidence was higher in females than in males and familial clustering of cases was observed in houses on the outskirts of villages. A leishmanin survey showed a 23.3% positivity rate in the populations of Malka and Um-Quais. The rate of positivity was low in the younger age groups and increased with age. There was some evidence that the disease is a zoonosis in this focus.


N-acetylglucosaminyltransferase V modifies TrKA protein, regulates the receptor function.
1. N-Acetylglucosaminyltransferases V (GnT-V/Mgat5) play a pivotal role in the processing of N-linked glycoproteins in the Golgi apparatus. The aim of the present study is to investigate whether the N-acetylglucosaminyltransferase V is able to modify TrKA, the high-affinity tyrosine kinase-type receptor for NGF, and thereby to regulate the receptor function. 2. Plasmids of the pcDNA3/GnT-V and pcDNA3 were transfected into PC12 cells. Expression of GnT-V protein was detected by Western blot. TrKA protein was examined by immunoprecipitation. Endocytosis of TrKA was investigated by the method of receptor internalization. 3. We report here that over-expression GnT-V directly modifies TrKA protein, accompanied by marked enhancement of axon outgrowth in rat pheochromocytoma cells (PC12) elicited by a low dose of NGF that alone is insufficient to induce neuronal differentiation. Further study indicated that modification of TrKA glycoprotein could directly enhance NGF-activated autophosphorylation of immunoprecipitated TrKA in vitro. To further elucidate the mechanism, we study the different time point of endocytosis of TrKA receptor. The results show that TrKA of GnT-V gene-transfected PC12 Cells delayed their removal by constitutive endocytosis as compared to the mock cells, suggesting high expression of GnT-V may affect their receptor TrKA endocytosis. 4. These results strongly suggest that N-acetylglucosaminyltransferase V functioning as a specific endogenous role of NGF receptor function, which appear to be due, at least in part, to the promotion of differentiation. This work is an important step toward intriguing innovative therapeutic strategies targeting glycosyltransferase.


Acetylcholine produces stimulus-specific receptive field alterations in cat auditory cortex.
Frequency receptive fields (RFs) were determined before and after pairing iontophoretic administration of acetylcholine (ACh) with a repeated single-frequency stimulus in the auditory cortex of barbiturate-anesthetized cats. In 58% of the cells, the paired ACh + tone treatment produced subsequent alterations of frequency RFs. In half of these cases, the RF modifications were highly specific to the frequency that had been paired with ACh. Atropine antagonized the frequency-specific effects of ACh, suggesting that they were mediated via muscarinic cholinergic receptors.


Erythropoietin responses and physical characterization of erythroid progenitor cells in Rauscher virus infected BALB/c mice.
Infection of BALB/c mice with Rauscher leukemia virus (RLV) gives rise to pronounced erythrocytopoiesis manifesting in splenomegaly and is associated with progressive development of anemia. In the spleen erythroid colony forming units (CFU-E) increase exponentially up to 800-fold that of normal levels by the third week of infection. In vitro these CFU-E are dependent on erythropoietin for colony formation, their erythropoietin requirements being higher than that of CFU-E from normal mice. Numbers of CFU-E in spleen and degree of splenomegaly in anemic RLV infected mice were also shown to be modified by red blood cell transfusion, but progression of the disease was not stopped. Erythroid burst forming units (BFU-E) were also responsive to erythropoietin. However, a small proportion of cells also formed BFU-E colonies at concentrations which did not support growth of normal marrow BFU-E. When compared to normal, CFU-E found in RLV-infected spleen have similar velocity sedimentation rates. However, buoyant density separation of leukemic spleen cells indicated that CFU-E were more homogeneous (modal density 1.0695 g/cm3) than CFU-E from normal spleen. Analysis of physical properties of CFU-E and the nonhemoglobinized erythroblast-like cells, which accumulate in the spleen showed that they differed mainly in their distribution of cell diameter. Our findings show that erythroid progenitor cells in RLV infected mice are responsive to erythropoietin in vitro. Also in vivo erythropoiesis appears to be under control of erythropoietin but other factors which lead to progression of RLV disease apparently exist. Most proerythroblast-like cells, which are characteristic of this disease, apparently lack the potential to form colonies and may be more mature than CFU-E.


Histochemical studies on eggshell formation in Paramphistomum cervi (Digenea: Paramphistomatidae).
The formation of the egg mass in the ootype, containing the oocyte, vitelline cells, numerous spermatozoa and Mehlis' gland secretion marks the beginning of eggshell formation. Mehlis' gland cells pour their lipoprotein secretion into the ootype; this secretion forms a thin template around the egg mass and upon this template the shell globules are deposited. Eggshell formation begins in the proximal uterus and is completed in the middle uterus. The eggshells are devoid of phenols and phenolase indicating that hardening is not by quinone tanning. The eggshells contain keratin and are stabilized by disulphide linkages.


Quinazolines and 1,4-benzodiazepines. 81. s-Triazolo[4,3-a][1,4]benzodiazepines by oxidative cyclization of hydrazones.
s-Triazolo[4,3-a][1,4]benzodiazepines bearing various substituents in the 1 position were prepared by oxidative cyclization of the appropriate aldehyde hydrazones of 2-hydrazinobenzodiazepines. Diethyl azodicarboxylate and activated manganese dioxide were used as oxidizing agents. The new triazolo compounds were active in the CNS tests but none of them reached the potency of the known triazolobenzodiazepines.


A high-sensitivity terahertz spectroscopy technology for tetracycline hydrochloride detection using metamaterials.
Antibiotic residues in animal-derived food due to their overuse in veterinary medicine will have potential adverse effects on human health. The rapid and accurate detection of these drugs is essential for ensuring human food safety. In particular, the current detection methods are usually limited by the low sensitivity or the tedious pre-treatment. Here we demonstrate that metamaterials operating at terahertz frequencies, acting as highly sensitive sensors, show promising potential for the detection of tetracycline hydrochloride (TCH). We were able to detect a trace amount of TCH, as small as 0.1mg/L, which was about 10(5) times enhancement compared to the measurement of TCH on a silicon substance. Our study is likely to constitute an important step toward the detection of antibiotic residues in a food matrix.


Combination strategy of CO2 pressurization and ultrasound: To improve the freezing quality of fresh-cut honeydew melon.
The effects of CO2 pressurization combined with ultrasound-assisted immersion freezing (CO2USIF) on improving the freezing quality of honeydew melon were studied. The cut melon samples were first subjected to 0.2, 0.5 and 0.8 MPa CO2 pressure for 2 h respectively, and then frozen by an ultrasound-assisted freezing device. The results indicated that the CO2 pressurization affected the water state and reduced the freezable water content. Cryo-observed results showed the ice crystal area of the 0.5CO2USIF sample was 66.6% smaller than that of the SF, and 60.8% smaller than that of the IF. The drip loss of 0.5CO2USIF sample was 58.2% lower than that of SF. The indexes of vitamin C, flavor, texture and color of CO2USIF samples were kept better. The SEM results showed that the cell structures of CO2USIF samples were better maintained. These demonstrated that CO2USIF technology has application potential in improving the quality of frozen food.


Effect of combined G6PD deficiency and diabetes on protein oxidation and lipid peroxidation.
Oxidative Stress, an imbalance in the pro-oxidant/antioxidant homeostasis, occurs in many physiological and non-physiological processes and several human diseases, including diabetes mellitus (DM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Since the incidence of G6PD deficiency in Jordan and many parts of the world is high, this study aimed to measure the effect of G6PD deficiency on the oxidative markers and the antioxidant glutathione (GSH) in diabetic and non-diabetic individuals. Whole blood G6PD deficiency was screened by the fluorescent spot method, and erythrocyte G6PD activity was determined using a quantitative assay. Since protein carbonyl (PC) and malondialdehyde (MDA) are the most widely measured markers for protein and lipid oxidation, respectively, plasma PC and MDA, in addition to blood GSH were determined by spectrophotometric assays, as biomarkers of oxidative stress. The incidence of G6PD deficiency among the diabetic subjects was 15%. PC level in patients with diabetes and in G6PD-deficient subjects was 5.5 to 6-fold higher than in non-diabetic subjects with sufficient G6PD levels (p<0.001). This fold increase was doubled in diabetic patients with G6PD deficiency (p<0.001). Furthermore, the MDA level was significantly increased by 28-41% in G6PD-deficient, diabetics with sufficient G6PD, and diabetics with G6PD deficiency compared to MDA level in non-diabetic with sufficient G6PD. On the other hand, GSH was significantly reduced to half in G6PD-deficient subjects and in diabetics with G6PD-deficiency. The results showed that diabetes and G6PD deficiency increased protein oxidation and lipid peroxidation. However, the combination of both disorders has an additive effect only on protein oxidation. On the other hand, GSH level is only reduced in G6PD deficiency. In addition, diabetes and G6PD deficiency appear to be genetically linked since the incidence of G6PD deficiency among people with diabetes is more than the general population.


An adapter for computed tomography-guided stereotaxis.
A new, versatile adapter for computed tomography-guided stereotaxis is presented. The instrument consists of a light aluminum frame, which by means of a nasion support and two ear plugs is fixed to the patient's head. Reproducibility of repeated fixations is very high. The adapter is fitted to most stereotactic frames and can be used in all adult patients. Comparison between computed tomography- and ventriculography-guided determinations of thalamic targets showed a mean difference of 0.6 and 0.7 mm for the x and y coordinates, respectively. The z coordinates seldom showed any measurable difference. We now perform all types of stereotactic neurosurgery (tumor biopsy, implantation of depth electrodes, thalamotomy, dentatotomy, cingulotomy, etc.) with computed tomography guidance only. The short-term results in a small number of patients have been at least as good as after conventional ventriculography-guided surgery. In addition to open stereotactic surgery, the adapter is also suitable for external stereotactic irradiation of intracranial targets with a linear accelerator.


Cell-mediated and humoral immune response to non-viable Mycoplasma pulmonis in mice enhanced by cross-linked ricin.
The enhancing effect of cross-linked ricin (CL-ricin) on the cell-mediated and humoral immune response of mice to non-viable Mycoplasma pulmonis was studied. The cell-mediated immune response was evaluated by means of the delayed-type footpad swelling, and the humoral immune response by means of the indirect hemagglutination test. Mice pre-treated subcutaneously with non-viable M. pulmonis and CL-ricin showed significantly increased delayed-type footpad swelling when they were injected in the footpad with the same antigen 7 days later. Delayed-type footpad swelling was not detected in mice pre-treated only with non-viable M. pulmonis or CL-ricin followed by footpad injection with non-viable M. pulmonis. Injection of non-viable M. pulmonis in the footpad on Days 3, 7, 14, 21, 28, 35 and 42 after pre-treatment with non-viable M. pulmonis and CL-ricin resulted in significant footpad swelling. Delayed-type footpad swelling was transferred by intravenous injection of spleen cells from mice which had been pre-treated 7 days previously with non-viable M. pulmonis and CL-ricin into non-treated recipient mice. Intravenous injection of anti-mouse thymus cell serum into mice previously pre-treated with non-viable M. pulmonis and CL-ricin reduced the delayed-type footpad swelling significantly. Mice pre-treated subcutaneously with non-viable M. pulmonis and CL-ricin showed a marked increase in serum antibody titers compared with those that received non-viable M. pulmonis alone.


Kernel principal component analysis residual diagnosis (KPCARD): An automated method for cosmic ray artifact removal in Raman spectra.
A new, fully automated, rapid method, referred to as kernel principal component analysis residual diagnosis (KPCARD), is proposed for removing cosmic ray artifacts (CRAs) in Raman spectra, and in particular for large Raman imaging datasets. KPCARD identifies CRAs via a statistical analysis of the residuals obtained at each wavenumber in the spectra. The method utilizes the stochastic nature of CRAs; therefore, the most significant components in principal component analysis (PCA) of large numbers of Raman spectra should not contain any CRAs. The process worked by first implementing kernel PCA (kPCA) on all the Raman mapping data and second accurately estimating the inter- and intra-spectrum noise to generate two threshold values. CRA identification was then achieved by using the threshold values to evaluate the residuals for each spectrum and assess if a CRA was present. CRA correction was achieved by spectral replacement where, the nearest neighbor (NN) spectrum, most spectroscopically similar to the CRA contaminated spectrum and principal components (PCs) obtained by kPCA were both used to generate a robust, best curve fit to the CRA contaminated spectrum. This best fit spectrum then replaced the CRA contaminated spectrum in the dataset. KPCARD efficacy was demonstrated by using simulated data and real Raman spectra collected from solid-state materials. The results showed that KPCARD was fast (<1 min per 8400 spectra), accurate, precise, and suitable for the automated correction of very large (>1 million) Raman datasets.


Pollen limitation of reproductive effort in willows.
Pollen limitation of seed set differs from resource limitation in its implications for the evolution of floral traits. Willow flowers attract insects, but also abundantly produce wind-dispersed pollen. I demonstrated pollen limitation in single branches bearing 2-4 inflorescences (catkins) in a field experiment with five species by artificially increasing or decreasing the pollen load. Because the responses by single branches might be explained by diversion of resources to better-pollinated branches within a plant, a second experiment with one species tested both pollen limitation of whole plants and the autonomy of catkins. Seed set of single willow catkins is unaffected by experimental alterations of seed set in other catkins on the same plant. Hand-pollination of single catkins and of whole plants increased seed set to the same degree, suggesting there is little or no competition for resources between catkins only 5-10 cm apart. Thus, seed set in willows appears to be pollen limited, favoring insect pollination and the evolution of entomophilous traits. The data support previous views that willows have a dual pollination system utilizing wind and insects.