Observations on structural features and characteristics of biological apatite crystals. 5. Three-dimensional observation on ultrastructure of human enamel crystals.
In a series of studies to investigate the structural features of the biological crystals, such as the tooth and bone, using an electron microscope, we examined the ultrastructure of the enamel, dentin, and bone crystals at near atomic resolution and showed the configuration of the hydroxyapatite structure through the cross and longitudinal sections of the crystals. Thereafter, based on the results of the observations by the authors of the ultrastructure of the tooth and bone crystals, thinking that it might be possible to conduct direct three-dimensional observation of the configuration composing the unit cell of the hydroxyapatite crystals, we conducted a study on this. These results indicated that it was possible to sterically observe the configuration of the hydroxyapatite structure composing the enamel crystal. The materials used for this study were the middle layer of the noncarious enamel from the freshly extracted human erupted permanent molars. The small cubes of the enamel were fixed in glutaraldehyde and osmium tetroxide and embedded in epoxy resin using the routine methods. The ultrathin sections were cut with a diamond knife without decalcification and were examined with the HITACHI H-9000 H type transmission electron microscope operated at 300 kV. Each crystal was observed at an initial magnification of 500,000 times and at the final magnification of 10,000,000 times and over. We sincerely believe that the electron micrographs shown in this report are the first to show three-dimensionally the configuration of the hydroxyapatite structure composing the crystal in the cross and longitudinal sections of an enamel crystal.


Hepatoprotective effect of Pergularia daemia (Forsk.) ethanol extract and its fraction.
Ethanol extract and its ethanol fraction from aerial parts of P. daemia exhibited significant hepatoprotective effect against CCl4 induced hepatotoxicity in rats. Glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, total bilirubin, total cholesterol, total protein and albumin in serum indicated hepatoprotective effect of the ethanol extract and its ethanol fraction. Histopathological examination of liver sections confirmed that, pre-treatment with ethanol extract and its ethanol fraction prevented hepatic damage induced by CCl4. The results were comparable with the standard hepatoprotective drug silymarin. The extract and its fraction showed no signs of toxicity up to a dose level of 2000 mg/kg. It is suggested that, the presence of flavonoids in ethanol extract and its ethanol fraction may be responsible for hepatoprotective properties. High Performance Thin Layer Chromatography profile of flavonoids of bio-active extracts was developed using quercetin-3-glucoside as a marker. Results indicate hepatoprotective properties of ethanol extract of P. daemia.


Oxalate-Promoted SO2 Uptake and Oxidation on Iron Minerals: Implications for Secondary Sulfate Aerosol Formation.
Mineral dust serves as a significant source of sulfate aerosols by mediating heterogeneous sulfur dioxide (SO2) oxidation in the atmosphere. Given that a considerable proportion of small organic acids are deposited onto mineral dust via long-range transportation, understanding their impact on atmospheric SO2 transformation and sulfate formation is of great importance. This study investigates the effect of oxalate on heterogeneous SO2 uptake and oxidation phenomenon by in situ FTIR, theoretical calculation, and continuous stream experiments, exploiting hematite (Fe2O3) as an environmental indicator. The results highlight the critical role of naturally deposited oxalate in mononuclear monodentate coordinating surface Fe atoms of Fe2O3 that enhances the activation of O2 for oxidizing SO2 into sulfate. Meanwhile, oxalate increases the hygroscopicity of Fe2O3, facilitating H2O dissociation into reactive hydroxyl groups and further augmenting the SO2 uptake capacity of Fe2O3. More importantly, other conventional iron minerals, such as goethite and magnetite, as well as authentic iron-containing mineral dust, exhibit similar oxalate-promoted sulfate accumulation behaviors. Our findings suggest that oxalate-assisted SO2 oxidation on iron minerals is one of the important contributors to secondary sulfate aerosols, especially during the nighttime with high relative humidity.


Oxazoloisoindolinones with in vitro antitumor activity selectively activate a p53-pathway through potential inhibition of the p53-MDM2 interaction.
One of the most appealing targets for anticancer treatment is the p53 tumor suppressor protein. In half of human cancers, this protein is inactivated due to endogenous negative regulators such as MDM2. Actually, restoring the p53 activity, particularly through the inhibition of its interaction with MDM2, is considered a valuable therapeutic strategy against cancers with a wild-type p53 status. In this work, we report the synthesis of nine enantiopure phenylalaninol-derived oxazolopyrrolidone lactams and the evaluation of their biological effects as p53-MDM2 interaction inhibitors. Using a yeast-based screening assay, two oxazoloisoindolinones, compounds 1b and 3a, were identified as potential p53-MDM2 interaction inhibitors. The molecular mechanism of oxazoloisoindolinone 3a was further validated in human colon adenocarcinoma HCT116 cells with wild-type p53 (HCT116 p53(+/+)) and in its isogenic derivative without p53 (HCT116 p53(-/-)). Indeed, using these cells, we demonstrated that oxazoloisoindolinone 3a exhibited a p53-dependent in vitro antitumor activity through induction of G0/G1-phase cell cycle arrest and apoptosis. The selective activation of a p53-apoptotic pathway by oxazoloisoindolinone 3a was further supported by the occurrence of PARP cleavage only in p53-expressing HCT116 cells. Moreover, oxazoloisoindolinone 3a led to p53 protein stabilization and to the up-regulation of p53 transcriptional activity with increased expression levels of several p53 target genes, as p21(WAF1/CIP1), MDM2, BAX and PUMA, in p53(+/+) but not in p53(-/-) HCT116 cells. Additionally, the ability of oxazoloisoindolinone 3a to block the p53-MDM2 interaction in HCT116 p53(+/+) cells was confirmed by co-immunoprecipitation. Finally, the molecular docking analysis of the interactions between the synthesized compounds and MDM2 revealed that oxazoloisoindolinone 3a binds to MDM2. Altogether, this work adds, for the first time, the oxazoloisoindolinone scaffold to the list of chemotypes activators of a wild-type p53-pathway with promising antitumor activity. Moreover, it may open the way to the development of a new class of p53-MDM2 interaction inhibitors.


Effects of O(2) and CO(2) Concentrations on Quantum Yields of Photosystems I and II in Tobacco Leaf Tissue.
The interactive effects of irradiance and O(2) and CO(2) levels on the quantum yields of photosystems I and II have been studied under steady-state conditions at 25 degrees C in leaf tissue of tobacco (Nicotiana tabacum). Assessment of radiant energy utilization in photosystem II was based on changes in chlorophyll fluorescence yield excited by a weak measuring beam of modulated red light. Independent estimates of photosystem I quantum yield were based on the light-dark in vivo absorbance change at 830 nanometers, the absorption band of P700(+). Normal (i.e. 20.5%, v/v) levels of O(2) generally enhanced photosystem II quantum yield relative to that measured under 1.6% O(2) as the irradiance approached saturation. Photorespiration is suspected to mediate such positive effects of O(2) through increases in the availability of CO(2) and recycling of orthophosphate. Conversely, at low intercellular CO(2) concentrations, 41.2% O(2) was associated with lower photosystem II quantum yield compared with that observed at 20.5% O(2). Inhibitory effects of 41.2% O(2) may occur in response to negative feedback on photosystem II arising from a build-up in the thylakoid proton gradient during electron transport to O(2). Covariation between quantum yields of photosystems I and II was not affected by concentrations of either O(2) or CO(2). The dependence of quantum yield of electron transport to CO(2) measured by gas exchange upon photosystem II quantum yield as determined by fluorescence was unaffected by CO(2) concentration.


Minilaparoscopy and laparoendoscopic single-site surgery: mini- and single-scar in urology.
To review the development of laparoscopic single-site surgery (LESS) and minilaparoscopy (ML), with particular attention to the urological field, focusing on nomenclature, history and outcomes. A literature search was conducted on laparoendoscopic single-site surgery, minilaparoscopy, needlescopy and microlaparoscopy. The most relevant papers were selected over the last 30 years. 830 manuscripts were found about LESS, 251 in urology, two CRTs and nine match-case controls. 258 papers were about ML and 55 in urology. ML is the main topic (169 papers), followed by needlescopy (58) and microlaparoscopy (32). The most significant articles are four non-randomized match-case control studies. Over the last few years, many urological laparoscopic operations have been successfully performed by LESS. However, the actual role of LESS remains to be determined with controversial data about postoperative pain control and almost no results on cosmesis. We are facing second-generation ML with superior performance granted by new endoscopes and most effective instruments. ML has demonstrated in almost all urologic indications to be feasible, safe and able to improve cosmetic and postoperative pain control. Anyway, CRTs are still lacking and only studies from other discipline can corroborate this trend.


Fluorescent Labeling of Polysaccharides from Masson Pine Pollen and Its Effect on RAW264.7 Macrophages.
In order to explore the immediate effect of polysaccharides and macrophages, polysaccharides from masson pine pollen (PPM60) were labeled with fluorescein isothiocyanate (FITC) by using a chemical-derived method, and the reactant was named PPM60-Tyr-FITC. Direct interaction of PPM60-Tyr-FITC and RAW264.7 macrophages could be detected by flow cytometer (FCM), and this interaction could be inhibited by Pitstop 2 (clathrin inhibitor) and TAK-242 (Toll-like receptor 4 inhibitor). The results of confocal laser scanning microscopy (CLSM) also revealed that there was a co-localization phenomenon between PPM60-Tyr-FITC and RAW264.7 macrophage receptors, and it could be suppressed by Pitstop 2 and TAK-242. It was confirmed that PPM60 enters into RAW264.7 macrophages mainly through endocytosis, rather than the phagocytosis, and TLR4 played a mediating role.


Application of ferrate(VI) in the treatment of industrial wastes containing metal-complexed cyanides : a green treatment.
Ferrate(VI) was employed for the oxidation of cyanide (CN) and simultaneous removal of copper or nickel in the mixed/complexed systems of CN-Cu, CN-Ni, or CN-Cu-Ni. The degradation of CN (1.00 mmol/L) and removal of Cu (0.095 mmol/L) were investigated as a function of Fe(VI) doses from 0.3-2.00 mmol/L at pH 10.0. It was found that Fe(VI) could readily oxidize CN and the reduction of Fe(VI) into Fe(III) might serve efficiently for the removal of free copper ions. The increase in Fe(VI) dose apparently favoured the CN oxidation as well as Cu removal. Moreover, the pH dependence study (pH 10.0-13.0) revealed that the oxidation of CN was almost unaffected in the studied pH range (10.0-13.0), however, the maximum removal efficiency of Cu was obtained at pH 13.0. Similarly, treatment was carried out for CN-Ni system having the initial Ni concentration of 0.170 mmol/L and CN concentration of 1.00 mmol with Fe(VI) dose 2.00 mmol at various pH values (10.0-12.0). Results showed a partial oxidation of CN and partial removal of Ni. It can be observed that Fe(VI) can partially degrade the CN-Ni complex in this pH range. Further, Fe(VI) was applied for the treatment of simulated industrial waste/effluent waters treatment containing CN, Cu, and Ni.


Laboratory evaluations of feed-grade and agricultural-grade phosphates.
Nine samples of pure, feed-grade (FP) and agricultural-grade (AP) phosphates were evaluated at seven laboratories (six in Brazil and one in the U.S.) for physical and chemical characteristics. Phosphates were one "standard" pure dicalcium phosphate; four FP, two dicalcium phosphates (FP-1 and FP-2) made in Brazil, one di-monocalcium phosphate (FP-3), and one defluorinated phosphate (FP-4) made in the U.S.; and four AP made in Brazil [single superphosphate (AP-1), triple superphosphate (AP-2) and monoammonium (AP-3), and thermomagnesium (AP-4) phosphates]. Average analytical values for FP and AP, respectively, were 3.3 and 6.3% moisture, 1.0 and 2.5% insoluble residue, 16.2 and 28.4% loss on ignition, 6.8 and 4.7 (pH), 1,028 and 1,023 g/L apparent density, 9.6 and 55.0% P solubility in water, 83.6 and 88.4% P solubility in 2% citric acid, and 85.2 and 97.0% P solubility in neutral ammonium citrate. Based on particle size, six products were classified as "fine," and three were classified as "irregular." Atomic absorption and plasma spectrometry determinations were performed for 31 essential and potentially harmful or radioactive minerals. The Na level was high in FP-4 (6.03%). Mineral concentrations were safe for all FP as compared with NRC standards. Levels in AP were toxic, exceeding the tolerance limits for F, Fe, Mg, and Ba, and were particularly high as compared with FP for S, Ti, and radioactive Th. The AP-1 was high in F, Ba, S, and Th; AP-2 and AP-3 were high in F and S; and AP-4 was high in F, Ba, Fe, Mg, Ti, and Th. X-ray diffraction assays detected impurities for all commercial samples and identified as major components CaHPO4*2H2O (standard phosphate), CaCO3 and CaHPO4 (FP-1, FP-2, and FP-3), Ca(H2PO4)2*H2O (FP-3), Na2Ca3Al2(PO4)2(SiO4)2 and Ca3(PO4)2 (FP-4), CaSO4*nH2O and (NH4)Fe3P6O20*(PO4)2 (AP-1), Ca(H2PO4)2*H2O and KFe3P6O20*10H2O (AP-2), (NH4)H2PO4 and CaSO4*nH2O (AP-3), and no definite molecular structure for AP-4, an amorphous product. The biological consequences of feeding animals a mineral source with no definite molecular structure, an amorphous product, is not known. A biological evaluation of all phosphates included in this article is being published as a separate report (Fernandes et al., 1999).


Managing obesity: a survey of attitudes and practices among Israeli primary care physicians.
To document and assess Israeli family physicians' (FPs) knowledge, attitudes and practices regarding the management of overweight and obesity. Anonymous questionnaires were completed by 510 family physicians (82% compliance rate). The questionnaires were distributed in various continuous medical education sites of FPs in Israel. The measures included attitudes to and resources of knowledge on weight management, views regarding the prescription of drugs, approaches to and strategies recommended for weight loss. In all, 73% of FPs viewed weight management as important and reported that they often treated cases of overweight and obesity, including for patients without concomitant risk factors. The medical advice most frequently offered is: increase physical activity, decrease number of total calories (eat less) and consultation with a dietitian (95, 81 and 58% respectively). However, most responders (72%) believed that they had limited efficacy in treating obesity and considered themselves not well prepared by medical school to treat overweight patients. Some 60% reported feeling that they have insufficient knowledge regarding nutritional issues. Regarding pharmacotherapy for treating obesity, only 66% knew the drugs' prescription indications. However, the vast majority (87%) knew about the gradual increase of weight after stopping drug treatment. Knowledge gaps and ambivalent attitudes toward obesity management were found. More education focusing on obesity, from medical school to post-graduate learning, seems warranted based on these findings.


The Rice Abscisic Acid-Responsive RING Finger E3 Ligase OsRF1 Targets OsPP2C09 for Degradation and Confers Drought and Salinity Tolerance in Rice.
Drought and salinity are major important factors that restrain growth and productivity of rice. In plants, many really interesting new gene (RING) finger proteins have been reported to enhance drought and salt tolerance. However, their mode of action and interacting substrates are largely unknown. Here, we identified a new small RING-H2 type E3 ligase OsRF1, which is involved in the ABA and stress responses of rice. OsRF1 transcripts were highly induced by ABA, salt, or drought treatment. Upregulation of OsRF1 in transgenic rice conferred drought and salt tolerance and increased endogenous ABA levels. Consistent with this, faster transcriptional activation of key ABA biosynthetic genes, ZEP, NCED3, and ABA4, was observed in OsRF1-OE plants compared with wild type in response to drought stress. Yeast two-hybrid assay, BiFC, and co-immunoprecipitation analysis identified clade A PP2C proteins as direct interacting partners with OsRF1. In vitro ubiquitination assay indicated that OsRF1 exhibited E3 ligase activity, and that it targeted OsPP2C09 protein for ubiquitination and degradation. Cell-free degradation assay further showed that the OsPP2C09 protein is more rapidly degraded by ABA in the OsRF1-OE rice than in the wild type. The combined results suggested that OsRF1 is a positive player of stress responses by modulating protein stability of clade A PP2C proteins, negative regulators of ABA signaling.


[Monitoring the trend of occupational injuries: comparison between different indicators].
to compare three injuries indicators to establish which are less affected by underreporting and therefore best suited for the monitoring of the occupational injuries time trend during economic crisis. open cohort. a national sample of employees in the private sector, blue collars, males aged 15-64 years, extracted from the Work History Italian Panel-Healt archive, which combines data about firms and employee from the National Social Security Institute (Inps) and occupational injuries data from the Italian National Institute for Insurance against Accidents at Work (Inail). annual injuries rates for the period 2001-2012 classified according to three severity definitions: • serious injuries according to the prognosis (IGP); • serious Injuries according to the type of lesion (IGL); • minor injuries. Time trends and their changes during the economic crisis (2008-2013) were analysed through negative binomial regression models, stratified by country of origin, macroarea of work, firm size, and economic activity. IGP rates decreased more than IGL and minor injuries rates during the economic crisis, highlighting their greater association with the economic cycle. Negatives and significant trend changes were observed in some subgroups: in manufacturing, among workers from high developed countries and Moroccans, in the Northern and Central macroareas of Italy, and in larger firms. variations in injuries rates were not so much influenced by the underreporting of injuries as by the changes in the working conditions following the economic crisis. To accurately monitor the injuries time trends, it is recommended to report at the same time at least one indicator based on minor injuries and one based on serious injuries.


Central American sex workers' introduction of the female condom to different types of sexual partners.
Formative research was conducted in El Salvador and Nicaragua to inform promotion of female condoms to sex workers. Two rounds of focus groups with sex workers were conducted, with female condom training and supplies provided. Structured interviews with sex workers and direct observations of health educators were conducted. One third of sex acts were protected with female condoms in the previous 7 days. Women recommended nonpaying partners as "first try" partners but most frequently reported trying female condoms with clients. With clients, women preferred female condoms over male condoms but expressed no preference with nonpaying partners. Lack of exposure to female condoms among men and women was cited as a key barrier to female condom use. Strategies for persuading all partner types to try the female condom are suggested, and we provided promotional messages, based on results, to assist sex workers in introducing female condoms to different partners.


Endocrine status in 29 patients treated by curative radiation therapy for nasopharyngeal carcinoma.
The basal endocrine status of 29 patients treated with curative radiation therapy for nasopharyngeal carcinoma was assessed; they were disease-free for a minimum of 4 years from the end of treatment. None showed clinical evidence of endocrine disease, and most of them had a substantially normal hormonal blood pattern. A slightly elevated TSH value, suggesting subclinical primary hypothyroidism, was found only in two male patients, which could be ascribed to the radiotherapeutic treatment of the neck. Although we cannot exclude more subtle alterations of hypothalamic-pituitary function, the percentage incidence of endocrine impairment in our patients seems lower than previously reported by other authors.


Bilateral internal carotid artery agenesis: a case study and review of the literature.
Bilateral internal carotid artery agenesis is a rare lesion, with only 18 cases previously reported. Blood supply to the anterior cerebral circulation is most commonly through enlarged basilar and posterior communicating arteries. Occasionally collateral flow is through abnormal transsellar anastomoses or anastomoses between the external carotid and intracranial systems. Associated intracranial aneurysms occur in 25% of patients, accounting for a significant incidence of intracranial hemorrhage as the initial symptom. Diagnosis is best made by cerebral arteriography with computed tomography to verify the congenital nature of the abnormality by demonstrating the absence of carotid canals. This is the second case to begin with transient ischemic attacks suggestive of carotid territory ischemia but originating from the vertebral system. Angiographic findings included absent internal carotid arteries, small common carotid arteries, and bilateral high-grade stenoses at the origins of large vertebral arteries. This is the first such case to be treated with reimplantation of the vertebral artery with resolution of symptoms.


Overexpression of cyclins D1 and D3 during estrogen-induced breast oncogenesis in female ACI rats.
A common feature of human breast oncogenesis is cell cycle deregulation. The expression of cyclins D1 and D3 was examined during estradiol-17beta (E(2))-induced mammary tumorigenesis in female August Copenhagen Irish (ACI) rats. Low serum E(2) levels ( approximately 60-120 pg/ml) were sufficient to induce mammary gland tumors (MGTs) that remarkably resemble human ductal breast cancer (BC) at the histopathologic and molecular levels. Western blot analysis of the E(2)-induced MGTs revealed a marked rise in cyclins D1 (24-fold), D3 (9-fold) and cdk4 (3-fold) expression compared with age-matched untreated controls. Small focal dysplasias with large, pale staining nuclei were commonly seen at 3-3.6 months, large focal dysplasias, including atypical ductal hyperplasia at 3.6-4.3 months, ductal carcinoma in-situ (DCISs) at 4.3-5.0 months, and 100% incidence of invasive ductal BC/frank tumors at 5-6 months were detected after E(2) treatment. Immunohistochemical analysis of serial sections of focal dysplasias, DCISs and invasive ductal carcinomas showed overexpression of cyclins D1, D3, estrogen receptor-alpha (ERalpha) and progesterone receptor (PR). However, cyclin D3 expression, unlike D1, was confined essentially to early pre-malignant lesions (focal dysplasias and DCISs) and primary MGTs with <1-5% of resting and normal hyperplastic breast cells staining positive. The kinase activity for cyclins D1 and D3, using retinoblastoma (Rb) as a substrate, in E(2)-induced MGTs and their binding to cdk4 was significantly elevated. Semi-quantitative reverse transcriptase PCR analysis of the E(2)-induced MGTs exhibited increased expression of cyclins D1 (2.9-fold) and D3 (1.4-fold) mRNA, indicating that their elevated protein expression was due in part to an increase in mRNA transcription. However, when analyzed by quantitative real-time Q-PCR, these genes were not amplified. These data indicate that in female ACI rat mammary glands, E(2)-induced pre-malignant lesions differentially and selectively express cyclins D1 and D3, thus contributing to a distinct growth advantage of these pre-neoplasias relative to E(2)-elicited normal hyperplasia.


Use of angiotensin converting enzyme inhibitors is associated with reduced risk of late bladder toxicity following radiotherapy for prostate cancer.
Genome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension. Prostate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437). Patients were assessed pre-radiotherapy and followed prospectively for development of toxicity for up to four years. The cumulative probability of hematuria was estimated by the Kaplan-Meier method. Multivariable grouped relative risk models assessed the effect of ACEi on time to hematuria adjusting for clinical factors and stratified by enrollment site. A polygenic risk score (PRS) for blood pressure was tested for association with hematuria in REQUITE and our Radiogenomics Consortium GWAS. Patients taking ACEi during radiotherapy had a reduced risk of hematuria (HR 0.51, 95%CI 0.28 to 0.94, p = 0.030) after adjusting for prior transurethral prostate and/or bladder resection, heart disease, pelvic node radiotherapy, and bladder volume receiving 70 Gy, which are associated with hematuria. A blood pressure PRS was associated with hypertension (odds ratio per standard deviation 1.38, 95%CI 1.31 to 1.46, n = 5,288, p < 0.001) but not hematuria (HR per standard deviation 0.96, 95%CI 0.87 to 1.06, n = 5,126, p = 0.41). Our study is the first to show a radioprotective effect of ACEi on bladder in an international, multi-site study of patients receiving pelvic radiotherapy. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects the bladder.


Similar effects of alpha- and beta-SNAP on Ca(2+)-regulated exocytosis.
Soluble N-ethylmaleimide-sensitive fusion protein attachment proteins (SNAP) proteins function in Ca(2+)-regulated exocytosis. Recent work (Schiavo et al. (1996) Nature 378, 733-736) based on in vitro protein interactions has raised the possibility that alpha- and beta-SNAPs have distinct roles in exocytosis. We have examined this possibility by comparing the activities of recombinant alpha- and beta-SNAPs. Both of these proteins were able to similarly bind NSF and activate its ATPase activity but to a lesser extent than gamma-SNAP. When introduced into digitoninpermeabilised chromaffin cells, both alpha- and beta-SNAP stimulated Ca(2+)-regulated exocytosis in a MgATP-dependent manner. The dose-response relationships for these proteins were essentially the same and addition of both proteins did not lead to any further increase in exocytosis above that due to each protein alone. We conclude that alpha- and beta-SNAPs are interchangeable isoforms with similar functions in regulated exocytosis.


The specific molecular architecture of plant 3-hydroxy-3-methylglutaryl-CoA lyase.
3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase (HMGL) is involved in branched-chain amino acid catabolism leading to acetyl-CoA production. Here, using bioinformatics analyses and protein sequence alignments, we found that in Arabidopsis thaliana a single gene encodes two HMGL isoforms differing in size (51 kDa, HMGL51 and 46 kDa, HMGL46). Similar to animal HMGLs, both isoforms comprised a C-terminal type 1 peroxisomal retention motif, and HMGL51 contained a mitochondrial leader peptide. We observed that only a shortened HMGL (35 kDa, HMGL35) is conserved across all kingdoms of life. Most notably, all plant HMGLs also contained a specific N-terminal extension (P100) that is located between the N-terminal mitochondrial targeting sequence TP35 and HMGL35 and is absent in bacteria and other eukaryotes. Interestingly, using HMGL enzyme assays, we found that rather than HMGL46, homodimeric recombinant HMGL35 is the active enzyme catalyzing acetyl-CoA and acetoacetate synthesis when incubated with (S)-HMG-CoA. This suggested that the plant-specific P100 peptide may inactivate HMGL according to specific physiological requirements. Therefore, we investigated whether the P100 peptide in HMGL46 alters its activity, possibly by modifying the HMGL46 structure. We found that induced expression of a cytosolic HMGL35 version in A. thaliana delays germination and leads to rapid wilting and chlorosis in mature plants. Our results suggest that in plants, P100-mediated HMGL inactivation outside of peroxisomes or mitochondria is crucial, protecting against potentially cytotoxic effects of HMGL activity while it transits to these organelles.


Investigation of the efficacy of flumethrin pour-on for the control of high tsetse and trypanosomiasis challenge in Kenya.
The effects of bi-weekly flumethrin pour-on treatments at 1 mg kg bodyweight on tsetse fly population and trypanosome infection rates were monitored over a one-year period (2/89-2/90) in 2000 head of cattle on a trial farm, located in the Lamu District in East Kenya, an adjacent control farm and a transsecting road for additional fly monitoring. The tsetse fly population on the trial farm dropped from pretreatment counts of 118 flies/trap/week (Feb. 1989) to 13 in June 1989 and 32 in Jan. 1990. During the same period and months the fly population in the control farm was 90.34 and 87 flies/trap/week. Fly counts on the transsecting road, however, increased from 72.53 to 163 flies/trap/week. The impact of tsetse fly control is clearly reflected in the reduction of trypanosome infection rates on the trial farm, e.g. 37% (pre-treatment infection rate), 10% and 11% in January, June and December 1989 respectively. On the control farm the infection rates remained at distinctly higher levels of 34%, 17% and 24% during the same period. Mean weekly weight gains were 66% higher in the treated herd as compared to the untreated control herd.


Outcome analysis for lip carcinoma.
Carcinoma of the lip is a relatively common malignancy of the head and neck region, accounting for approximately one quarter of oral cavity cancers. Although this form of cancer is generally readily curable compared with malignancies at other head and neck sites, regional metastases, local recurrence, and even death from this disease may occasionally occur. A review of 1252 patients who were diagnosed with lip cancer from 1940 to 1987 was undertaken to identify and rank prognostic variables, clarify differential incidences of site predilection between male and female patients, and examine the correlation between tumor site and histopathologic diagnoses. Large tumor size, high tumor grade, the presence of adenopathy, a subsite other than the lower lip, and inadequate surgical margins were found to have a negative impact on determinate survival of patients with lip carcinoma. Twenty-one percent of lip cancers in female patients arose on the upper lip, whereas only 3% of lip cancers in male patients developed on the upper lip. Basal cell carcinomas comprised 13% of upper lip cancers and only less than 1% of lower lip cancers. Recurrence developed in 15.1% of the patients reviewed and was strongly associated with large tumor size and poor differentiation. Local recurrence was associated with a determinate survival of 78%, whereas patients having regional recurrences had a survival rate of 52%. These data support aggressive treatment of lip cancers greater than 3 cm in diameter, high-grade tumors, tumors associated with cervical lymphadenopathy, and upper lip and commissure tumors. Lip cancer in women seems to be slightly more aggressive than in men.


Red degeneration of a large leiomyoma in a non-pregnant woman in pursuit of 17 pregnancies: a case report.
Leiomyoma is a common benign tumor in women of reproductive age. Increasing the number of pregnancy has a significant role in reducing the risk of tumor development. Red degeneration is a rare complication and often occurs during pregnancy. However, its incidence in non-pregnant women is tremendously rare. Herein, we present a case of 51-year-old non-pregnant women with a history of 17 pregnancies, diagnosed with leiomyoma that underwent red degeneration.


GLUT4 ablation in mice results in redistribution of IRAP to the plasma membrane.
Glucose transporter (GLUT) 4 is the insulin responsive glucose transporter in adipose tissue, skeletal muscle, and heart. Insulin elicits increased glucose uptake by recruiting GLUT4 from a specialized intracellular storage site to the cell surface. Expression of various proteins that colocalize with GLUT4 and/or are involved in insulin-stimulated GLUT4 translocation was examined in adipocytes as well as skeletal and cardiac muscles from GLUT4 null mice. Our data demonstrate that expression of insulin-regulated aminopeptidase (IRAP) is divergently regulated in GLUT4 null tissues, e.g., upregulated 1.6-fold in GLUT4 null adipocytes and downregulated in GLUT4 null skeletal muscle (40%) and heart (60%). IRAP exhibited abnormal subcellular distribution and impaired insulin-stimulated translocation in GLUT4-deficient tissues. We propose the compartment containing IRAP and proteins normally associated with GLUT4 vesicle traffics constitutively to the cell surface in GLUT4 null adipocytes and skeletal muscle.


A labile component of AMPA receptor-mediated synaptic transmission is dependent on microtubule motors, actin, and N-ethylmaleimide-sensitive factor.
Glutamate receptor channels are synthesized in the cell body, are inserted into intracellular vesicles, and move to dendrites where they become incorporated into synapses. Dendrites contain abundant microtubules that have been implicated in the vesicle-mediated transport of ion channels. We have examined how the inhibition of microtubule motors affects synaptic transmission. Monoclonal antibodies that inactivate the function of dynein or kinesin were introduced into hippocampal CA1 pyramidal cells through a patch pipette. Both antibodies substantially reduced the AMPA receptor-mediated responses within 1 hr but had no effect on the NMDA receptor-mediated response. Heat-inactivated antibody or control antibodies had a much smaller effect. A component of transmission appeared to be resistant even to the combination of these inhibitors, and we therefore explored whether other agents also produce only a partial inhibition of transmission. A similar resistant component was found by using an actin inhibitor (phalloidin) or an inhibitor of NSF (N-ethylmaleimide-sensitive fusion protein)/GluR2 interaction. We then examined whether these effects were independent or occluded each other. We found that a combination of phalloidin and NSF/GluR2 inhibitor reduced the response to approximately 30% of baseline level, an effect only slightly larger than that produced by each agent alone. The addition of microtubule motor inhibitors to this combination produced no further inhibition. We conclude that there are two components of AMPA receptor-mediated transmission; one is a labile pool sensitive to NSF/GluR2 inhibitors, actin inhibitors, and microtubule motor inhibitors. A second, nonlabile pool resembles NMDA receptor channels in being nearly insensitive to any of these agents on the hour time scale of our experiments.


2,3-Dichloro-1,4-hydro-quinone 2,3-dichloro-1,4-benzoquinone monohydrate: a quinhydrone-type 1:1 donor-acceptor [D-A] charge-transfer complex.
IN THE CRYSTAL STRUCTURE OF THE TITLE COMPOUND (SYSTEMATIC NAME: 2,3-dichloro-benzene-1,4-diol 2,3-dichloro-cyclo-hexa-2,5-diene-1,4-dione monohydrate), C(6)H(4)Cl(2)O(2)·C(6)H(2)Cl(2)O(2)·H(2)O, the 2,3-dichloro-1,4-hydro-quinone donor (D) and the 2,3-dichloro-1,4-benzoquinone acceptor (A) mol-ecules form alternating stacks along [100]. Their mol-ecular planes [maximum deviations for non-H atoms: 0.0133 (14) (D) and 0.0763 (14) Å (A)] are inclined to one another by 1.45 (3)° and are thus almost parallel. There are π-π inter-actions involving the D and A mol-ecules, with centroid-centroid distances of 3.5043 (9) and 3.9548 (9) Å. Inter-molecular O-H⋯O hydrogen bonds involving the water mol-ecule and the hy-droxy and ketone groups lead to the formation of two-dimensional networks lying parallel to (001). These networks are linked by C-H⋯O inter-actions, forming a three-dimensional structure.


Cloning and Sequencing of the cDNA Encoding the Rubber Elongation Factor of Hevea brasiliensis.
In Hevea brasiliensis, the rubber particle in the laticiferous vessel is the site of rubber (cis-1-4-polyisoprene) biosynthesis. A 14 kilodalton protein, rubber elongation factor (REF), is associated with the rubber particle in a ratio of one REF to one rubber molecule (Dennis M, Henzel W, Bell J, Kohr W, Light D [1989] J Biol Chem 264: 18618-18628; Dennis M, Light D [1989] J Biol Chem 264: 18608-18617). To obtain more information concerning the function of REF and its synthesis and assembly in the rubber particle, we isolated cDNA clones encoding REF. We used antibodies to REF to screen a Hevea leaf gammagt11 cDNA expression library and obtained several positive clones. Sequence analysis of the REF cDNA clones showed that the REF mRNA contains 121 nucleotides of 5'-nontranslated sequences and a 205 nucleotide 3'-nontranslated region. The open reading frame encodes the entire 14 kilodalton REF protein without any extra amino acids (Dennis M, Henzel W, Bell J, Kohr W, Light D [1989] J Biol Chem 264: 18618-18628). The REF cDNA was subcloned in pGEM-3Z/-4Z and expressed in vitro. The translation product is a 14 kilodalton protein that can be immunoprecipitated with antibodies to REF. Addition of microsomal membranes to the in vitro translation product did not alter the mobility of the REF protein. This, and the sequence data, indicate that REF is not made as a preprotein. Our results suggest that REF is synthesized on free polysomes in the laticifer cytoplasm and that assembly of the rubber particles is likely to occur in the cytosol.


Antioxidant and Anticholinesterase Activities of Macrosphyra Longistyla (DC) Hiern Relevant in the Management of Alzheimer's Disease.
Macrosphyra longistyla has been used in many traditional systems of medicine for its anti-hemorrhagic, antidiabetic, anti-ulcer, and anti-diarrhea properties. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitions of the crude methanol extracts and its various partitioned fractions were determined by a modified method of Ellman. An evaluation of the antioxidant activity was carried out using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging, ferric reducing power, and nitric oxide scavenging assays. The total flavonoids were estimated based on the aluminum chloride method, while the total tannins and phenolics were estimated based on the vanillin-HCl and Folin-Ciocalteu method, respectively. The ethyl acetate fraction had the highest DPPH radical scavenging activity, and the highest ferric reducing power with a concentration providing 50% inhibition (IC50) of 0.079 mg/mL and 0.078 mg/mL, respectively, while the crude methanol extract had the highest nitric oxide scavenging activity with an IC50 of 0.008 mg/mL. The methanol extract had the highest phenolics and flavonoids contents, while the aqueous fraction had the highest tannin content. The crude methanol extract had the best AChE and BuChE inhibitory action, with an IC50 of 0.556 µg/mL and 5.541 µg/mL, respectively, suggesting that the plant had a better AChE inhibiting potential. A moderate correlation was observed between the phenolic content and DPPH radical scavenging, NO radical scavenging, and AChE inhibitory activities (r2 = 0.439, 0.430, and 0.439, respectively), while a high correlation was seen between the flavonoid content and these activities (r2 = 0.695, 0.724, and 0.730, respectively), and the ferric reducing antioxidant power correlated highly with the proautocyanidin content (r2 = 0.801). Gas chromatography mass spectrometry (GCMS) revealed decanoic acid methyl ester (24.303%), 11,14-eicosadienoic acid methyl ester (16.788%), linoelaidic acid (10.444%), pentadecanoic acid (9.300%), and 2-methyl-hexadecanal (9.285%). Therefore, we suggest that M. longistyla contain bioactive chemicals, and could be a good alternative for the management of Alzheimer's and other neurodegenerative diseases.


Interest of the preventive and curative use of defibrotide on the occurrence and severity of sinusoidal obstruction syndrome after hematopoietic stem cell transplant in children.
Defibrotide (DF) is indicated for the treatment of severe sinusoidal obstruction syndrome (SOS) following hematopoietic stem cell transplantation (HSCT), but its prophylactic use against SOS is not recommended yet. This study describes the impact of the preventive and curative use of DF on reducing the incidence and severity of SOS in children. Patients aged 0-19 years, who received allogenic HSCT after myeloablative conditioning regimen with busulfan or total body irradiation in our comprehensive cancer center, between 2013 and 2017, were included. The Baltimore or modified Seattle criteria were used for SOS diagnosis. SOS was graded using the 2017 European Society for Blood and Marrow Transplantation classification defining severity criteria of SOS in children. SOS occurrence tended to decrease with prophylactic DF, but no significant difference was observed in terms of severity. When not treated with preventive DF, 50% (19/38) of the patients with SOS were graded severe to very severe, but only 37% (7/19) had organ dysfunction. Curative DF was administered at a median of 2 days post-HSCT, for a median of 6.5 days. The absence of fatal SOS supports the use of early curative DF with acceptable toxicities and questions the optimal duration of DF treatment.


A literature review on the antiphospholipid syndrome and the effect on childbearing.
to review the literature on antiphospholipid antibodies and their significance to midwifery practice. databases using the keywords anticardiolipin antibodies, antiphospholipid antibodies, lupus antibodies, antiphospholipid syndrome, systemic lupus erythematosis, pregnancy loss, pre-eclampsia were searched, 548 articles were generated and 52 were used in the review. anticardiolipin antibodies are detrimental to successful pregnancy being implicated in failure of implantation, loss of the embryo and the fetus. There is also a risk of prematurity, intrauterine growth retardation and neonatal embolism. The risks to the mother are of pre-eclampsia and embolic complications. If diagnosed and treated early in pregnancy with low-dose aspirin and subcutaneous heparin the outlook for a successful pregnancy is much improved. much research remains to be undertaken. Researchers need to standardise their criteria so that findings are comparable and larger sample groups are necessary. antiphospholipid syndrome is an important disorder and a preventable cause of pregnancy loss. Midwives need to encourage women to persevere with therapy to preserve pregnancy and maybe prevent pre-eclampsia or thrombosis. When pregnancies are lost one of the hardest things is when the parents cannot understand why. Midwives need to understand the syndrome to collaborate with doctors in explaining it and supporting grieving parents.


Transperitoneal versus extraperitoneal laparoscopic radical prostatectomy: experience of a single center.
To analyze, in a consecutive study, the perioperative, postoperative, and functional results of the transperitoneal and extraperitoneal approaches for laparoscopic radical prostatectomy. A total of 160 patients underwent radical prostatectomy and were subdivided into two groups. Group 1 underwent the transperitoneal approach and group 2, the extraperitoneal approach. The preoperative parameters, age, prostate-specific antigen level, biopsy Gleason score, American Society of Anesthesiologists class, body mass index, and clinical stage, were considered. The perioperative parameters evaluated were the operative time, blood loss, blood transfusion, hospital stay, catheterization time, complications, histopathologic findings, TNM stage, Gleason score, prostate and tumor volumes, and functional results. The patients in both groups had comparable preoperative data. No differences were observed between the two groups in the intraoperative data, except for the mean operative time (179 +/- 54.6 for group 1 versus 133.7 +/- 27 minutes for group 2). Also, no differences were observed between the two groups in terms of the postoperative data. The proportion of complications was 21.25% in group 1 and 22.5% in group 2. We recorded symptomatic lymphocele requiring treatment with a drain or reoperation in 8 patients (10%) in group 2 and 0% in group 1 (P <0.001) of all the patients who underwent lymphadenectomy. The rate of positive surgical margins was 25% for group 1 and 21.25% for group 2 (P = NS). For those with Stage pT2, the positive margin rate was 7.3% and 10% for groups 1 and 2, respectively. The recovery of continence at 3 months was faster in group 2 (75% of patients versus 50.9% in group 1; P <0.01). The extraperitoneal approach required less operative time and enabled faster recovery of continence and the transperitoneal approach prevented the formation of lymphocele.


Effect of frusemide on lithium clearance and proximal tubular reabsorption in anaesthetized rats.
1. In order to investigate the lithiuretic effect of frusemide, simultaneous measurements of fractional lithium excretion (FELi) and fractional fluid delivery to the end of the proximal convoluted tubules were made in Inactin-anaesthetized rats, first during a control period, then during intravenous infusion of frusemide at either 0.8 or 8.0 mg kg-1 h-1. Fluid balance was maintained by infusion of NaCl-KCl solution adjusted to match urinary excretion rates; measurements were made after urine flow had stabilized. 2. In time-control animals, which did not receive frusemide, no significant changes were observed in either FELi or fractional fluid delivery to the end of the proximal convoluted tubules (determined as the plasma/tubular fluid inulin concentration ratio, P/TFIn). 3. In animals given the high dose of frusemide, FELi increased from 0.22 +/- 0.02 (mean +/- S.E.M.) during the control period to 0.45 +/- 0.03 during frusemide infusion (P less than 0.001); this was accompanied by a modest increase in P/TFIn, from 0.43 +/- 0.02 to 0.51 +/- 0.02 (P less than 0.01). 4. In animals given the lower dose of frusemide, FELi increased from 0.21 +/- 0.01 to 0.37 +/- 0.01 (P less than 0.001). In this group, however, there was no discernible change in P/TFIn (0.43 +/- 0.02 vs. 0.44 +/- 0.01, not significant). 5. These results suggest that under control conditions a significant component of lithium reabsorption may occur beyond the proximal tubule, most likely in the loop of Henle.


Enzyme-Responsive Nanoparticles for Anti-tumor Drug Delivery.
The past few decades have seen great progress in the exploration of nanoparticles (NPs) as novel tools for cancer treatments and diagnosis. Practical and reliable application of nanoparticle-based technology in clinical transformation remains nevertheless an ongoing challenge. The design, preparation, and evaluation of various smart NPs with specific physicochemical responses in tumor-related physiological conditions have been of great interests in both academic and clinical research. Of particular, smart enzyme-responsive nanoparticles can predictively and selectively react with specific enzymes expressed in tumor tissues, leading to targeted delivery of anti-tumor drugs, reduced systemic toxicity, and improved therapeutic effect. In addition, NPs interact with internal enzymes usually under mild conditions (low temperature, aqueous media, neutral or close to neutral pH) with high efficiency. In this review, recent advances in the past 5 years in enzyme-responsive nanoparticles for anti-tumor drug delivery are summarized and discussed. The following contents are divided based on the different action sites of enzymes toward NPs, notably hydrophobic core, cleavable/uncleavable linker, hydrophilic crown, and targeting ligand. Enzyme-engaged destruction of any component of these delicate nanoparticle structures could result in either targeting drug delivery or controlled drug release.


Fluoroscopically-guided injections to treat "kissing spine" disease.
Any spine structure that is innervated by afferent nociceptive nerve fibers is a potential pain generator. In the lumbar spine, the most studied pain generators include: sacroiliac joints, the zygapophysial joints, the intervertebral discs, myofascial structures. Anomalous lumbosacral articulations, the spinous processes, and lumbar spine osteophytes are less commonly reported. To describe the diagnostic and therapeutic features of "kissing spine" disease or Baastrup's Sign with particular attention to MRI findings and fluoroscopically-guided injection therapy. A series of 3 patients with axial low back pain presented with exam findings and MRI changes suggestive of pain emanating from adjacent spinous processes that appeared to be in direct contact or very closely opposed. This has been described in the literature as "kissing spine" disease or Baastrup's sign. Fluoroscopically-guided injections were performed and the responses were studied. The 3 patients had MRI findings consisting of inflammation and/or edema in the spinous processes and surrounding soft tissues. Fluoroscopically-guided injections provided pain relief in all 3 patients. One patient with recurrent pain eventually underwent successful surgical resection of the involved spinous processes. Painful adjacent and closely opposed spinous processes can be a source of axial low back pain. We have described MRI features and the responses to fluoroscopically-guided injections in 3 patients with this condition.


Minimization and optimization of designed beta-hairpin folds.
Minimized beta hairpins have provided additional data on the geometric preferences of Trp interactions in TW-loop-WT motifs. This motif imparts significant fold stability to peptides as short as 8 residues. High-resolution NMR structures of a 16- (KKWTWNPATGKWTWQE, DeltaG(U)(298) >or= +7 kJ/mol) and 12-residue (KTWNPATGKWTE, DeltaG(U)(298) = +5.05 kJ/mol) hairpin reveal a common turn geometry and edge-to-face (EtF) packing motif and a cation-pi interaction between Lys(1) and the Trp residue nearest the C-terminus. The magnitude of a CD exciton couplet (due to the two Trp residues) and the chemical shifts of a Trp Hepsilon3 site (shifted upfield by 2.4 ppm due to the EtF stacking geometry) provided near-identical measures of folding. CD melts of representative peptides with the -TW-loop-WT- motif provided the thermodynamic parameters for folding, which reflect enthalpically driven folding at laboratory temperatures with a small DeltaC(p) for unfolding (+420 J K(-)(1)/mol). In the case of Asx-Pro-Xaa-Thr-Gly-Xaa loops, mutations established that the two most important residues in this class of direction-reversing loops are Asx and Gly: mutation to alanine is destabilizing by about 6 and 2 kJ/mol, respectively. All indicators of structuring are retained in a minimized 8-residue construct (Ac-WNPATGKW-NH(2)) with the fold stability reduced to DeltaG(U)(278) = -0.7 kJ/mol. NMR and CD comparisons indicate that -TWXNGKWT- (X = S, I) sequences also form the same hairpin-stabilizing W/W interaction.


Indoleacetic Acid oxidase: a dual catalytic enzyme?
The isolation of a unique enzyme capable of oxidizing indoleacetic acid, but devoid of peroxidase activity, has been reported for preparations from tobacco roots and commercial horseradish peroxidase. Experiments were made to verify these results using enzyme obtained from Betula leaves and commercial horseradish peroxidase. Both indoleacetic acid oxidase and guaiacol peroxidase activity appeared at 2.5 elution volumes from sulfoethyl-Sephadex. These results were obtained with both sources of enzyme. In no case was a separate peak of indoleacetic acid oxidase activity obtained at 5.4 elution volumes as reported for the tobacco enzyme using the same chromatographic system. Both types of activity, from both sources of enzyme, also eluted together during gel filtration. Successful column chromatography of Betula enzyme was dependent upon previous purification by membrane ultrafiltration. These results indicate indoleacetic acid oxidase activity and guaiacol peroxidase activity are dual catalytic functions of a single enzyme.


Burst firing synchronizes prefrontal and anterior cingulate cortex during attentional control.
It is widely held that single cells in anterior cingulate and lateral prefrontal cortex (ACC/PFC) coordinate their activity during attentional processes, although cellular activity that may underlie such coordination across ACC/PFC has not been identified. We thus recorded cells in five ACC/PFC subfields of macaques engaged in a selective attention task, characterized those spiking events that indexed attention, and identified how spiking of distinct cell populations synchronized between brain areas. We found that cells in ACC/PFC increased the firing of brief 200 Hz spike bursts when subjects shifted attention and engaged in selective visual processing. In contrast to nonburst spikes, burst spikes synchronized over large distances to local field potentials at narrow beta (12-20 Hz) and at gamma (50-75 Hz) frequencies. Long-range burst synchronization was anatomically specific, functionally connecting those subfields in area 24 (ACC) and area 46 (PFC) that are key players of attentional control. By splitting cells into putative excitatory (pE) and inhibitory (pI) cells by their broad and narrow spikes, we identified that bursts of pI cells preceded and that bursts of pE cells followed in time periods of maximal beta coherent network activity. In contrast, gamma bursts were transient impulses with equal timing across cell classes. These findings suggest that processes underlying burst firing and burst synchronization are candidate mechanisms to coordinate attention information across brain areas. We speculate that distinct burst-firing motifs realize beta and gamma synchrony to trigger versus maintain functional network states during goal-directed behavior.


Endothelin-1 gene and endothelin receptor A gene polymorphisms in severe pulmonary hypertension associated with rheumatic mitral valve disease.
Endothelin-1 (ET-1) gene polymorphisms are implicated in pathogenesis of idiopathic pulmonary arterial hypertension. We studied ET-1 (Lys198Asn and 3A/4A) and endothelin receptor A (ETA) gene (His323His) polymorphisms in 123 subjects with pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD) and 123 healthy controls. The mutant homozygous Asn/Asn genotype in Lys198Asn and T/T genotype in His323His polymorphism was more prevalent in the PH-MVD group. Presence of Asn/Asn genotype was significantly associated with an increased risk (odds ratio 3.9). ET-1 and ETA gene polymorphisms are prevalent in the PH-MVD group suggesting that they may predispose to the development of PH.


Pancreatic and intestinal endocrine cells in zebrafish share common transcriptomic signatures and regulatory programmes.
Endocrine cells of the zebrafish digestive system play an important role in regulating metabolism and include pancreatic endocrine cells (PECs) clustered in the islets of Langerhans and the enteroendocrine cells (EECs) scattered in the intestinal epithelium. Despite EECs and PECs are being located in distinct organs, their differentiation involves shared molecular mechanisms and transcription factors. However, their degree of relatedness remains unexplored. In this study, we investigated comprehensively the similarity of EECs and PECs by defining their transcriptomic landscape and comparing the regulatory programmes controlled by Pax6b, a key player in both EEC and PEC differentiations. RNA sequencing was performed on EECs and PECs isolated from wild-type and pax6b mutant zebrafish. Data mining of wild-type zebrafish EEC data confirmed the expression of orthologues for most known mammalian EEC hormones, but also revealed the expression of three additional neuropeptide hormones (Proenkephalin-a, Calcitonin-a and Adcyap1a) not previously reported to be expressed by EECs in any species. Comparison of transcriptomes from EECs, PECs and other zebrafish tissues highlights a very close similarity between EECs and PECs, with more than 70% of genes being expressed in both endocrine cell types. Comparison of Pax6b-regulated genes in EECs and PECs revealed a significant overlap. pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. Finally, we show that the homeodomain of Pax6b is dispensable for its action in both EECs and PECs. We have analysed the transcriptomic landscape of wild-type and pax6b mutant zebrafish EECs and PECs. Our study highlights the close relatedness of EECs and PECs at the transcriptomic and regulatory levels, supporting the hypothesis of a common phylogenetic origin and underscoring the potential implication of EECs in metabolic diseases such as type 2 diabetes.


FGF-23 Levels before and after Renal Transplantation.
Phosphatonin fibroblast growth factor-23 (FGF-23) is involved in phosphate (P) excretion and vitamin D metabolism. Recently, FGF-23 has been suggested to be responsible for the hypophosphatemia and inappropriately low calcitriol levels observed after renal transplantation. We performed a prospective study to investigate FGF-23 levels in patients with end-stage renal disease before and after renal transplantation and their probable association with markers of bone and mineral metabolism. Intact FGF-23 levels were determined before and at 3, 6, and 12 months posttransplantation in 18 renal transplant recipients. Intact parathyroid hormone (iPTH), calcium (Ca), P, 25(OH)VitD, and 1,25(OH)(2)VitD levels were measured at the same time periods. Renal threshold phosphate concentration (TmPO(4)/GFR) was also calculated at 3, 6, and 12 months posttransplantation. The results showed that FGF-23 levels decreased by 89% 3 months posttransplantation (346 +/- 146 versus 37 +/- 9 pg/mL, P < .01) and remained stable throughout the study period. iPTH and P levels also decreased significantly after renal transplantation, while Ca and 1,25(OH)(2)VitD increased. Pretransplantation FGF-23 was significantly correlated with P levels at 3 months posttransplantation (P < .005). In conclusion, FGF-23 levels decrease dramatically after successful renal transplantation. Pre-transplantation FGF-23 correlate with P levels 3 months posttransplantation.


Golf--recognising the risk of severe eye injury.
Golf related ocular injuries are uncommon but frequently result in severe injury necessitating removal of the eye. As golf increases in popularity, it is vital that awareness is raised among both players and spectators regarding the potential hazards. We determined the nature and frequency of golf related eye injury at our unit from 1990 to 2007. Patient age, nature of injury, management and visual outcome were documented. 10 patients (7 adults, 3 children) sustained golf related eye trauma over this time. 7 cases involved injury inflicted by a golf ball and 3 by a golf club. 7 eyes required enucleation or evisceration. Visual acuity in the remaining 3 eyes ranged from 6/6 to less than 6/60. Golf related ocular injuries while uncommon, frequently have devastating consequences. Public awareness must be raised in order to promote greater safety on the golf course.


Female CEOs and the compensation of other top managers.
We study the implications of having a female chief executive officer (CEO) for the compensation levels of other top managers of a firm. Extant theoretical perspectives, such as social identity theory, gendered notions of firm status, and loss of diversity benefits, among others, make competing predictions about the effect of having a female, as opposed to a male, CEO: (a) that only female top managers may earn more, (b) that both female and male top managers may earn less, and (c) that only female top managers may earn less. Using over 20 years of data on the top management teams (TMTs) of the largest 1,500 U.S. firms, we find that women (but not men) in top management earn significantly less with a female CEO than what they would have earned with a male CEO in a given year within a particular firm. We theorize that these results are consistent with the argument that a female top manager confers diversity benefits on her firm, which become redundant when there is a female CEO. Thus, the focal female top manager is paid less with a female CEO than what she would have earned with a male CEO. Our post-hoc test related to the effect of the percentage of female members on the TMT provides further empirical evidence for the diversity benefits perspective. This study contributes to research on TMTs, gender, and compensation and should inspire further work investigating the psychological mechanisms through which CEO gender influences TMT compensation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Comparison of the cleaning efficacy of XP-endo shaper and Mtwo rotary files in oval-shaped canals.
Cleaning and shaping of root canals are essential steps for the success of endodontic therapy. This study compared two types of rotary files in oval-shaped root canals: XP-endo shaper (FKG, La Chaux-de- Fonds, Switzerland) and Mtwo (VDW, Germany, Munich) with regard to cleaning ability and canal preparation. Mtwo is a system of nickel-titanium files with S-shaped cross-sectional design and XP-endo shaper can change its shape according to the temperature. This in vitro study was performed on 16 pairs of freshly extracted contralateral mandibular premolars with a single oval-shaped canal that were selected and divided into two groups according to the root canal instrumentation technique: XP-endo shaper and Mtwo. Then, each root cut into three coronal, middle and apical sections and processed for histologic evaluation of canal wall planning and the presence of debris. Sections were evaluated by using AutoCAD 2017 software. Statistical analysis was used to compare between both the groups using repeated measures multivariate analysis of variance with Bonferroni correction for post hoc comparison and independent sample t-tests. The level of statistical significance was set at P < 0.05. With a statistically significant difference in the middle third, untouched area and area with debris in XP-endo shaper group were smaller (respectively P = 0.013 and P = 0.011). Despite the percentage difference between groups, there was not a statistically significant difference in other sections. Statistically in the middle section of the oval-shaped canals, the XP-endo shaper performs better than the Mtwo rotary files.


Testicular plasmacytoma. A case report with immunohistochemical studies and literature review.
Plasmacytomas of the testes are extremely rare tumors, especially when occurring in the absence of a previous or concurrent diagnosis of multiple myeloma. We present a case of solitary testicular plasmacytoma in a 71-year-old man who had no clinical evidence of myeloma. Immunohistochemical stains showed monoclonal cytoplasmic production of IgA-kappa within tumor cells. A summary of the other reported cases of testicular plasmacytoma is presented. Plasmacytoma of the testes, while occasionally manifesting as a solitary, primary lesion, most likely is a precocious, highly unusual manifestation of systemic multiple myeloma.


[Absence of litholytic effects of zinc sulfate and copper sulfate in experimental lithiasis in rats].
Seventy two male Wistar-strain rats were fed lithogenic diet with ethylene-glycol within three weeks. At the end of this treatment, six rats were killed in order to determine the oxalate and calcium concentrations in renal tissue. Remained rats was randomly divided in four series, each series consisting of three groups. In first series (T), the animals were treated with distilled water; in the second (D1Zn), the animals were treated intramuscularly with the zinc at the rate of 24 micrograms per 100 grams of body weight and per day; in the third (D2Zn), 240 micrograms of zinc were administrated to animals and in the last series (D2Cu), the animals were treated at the same dose as the previous series, but with the copper. The groups which making up each series were killed successively at the 5th, 10th and 15th day after ending treatment with ethyleneglycol in order to determine urinary pH, percentage of water in renal tissue, uremia and concentrations of oxalate and calcium in renal tissue. Then, the comparisons of means were carried out, at each time, between different treated groups and reference group which was treated with distilled water. Litholytic effect was found in all series, including that which had been treated with distilled water. However, compared to reference animals, no acceleration of litholytic process was induced by zinc or copper. The high doses used in these experimentations proved therefore that calcium oxalate calculi were insoluble by zinc and copper.


Membrane-specific antibodies induced by liposomes can simultaneously bind to HIV-1 protein, peptide, and membrane lipid epitopes.
Liposomes containing lipid A as an adjuvant and also containing either both (a) cholesterol and gp140 HIV envelope protein or (b) galactosylceramide and a 48 amino acid peptide from the membrane proximal external region of gp41 from HIV, as liposomal antigens were used for immunizing mice. Monoclonal antibodies from each type of immunization were obtained, which recognized either the lipid antigen or the protein (or peptide) antigen separately, or that simultaneously bound to both the lipid and protein (or peptide) antigens, by ELISA. After immunizing with liposomes containing both phosphatidylinositol 4-phosphate (PIP) and peptide antigen, a unique monoclonal antibody was also obtained, which did not bind separately either to the lipid or peptide antigen, or to the liposomes alone, but did bind to the original liposomal antigen containing the peptide but lacking PIP. Our data suggest that immunization with liposomes containing lipid A and also containing both a lipid and protein (or peptide) antigen induces antibodies that recognize broad topographical antigenic liposomal membrane surface patterns. These membrane-specific antibodies have unique binding characteristics.


Reliability of mandibular canines as indicators for sexual dichotomy.
Amongst the various calcified structures in the human body, teeth have gained lot of popularity in estimating the sex of an individual as they are highly resistant to destruction and decomposition. Using permanent mandibular canines many researchers have predicted a high level of accuracy in identifying the sex correctly. The purpose of our study was to gauge the effectiveness of mandibular canines in discerning sex. Fifty dental casts each of males and females were utilized for the study. Mesio-distal dimension and inter-canine distance of mandibular right and left canine was recorded using digital vernier caliper and mandibular canine index was calculated. The mean value of mesio-distal dimensions of right and left mandibular canine was slightly greater in males compared to females. The mandibular canine index was equal in both sexes. Inter-canine distance was marginally higher in males compared to females. Despite of higher values in males none of the parameters were statistically significant. The results herein bolster contemporary studies that mesio-distal dimensions of mandibular canines and mandibular canine index do not reflect sexual dimorphism and that its application should be discontinued in sex prediction among Indian populations. How to cite this article: Hosmani J V, Nayak R S, Kotrashetti V S, Pradeep S, Babji D. Reliability of Mandibular Canines as Indicators for Sexual Dichotomy. J Int Oral Health 2013; 5(1):1-7.


Stem Cells and the Differentiation Hierarchy in Mammary Gland Development.
The mammary gland is a highly dynamic organ that undergoes profound changes within its epithelium during puberty and the reproductive cycle. These changes are fueled by dedicated stem and progenitor cells. Both short- and long-lived lineage-restricted progenitors have been identified in adult tissue as well as a small pool of multipotent mammary stem cells (MaSCs), reflecting intrinsic complexity within the epithelial hierarchy. While unipotent progenitor cells predominantly execute day-to-day homeostasis and postnatal morphogenesis during puberty and pregnancy, multipotent MaSCs have been implicated in coordinating alveologenesis and long-term ductal maintenance. Nonetheless, the multipotency of stem cells in the adult remains controversial. The advent of large-scale single-cell molecular profiling has revealed striking changes in the gene expression landscape through ontogeny and the presence of transient intermediate populations. An increasing number of lineage cell-fate determination factors and potential niche regulators have now been mapped along the hierarchy, with many implicated in breast carcinogenesis. The emerging diversity among stem and progenitor populations of the mammary epithelium is likely to underpin the heterogeneity that characterizes breast cancer.


Physician-based transactions: the sale of medical practices, ambulatory surgery centers, and dialysis facilities.
This article provides an overview of the critical business and legal issues encountered in sales of practices, ambulatory surgery centers, and dialysis facilities. Specifically, it discusses prototypical valuations, transaction structures, and the principal legal issues that must be addressed.


In vitro activity of fosfomycin combined with rifampin, pefloxacin and imipenem against staphylococci: a study by the time-kill curve method.
The in vitro activity of fosfomycin alone and in combination with rifampin, pefloxacin and imipenem was studied by the time-kill method against staphylococci. Fosfomycin, pefloxacin and imipenem used at concentrations within the therapeutic range, exerted a bactericidal effect, whereas rifampin acted as a bacteriostatic drug. The combination of fosfomycin and rifampin was found to be antagonistic against rifampin-susceptible strains and indifferent for rifampin-resistant isolates. Fosfomycin combined with pefloxacin usually produced an indifferent effect. The interaction between fosfomycin and imipenem was mainly indifferent but synergism occurred with methicillin-resistant strains and antagonism was observed for one methicillin-susceptible isolate of Staphylococcus aureus.


Current concepts in the management of Parkinson disease.
Parkinson disease (PD) is a multisystem neurodegenerative disorder that affects about 1% of the population over the age of 55 years and has mean age of onset of about 60 years. The Braak hypothesis proposes that the earliest pathological evidence of PD is found in the enteric nervous system, medulla and olfactory bulb, and only subsequently progresses (over years) to the substantia nigra and cortex. Non-motor symptoms, such as constipation, hyposmia and sleep disorders, may precede typical motor features of PD by several years. No treatment has been convincingly shown to slow PD progression (ie, a neuroprotective drug remains elusive). Symptomatic benefit from dopaminergic therapy is usually maintained throughout the course of the disease. The decision as to whether to commence treatment with either levodopa or a dopamine agonist needs to be individually tailored, but long-term outcomes appear to be equivalent. Advanced PD is complicated by the loss of non-dopaminergic neurones, resulting in symptoms that are largely unresponsive to dopaminergic therapy. Treatment with apomorphine, Duodopa or deep-brain stimulation surgery may be beneficial for selected patients with advanced PD. Non-motor symptoms, such as mood disorders, cognitive impairment, autonomic dysfunction and sleep disorders, are responsible for significant morbidity. Management often requires a multidisciplinary approach.


Involvement of Rho GAP GRAF1 in maintenance of epithelial phenotype.
Adhesion of epithelial cell to each other and to extracellular matrix, as well as cell migration ability and cytoskeleton organization undergo significant alterations in the course of neoplastic transformation, but regulatory mechanisms involved in these processes are not fully understood. Here, we studied the role of a Rho GAP protein GRAF1 (GTPase Regulator Associated with Focal adhesion kinase-1) in the regulation of the epithelial phenotype in cells of breast derived, non-malignant, MCF10A cell line. GRAF1 was shown to be localized to cell-cell junctions, and its depletion resulted in accelerated cell migration velocity, elongation of the cells and cell colonies, impaired monolayer integrity and significant disruption of desmosomes with a loss of associated keratin filaments. These processes were accompanied by formation of larger focal adhesions, an increased number of contractile actin stress fibers, reduction in epithelial markers and increase in mesenchymal markers such as epithelial-mesenchymal transition (EMT)-specific transcription factors Snail-1 and Snail-2, as well as N-cadherin, and vimentin. Moreover, unlike control cells, GRAF1 knocked-down cells demonstrated anchorage-independent growth in soft agar. GRAF1 expression in several highly invasive breast cancer cell lines was low, as compared to the non-malignant MCF10A cells, while overexpressing of GRAF1 in the malignant BT-549 cell line led to a decrease of mesenchymal markers, especially the Snail-1 and 2. Altogether, our analysis suggests that GRAF1 plays a role in the maintenance of normal epithelial phenotype and its depletion leads to an EMT-like process that might be involved in neoplastic transformation.


Circulating Cytokines and Cytokine Receptors in Infliximab Treatment Failure Due to TNF-α Independent Crohn Disease.
The inflammatory response at infliximab (IFX) treatment failure due to tumor necrosis factor (TNF)-α-independent Crohn disease activity is unknown. This is an exploratory, hypothesis-generating study based on samples collected in a clinical trial among patients failing conventional IFX dosages and treated with an intensified IFX regimen for 12 weeks. Patients with clinical response at week 12, as defined by a reduction of Crohn disease activity index by ≥70, were considered to suffer from nonimmune pharmacokinetic (PK) treatment failure (n = 18), and nonresponders had a presumed pharmacodynamic (PD) failure due to non-TNF-driven disease (n = 8). Patients failing IFX due to functional anti-IFX antibodies (n = 2) were excluded. The study population also comprised a group of 12 patients in long-term remission on IFX. A functional cell-based reporter gene assay was applied to measure IFX and anti-IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic protein 1. The IFX levels were similar between patients with IFX failure caused by nonimmune PK or PD at treatment failure (median 1.4 vs 2.4 μg/mL; P = 0.52), during treatment intensification (8.1 vs 5.6; P = 0.85), and after 12 weeks (8.8 vs 7.7; P = 0.93), congruent with nonresponders failing IFX due to predominantly TNF-α-independent signaling pathways in their disease. Cytokine and cytokine receptor levels were comparable between patients with nonimmune PK failure and PD failure at time of manifestation of IFX failure, but with higher IL-6 and sTNF-R2 levels among IFX treatment failures as compared with patients in remission (IL-6 median 3.6 vs <3.1 pg/mL; P = 0.03; sTNF-R2 3207 vs 2547 pg/mL; P = 0.01). IL-6 and sTNF-R2 were lower after 12 weeks in nonimmune PK failures than in PD failures (<3.1 vs 4.0; P = 0.02; 3209 vs 4740; P = 0.04, respectively), and were measured at levels comparable with patients in remission. Further, trends of decreased IL-6 and sTNF-R2 levels among nonimmune PK failures during IFX intensification (P < 0.05 and P = 0.12) were observed. These observations indicate that IL-6 and sTNF-R2 are of potential relevance in driving the inflammatory response in IFX refractory Crohn disease caused by TNF-α-independent disease activity.


'Finishing the race' - a cohort study of weight and blood glucose change among the first 36,000 patients in a large-scale diabetes prevention programme.
The NHS Diabetes Prevention Programme for England, "Healthier You", encourages behaviour change regarding healthy eating and physical exercise among people identified to be at high risk of developing type 2 diabetes. The aim of this research was to examine change, and factors associated with change, in measures of HbA1c and weight in participants and completers of the programme between 2016 and 2019. Participant-level data collected by programme service providers on referrals prior to March 2018 was analysed. Changes from baseline to both 6 months and completion in HbA1c and weight were examined using mixed effects linear regression, adjusting for patient characteristics, service provider and site. Completers had average improvements in HbA1c of 2.1 mmol/mol [95% CI: - 2.2, - 2.0] (0.19% [95% CI: - 0.20, - 0.18]) and reductions of 3.6 kg [95% CI: - 3.6, - 3.5] in weight, in absolute terms. Variation across the four providers was observed at both time points: two providers had significantly smaller average reductions in HbA1c and one provider had a significantly smaller average reduction in weight compared to the other providers. At both time points, ex- or current smokers had smaller reductions in HbA1c than non-smokers and those from minority ethnic groups lost less weight than White participants. For both outcomes, associations with other factors were small or null and variation across sites remained after adjustment for provider and case mix. Participants who completed the programme, on average, experienced improvements in weight and HbA1c. There was substantial variation in HbA1c change and smaller variation in weight loss between providers and across different sites. Aside from an association between HbA1c change and smoking, and between weight loss and ethnicity, results were broadly similar regardless of patient characteristics.


Redox control of endoplasmic reticulum function.
The lumen of the endoplasmic reticulum constitutes a separate intracellular compartment with a special proteome and metabolome. The redox conditions of the organelle are also characteristically different from those of the other subcellular compartments. The luminal environment has been considered more oxidizing than the cytosol due to the presence of oxidative protein folding. However, recent observations suggest that redox systems in reduced and oxidized states are present simultaneously. The concerted action of membrane transporters and oxidoreductase enzymes maintains the oxidized state of the thiol-disulfide and the reduced state of the pyridine nucleotide redox systems, which are prerequisites for the normal redox reactions localized in the organelle. The powerful thiol-oxidizing machinery of oxidative protein folding continuously challenges the local antioxidant defense. Alterations of the luminal redox conditions, either in oxidizing or reducing direction, affect protein processing, are sensed by the accumulation of misfolded/unfolded proteins, and may induce endoplasmic reticulum stress and unfolded protein response. The activated signaling pathways attempt to restore the balance between protein loading and processing and induce programmed cell death if these attempts fail. Recent findings strongly support the involvement of redox-based endoplasmic reticulum stress in a plethora of human diseases, either as causative agents or as complications.


Lumbosacral chordoma resection: image integration and surgical planning.
Clinical, radiographic, and functional outcome parameters were analyzed before and after treatment of eight individuals with lumbosacral chordomas studied over a 3-year period. Emphasis was placed upon correlation of multiplane images and the pathoanatomy of the gross specimen. Surgical resections achieving wide margins can be curative. Magnetic resonance imaging of lumbosacral chordomas has revolutionized the preoperative anatomic localization of these tumors. Therefore, it is critical that the operating surgeon scrutinize the three-dimensional location of the tumor and its spatial relationship to surrounding structures prior to surgical eradication. A systematic approach for the radiographic analysis of tumor extent in lumbosacral chordomas is presented. Four strategic areas of preoperative analysis are identified for sacral chordomas and two for lumbar neoplasms. Functional outcome after resection is predicted by Stener's work. Contamination-free surgery is facilitated by accurate preoperative radiographic interpretation of the pathoanatomy by the surgeon.


Pulmonary embolectomy by catheter device in massive pulmonary embolism.
From 1982 to 1989, ECD was performed on 18 patients suffering from poorly-tolerated massive pulmonary embolism, for whom classic treatments (fibrinolytics and surgery) were impossible. Eleven of these 18 patients immediately improved (S group). This procedure was unsuccessful in other seven patients (F group). Thirteen patients survived (72 percent). The time lag between the first episode of pulmonary embolism and ECD was significantly shorter in the S group than in the F group (4.7 +/- 5.4 days vs 18.3 +/- 6.9 days, p = 0.0004). So was the elapsed time between the onset of hemodynamic impairment and ECD (13 +/- 12 hours vs 59 +/- 38 hours, p = 0.003). We conclude that ECD should be considered when other treatments are impossible especially when the first symptoms date back less than 15 days and the hemodynamic impairment less than 48 h.


Two independent, light-sensing two-component systems in a filamentous cyanobacterium.
Two ORFs, cphA and cphB, encoding proteins CphA and CphB with strong similarities to plant phytochromes and to the cyanobacterial phytochrome Cph1 of Synechocystis sp. PCC 6803 have been identified in the filamentous cyanobacterium Calothrix sp. PCC7601. While CphA carries a cysteine within a highly conserved amino-acid sequence motif, to which the chromophore phytochromobilin is covalently bound in plant phytochromes, in CphB this position is changed into a leucine. Both ORFs are followed by rcpA and rcpB genes encoding response regulator proteins similar to those known from the bacterial two-component signal transduction. In Calothrix, all four genes are expressed under white light irradiation conditions, albeit in low amounts. For heterologous expression and convenient purification, the cloned genes were furnished with His-tag encoding sequences at their 3' end and expressed in Escherichia coli. The two recombinant apoproteins CphA and CphB bound the chromophore phycocyanobilin (PCB) in a covalent and a noncovalent manner, respectively, and underwent photochromic absorption changes reminiscent of the P(r) and P(fr) forms (red and far-red absorbing forms, respectively) of the plant phytochromes and Cph1. A red shift in the absorption maxima of the CphB/PCB complex (lambda(max) = 685 and 735 nm for P(r) and P(fr), respectively) is indicative for a noncovalent incorporation of the chromophore (lambda(max) of P(r), P(fr) of CphA: 663, 700 nm). A CphB mutant generated at the chromophore-binding position (Leu246-->Cys) bound the chromophore covalently and showed absorption spectra very similar to its paralog CphA, indicating the noncovalent binding to be the only cause for the unexpected absorption properties of CphB. The kinetics of the light-induced P(fr) formation of the CphA-PCB chromoprotein, though similar to that of its ortholog from Synechocystis, showed differences in the kinetics of the P(fr) formation. The kinetics were not influenced by ATP (probing for autophosphorylation) or by the response regulator. In contrast, the light-induced kinetics of the CphB-PCB complex was markedly different, clearly due to the noncovalently bound chromophore.


Unusual coelom formation in the direct-type developing sand dollar Peronella japonica.
Peronella japonica is a sand dollar with a zygote that develops into an abbreviated pluteus but then metamorphoses on day three. The adult rudiment formation is unique; it uses a median position of the hydrocoel and a stomodeum-like invagination of vestibule that covers the dorsal side of the hydrocoel. However, the developmental processes underlying coelom formation remain unclear. In this study, we examined this process by reconstructing three-dimensional images from serial sections of larvae. We show that the left coelom developed by both schizocoely and enterocoely from the archenteron tip, whereas the hydrocoel and right coelom formed by enterocoely from the archenteron. This coelom formation arranged the coelomic compartments directly along the adult oral-aboral axis by skipping the initial bilateral phases. Furthermore, our data indicate P. japonica retains ancestral asymmetry along the left-right axis in the location of the adult rudiment.


Meaning-in-life in nursing-home patients: a valuable approach for enhancing psychological and physical well-being?
To investigate the associations between meaning-in-life and physical, emotional, functional and social well-being in a cognitively intact nursing-home population. Meaning-in-life is understood as an influential psychological variable that promotes health and well-being; meaning-in-life has been found to be a mediating variable in both psychological and physical health. The study employed a cross-sectional design. Data were collected in 2008 and 2009 using the purpose-in-life test and the FACT-G quality-of-life questionnaire. A total of 250 cognitively intact nursing-home patients who met the inclusion criteria were approached and 202 attended. The hypothesised relationships between meaning and multidimensional well-being were tested by means of structural equation modelling. The structural equation modelling model fit well with the present data, showing significant direct relationships between meaning-in-life and emotional and functional well-being, and a significant mediated influence of meaning on social and physical well-being. Meaning-in-life is associated with all dimensions of well-being and likely plays an important role in both emotional and physical well-being. Facilitating patients' perceived meaning-in-life might help ease emotional distress and physical symptoms, thus fostering well-being in cognitively intact nursing-home patients. Therefore, advancing staff nurses' competence in facilitating meaningful involvement, connectedness, nurse-patient interaction and symptom management is important for care quality and global well-being in nursing homes.


Bronchospasm: prevention and treatment.
We compared the results obtained in the treatment of bronchospastic conditions in two groups of 20 patients, one treated with an extempore combination of salbutamol (2 mg tablets) and oxatomide (30 mg tablets) and the other with salbutamol (2 mg tablets) alone. Positive results were obtained with the combination in 95% of cases, as against 55% in those treated with salbutamol alone. Generally speaking, treatment with the combination produced resolution of the bronchospasm, prevention of dyspnea attacks and an improvement in the respiratory status of the patients. The combination was well tolerated in all cases with no incidence of side effects, whereas in the patients on treatment with salbutamol alone, 3 cases of mild muscular tremors were observed, accompanied by tachycardia, but did not require discontinuation of the treatment.


Sulphoacetaldehyde acetyltransferase yields acetyl phosphate: purification from Alcaligenes defragrans and gene clusters in taurine degradation.
The facultatively anaerobic bacterium Alcaligenes defragrans NKNTAU was found to oxidize taurine (2-aminoethanesulphonate) with nitrate as the terminal electron acceptor. Taurine was transaminated to 2-sulphoacetaldehyde. This was not converted into sulphite and acetate by a "sulphoacetaldehyde sulpho-lyase" (EC 188.8.131.52), but into sulphite and acetyl phosphate, which was identified by three methods. The enzyme, which required the addition of phosphate, thiamin diphosphate and Mg(2+) ions for activity, was renamed sulphoacetaldehyde acetyltransferase (Xsc; EC 2.3.1.-). Inducible Xsc was expressed at high levels, and a three-step 11-fold purification yielded an essentially homogeneous soluble protein, which was a homotetramer in its native form; the molecular mass of the subunit was found to be between about 63 kDa (SDS/PAGE) and 65.3 kDa (matrix-assisted laser-desorption ionization-time-of-flight MS). The N-terminal and two internal amino acid sequences were determined, and PCR primers were generated. The xsc gene was amplified and sequenced; the derived molecular mass of the processed protein was 65.0 kDa. The downstream gene presumably encoded the inducible phosphate acetyltransferase (Pta) found in crude extracts. The desulphonative enzymes ("EC 126.96.36.199") from Achromobacter xylosoxidans NCIMB 10751 and Desulfonispora thiosulfatigenes GKNTAU were shown to be Xscs. We detected at least three subclasses of xsc in Proteobacteria and in Gram-positive bacteria, and they comprised a distinct group within the acetohydroxyacid synthase supergene family. Genome sequencing data revealed xsc genes in Burkholderia fungorum (80% sequence identity) and Sinorhizobium meliloti (61%) with closely linked pta genes. Different patterns of regulation for the transport and dissimilation of taurine were hypothesized for S. meliloti and B. fungorum.


Mild brain injury: an overview.
This special issue of Applied Neuropsychology focuses on mild brain injury. This article provides an overview of mild brain injury, including its epidemiology, etiology, diagnostic criteria, and clinical symptoms. The contributing authors discuss various issues related to this topic, and divergent views are presented. Specifically, these include causes, symptoms, assessment, and recovery from mild brain injury. In addition, rehabilitation and forensic aspects of mild brain injury are discussed. Collectively, it is anticipated that this special issue will help to clarify the nature of mild brain injury and stimulate additional interest and research into this phenomenon.


Inter-rater reliability of expressed emotion ratings based on the Camberwell Family Interview.
High expressed emotion in relatives has been shown to predict a poorer outcome in a range of disorders and cultures. However, variation in predictive power is considerable, and this could partly be due to low inter-rater reliability. Sixty-nine relatives of 47 acutely admitted schizophrenic patients were interviewed using the Camberwell Family Interview. Audiotapes were assessed by pairs of raters drawn from a group of seven approved raters. Inter-rater reliability was good for criticism, hostility, emotional over-involvement (as a six level scale) and expressed emotion index (EOI cut-off score 2-3); and it was fair, but unsatisfactory, for emotional over-involvement (binary scales), warmth, positive remarks and expressed emotion (EOI cut-off score 3-4). These findings suggest that the warmth scale and the dichotomized versions of the EOI scale should be used with caution. The influence of warmth on the outcome in schizophrenia may have been underestimated because of low reliability.


[Endocrine therapy of stage D2 prostate cancer--comparison of drugs used for total androgen blockade].
Patients with Stage D2 prostate cancer were treated with surgical or medical (LHRH analog) castration combined with either estrogen, chlormadinone acetate or flutamide as initial therapy. The effect of each medication was compared. The overall survival, cause-specific survival and relapse-free survival were not different among the three medications. Patients given each medication were divided into two groups each according to grade, extent of diseases on bone metastases, and levels of tumor marker. Survivals of the corresponding two groups were compared with each other among different medications. No differences were revealed with any medication. There were no serious side effects in whole patients, except that grade 2 liver dysfunction was accompanied in 12% of flutamide-treated group. It is concluded that the three drugs used with castration did not make any difference in the survival of stage D2 patients, and differences between medications were seen in the frequency of side effects.


Hydrodynamic and geometric effects in the sedimentation of model run-and-tumble microswimmers.
The sedimentation process in an active suspension is the result of the competition between gravity and the autonomous motion of particles. We carry out simulations of run-and-tumble squirmers that move in a fluid medium, focusing on the dependence of the non-equilibrium steady state on the swimming properties. We find that for large enough activity, the density profiles are no longer simple exponentials; we recover the numerical results through the introduction of a local effective temperature, suggesting that the breakdown of the Perrin-like exponential form is a collective effect due to fluid-mediated dynamic correlations among particles. We show that analogous concepts can also fit the case of active non-motile particles, for which we report the first study of this kind. Moreover, we provide evidence of scenarios where the solvent hydrodynamics induces non-local effects which require the full three-dimensional dynamics to be taken into account in order to understand sedimentation in active suspensions. Finally, analyzing the statistics of the orientations of microswimmers, the emergence of a height-dependent polar order in the system is discussed.


Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells.
The aim of this study was to observe the effect of Rehmannia glutinosa oligosaccharide (RGO) on differentiation of bone marrow mesenchymal stem cells (MSCs) into cardiomyocyte-like cells . Rat MSCs were isolated, treated, and grouped as follows: RGO treatment group, 5-azacytidine (5-aza) treatment group, RGO + 5-aza treatment group, and control group. Following a four-week induction period, cardiac troponin I (cTnI) levels in MSCs were quantified by chemiluminescence, and the levels of myocardial enzymes creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB) were measured using a dry chemistry analyzer. The cTnI- and connexin 43 (Cx43)-positive MSC population was identified by immunofluorescence, and expression levels of cTnI and Cx43 were analyzed by western blots. Following induction, cTnI, CK, and CK-MB levels were significantly higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups (P < 0.05). In addition, fluorescence intensity of cTnI and Cx43 was higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups. No cTnI- or Cx43-positive cells were detected in the control group. Western blot analysis further confirmed that cTnI and Cx43 were not expressed in the control group, while cTnI and Cx43 was higher in the RGO + 5-aza group than in the RGO and 5-aza groups. These results suggest that MSCs can be induced by RGO to differentiate into cardiomyocyte-like cells in vitro, and that RGO in combination with 5-aza enhance differentiation of MSCs.


Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT.
Striatal dopamine transporter (DAT) function was evaluated in rats by in vivo SPECT-MRI coregistration using the radioligand 2-beta-carbomethoxy-3-beta-(4-[123I]iodophenyl)tropane (beta-[123I]CIT). The reconstructed transaxial resolution of 3.5 mm full width at half-maximum and the system sensitivity of 0.081 c/s/kBq using a 2.0-mm pinhole collimator aperture provided adequate spatial detail and sufficient sensitivity for imaging striatal beta-[123I]CIT uptake. SPECT images, coregistered onto a MRI template, showed high accuracy in the coronal and transverse planes (maximum mismatch of 1.3 mm). Following estimation of the in vivo binding equilibrium of beta-[123I]CIT in the healthy rat striatum, we evaluated the 6-hydroxydopamine-induced loss of striatal DAT function using beta-[123I]CIT SPECT and MRI coregistration and correlated these findings with dopaminergic cell counts in the substantia nigra pars compacta using TH immunohistochemistry. A subtotal unilateral DAT deficit was detected by beta-[123I]CIT SPECT in all animals which correlated significantly with the cell counting of the remaining dopaminergic neurons. beta-[123I]CIT pinhole SPECT provides a powerful and widely available tool for in vivo investigations of rat striatal DAT function. In contrast to classical autoradiography, the present method will be helpful in imaging dynamic changes of neurotransmission in the CNS by virtue of serial study designs. Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique.