Kinetin incorporated into tobacco callus ribosomal RNA and transfer RNA preparations.
Kinetin, N(6)-furfuryladenine, was incorporated into tobacco (nicotiana tabacum L., var. Wis. No. 38) callus RNA isolated from rapidly growing tissue cultured in the presence of N(6)-furfuryladenine-8-(14)C or unlabeled kinetin. Approximately 0.7% of the radioactivity in the labeled kinetin added to the medium was recovered as N(6)-furfuryladenosine (fr(6)A) in the rRNA and tRNA preparations from the tobacco callus. The rRNA contained over 90% of these fr(6) A moieties. The extent of kinetin incorporation was four times greater than that observed for N(6)-benzyladenine. The radiochemical purity of the recovered fr(6) A was confirmed by three successive chromatographic purifications on Sephadex columns (LH-20 eluted with 35% ethanol, G-10 eluted with 20% ethanol, and LH-20 eluted with water). A cytokinin-active ribonucleoside with elution volumes corresponding to fr(6) A was isolated from the tobacco callus rRNA preparation. This compound was analyzed by gas-liquid chromatography and rigorously characterized as N(6)-furfuryladenosine by gas-liquid chromatography-mass spectrometry of the trimethylsilyl derivative.


A patient with Castleman's disease initially manifesting symmetrical synovitis with pitting oedema.
Castleman's disease (CD), especially multicentric CD (MCD) has been known to manifest a variety of clinical features such as fatigue, anaemia, fever, and hypergammaglobulinaemia. Here, we report a 72-year-old female patient who had complicated severe synovitis, as an initial manifestation of the disease, lastly diagnosed as MCD. Initially, she had been diagnosed as remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome because of bilateral leg pitting oedema with significant C-reactive protein and matrix metalloproteinase-3 elevation but no disease-specific autoantibodies. Promptly, corticosteroid and additionally weekly methotrexate were introduced, but her leg oedema and inflammatory findings did not adequately come to be a remission. A lymph node biopsy from the groin region was performed because multiple lymph node swelling in ultrasound examination appeared even after introducing treatments, which revealed mixed-type CD. Multiple lymphadenopathies were observed in the axilla and inguinal region; finally, we diagnosed her as idiopathic MCD and introduced tocilizumab, which significantly improved leg oedema as well as inflammatory findings. As is shown in this case, manifestations included in RS3PE syndrome could be one of the clinical phenotypes in MCD, which should be considered as a differential diagnosis of MCD.


Diel patterns of leaf and root growth: endogenous rhythmicity or environmental response?
Plants are sessile organisms forced to adjust to their surrounding environment. In a single plant the photoautotrophic shoot is exposed to pronounced environmental variations recurring in a day-night 24 h (diel) cycle, whereas the heterotrophic root grows in a temporally less fluctuating environment. The contrasting habitats of shoots and roots are reflected in different diel growth patterns and their responsiveness to environmental stimuli. Differences between diel leaf growth patterns of mono- and dicotyledonous plants correspond to their different organization and placement of growth zones. In monocots, heterotrophic growth zones are organized linearly and protected from the environment by sheaths of older leaves. In contrast, photosynthetically active growth zones of dicot leaves are exposed directly to the environment and show characteristic, species-specific diel growth patterns. It is hypothesized that the different exposure to environmental constraints and simultaneously the sink/source status of the growing organs may have induced distinct endogenous control of diel growth patterns in roots and leaves of monocot and dicot plants. Confronted by strong temporal fluctuations in environment, the circadian clock may facilitate robust intrinsic control of leaf growth in dicot plants.


Adverse effects of 4-tert-octylphenol on the production of oxytocin and hCG in pregnant rats.
Endocrine-disrupting chemicals (EDCs) are exogenous substances that alter the structure or function of the endocrine system. 4-Tert-octylphenol (OP) is one of the most representative EDCs and has estrogenic effects. In this study, we examined the effects of ethinyl estradiol (EE) and OP on the pituitary gland, placenta, and uterus of pregnant rats. Expression levels of human chorionic gonadotropin (hCG), oxytocin (OT), and contraction-associated proteins (CAPs) were determined, and uterine contractile activity was measured by uterine contraction assay. EE and OP both increased mRNA expression of OT and hCG in the pituitary gland but not the placenta. Since OT and hCG control uterine contraction, we next examined CAP expression in the uterus. Expression of 15-hydroxyprostaglandin-dehydrogenase (PGDH) was upregulated by OP, whereas expression of other CAPs was unaffected. To clarify the effect of OP on uterine contraction in pregnant rats, uterine contraction assay was performed. The 17β-Estradiol (E2) did not affect contraction of primary uterine cells harvested from pregnant rats in a 3D collagen gel model. However, OP showed different effects from E2 by significantly reducing contraction activity. In summary, we demonstrated that OP interferes with regulation of OT and hCG in the pituitary gland as well as PGDH in the uterus, thereby reducing uterine contraction activity. This result differs from the action of endogenous E2. Collectively, these findings suggest that exposure to EDCs such as OP during pregnancycan reduce uterine contractile ability, which may result in contraction-associated adverse effects such as metratonia, bradytocia, and uterine leiomyomata.


Utility of Baseline Home Visit Audit in Home Hemodialysis.
We conducted a retrospective cohort study in a university hospital-based home hemodialysis (HHD) program to evaluate the effectiveness of a home visit audit tool. We aimed to delineate safety risk in HHD patients and to ascertain whether this is associated with clinical outcomes. All incident HHD patients between July 18, 2008, and June 30, 2013 with follow-up until December 31, 2013, were included in the cohort. Primary outcome was the description of the presence of safety risk evaluated by the home visit audit at the start of HHD. Secondary outcomes were patient-reported adverse events and technique survival. In our cohort of 84 patients, a baseline home visit audit was surveyed in 56 (67%) patients. Overall, patients were 45.8 ± 14.1 years old, and 51.2% were men. Eighteen of the 35 potential safety risks were documented at least once in the cohort. Thrity-three of the 56 surveyed subjects presented more than one safety risk. The performance of an audit did not influence adverse events or technique survival. Process and methods of auditing a home visit should be reviewed to improve judicious resource use.


Tunable double photochromism of a family of bis-DTE bipyridine ligands and their dipolar Zn complexes.
The photoinduced ring-closure/ring-opening reactions of a series of bis-dithienylethene derivatives, as free ligands and Zn(II)-complexes, are investigated by resorting to theoretical (time-dependent density functional theory) and kinetic analyses in solution. The originality of the system stems from the tunability of the photoreaction quantum yields and conversion yields as a function of the electronic structure. The latter could be varied by modifying the electron-donating character of the DTE-end substituents L(a-d) (o,o) (a, D = H; b, D = OMe; c, D = NMe(2); d, D = NBu(2)) and/or the Lewis character of the metal ion center L(a-d)ZnX(2) (o,o) (L(a-c), X = OAc; L(d), X = Cl). The orbital description of the doubly-open form (o,o) and half-closed form (o,c) predicts that double closure to the form (c,c) would occur using UV irradiation. Photokinetic studies on the complete series demonstrate that photocyclization proceeds following a sequential ring closure mechanism. They clearly point out distinct quantum yields for the first and second ring closures, the latter being characterized by a significantly lower value. Dramatic decrease in both the quantum yields of the ring-closure and ring-opening processes is demonstrated for the complex L(d)ZnCl(2) exhibiting the strongest charge-transfer character in the series investigated. These studies show that this series of DTE derivatives provides an efficient strategy to tune the photochromic properties through the combination of the electron-donor and electron-acceptor (D-A) groups.


Three functional transporters for constitutive, diurnally regulated, and starvation-induced uptake of ammonium into Arabidopsis roots.
Ammonium and nitrate are the prevalent nitrogen sources for growth and development of higher plants. 15N-uptake studies demonstrated that ammonium is preferred up to 20-fold over nitrate by Arabidopsis plants. To study the regulation and complex kinetics of ammonium uptake, we isolated two new ammonium transporter (AMT) genes and showed that they functionally complemented an ammonium uptake-deficient yeast mutant. Uptake studies with 14C-methylammonium and inhibition by ammonium yielded distinct substrate affinities between </=0.5 and 40 microM. Correlation of gene expression with 15NH4+ uptake into plant roots showed that nitrogen supply and time of day differentially regulated the individual carriers. Transcript levels of AtAMT1;1, which possesses an affinity in the nanomolar range, steeply increased with ammonium uptake in roots when nitrogen nutrition became limiting, whereas those of AtAMT1;3 increased slightly, with AtAMT1;2 being more constitutively expressed. All three ammonium transporters showed diurnal variation in expression, but AtAMT1;3 transcript levels peaked with ammonium uptake at the end of the light period, suggesting that AtAMT1;3 provides a link between nitrogen assimilation and carbon provision in roots. Our results show that high-affinity ammonium uptake in roots is regulated in relation to the physiological status of the plant at the transcriptional level and by substrate affinities of individual members of the AMT1 gene family.


Drosophila glypicans control the cell-to-cell movement of Hedgehog by a dynamin-independent process.
The signalling molecule Hedgehog (Hh) functions as a morphogen to pattern a field of cells in animal development. Previous studies in Drosophila have demonstrated that Tout-velu (Ttv), a heparan sulphate polymerase, is required for Hh movement across receiving cells. However, the molecular mechanism of Ttv- mediated Hh movement is poorly defined. We show that Dally and Dally-like (Dly), two Drosophila glypican members of the heparan sulphate proteoglycan (HSPG) family, are the substrates of Ttv and are essential for Hh movement. We show that embryos lacking dly activity exhibit defects in Hh distribution and its subsequent signalling. However, both Dally and Dly are involved and are functionally redundant in Hh movement during wing development. We further demonstrate that Hh movement in its receiving cells is regulated by a cell-to-cell mechanism that is independent of dynamin-mediated endocytosis. We propose that glypicans transfer Hh along the cell membrane to pattern a field of cells.


SAIDE: A Semi-Automated Interface for Hydrogen/Deuterium Exchange Mass Spectrometry.
Deuterium/hydrogen exchange in combination with mass spectrometry (DH MS) is a sensitive technique for detection of changes in protein conformation and dynamics. Since temperature, pH and timing control are the key elements for reliable and efficient measurement of hydrogen/deuterium content in proteins and peptides, we have developed a small, semiautomatic interface for deuterium exchange that interfaces the HPLC pumps with a mass spectrometer. This interface is relatively inexpensive to build, and provides efficient temperature and timing control in all stages of enzyme digestion, HPLC separation and mass analysis of the resulting peptides. We have tested this system with a series of standard tryptic peptides reconstituted in a solvent containing increasing concentration of deuterium. Our results demonstrate the use of this interface results in minimal loss of deuterium due to back exchange during HPLC desalting and separation. For peptides reconstituted in a buffer containing 100% deuterium, and assuming that all amide linkages have exchanged hydrogen with deuterium, the maximum loss of deuterium content is only 17% of the label, indicating the loss of only one deuterium molecule per peptide.


Enhanced host cell reactivation capacity and expression of DNA repair genes in human breast cancer cells resistant to bi-functional alkylating agents.
Human breast carcinoma (MCF7-MLNr) cells resistant to the bifunctional drugs L-phenylalanine mustard (L-PAM, 5-fold resistance), mechlorethamine (9-fold), cisplatin (3-fold), and BCNU (3-fold) were used to investigate the role of DNA repair in the development of resistance to alkylating agents. We have previously shown that neither L-PAM transport and metabolism nor glutathione-associated enzymes were altered in MCF7-MLNr cells, compared to the sensitive cells MCF7-WT. This study shows that treatment of pRSV-CAT plasmid with L-PAM at concentrations up to 1 microM proportionally inhibit the expression of chloramphenicol acetyl transferase (CAT) activity, while higher concentrations abolished CAT activity. pRSV-CAT reactivation was significantly increased when plasmid was transfected into MCF7-MLNr cells, compared to MCF7-WT cells. This indicates that resistant cells have more efficient capacity to recognize and repair L-PAM induced DNA damage. The mRNA expression of DNA nucleotide excision repair genes ERCC1, XPD (ERCC2), XPB (ERCC3), and polymerase beta was found to be similar in both the MCF7-WT and MCF7-MLNr cells. Western blot analysis also reveals no difference in the expression of ERCC1, AP endonuclease, poly (ADP-ribose) polymerase, and alkyl-N-purine-DNA glycosylase proteins. The lack of correlation between enhanced host cell reactivation capacity in resistant cells, and the expression of these specific DNA repair genes suggests that proteins encoded by these genes are not rate limiting steps for resistance to bi-functional alkylating drugs in human breast cancer cells.


Medicine and dentistry: Understanding the language of dentistry.
Dental problems are common in general practice and are responsible for many avoidable hospitalisations. Medicine and dentistry are often practised in isolation, with little shared language or understanding. The aim of this article is to help general practitioners (GPs) maximise effective dental referral strategies by briefly outlining basic dental nomenclature and describing the roles of different types of oral healthcare providers. The oral cavity contains hard and soft tissues that are all prone to oral disease, which can lead to systemic disease. It is important for GPs to have some basic familiarity with dental nomenclature, anatomy and tooth eruption times. In Australia, there are seven different oral healthcare providers and 13 dental specialities. This article will summarise their distinct roles and explain some common dental procedures used to definitively treat oral health problems. This knowledge should encourage more efficient interprofessional communication and enable general practitioners to optimise referral pathways for patients with oral health problems.


Root Traits, Nodulation and Root Distribution in Soil for Five Wild Lentil Species and Lens culinaris (Medik.) Grown under Well-Watered Conditions.
The efficient use of resources such as water and nutrients by plants is increasingly important as the world population food demand continues to grow. With the increased production of lentil in the temperate zones of North America, improvement in yield needs to be maintained. The use of wild lentil genotypes as sources of genetic diversity for introgression into cultivated lentil is an important breeding strategy, but little is known about their root systems. We evaluated the root systems of five wild lentil species and Lens culinaris under fully watered conditions. Plants were grown in 60 cm tubes containing equal volumes of soil collected from the reconstructed A, B, and C horizons. Significant differences were observed for root traits and fine root distribution between and within species and the proportion of root biomass partitioned into each soil layer was unique for each genotype. We also observed variability in nodule number and nodule shape within and between genotypes. Some genotypes more efficiently used water for either biomass or seed production. The allocation of resources to seed production also varied between genotypes. These observations could have impact on the design of future lentil breeding in the context of strategies for managing changes in rainfall amount and distribution for lentil production ecosystems.


The Efficacy and Health Economics of Different Treatments for Type 1 Cesarean Scar Pregnancy.
Objectives: To evaluate the efficacy and health economics of four treatments for type 1 cesarean scar pregnancy (CSP). Methods: From January 2009 to December 2018, 326 patients diagnosed with type 1 CSP were examined, among whom 31 received ultrasound-guided local injection of methotrexate (local injection group), 160 patients received uterine artery embolization combined with suction aspiration (UAE group), 25 patients received ultrasound-guided suction aspiration (aspiration group) and 90 received ultrasound-guided local injection of lauromacrogol combined with suction aspiration (lauromacrogol group). Clinical data and outcomes were analyzed. The decision tree model was used to compare the economics of four treatments. Results: The success rate of the local injection group was 71.0% (22/31), which was significantly different from 98.8% (158/160) of the UAE group and 100.0% (90/90) of the lauromacrogol group. The success rate of the aspiration group was 92.0% (23/25), which was significantly lower than that of the lauromacrogol group. The cost-effectiveness ratio was 1,876.53 yuan for the aspiration group, 2,164.63 yuan for the lauromacrogol group, 4,383.56 yuan for the local injection group, and 7,850.81 yuan for the UAE group. The Incremental cost effectiveness ratio (ICER) of the lauromacrogol group to the aspiration group was 5,477.75 yuan, indicating that if the willing to pay of patients was higher than 5,477.75 yuan, the lauromacrogol group had a cost-effectiveness advantage in treating type 1 CSP, compared to aspiration group. On the contrary, aspiration group has a higher cost-effectiveness advantage. The ICER of the lauromacrogol group to the local injection group or the UAE group were both less than 0, indicating that local injection group and UAE group was not cost-effective in the treatment of type 1 CSP. Conclusion: For type 1 CSP, the ultrasound-guided local injection of lauromacrogol combined with suction aspiration and ultrasound-guided suction aspiration, are effective and economical, and the choice between the two can be based on the patient's willing to pay.


Sevoflurane plays a reduced role in cognitive impairment compared with isoflurane: limited effect on fear memory retention.
Isoflurane and sevoflurane are both inhalation anesthetics, but in clinical application, sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential nephrotoxicity. Nevertheless, recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity, cost, and long-term anesthetic effect. Moreover, sevoflurane possibly has less cognitive impact on young mice. In this study, C57BL/6 mice aged 8-10 weeks were exposed to 1.2% isoflurane or 2.4% sevoflurane for 6 hours. Cognitive function and memory were examined in young mice using the novel object recognition, contextual fear conditioning, and cued-fear extinction tests. Western blot assay was performed to detect expression levels of D1 dopamine receptor, catechol-O-methyltransferase, phospho-glycogen synthase kinase-3β, and total glycogen synthase kinase-3β in the hippocampus. Our results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition test. Contextual memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane group. Long-term sevoflurane exposure did not affect memory consolidation, while isoflurane led to memory consolidation and reduced retention. Downregulation of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3β/total glycogen synthase kinase-3β and upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or sevoflurane. These results confirm that sevoflurane has less effect on cognitive impairment than isoflurane, which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3β in the hippocampus. This study was approved by the Institutional Animal Care and Use Committee, Nanjing University, China on November 20, 2017 (approval No. 20171102).


Quality control concerns in relation to lamotrigine and their impact.
To pursue explanations for compromised efficacy and induction of side-effects in some generic brands of lamotrigine distributed in Australia. Bioassays of the non-generic and five generic lamotrigine tablets were undertaken (also after exposure to heat and cold), as well as assays of two generic drugs generating concerning side-effects in two patients, while enquiries were made of manufacturing companies. Mass spectrometry of the six tested products showed comparable properties and no compromising when those tablets were heated and cooled, while analyses of the products taken by the two patients reporting significant side-effects showed an increase in the peak area lamotrigine concentration. We failed to identify any intrinsically compromised product in our comparison analyses of the six preparations. We consider alternate explanations for an issue leading to widespread international reporting of distinct side-effects and deaths following brand switching, with analyses of the two problematic preparations supporting a 'faulty' batch explanation.


Effects of water uptake on melamine renal stone formation in mice.
Melamine-tainted food can induce kidney stones both in humans and animals and in domestic animals, severe cases caused acute kidney failure and death. Although increasing water intake can ameliorate kidney stone formation, its effect on melamine (Mel)-induced kidney stones has not been studied. We have analysed the effect of restricted ingestion of drinking water on melamine stone formation in mice. They were given melamine and cyanuric acid orally and received drinking water either freely or for a restricted time. Kidney stone formation and renal function were monitored. Mice receiving drinking water for a restricted 10-h period initially lost body weight, which returned to normal within 2 days. No other abnormalities were observed. Ingestion of melamine alone failed to induce kidney stones even under conditions of restricted drinking water. In mice treated with melamine together with cyanuric acid for 3 days, no renal stones were formed when the supply of drinking was normal. However, when drinking water was limited, stone formation was observed and accompanied by high levels of serum urea and creatinine. An increase in urine haemoglobin and glucose levels was also found. The administration resulted in up-regulated tissue osteopontin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin messenger RNA expression and macrophage infiltration. Our results indicate the importance of water intake in the formation of melamine-induced renal stone formation in the mouse and provide new information on the mechanisms of melamine stone formation.


Hypoxia-inducible factor 1 regulation through cross talk between mTOR and MT1-MMP.
Hypoxia-inducible factor 1 (HIF-1) plays a key role in the cellular adaptation to hypoxia. Although HIF-1 is usually strongly suppressed by posttranslational mechanisms during normoxia, HIF-1 is active and enhances tumorigenicity in malignant tumor cells that express the membrane protease MT1-MMP. The cytoplasmic tail of MT1-MMP, which can bind a HIF-1 suppressor protein called factor inhibiting HIF-1 (FIH-1), promotes inhibition of FIH-1 by Mint3 during normoxia. To explore possible links between HIF-1 activation by MT1-MMP/Mint3 and tumor growth signals, we surveyed a panel of 252 signaling inhibitors. The mTOR inhibitor rapamycin was identified as a possible modulator, and it inhibited the mTOR-dependent phosphorylation of Mint3 that is required for FIH-1 inhibition. A mutant Mint3 protein that cannot be phosphorylated exhibited a reduced ability to inhibit FIH-1 and promoted tumor formation in mice. These data suggest a novel molecular link between the important hub proteins MT1-MMP and mTOR that contributes to tumor malignancy.


Chemical Shift Tensors - Why Should We Care?
Chemical shift tensors give valuable insights into the nature and the relative energy of frontier orbitals and their analysis allows for rationalizing the reactivities of molecules. In this article, we point out the principles that allow for the analysis of chemical shift. Through selected, illustrative examples we show how one can relate chemical shift to molecular electronic structure and thus to reactivity.


Clinical educators' views on the quality of undergraduate clinical restorative dentistry in the UK and ROI.
Following concerns expressed regarding recently expanded dental education, a survey was conducted on United Kingdom and Republic of Ireland clinical educators' perceptions of their work and the educational experiences they provide in clinical restorative dentistry. Many of the challenges facing dental education are common to all countries, and it would be of interest to note if the views reported are representative of the greater European perspective. The results of this survey represent a European regional picture. This is a survey of clinical staff in restorative dentistry departments across all of the fully established UK and ROI dental schools. The survey covered factors affecting the quality of undergraduate learning in restorative dentistry and the implications of these for programme delivery. Thematic analysis was applied to qualitative responses. One hundred and eighty-eight responses were received across the gamut of clinical educators' roles and across 15 of the 16 schools. Themes identified were personal workload, teaching effectiveness, students' clinical experiences, provision of teaching, departmental organisation and job satisfaction. The survey findings had many parallels with other recent reports but also suggested some developments. The survey provided an accurate snapshot of staff views on the quality of undergraduate clinical training in restorative dentistry. Despite experiencing difficulties in many areas of their work resulting in poor morale, staff considered teaching rewarding although undervalued by others. A number of recommendations are made for the development of undergraduate teaching.


An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.
Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings. Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).


Radiation-induced changes in refractive index and absorption coefficient for several optical materials.
An experiment was performed to determine the change in refractive index and absorptivity upon x radiation of several optical materials. Exposure to a radiation dose of 10(5) rad produced measurable changes at lambda = 0.5330 microm in the index of refraction and at lambda = 0.5000, microm in the absorption coefficient of ~5.8 x 10(-6) and ~0.1 cm(-1) for calcium fluoride. Optical glasses exhibited changes of ~5.8 x 10(-6) and ~1.1 cm(-1) for LaK 8, ~4.3 x 10(-6) and ~1.7 cm(-1) for PSK 53, ~5.1 x 10(-6) and ~1.4 cm(-1) for FK 50, and ~6.0 x 10(-6) and ~1.0 cm(-1) for SF 8. A change in the absorption coefficient of the optical glass KzFS 5 of ~0.52 cm(-1) was measured. Changes induced in an SiO(2) (Suprasil 2B) control sample were below measurement capability.


Higher risk factor burden and worse outcomes in urban carotid endarterectomy patients.
Previous multicenter carotid endarterectomy (CEA) studies had screening criteria for patient comorbidities and very few blacks. We assessed the hypothesis that CEA results from two urban hospitals would approximate those of the previous multicenter trials. A retrospective chart review was completed at two urban hospitals for CEA procedures done in 2003 and 2004. Demographic information and past medical history was recorded. In hospital perioperative complications (stroke or myocardial infarction [MI]) were noted. We calculated an expected perioperative stroke rate based on trial figures and our proportion of symptomatic and asymptomatic patients. Patients in our cohort had significantly higher rates of hypertension, diabetes, smoking, black race, and elderly status compared to previous trials. The expected perioperative stroke was 3.1%, and the observed stroke rate was 4.7% (P=0.36). Observed rates of MI (6.7%, P<0.001)) and stroke or MI (11.3%, P<0.0001) were higher than expected based on the previous trials. The stroke or MI rate in black subjects was higher (15.4% versus 5.6%, P=0.065) and this was significant at the hospital with lower CEA volume. In two urban hospitals, CEA results were significantly worse than previous trials. Patient selection is likely to play a role because our cohort had higher numbers of hypertensives, diabetics, smokers, blacks, and elderly patients. Clinicians need to carefully consider the risk/benefit ratio of CEA in urban patients because our study shows that these patients have a large number of medical comorbidities and worse outcomes after CEA.


Medical text analytics tools for search and classification.
A text-analytic tool has been developed that accepts clinical medical data as input in order to produce patient details. The integrated tool has the following four characteristics. 1) It has a graphical user interface. 2) It has a free-text search tool that is designed to retrieve records using keywords such as "MI" for myocardial infarction. The result set is a display of those sentences in the medical records that contain the keywords. 3) It has three tools to classify patients based on the likelihood of being diagnosed for myocardial infarction, hypertension, or their smoking status. 4) A summary is generated for each patient selected. Large medical data sets provided by the Institute for Clinical Evaluative Sciences were used during the project.


Drug-resistant Escherichia coli, Rural Idaho.
Stool carriage of drug-resistant Escherichia coli in home-living residents of a rural community was examined. Carriage of nalidixic acid-resistant E. coli was associated with recent use of antimicrobial agents in the household. Household clustering of drug-resistant E. coli was observed. Most carriers of drug-resistant E. coli lacked conventional risk factors.


Functional properties of the separate subunits of human DNA helicase II/Ku autoantigen.
The Ku antigen consists of two subunits of 70 and 83 kDa and is endowed with both duplex DNA end-binding capacity and helicase activity (human DNA helicase II). HeLa Ku can be isolated from in vitro cultured human cells uniquely as a heterodimer, and the subunits can be separated by electrophoresis only under denaturing conditions. To dissect the molecular functions of the two subunits of the heterodimer, we have cloned and expressed their cDNAs separately in Escherichia coli. The two activities of Ku (DNA binding and unwinding) were reconstituted by mixing and refolding both subunits in equimolar amounts (Tuteja, N., Tuteja, R., Ochem, A., Taneja, P., Huang, N-W., Simoncsits, A., Susic, S., Rahman, K., Marusic, L., Chen, J., Zang, J., Wang, S., Pongor, S., and Falaschi, A. (1994) EMBO J. 13, 4991-5001). Renaturation of the separate subunits can be achieved in the presence of a synthetic solubilizing and stabilizing agent, dimethyl ethylammonium propane sulfonate (NDSB 195). The helicase activity of the Ku protein resides uniquely in the 70-kDa subunit, whereas the DNA end-binding activity can be reconstituted only through renaturation of the two subunits in the heterodimeric form and is practically absent in the separate subunits. The 83-kDa subunit, when refolded in the absence of the 70-kDa subunit, forms homodimers unable to unwind DNA and bind duplex ends. The three separate species (heterodimer, 70-kDa subunit, and 83-kDa subunit homodimer) all have ssDNA-dependent ATPase activity.


Phosphatidylethanolamine synthesis by castor bean endosperm : membrane bilayer distribution of phosphatidylethanolamine synthesized by the ethanolaminephosphotransferase and ethanolamine exchange reactions.
The bilayer distribution of phosphatidylethanolamine (PtdEtn) in the endoplasmic reticulum of castor bean (Ricinus communis L. var Hale) endosperm following synthesis by both the CDP-ethanolamine: 1,2-diacylglycerol ethanolaminephosphotransferase and ethanolamine base exchange reactions have been studied. Two chemical probes, 1-fluoro-2,4-dinitrobenzene (FDNB) and 2,4,6-trinitrobenzenesulfonic acid (TNBS), which covalently bind to the free amino groups, were utilized. The endoplasmic reticulum membranes were impermeable to TNBS at 4 and 25 degrees C, but were permeable to FDNB at both temperatures. FDNB treatment of the PtdEtn from the base exchange reacted with 92% of the PtdEtn, while 80% of the lipid reacted with TNBS. Thus, at least 80% of the PtdEtn synthesized by the base exchange reaction was localized in the outer leaflet of the membrane, with about 12% occurring on the inner leaflet and about 8% being inaccessible. For PtdEtn formed by the CDP-ethanolamine pathway, 85% reacted with FDNB and 70% with TNBS, indicating that at least 70% was produced to the cytoplasmic face of the ER and 15% to the lumen side. The remainder was inaccessible to the probes. The sensitivity to trypsin of the two reactions also was tested. The ethanolamine base exchange enzyme, as well as that for l-serine exchange, retained activity following exposure to trypsin, but the activity of ethanolaminephosphotransferase disappeared after such treatment. This indicates that both base exchange enzymes are exposed to the lumenal side of the ER, while CDP-ethanolamine: 1,2-diacylglycerol ethanolaminephosphotransferase is exposed on the outer or cytoplasmic side. These results are discussed with respect to the final phospholipid distributions and the presumed sources of the water-soluble substrates.


Intravascular Versus Surface Cooling in Patients Resuscitated From Cardiac Arrest: A Systematic Review and Network Meta-Analysis With Focus on Temperature Feedback.
The aim of the study was to compare the effect of intravascular cooling (IC), surface cooling with temperature feedback (SCF), and surface cooling without temperature feedback (SCnoF) on neurologic outcome and survival in patients successfully resuscitated from cardiac arrest (CA) and treated with targeted temperature management (TTM) at 32-34°C. We performed a systematic review on Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, SCOPUS, CINAHL, Web of Science, and Clinical Trials up to June 30, 2021. We included randomized and nonrandomized studies on IC, SCF, and SCnoF in adult humans resuscitated from CA undergoing TTM, reporting neurologic outcome or survival. We performed a network meta-analysis to assess the comparative effects of IC, SCF, and SCnoF. The overall effect between two cooling methods included the effect of direct and indirect comparisons. Results are given as odds ratios (OR) and 95% CIs. Rankograms estimated the probability of TTM methods being ranked first, second, and third best interventions. A total of 14 studies involving 4,062 patients met the inclusion criteria. Four studies were randomized controlled studies, and 10 studies were nonrandomized observational studies. IC compared with SCnoF was significantly associated with better neurologic outcome (OR, 0.6; 95% CI, 0.49-0.74) and survival (OR, 0.8; 95% CI, 0.66-0.96). IC compared with SCF, and SCF compared with SCnoF did not show significant differences in neurologic outcome and survival. The rankogram showed that IC had the highest probability to be the most beneficial cooling method, followed by SCF and SCnoF. Our results suggest that in patients resuscitated from CA and treated with TTM at 32-34°C, IC has the highest probability of being the most beneficial cooling method for survival and neurologic outcome.


Clarkson disease - systemic capillary leak syndrome in a 6-year-old girl: case report.
Idiopathic systemic capillary leak syndrome is a rare and life-threatening disorder of unknown pathology. It results from leakage of plasma from the intravascular into the interstitial space and is characterised by recurrent episodes of shock, weight gain and generalised oedema. Recurrent episodes of this syndrome are reported in a 6-year-old girl who presented with the characteristic symptoms of shock, oedema and hypoalbuminaemia. She was treated effectively with fluid resuscitation, ionotropes and intravenous immunoglobin. Since systemic capillary leak syndrome is rare and the diagnosis is often missed, further research regarding its pathogenesis and treatment in children is warranted.


Age and solubility of volatile anesthetics in blood.
The more rapid rate of rise of alveolar anesthetic partial pressure in children compared with adults may be explained in part by an increasing solubility of volatile anesthetics in blood with age. To investigate this possibility, the authors measured the blood-gas partition coefficients of isoflurane, enflurane, halothane, and methoxyflurane in four groups of fasting subjects: 10 full-term newborns (at delivery), 11 children (3-7 years old), 11 adults (20-40 years old), and 10 elderly adults (75-85 years old). The blood-gas partition coefficients were greatest in adults: isoflurane 1.46, enflurane 2.07, halothane 2.65, and methoxyflurane 16.0; and least in newborns: 1.19, 1.78, 2.14, 13.3, respectively. The blood-gas partition coefficients in children (1.28, 1.78, 2.39, 15.0, respectively), which were intermediate between those in newborns (P less than 0.005) and those in adults (P less than 0.005), were not significantly different from those in elderly adults (1.29, 1.79, 2.41, 15.0, respectively). The blood-gas partition coefficients of both isoflurane and enflurane correlated directly with the serum albumin and triglyceride concentrations; that of halothane correlated directly with the serum cholesterol, albumin, triglyceride, and globulin concentrations; and that of methoxyflurane correlated directly with the serum cholesterol, albumin, and globulin concentrations. The authors conclude that age significantly affects blood-gas partition coefficients, and the lower blood-gas partition coefficients in children explain in part the more rapid rise of alveolar anesthetic partial pressure in this age group.


Schizophyllans carrying oligosaccharide appendages as potential candidates for cell-targeted antisense carrier.
Schizophyllans carrying beta-lactoside and alpha-mannoside appendages were prepared from native schizophyllan through NaIO4 oxidation followed by reductive amination using aminoethyl-beta-lactoside and alpha-mannoside, respectively. The resulting schizophyllans form stable macromolecular complexes with polynucleotides, such as poly(C) and poly(dA). Specific affinity between these macromolecular complexes and saccharide-binding proteins was demonstrated by surface plasmon resonance and agarose gel staining assays. beta-lactoside-appended schizophyllan enhanced an antisense activity in hepatocytes which express lactoside-binding proteins on their cell surfaces.


Structural and metallo selectivity in the assembly of [2 × 2] grid-type metallosupramolecular species: mechanisms and kinetic control.
An unsymmetrical bis(tridentate) ligand LH in which one binding site can be readily deprotonated forms a kinetically inert [Co(III)L(2)](+) complex which can be used as a "corner" species for the "Coupe du Roi" assembly of trans,trans-[Co(2)M(2)L(4)](6+) metallogrids (M = Fe(II), Co(II), Cu(II), Zn(II)). In the mixed Co(III)/Co(II) species, the oxidation states appear to be localised. In solution, the ligand LH forms octacationic, homometallic [2 × 2] grids with the individual labile metal ions Fe(II), Co(II), Cu(II), Zn(II), seemingly as mixtures of all possible isomers arising from the unsymmetrical nature of the ligand. In the solid state, however, [Zn(4)L(4)](CF(3)SO(3))(8)·4CH(3)CN crystallises as a single species where the cation has S(4) symmetry. This stereoselectivity in the crystalline lattice is associated with interactions between the cation and triflate anions which can again be analysed in terms of the Coupe du Roi concept.


Covariates of production and perseveration on tests of phonemic, semantic and alternating fluency in normal aging.
Standard measures of phonemic and semantic fluency, as well as fluency measures that impose additional demands upon set-switching were administered to younger and older adults. No age effect was found for total output on semantic fluency, while older participants generated significantly more responses relative to their younger counterparts on the phonemic measure. However, older adults made significantly more perseverative errors on both these measures. For tests of alternating fluency, only where participants were required to switch between two semantic dimensions, was an age deficit observed. Although the correlation between phonemic repetitions and age remained significant when performance on the Digit Symbol Test or a measure of fluid intelligence was partialled out, age effects for semantic repetitions and semantic alternating fluency were substantially reduced. The age benefit for number of correct responses upon phonemic fluency was significantly attenuated when a measure of crystallized intelligence was entered as a control variable. The theoretical and practical implications of these results are discussed.


Transposition of a 600 thousand-year-old LTR retrotransposon in the model legume Lotus japonicus.
We have identified a new Ty3-gypsy retrotransposon family named LORE2 (Lotus retrotransposon 2) and documented its activity in the model legume Lotus japonicus. Three new LORE2 insertions were found in symbiotic mutant alleles isolated from a plant population, established by tissue culture mediated transformation of the L. japonicus Gifu accession. Low transcriptional and transpositional activities of LORE2 in cultured cells suggested that the LORE2 transpositions identified in the three symbiotic mutants occurred in intact plants, not in callus. Tracing of the transpositional events identified two active LORE2 members in Gifu. One of them named LORE2A possesses a deletion in its coding region and polymorphisms between intraelemental LTRs. LORE2A is thus an aged element, estimated as 600 thousand years old. Our findings indicate that plant genomes carry more cryptic LTR retrotransposons, i.e., aged yet active, than estimated before, and that these cryptic elements may have contributed to plant genome dynamics, for example, the burst of transpositions reported in several plant species.


Diabetes insipidus.
To review the pathophysiology, diagnosis, and treatment of the syndromes of diabetes insipidus with an emphasis on those situations likely to be encountered in the critical care setting. Extensive clinical experience and relevant publications from the English literature identified via MEDLINE search, citation in reviews, publications of original data, and endocrine texts. Landmark papers pertaining to all aspects of diabetes insipidus were selected. Reviews, primary articles, and case reports pertaining to diabetes insipidus in the critical care setting were identified and selected according to their content of clinically useful information. Diabetes insipidus may result from impaired synthesis and release of vasopressin from the hypothalamic-pituitary unit (neurogenic) or renal insensitivity to circulating vasopressin (nephrogenic). A number of interventions, diseases, and drugs commonly encountered in the critical care setting may result in the development or exacerbation of diabetes insipidus. The diagnosis of diabetes insipidus requires the exclusion of other causes of polyuria and a systematic demonstration of the response of homeostatic mechanisms to controlled dehydration. The treatment of diabetes insipidus depends on many factors, including the clinical setting, degree and pathophysiologic classification, ability of the patient to compensate for free water losses, and expected duration of the abnormality. Underlying disorders should be treated appropriately whenever possible.


L-selective amidase with extremely broad substrate specificity from Ochrobactrum anthropi NCIMB 40321.
An industrially attractive L-specific amidase was purified to homogeneity from Ochrobactrum anthropi NCIMB 40321 wild-type cells. The purified amidase displayed maximum initial activity between pH 6 and 8.5 and was fully stable for at least 1 h up to 60 degrees C. The purified enzyme was strongly inhibited by the metal-chelating compounds EDTA and 1,10-phenanthroline. The activity of the EDTA-treated enzyme could be restored by the addition of Zn2+ (to 80%), Mn2+ (to 400%), and Mg2+ (to 560%). Serine and cysteine protease inhibitors did not influence the purified amidase. This enzyme displayed activity toward a broad range of substrates consisting of alpha-hydrogen- and (bulky) alpha,alpha-disubstituted alpha-amino acid amides, alpha-hydroxy acid amides, and alpha-N-hydroxyamino acid amides. In all cases, only the L-enantiomer was hydrolyzed, resulting in E values of more than 150. Simple aliphatic amides, beta-amino and beta-hydroxy acid amides, and dipeptides were not converted. The gene encoding this L-amidase was cloned via reverse genetics. It encodes a polypeptide of 314 amino acids with a calculated molecular weight of 33,870. Since the native enzyme has a molecular mass of about 66 kDa, it most likely has a homodimeric structure. The deduced amino acid sequence showed homology to a few other stereoselective amidases and the acetamidase/formamidase family of proteins (Pfam FmdA_AmdA). Subcloning of the gene in expression vector pTrc99A enabled efficient heterologous expression in Escherichia coli. Altogether, this amidase has a unique set of properties for application in the fine-chemicals industry.


Selective neurofibrillary degeneration of the hippocampal CA2 sector is associated with four-repeat tauopathies.
The CA2 sector of the hippocampus is relatively resistant to neurofibrillary tangles in aging and Alzheimer disease; however, some cases have selective neurofibrillary degeneration in CA2 with sparing of the more vulnerable CA1 sector. Cases such as this do not fit in the Braak and Braak staging scheme and can be considered to have an atypical pattern of neurofibrillary degeneration. We identified 24 atypical cases with an average age at death of 78.6 +/- 1.4 yr and average Braak stage of 3.2 +/- 0.4 and describe their pathologic and genetic characteristics with Gallyas silver staining, immunohistochemistry for tau and alphaB-crystallin, as well as apolipoprotein-E (ApoE) and tau genotyping. Three cases were excluded from further analysis due to presence of hippocampal sclerosis. All but 1 of the remaining 21 atypical cases were four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease (AGD). Remarkably, 19 of the 21 atypical cases were pure or mixed cases of AGD. The ApoE epsilon4 allele frequency was similar to normal controls, while there was a trend for an increased frequency of the extended tau H1 haplotype in atypical cases. Selective neurofibrillary degeneration in CA2 sector of the hippocampus is not widely recognized, but when detected should suggest the possibility of a 4R-tauopathy, particularly AGD.


Changes in uranium speciation through a depth sequence of contaminated Hanford sediments.
The disposal of basic sodium aluminate and acidic U(VI)-Cu(ll) wastes in the now-dry North and South 300 A Process Ponds atthe Hanford site resulted in a groundwater plume of U(VI). To gain insight into the geochemical processes that occurred during waste disposal and those affecting the current and future fate and transport of this uranium plume, the solid-phase speciation of uranium in a depth sequence of sediments from the base of the North Process Pond through the vadose zone to groundwater was investigated using standard chemical and mineralogical analyses, electron and X-ray microprobe measurements, and X-ray absorption fine structure spectroscopy. Near-surface sediments contained uranium coprecipitated with calcite, which formed due to overneutralization of the waste ponds with base (NaOH). At intermediate depths in the vadose zone, metatorbernite [Cu(UO2PO4)2 x 8H2O] precipitated, likely during pond operations. Uranium occurred predominantly sorbed onto phyllosilicates in the deeper vadose zone and groundwater; sorbed uranium was also an important component at intermediate depths. Since the calcite-bearing pond sediments have been removed in remediation efforts, uranium fate and transport will be controlled primarily by desorption of the sorbed uranium and dissolution of metatorbernite.


Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats.
Retinal melatonin synthesis occurs in the photoreceptor layer in a circadian manner, controlling several physiologic rhythmic phenomena, besides being the most powerful natural free radical scavenger. The purpose of the present work was to evaluate the diurnal profile of retinal melatonin content and the regulation of its synthesis in the retina of streptozotocin-induced diabetic rats. Diabetes was induced in male Wistar rats (12 hour-12 hour light/dark cycle) with streptozotocin. Control, diabetic, and insulin-treated diabetic animals were killed every 3 hours throughout the light-dark cycle. Retinal melatonin content was measured by high-performance liquid chromatography, arylalkylamine N-acetyltransferase (AANAT) activity was analyzed by radiometric assay, Bmal1 gene expression was determined by qPCR, and cyclic adenosine monophosphate (cAMP) content was assessed by ELISA. Control animals showed a clear retinal melatonin and AANAT activity daily rhythm, with high levels in the dark. Diabetic rats had both parameters reduced, and the impairment was prevented by immediate insulin treatment. In addition, the Bmal1 expression profile was lost in the diabetic group, and the retinal cAMP level was reduced 6 hours after lights on and 3 hours after lights off. The present work shows a melatonin synthesis reduction in diabetic rats retinas associated with a reduction in AANAT activity that was prevented by insulin treatment. The Bmal1-flattened gene expression and the cAMP reduction seem to be responsible for the AANAT activity decrease in diabetic animals. The melatonin synthesis reduction observed in the pineal gland of diabetic rats is also observed in a local melatonin tissue synthesizer, the retina.


Isolation of gibberellin precursors from heavily pigmented tissues.
The kauranoid precursors of gibberellins are difficult to isolate from heavily pigmented plant tissues. In this paper, we describe relatively simple and efficient procedures for the purification of these compounds from tissues containing chlorophyll and other high molecular weight pigments. Extracts of shoots from Thlaspi arvense L. were subjected first to size exclusion chromatography using ethyl acetate as the eluting solvent. This procedure resulted in the separation of kauranoids as a class of compounds from chlorophyll. Typically, a 90% reduction in mass of the kauranoid enriched-fraction was observed. This fraction was subjected to reverse phase high performance liquid chromatography and individual fractions analyzed by combined gas chromatography-mass spectrometry. Five kauranoids were identified in shoot extracts of T. arvense: ent-kaur-16-ene, ent-kaur-16-en-19-ol, ent-kaur-16-en-19-oic acid, trachylobanoic acid, and 7beta, 13-dihydroxykaurenolide. The metabolic relationships of these compounds to the gibberellins previously identified in this species (JD Metzger, MC Mardaus [1986] Plant Physiol 80: 396-402) are discussed. In addition, the utility of size exclusion chromatography in preparative situations is demonstrated by the purification of ent-kaurenoic acid in milligram quantities from the florets of Helianthus annuus L.


[Effects of diesel exhaust particle on gap junction intercellular communication].
Scrape-loading and dye transfer technique (SLDT) was used to study the effects of diesel exhaust particle (DEP) on gap junction intercellular communication (GJIC). The results demonstrated that the extract of DEP caused inhibition of gap junction intercellular communication in Balb/c 3T3 cells. It was suggested that inhibition of gap junction intercellular communication in cells may be one of the cause to induce cell transformation.


Mobile app self-care versus in-office care for stress reduction: a cost minimization analysis.
We calculated the cost of providing stress reduction care with a mobile phone app (Breathe2Relax) in comparison with normal in-person care, the standard method for managing stress in military and civilian populations. We conducted a cost-minimization analysis. The total cost to the military healthcare system of treating 1000 patients with the app was $106,397. Treating 1000 patients with in-office care cost $68,820. Treatment using the app became less expensive than in-office treatment at approximately 1600 users. From the perspective of the civilian healthcare system, treatment using the app became less expensive than in-office treatment at approximately 1500 users. An online tool was used to obtain data about the number of app downloads and usage sessions. A total of 47,000 users had accessed the app for 10-30 min sessions in the 2.5 years since the release of the app. Assuming that all 47,000 users were military beneficiaries, the savings to the military healthcare system would be $2.7 million; if the 47,000 users were civilian, the savings to the civilian healthcare system would be $2.9 million. Because of the large number of potential users, the total societal savings resulting from self-care using the app may be considerable.


Enhanced seed dispersal of Prunus africana in fragmented and disturbed forests?
Forest destruction and disturbance can have long-term consequences for species diversity and ecosystem processes such as seed dispersal. Understanding these consequences is a crucial component of conserving vulnerable ecosystems. In the heavily fragmented and disturbed Kakamega Forest, western Kenya, we studied seed dispersal of Prunus africana (Rosaceae). In the main forest, five forest fragments, and differently disturbed sites, we quantified the overall frugivore community as an indicator for species diversity. Furthermore, we determined the frugivores on 28 fruiting P. africana trees, estimated seed dispersal, crop size and the general fruit availability of surrounding trees. During the overall frugivore census we recorded 49 frugivorous species; 36 of them were observed visiting P. africana trees and feeding on their fruits. Although overall frugivore species richness was 1.1 times lower in fragments than in main forest sites and 1.02 times higher in highly disturbed than in less disturbed sites, P. africana experienced 1.1 times higher numbers of frugivores in fragments than in main forest sites and 1.5 times higher numbers of frugivores in highly disturbed than in less disturbed sites. Correspondingly, seed dispersal was 1.5 times higher in fragments than in main forest sites and 1.5 times higher in more disturbed than less disturbed sites. Fruit availability of surrounding trees and crop size influenced the number of visitors to some degree. Thus, the number of dispersed seeds seemed to be slightly higher in fragmented and highly disturbed sites. This indicates that loss of single species does not necessarily lead to a decrease of ecosystem services. However, loss of diversity could be a problem in the long term, as a multitude of species might act as buffer against future environmental change.


Perturbation of a hippocampal zinc-binding pool after postnatal lead exposure in rats.
Morphologic alterations of the hippocampal mossy fiber pathway after postnatal lead exposure have been observed in rats. It is hypothesized that lead might perturb zinc pools found in this pathway. To test this hypothesis, rat pups were exposed to lead indirectly by administering 0.2% lead acetate to dams via the drinking water during lactation for 21 days and control litters were maintained on tap water. To evaluate whether or not the effects of postnatal lead exposure were selective for hippocampal zinc pools, the hippocampus was compared with the cerebellum. There were no significant differences between lead-treated and control rats in total zinc content in either the hippocampus or the cerebellum in rats at 30 and 90 days of age. Furthermore, no differences in the subcellular distribution of zinc were observed between control and lead-treated animals. Because the effects on zinc content may be more subtle, the amounts of cytosolic zinc-binding species, isolated using Ultrogel AcA 34 gel chromatography, were measured in control and lead-treated animals. A striking decrease was observed in the amount of zinc associated with one of the cytosolic zinc-binding species, a putative zinc-glutathione complex, shown in previous studies to be the major hippocampal zinc pool. This effect was observed only in the hippocampus of 30-day-old lead-treated rats. By 90 days of age, the effect was no longer present. These data suggest that lead preferentially affects a zinc pool found in the hippocampus and supports our hypothesis that postnatal lead exposure results in an alteration in hippocampal zinc.


The reciprocal relationship between sickness presenteeism and psychological distress in response to job stressors: evidence from a three-wave cohort study.
Sickness presenteeism (SP) is postulated as workers' response to their general state of health; hence, SP is expected to affect workers' future health. In the present study, we examined the reciprocal relationship between SP and health in response to job stressors, with specific reference to psychological distress (PD) as workers' state of health. We conducted mediation analysis, using data from a three-wave cohort occupational survey conducted at 1-year intervals in Japan; it involved 1,853 employees (1,661 men and 192 women) of a manufacturing firm. We measured SP and PD, using the World Health Organization Health and Work Performance Questionnaire and Kessler 6 score, respectively. For job stressors, we considered job demands and control, effort and reward, and procedural and interactional justice. PD mediated 11.5%-36.2% of the impact of job control, reward, and procedural and interactional justice on SP, whereas SP mediated their impact on PD, albeit to a much lesser extent in the range of 3.4%-11.3%. Unlike in the cases of these job stressors related to job resources, neither SP nor PD mediated the impact of job demands or effort. Our results confirmed the reciprocal relationship between SP and PD in response to selected types of job stressors, emphasizing the need for more in-depth analysis of the dynamics of these associations.


Hydroxychloroquine prophylaxis and treatment is ineffective in macaque and hamster SARS-CoV-2 disease models.
We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human COVID-19 clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies to help guide decisions. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in 2 animal disease models. The standard human malaria HCQ prophylaxis (6.5 mg/kg given weekly) and treatment (6.5 mg/kg given daily) did not significantly benefit clinical outcome, nor did it reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. Similarly, when used for prophylaxis or treatment, neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Results from these 2 preclinical animal models may prove helpful in guiding clinical use of HCQ for prophylaxis/treatment of COVID-19.


Selenium and sulfur in exchange reactions: a comparative study.
Cysteamine reduces selenocystamine to form hemiselenocystamine and then cystamine. The rate constants are k(1) = 1.3 × 10(5) M(-1) s(-1); k(-1) = 2.6 × 10(7) M(-1) s(-1); k(2) = 11 M(-1) s(-1); and k(-2) = 1.4 × 10(3) M(-1) s(-1), respectively. Rate constants for reactions of cysteine/selenocystine are similar. Reaction rates of selenium as a nucleophile and as an electrophile are 2-3 and 4 orders of magnitude higher, respectively, than those of sulfur. Sulfides and selenides are comparable as leaving groups.


85-Year-Old Postsurgical Complex Patient Successfully Managed Remotely at the Novel Mayo Clinic's Hospital at Home.
An 85-year-old male presented to the podiatry clinic following a 1st to 5th left toe amputation as a complication of severe peripheral arterial disease and nonhealing wound despite endovascular intervention with an angiogram. At the visit, cellulitis with gangrene of the surgical site was noted. The patient was admitted to the brick and mortar (BAM) hospital and taken to surgery for a transmetatarsal amputation of the left limb. In the immediate postoperative period, the incisional margins appeared dusky creating concern for flap viability. The medical team recommended a vascular bypass versus a below-knee amputation. However, given the age, comorbidities, and nutritional status, the family refused further surgical intervention. As such, Mayo Clinic's home hospital program, Advanced Care at Home (ACH), was consulted for continued nonsurgical acute management at home. The patient was transferred to ACH and transported home three days after BAM admission to continue IV antibiotic therapy and wound care. Discharge from ACH occurred 11 days after admission to the BAM hospital. This case highlights the importance of developing health care alternatives to traditional hospitalization and demonstrates that ACH can manage highly complex, elder postoperative patients from the comfort of their homes.


Proteasomal degradation of glutamine synthetase regulates schwann cell differentiation.
Rapid saltatory nerve conduction is facilitated by myelin structure, which is composed of Schwann cells in the peripheral nervous system. Schwann cells drastically change their phenotype following peripheral nerve injury. These phenotypic changes are required for efficient degeneration/regeneration. We previously identified ZNRF1 as an E3 ubiquitin ligase containing a RING finger motif, whose expression is upregulated in the Schwann cells following nerve injury. This suggested that posttranscriptional regulation of protein expression in Schwann cells may be involved in their phenotypic changes during nerve degeneration/regeneration. Here we report the identification of glutamine synthetase (GS), an enzyme that synthesizes glutamine using glutamate and ammonia, as a substrate for E3 activity of ZNRF1 in Schwann cells. GS is known to be highly expressed in differentiated Schwann cells, but its functional significance has remained unclear. We found that during nerve degeneration/regeneration, GS expression is controlled mostly by ZNRF1-dependent proteasomal degradation. We also found that Schwann cells increase oxidative stress upon initiation of nerve degeneration, which promotes carbonylation and subsequent degradation of GS. Surprisingly, we discovered that GS expression regulates Schwann cell differentiation; i.e., increased GS expression promotes myelination via its enzymatic activity. Among the substrates and products of GS, increased glutamate concentration inhibited myelination and yet promoted Schwann cell proliferation by activating metabotropic glutamate receptor signaling. This would suggest that GS may exert its effect on Schwann cell differentiation by regulating glutamate concentration. These results indicate that the ZNRF1-GS system may play an important role in correlating Schwann cell metabolism with its differentiation.


Sump catheter drainage of parotid abscess: an alternative to surgery.
It is a clinical challenge to distinguish patients with parotid abscesses from those with acute sialadenitis. A case of parotid abscess is presented in which a CT scan with intravenous contrast enhancement localized the abscess cavity and guided its aspiration and drainage with an indwelling catheter. By using this percutaneous technique, the need for early surgical intervention by incision and drainage was eliminated. The dense overlying parotid fascia and position of the deep parotid lobe make differentiating between these two clinical entities difficult. Parotid abscesses are readily apparent on computerized tomographic (CT) scanning evaluation with intravenous contrast enhancement, presenting as discrete fluid-filled areas unlike the amorphous appearance of acute sialadenitis. CT scanning with intravenous contrast enhancement has been the preferred radiographic study of choice for evaluating parotid masses or parapharyngeal masses. The treatment of a patient with acute sialadenitis differs from that of a patient with a parotid abscess. Patients with acute sialadenitis will usually respond to vigorous intravenous (IV) hydration, use of sialagogues and appropriate antibiotic coverage. Following a period of conservative treatment with antibiotics and warm soaks, patients with parotid abscesses will usually undergo an incision and drainage procedure, and later, parotidectomy. A case of parotid abscess is presented in which a CT scan with intravenous contrast enhancement localized the abscess cavity and guided its aspiration and drainage with an indwelling catheter. Percutaneous drainage of parapharyngeal abscesses guided by CT has been previously described by Cole. By using this percutaneous technique, the need for early surgical intervention by incision and drainage was eliminated.


[Foreign immigration in contemporary France].
Immigration trends in France since 1946 are first reviewed. The author notes that immigration peaked in the period prior to the oil crisis of the early 1970s. Tighter immigration controls adopted in 1974 have affected the characteristics of the immigrant population concerning intention to return to country of origin, length of stay, and reuniting of family members. Consideration is also given to immigrant characteristics by nationality, unemployment among foreigners, and fertility differentials. "The second part of the article examines the new terms of the immigration problem (the alternative between the foreigners' integration and the maintainance of the immigrant statute) and the programs to be proposed." (SUMMARY IN ENG)


How Does the Central Nervous System Control Forthcoming Movement with Different Emotional Stimuli?
Maintaining postural balance is a key factor in human motor skills, based in part on emotional stimuli. Our objective in this study was to measure the effect of emotion on postural control as influenced by the direction of forthcoming movement. Eighteen right-handed women initiated a step forward or backward or remained in a static position after visualizing an emotional stimulus (positive, negative, or neutral). Center of pressure (COP) parameters (2D velocity, Medio-lateral (ML), and antero-posterior (AP) amplitude) were recorded for 3-second windows for movement direction and emotional stimulus. We observed a motion * direction effect on 2D velocity, characterized by a decrease in the emotional stimulus and static direction windows. The participants' ML amplitude was influenced by direction, and their reduced amplitude was evident in the presence of emotions. AP amplitude was high in the direction versus emotion window. In the static position, the AP amplitude was high in the direction window and low in the emotion window. The participants' movement planning and programming phase (direction window) was characterized by less oscillation for forward or backward movements and more oscillation before movement, suggesting anticipatory postural adjustments in the emotion window. Static direction was characterized by low oscillation, compared to forward and backward movement and in negative versus positive emotional context, proving the interactive impact of direction and emotion on COP amplitudes. Thus, postural control was influenced by both movement (direction) and emotional content (valence). This study provided insight regarding the interactive effect of emotion and direction on planning and programming forthcoming movement.


Glioblastoma cell death induced by asiatic acid.
Asiatic acid (AA), a triterpene, is known to be cytotoxic to several tumor cell lines. AA induces dose- and time-dependent cell death in U-87 MG human glioblastoma. This cell death occurs via both apoptosis and necrosis. The effect of AA may be cell type-specific as AA-induced cell death was mainly apoptotic in colon cancer RKO cells. AA-induced glioblastoma cell death is associated with decreased mitochondrial membrane potential, activation of caspase-9 and -3, and increased intracellular free Ca2+. Although treatment of glioblastoma cells with the caspase inhibitor zVAD-fmk completely abolished AA-induced caspase activation, it did not significantly block AA-induced cell death. AA-induced cell death was significantly prevented by an intracellular Ca2+ inhibitor, BAPTA/AM. Taken together, these results indicate that AA induces cell death by both apoptosis and necrosis, with Ca2+-mediated necrotic cell death predominating.


DR2 short antigen in Japanese. A strong association with Bw67 and TB23.
A variant of the DR2 antigen, DR2 short (DR2S), was investigated in Japanese subjects by using a 9th International Histocompatibility Workshop reagent and locally-obtained alloantisera. A significant positive association between DR2S, Bw67 and TB23 was demonstrated. Haplotype analysis on four Japanese families showed that DR2S was segregated with the A11-Cw7-Bw67-DR2S-DQw1-TB23 haplotype.


Spatial-CUT&Tag: Spatially resolved chromatin modification profiling at the cellular level.
Spatial omics emerged as a new frontier of biological and biomedical research. Here, we present spatial-CUT&Tag for spatially resolved genome-wide profiling of histone modifications by combining in situ CUT&Tag chemistry, microfluidic deterministic barcoding, and next-generation sequencing. Spatially resolved chromatin states in mouse embryos revealed tissue-type-specific epigenetic regulations in concordance with ENCODE references and provide spatial information at tissue scale. Spatial-CUT&Tag revealed epigenetic control of the cortical layer development and spatial patterning of cell types determined by histone modification in mouse brain. Single-cell epigenomes can be derived in situ by identifying 20-micrometer pixels containing only one nucleus using immunofluorescence imaging. Spatial chromatin modification profiling in tissue may offer new opportunities to study epigenetic regulation, cell function, and fate decision in normal physiology and pathogenesis.


Evaluation of selectable markers for rice transformation.
A variety of expression systems and selection régimes have been developed to transform plants such as tobacco, petunia, and tomato. We investigated several of these to determine whether the promoters and selectable markers used in dicotyledonous plants are suitable for selecting transformed rice callus. We compared transient expression driven by constitutive and regulated promoters in rice (Oryza sativa) protoplasts and found that the 2' promoter of the octopine T-DNA is approximately 3 to 4 times more efficient than the CAMV 35S promoter, 10 times more efficient than the nos promoter and the 1' promoter, and more than 100 times better than two other regulated plant promoters. Similar results were obtained in tobacco (Nicotiana tabacum) protoplasts with the exception that the nos promoter was expressed nearly 10 times better in rice. Further studies demonstrated that rice callus growth is sensitive to low concentrations of methotrexate, phosphinothricin, and bleomycin, and to moderate concentrations of G418 and hygromycin, but is only partially inhibited by relatively high concentrations of kanamycin. Finally, we tested the ability of stably introduced resistance genes to protect callus against some of the selective agents. Genes that inactivated phosphinothricin or G418 permitted transformed calli to grow almost unimpeded on toxic concentrations of these selective agents. However, a gene conferring resistance to methotrexate could not be used to select for activily growing transformants. Southern analysis of the transformed cell lines demonstrated that 50% of the transformants contained a single plasmid copy and that nearly all integrated copies showed rearrangements. These results on the use of selectable markers in rice should facilitate efforts to obtain transformants of this important grain.


Longitudinal changes in personalized platelet count metrics are good indicators of initial 3-year outcome in colorectal cancer.
Platelet count or complete blood count (CBC)-based ratios including lymphocyte-to-monocyte (LMR), neutrophil-to-lymphocyte (NLR), hemoglobin-to-platelet (HPR), red blood cell count distribution width-to-platelet (RPR), and platelet-to-lymphocyte (PLR) ratio are good predictors of colorectal cancer (CRC) survival. Their change in time is not well documented, however. To investigate the effect of longitudinal CBC ratio changes on CRC survival and their possible associations with clinicopathological properties, comorbidities, and anamnestic data. A retrospective longitudinal observational study was conducted with the inclusion of 835 CRC patients, who attended at Semmelweis University, Budapest. CBC ratios and two additional newly defined personalized platelet count metrics (pPLTD and pPLTS, the platelet counts relative to the measurement at the time of CRC diagnosis and to the one 4-6 wk after tumor removal surgery, respectively) were recorded. The 835 CRC patients had a total of 4608 measurements (5.52 visits/patient, in average). Longitudinal survival models revealed that the increases/decreases in LMR [hazard ratio (HR): 0.4989, P < 0.0001], NLR (HR: 1.0819, P < 0.0001), HPR (HR: 0.0533, P = 0.0038), pPLTD (HR: 4.9229, P < 0.0001), and pPLTS (HR: 4.7568, P < 0.0001) values were poor prognostic signs of disease-specific survival. The same was obtained for all-cause mortality. Most abnormal changes occurred within the first 3 years after the diagnosis of CRC. RPR and PLR had an only marginal effect on disease-specific (P = 0.0675) and all-cause mortality (Bayesian 95% credible interval: 0.90-186.05), respectively. LMR, NLR, and HPR are good metrics to follow the prognosis of the disease. pPLTD and pPLTS perform just as well as the former, while the use of RPR and PLR with the course of the disease is not recommended. Early detection of the abnormal changes in pPLTD, pPLTS, LMR, NLR, or HPR may alert the practicing oncologist for further therapy decisions in a timely manner.


Mutations in the human adenosine deaminase gene that affect protein structure and RNA splicing.
Adenosine deaminase (ADA; adenosine aminohydrolase, EC 126.96.36.199) deficiency is one cause of the genetic disease severe combined immunodeficiency. To identify mutations responsible for ADA deficiency, we synthesized cDNAs to ADA mRNAs from two cell lines, GM2756 and GM2825A, derived from ADA-deficient immunodeficient patients. Sequence analysis of GM2756 cDNA clones revealed a different point mutation in each allele that causes amino acid changes of alanine to valine and arginine to histidine. One allele of GM2825A also has a point mutation that causes an alanine to valine substitution. The other allele of GM2825A was found to produce an mRNA in which exon 4 had been spliced out but had no other detrimental mutations. S1 nuclease mapping of GM2825A mRNAs showed equal abundance of the full-length ADA mRNA and the ADA mRNA that was missing exon 4. Several of the ADA cDNA clones extended 5' of the major initiation start site, indicating multiple start sites for ADA transcription. The point mutations in GM2756 and GM2825A and the absence of exon 4 in GM2825A appear to be directly responsible for the ADA deficiency. Comparison of a number of normal and mutant ADA cDNA sequences showed a number of changes in the third base of codons. These changes do not affect the amino acid sequence. Analyses of ADA cDNAs from different cell lines detected aberrant RNA species that either included intron 7 or excluded exon 7. Their presence is a result of aberrant splicing of pre-mRNAs and is not related to mutations that cause ADA deficiency.


Cystic fibrosis. Carbohydrate metabolism in CF and in animal models for CF.
Cystic fibrosis (CF) is a chronic genetic disease mainly affecting the exocrine glands. Its main clinical symptoms are: abnormal production of mucus which blocks the airways, pancreatic insufficiency and increased sweat electrolytes. In the present investigation a series of enzymes and metabolites--mainly of carbohydrate metabolism--was investigated in biological fluids from CF homozygotes, CF heterozygotes and healthy controls under different conditions. CF homozygotes--and to a lesser degree CF heterozygotes--had increased activity of ribonuclease, and increased concentrations of electrolytes and lactate in their saliva and urine at rest. Saliva of CF patients also had augmented levels of protein. When healthy persons were submitted to anaerobic effort, the activity of ribonuclease and the concentrations of protein, electrolytes and lactate increased in their saliva, and thereby, mimicked the values found in the saliva of cystic fibrosis patients at rest. An abnormal response to a sucrose load was found in both CF-homozygotes and CF-heterozygotes. Greater increase in both glucose and lactate concentrations in the blood as well as a more rapid clearance of these metabolites was observed after the sucrose intake. A possible cause for these findings could be a disturbed carbohydrate metabolism in CF. Therefore, enzymes and metabolites connected to the metabolic pathway of glucose were investigated in CF fibroblasts and in animal models for CF. An increased activity of glycolytic enzymes in CF fibroblast were shown. Similar increases in activities of glycolytic enzymes were found in cells of submandibular glands of rats that were killed in a state of induced metabolic acidosis. These cells also showed increased protein and mucus contents, and elemental changes similar to those observed in fibroblasts of cystic fibrosis patients. Contrary to this, decreased activities of the enzymes of the glycolytic pathway were found in the submandibular gland of chronically reserpinized rats. The end-products of glycolysis, pyruvate and lactate, were also decreased, whereas the concentration of phosphoenolopyruvate and creatinphosphate were increased, possibly causing acidosis in the gland. Thus a disturbed glycolytic pathway in CF cells and a decreased intracellular pH might play an important role in the pathogenesis of this disease.


Synthesis of Ergosterol Peroxide Conjugates as Mitochondria Targeting Probes for Enhanced Anticancer Activity.
Inspired by the significant bioactivity of ergosterol peroxide, we designed and synthesized four fluorescent coumarin and ergosterol peroxide conjugates 8a-d through the combination of ergosterol peroxide with 7-N,N-diethylamino coumarins fluorophore. The cytotoxicity of synthesized conjugates against three human cancer cells (HepG2, SK-Hep1, and MCF-7) was evaluated. The results of fluorescent imaging showed that the synthesized conjugates 8a-d localized and enriched mainly in mitochondria, leading to significantly enhanced cytotoxicity over ergosterol peroxide. Furthermore, the results of biological functions of 8d showed that it could suppress cell colony formation, invasion, and migration; induce G2/M phase arrest of HepG2 cells, and increase the intracellular ROS level.


Sprawling and diverse: The changing U.S. population and implications for public lands in the 21st Century.
Public lands are typically established in recognition of their unique ecological value, yet both ecological and social values of public lands change over time, along with human distribution and land use. These transformations are evident even in developed countries with long histories of public land management, such as the United States. The 20th Century saw dramatic changes in the American population, in distribution and in racial and ethnic diversity, leading to new challenges and new roles for public lands. Our goal with this paper is to review changing demographics and implications for terrestrial protected areas in the U.S. We overview the fundamentals of population change and data, review past trends in population change and housing growth and their impacts on public lands, and then analyze the most recent decade of demographic change (2000-2010) relative to public lands. Discussions of demographic change and public lands commonly focus on the rural West, but we show that the South is also experiencing substantial change in rural areas with public lands, including Hispanic population growth. We identify those places, rural and urban, where demographic change (2000-2010), including diversification and housing growth, coincide with public lands. Understanding the current trends and long-term demographic context for recent changes in populations can help land managers and conservation scientists mitigate the effects of residential development near public lands, serve a more diverse population, and anticipate future population changes.


Identifying native-like protein structures using physics-based potentials.
As the field of structural genomics matures, new methods will be required that can accurately and rapidly distinguish reliable structure predictions from those that are more dubious. We present a method based on the CHARMM gas phase implicit hydrogen force field in conjunction with a generalized Born implicit solvation term that allows one to make such discrimination. We begin by analyzing pairs of threaded structures from the EMBL database, and find that it is possible to identify the misfolded structures with over 90% accuracy. Further, we find that misfolded states are generally favored by the solvation term due to the mispairing of favorable intramolecular ionic contacts. We also examine 29 sets of 29 misfolded globin sequences from Levitt's "Decoys 'R' Us" database generated using a sequence homology-based method. Again, we find that discrimination is possible with approximately 90% accuracy. Also, even in these less distorted structures, mispairing of ionic contacts results in a more favorable solvation energy for misfolded states. This is also found to be the case for collapsed, partially folded conformations of CspA and protein G taken from folding free energy calculations. We also find that the inclusion of the generalized Born solvation term, in postprocess energy evaluation, improves the correlation between structural similarity and energy in the globin database. This significantly improves the reliability of the hypothesis that more energetically favorable structures are also more similar to the native conformation. Additionally, we examine seven extensive collections of misfolded structures created by Park and Levitt using a four-state reduced model also contained in the "Decoys 'R' Us" database. Results from these large databases confirm those obtained in the EMBL and misfolded globin databases concerning predictive accuracy, the energetic advantage of misfolded proteins regarding the solvation component, and the improved correlation between energy and structural similarity due to implicit solvation. Z-scores computed for these databases are improved by including the generalized Born implicit solvation term, and are found to be comparable to trained and knowledge-based scoring functions. Finally, we briefly explore the dynamic behavior of a misfolded protein relative to properly folded conformations. We demonstrate that the misfolded conformation diverges quickly from its initial structure while the properly folded states remain stable. Proteins in this study are shown to be more stable than their misfolded counterparts and readily identified based on energetic as well as dynamic criteria. In summary, we demonstrate the utility of physics-based force fields in identifying native-like conformations in a variety of preconstructed structural databases. The details of this discrimination are shown to be dependent on the construction of the structural database.


Atypical retinocytoma with diffuse vitreous seeds: An insight.
Retinocytoma is a rare benign form of retinoblastoma. It is usually found on routine examinations and also while screening families of patients with retinoblastoma. Distinctive features are a translucent retinal mass with calcification, retinal pigment epithelial disturbance, chorioretinal atrophy and absence of growth. We report a case with all the above features along with diffuse vitreous seeds and optical coherence tomographic documentation of intralesional cavitary lesions.


Efficacy of plasma beta-hydroxybutyrate concentration as a marker for diabetes mellitus in acutely sick cats.
Urine ketone measurement is routinely performed in cats with diabetes mellitus to identify impending or established ketoacidosis. Studies using the urinary ketone dipstick test have shown that ketonuria is common in cats with newly diagnosed untreated diabetes mellitus. This test has a low sensitivity as it quantifies the less abundant ketone acetoacetate. The objective of the present study was to determine if ketonaemia is an inherent biochemical finding in untreated feline diabetes mellitus by measuring plasma ss-hydroxybutyrate (ss-OHB) in acutely sick cats. In 122 sick cats (37 diabetic and 85 non-diabetic cats) plasma ss-OHB, glucose, fructosamine, total protein and thyroxine were measured as part of the routine work up. Diabetic cats had significantly elevated ss-OHB values and ss-OHB measurement was a sensitive and specific test to identify diabetes mellitus. The area under the receiver operating characteristic (ROC) curve was 0.93. The cut off value with the highest positive likelihood ratio was 0.58 mmol/l. These results suggest that determination of plasma ss-OHB concentration is a useful method to distinguish between diabetic and non-diabetic sick cats.


Combined low temperature-high light effects on gas exchange properties of jojoba leaves.
Jojoba (Simmondsia chinensis [Link] Schneider) is an important crop in desert climates. A relatively high frequency of periods of chilling and high photon flux density (PFD) in this environment makes photoinhibition likely, resulting in a reduction of assimilation capacity in overwintering leaves. This could explain the low net photosynthesis found in shoots from the field (4-6 micromoles per square meter per second) when compared to greenhouse grown plants (12-15 micromoles per square meter per second). The responses of photosynthesis and stomatal conductance to changes in absorbed PFD and in substomatal partial pressure of CO(2) were measured on jojoba leaves recovering from chilling temperature (4 degrees C) in high or low PFD. No measurable gas exchange was found immediately after chilling in either high or low PFD. For leaves chilled in low PFD, the original quantum yield was restored after 24 hours. The time course of recovery from chilling in high PFD was much longer. Quantum yield recovered to 60% of its original value in 72 hours but failed to recover fully after 1 week. Measurements of PSII chlorophyll fluorescence at 77 K showed that the reduced quantum yield was caused by photoinhibition. The ratio of variable to maximal fluorescence fell from a control level of 0.82 to 0.41 after the photoinhibitory treatment and recovery was slow. We also found a large increase in net assimilation rate and little closure of stomata as CO(2) was increased from ambient partial pressure of 35 to 85 pascals. For plants grown in full light, the increase in net assimilation rate was 100%. The photosynthetic response at high CO(2) concentration may constitute an ecological advantage of jojoba as a crop in the future.


Structure of the photoreactive iron center of the nitrile hydratase from Rhodococcus sp. N-771. Evidence of a novel post-translational modification in the cysteine ligand.
Nitrile hydratase (NHase) from Rhodococcus sp. N-771 is a photoreactive enzyme that is inactivated by nitrosylation of the non-heme iron center and activated by photodissociation of nitric oxide (NO). To obtain structural information on the iron center, we isolated peptide complexes containing the iron center by proteolysis. When the tryptic digest of the alpha subunit isolated from the inactive form was analyzed by reversed-phase high performance liquid chromatography, the absorbance characteristic of the nitrosylated iron center was observed in the peptide fragment, Asn105-Val-Ile-Val-Cys-Ser-Leu-Cys-Ser-Cys-Thr-Ala-Trp-Pro-Ile-Leu - Gly-Leu-Pro-Pro-Thr-Trp-Tyr-Lys128. The peptide contained 0.79 mol of iron/mol of molecule as well as endogenous NO. Subsequently, by digesting the peptide with thermolysin, carboxypeptidase Y, and leucine aminopeptidase M, we found that the minimum peptide segment required for the nitrosylated iron center is the 11 amino acid residues from alphaIle107 to alphaTrp117. Furthermore, by using mass spectrometry, protein sequence, and amino acid composition analyses, we have shown that the 112th Cys residue of the alpha subunit is post-translationally oxidized to a cysteine-sulfinic acid (Cys-SO2H) in the NHase. These results indicate that the NHase from Rhodococcus sp. N-771 has a novel non-heme iron enzyme containing a cysteine-sulfinic acid in the iron center. Possible ligand residues of the iron center are discussed.


HPLC-DAD stability indicating determination of nitrofurazone and lidocaine hydrochloride in their combined topical dosage form.
In this work, a simple, rapid, and selective high-performance liquid chromatography (HPLC) method with diode array detection was developed for the simultaneous determination of nitrofurazone (NZ) and lidocaine hydrochloride (LD). The chromatographic separation was achieved by using Zorbax Eclipse XDB-C(18) (4.6 x 150 mm, 5 mum p.s.) analytical column and a mobile phase composed of 0.025 M disodium hydrogen phosphate-methanol-triethylamine (70:30:0.1, v/v/v) (pH 4.0) at a flow rate of 1 mL/min. The detector was set at wavelengths 374 and 220 nm for NZ and LD, respectively, and quantification of the analytes was based on measuring their peak areas. The retention times for NZ and LD were approximately 4.5 and 5.7 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, selectivity, robustness, and detection and quantification limits. The linear dynamic ranges were 0.5-25 and 2.5-100 mug/mL for NZ and LD, respectively, with correlation coefficients > 0.999. The stability-indicating aspects of the proposed method were demonstrated by the resolution of the two analytes from the related substance and potential impurity (2,6-dimethylaniline) as well as from forced-degradation products. The validated HPLC method was successfully extended to the analysis of the combined topical dosage form (soluble dressing) where no interfering peaks were encountered from the dosage form matrix or the inactive ingredients.


Oxidative Stress and Respiratory Diseases in Preterm Newborns.
Premature infants are exposed to increased generation of reactive oxygen species, and on the other hand, they have a deficient antioxidant defense system. Oxidative insult is a salient part of lung injury that begins as acute inflammatory injury in respiratory distress disease and then evolves into chronic and structural scarring leading to bronchopulmonary dysplasia. Oxidative stress is also involved in the pathogenesis of pulmonary hypertension in newborns through the modulation of the vascular tone and the response to pulmonary vasodilators, with consequent decrease in the density of the pulmonary vessels and thickening of the pulmonary arteriolar walls. Oxidative stress has been recognized as both a trigger and an endpoint for several events, including inflammation, hypoxia, hyperoxia, drugs, transfusions, and mechanical ventilation, with impairment of pulmonary function and prolonged lung damage. Redoxomics is the most fascinating new measure to address lung damage due to oxidative stress. The new challenge is to use omics data to discover a set of biomarkers useful in diagnosis, prognosis, and formulating optimal and individualized neonatal care. The aim of this review was to examine the most recent evidence on the relationship between oxidative stress and lung diseases in preterm newborns. What is currently known regarding oxidative stress-related lung injury pathogenesis and the available preventive and therapeutic strategies are also discussed.


Supervision needs of nurses working in the community.
The aim of this research was to develop and evaluate a programme comprising a series of supervision sessions (based on a social work model) to meet the needs of nurses working in the community. Nurses are now working in programmes such as drug and alcohol withdrawal and community-based palliative care where they are increasingly assuming more of a counselling role with their clients. This is typified by an increase in the emotional intensity of the relational engagement. In this new environment, the old skills, strategies and support frameworks are no longer sufficient. Nurses in the project were asked to evaluate their experience of the programme in relation to self-regulated learning, developing self-awareness, skills competence and increase in counselling knowledge. The small sample size means that there are important restrictions on generalising the findings. Nevertheless, the findings show that the programme has been evaluated positively by the participants and should encourage further research.


Statistical mechanics of glass formation in molecular liquids with OTP as an example.
We extend our statistical mechanical theory of the glass transition from examples consisting of point particles to molecular liquids with internal degrees of freedom. As before, the fundamental assertion is that supercooled liquids are ergodic, although becoming very viscous at lower temperatures, and are therefore describable in principle by statistical mechanics. The theory is based on analyzing the local neighborhoods of each molecule, and a statistical mechanical weight is assigned to every possible local organization. This results in an approximate theory that is in very good agreement with simulations regarding both thermodynamical and dynamical properties.


Sleep and chronotype in adults with persistent tic disorders.
This study examined sleep disorders and sleep medication use rates, nighttime tics, and sleep and chronotype in relation to tic and co-occurring symptoms in adults with persistent tic disorders (PTDs), including Tourette's disorder (TD). One hundred twenty-five adult internet survey respondents rated sleep history, sleep, chronotype, tic severity, impairment, attention deficit hyperactivity disorder, obsessive-compulsive symptoms, anxiety, depression, and emotional and behavioral dyscontrol. Bruxism, insomnia, tic-related difficulty falling asleep, and melatonin use were commonly endorsed. Sleep disturbance correlated with impairment, obsessive-compulsive symptoms, and emotional and behavioral dyscontrol. Eveningness correlated with vocal and total tic severity only in TD. Controlling for age and sex, age, impairment, and obsessive-compulsive symptoms predicted sleep disturbance, and age and tic severity predicted chronotype. Impairment and obsessive-compulsive symptoms play a role in sleep disturbance in adults with PTDs, and may be intervention targets. Eveningness relates to tic severity, which may suggest the utility of interventions to advance chronotype.