Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis.
Plasma endothelin concentrations are elevated in cirrhosis and correlate with disease severity. This study assessed forearm vascular responses to exogenous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET-1 to the maintenance of basal peripheral vascular tone in patients with well-compensated cirrhosis (n = 11) and matched healthy controls (n = 8). Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ET(A) receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ET(B) receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography. Baseline systemic hemodynamics and plasma ET-1 and big ET-1 concentrations were measured using electrical bioimpedance and radioimmunoassay, respectively. Patients and controls had similar baseline FBF, systemic hemodynamics, and plasma ET-1 and big ET-1 concentrations. In both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .001) and BQ-123 caused significant vasodilatation (P < .001). Compared with controls, cirrhotic patients had attenuated ET-1 responses (P < .001), augmented BQ-123 responses (P < .001), and similar BQ-788 responses (P = .62). Despite normal systemic hemodynamics and plasma ET-1 concentrations, forearm vascular responses to exogenous ET-1 are reduced in cirrhotic patients. The augmented vasodilatation to BQ-123 in cirrhotic patients is consistent with a compensated vasodilated state, and a greater contribution of ET-1 to the maintenance of basal vascular tone acting through the ET(A) receptor.


Acquired long QT interval: a case series of multifactorial QT prolongation.
Acquired long QT (LQT) interval is thought to be a consequence of drug therapy and electrolyte disturbances. We characterize the potential effects of polypharmacy in a case series of acquired LQT and torsades de pointes (TdP) in order to determine whether multiple risk factors play a role in the development of LQT. The case series consisted of 11 patients presenting to 4 tertiary care hospitals with LQT and ≥ 2 risk factors for developing LQT. Clinical characteristics, medications, electrolyte disturbances, and course in hospital were analyzed. Mean age was 49.1 ± 5.8 years. Eight patients were female. Four had hypertension, 1 had a history of dilated cardiomyopathy, and 1 patient demonstrated complete atrioventricular block. Average QTc interval at presentation was 633.8 ± 29.2 ms. Nine patients developed TdP. In 3, LQT was not initially detected and amiodarone was administered, followed by development of TdP. Patients were taking an average of 2.8 ± 0.3 QT-prolonging medications-an antidepressant in 6 cases and a diuretic in 8 cases. All patients had an electrolyte abnormality; 8 patients presented with severe hypokalemia (<3.0 mmol/L). Average serum potassium and magnesium were 2.82 ± 0.10 mmol/L and 0.75 ± 0.03 mmol/L, respectively. There were no deaths. This case series highlights the risks of polypharmacy in the development of LQT and TdP. It illustrates the importance of early detection of LQT in patients with multiple risk factors in ensuring appropriate treatment.


Field observations with Salmonella enteritidis bacterins.
A study involving 11 commercial layer flocks was conducted to determine the efficacy of Salmonella enteritidis bacterins (autogenous or federally licensed). The criterion for evaluation of vaccine efficacy was the presence or absence of S. enteritidis in the environment, the organs of the bird (including ovary and oviduct), and eggs. Environmental, rodent, and organ specimens from dead birds as well as eggs were cultured throughout the life of the flock. All layers were obtained from pullet sources that were negative for S. enteritidis, as determined by organ and environmental cultures. Despite the use of S. enteritidis vaccination, 63.6% of the houses had S. enteritidis-positive environmental cultures and 100% of the flocks had S. enteritidis organ-culture-positive birds. The range of positive cultures for S. enteritidis in the environment in vaccinated flocks was between 0 and 45.5%. Birds in vaccinated flocks were organ-culture positive for S. enteritidis between 10% and 40% of the time. The unvaccinated portion of flocks in the same house and the unvaccinated flock in a complex had similar results compared with the vaccinated portion of the flocks.


Root coverage with connective tissue grafts: an evaluation of short- and long-term results.
Subepithelial connective tissue grafts have been shown to be effective in obtaining root coverage. However, little is known about the long-term results. The goal of this study was to evaluate and compare the short-term (13.0 weeks) and long-term (27.5 months) root coverage results obtained with subepithelial connective tissue grafts. One-hundred patients with 146 Miller Class I or Class II recession defects were treated with subepithelial connective tissue grafts to obtain root coverage. The changes in the clinical measurements were compared between the preoperative and short-term results, between preoperative and long-term results, and between short-term and long-term results. The mean root coverage at 13.0 weeks was 97.1% and 98.4% at 27.5 months. This difference was statistically significant. There was a statistically significant decrease in recession and probing depth, reduction in attachment loss, and increase in quantity of keratinized tissue between the preoperative and short-term results and between the preoperative and long-term results. There was a statistically significant decrease in recession, increase in the quantity of keratinized tissue, increase in probing depth, and increase in attachment loss between short-term and long-term results. The results of this study demonstrate that the subepithelial connective tissue graft is an effective method to cover exposed roots. The mean root coverage tended to improve with time.


Rapidly Progressive Nephronophthisis in a 2-Year-Old Boy with a Homozygous SDCCAG8 Mutation.
Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is characterized by primary ciliary dysfunction (ciliopathy) and progresses to end-stage kidney disease (ESKD) during the second decade of life (juvenile and adolescent NPHP) or before the age of 3 years (infantile NPHP). Here we describe the case of an infant with NPHP who carries a homozygous mutation in SDCCAG8 (also called NPHP10 or BBS16) that encodes SDCCAG8 (serologically defined colon cancer antigen 8). SDCCAG8 is localized at the centrioles of both renal epithelial cells and retinal photoreceptor cells. A mutation in SDCCAG8 is also associated with Bardet-Biedl syndrome (BBS), characterized by NPHP, obesity, polydactyly, and rod-cone dystrophy. A 2-year-old boy was referred to our hospital due to kidney dysfunction of unknown etiology; the patient presented with delayed development and opsoclonus but did not exhibit the clinical characteristics of BBS. Histological findings such as dilatation of tubules and irregular thickness of tubular basement membrane confirmed the diagnosis of NPHP. Four months after referral, the patient's renal function was rapidly deteriorated, and emergency peritoneal dialysis was initiated. Next-generation sequencing (NGS) was performed, showing that the patient carries a homozygous four-base-pair deletion in SDCCAG8 (c.849_852delTTTG, p.Cys283Ter). The patient's parents were also found to be heterozygous for this loss-of-function mutation. To the best of our knowledge, the present patient is the first case of biopsy-proven infantile NPHP with a homozygous SDCCAG8 mutation. We conclude that NGS is extremely useful in the identification of SDCCAG8-related NPHP as a cause of sudden-onset ESKD during infancy.


The S15 self-incompatibility haplotype in Brassica oleracea includes three S gene family members expressed in stigmas.
Self-incompatibility in Brassica is controlled by a single, highly polymorphic locus that extends over several hundred kilobases and includes several expressed genes. Two stigma proteins, the S locus receptor kinase (SRK) and the S locus glycoprotein (SLG), are encoded by genes located at the S locus and are thought to be involved in the recognition of self-pollen by the stigma. We report here that two different SLG genes, SLGA and SLGB, are located at the S locus in the class II, pollen-recessive S15 haplotype. Both genes are interrupted by a single intron; however, SLGA encodes both soluble and membrane-anchored forms of SLG, whereas SLGB encodes only soluble SLG proteins. Thus, including SRK, the S locus in the S15 haplotype contains at least three members of the S gene family. The protein products of these three genes have been characterized, and each SLG glycoform was assigned to an SLG gene. Evidence is presented that the S2 and S5 haplotypes carry only one or the other of the SLG genes, indicating either that they are redundant or that they are not required for the self-incompatibility response.


On Old-Fashioned Versus Modern Homonegativity Distinction: Evidence From Poland.
Psychological research on prejudice against homosexuals distinguishes between old-fashioned (traditional) and modern (contemporary) homonegativity, which differ with regard to their content, correlates, and consequences. The current research offers evidence for the validity of old-fashioned versus modern homonegativity distinction in the post-communist, East European context. In Studies 1 and 2 (Ns = 295 and 327, respectively) the Polish adaptations of the non-gendered and gendered Homonegativity Scale (Morrison, Parriag, & Morrison, 1999) and the Modern Homonegativity Scale (Morrison & Morrison, 2003) were developed. Furthermore, divergent (discriminant) validity of traditional and contemporary anti-homosexual prejudice was demonstrated. Old-fashioned and modern homonegativity exhibited differential relationships with social distance and support for same-sex couples' relational rights.


Exopericyclic stereocontrol in Johnson-Claisen rearrangements of allylic sulfides.
A study of the effects of exopericyclic stereocentres on the stereoselectivity of Johnson-Claisen rearrangements of thioether-containing allylic alcohols shows that selectivity is highly dependent upon allylic substitution patterns.


Health: IT leader or laggard? A comparative assessment of IT maturity.
The health industry has acquired a reputation as lagging in the use of IT. This reputation is usually based upon the relatively narrow measure of comparative IT expenditure, often examined as a proportion of total revenue. This study has been undertaken to assess health's use of IT using a broader frame of reference. The health industry was compared to the banking industry, on the basis that the banking industry is widely perceived as a leading IT user. The research confirmed that in these two 'knowledge' industries, health is slower to adopt IT with an apparent lower maturity level. This was the case across a range of best practice management, procedural and cultural topics as well as in the level of resources applied to IT.


Vitronectin or fibronectin is required for corneal fibroblast-seeded collagen gel contraction.
The wound healing process in the corneal stroma involves the activation of corneal keratocytes and the expression of associated phenotypes (fibroblasts and myofibroblasts). One of these phenotypes, the myofibroblasts, synthesizes alpha-smooth muscle actin in order to affect wound closure by contracting the surrounding matrix. Excessive contraction results in the formation of unresolvable scars that are undesirable in the corneal stroma. The authors tested the effect of vitronectin and fibronectin on the contraction process associated with corneal wound healing. Collagen gels were prepared and were exposed to different treatments of fetal calf serum (FCS). The FCS used was either depleted of fibronectin and vitronectin or contained a known concentration of fibronectin, vitronectin, or both at 50 microg/ml. Contraction was measured using image analysis and cross sections of contracted gels were examined for alpha-smooth muscle actin expression using laser confocal microscopy. Fibroblasts seeded in collagen gels paralleled the morphologic characteristics and cell distribution of keratocytes in unwounded cornea. Matrix contraction was dependent on the presence of fibronectin and/or vitronectin where myofibroblasts were present. The cell-mediated contraction process was maximal at 0.5 x 10(5) fibroblasts/ml. These studies showed that vitronectin or fibronectin is required for the myofibroblast-associated contraction to occur in this in vitro model of stromal wound healing. This model system shows a distinct potential for further studies relating to the corneal wound healing process.


Duration of urethral catheterization after urethroplasty: how long is enough?
To report the impact of duration of urethral catheterization (DUC) on the rate of extravasation on voiding cysto-urethrography (VCUG) and the subsequent need of catheter replacement in urethroplasty. Two hundred nineteen consecutive patients undergoing urethroplasty between October 2010 and November 2014 were evaluated for the impact of DUC. Patients were divided into 2 groups, based on the scheduled DUC≤10 days (group 1, N.=86) or >10 days (group 2, N.=133). Fourteen patients (6.4%) had extravasation on VCUG with an additional period of catheter usage. In 10 of the 14 patients (71.4%) clinical signs of impaired wound healing were present. In group 1 (median DUC 8 days) 3 patients (3.5%) needed an additional period of urethral catheterization, compared to 11 patients (8.3%) in group 2 (median DUC 14 days). Strictures in group 2 were longer (4 vs. 2 cm, P<0.001) and more complex. Redo urethroplasty was needed in 9 of the 14 patients with extravasation. In uncomplicated cases of urethroplasty, the urethral catheter can be safely removed after 8 to 10 days postoperatively. Extravasation on VCUG occurs in around 6% of urethroplasties and is a prognostic factor for stricture recurrence and reoperation.


An Update on the Diagnosis of Diabetes.
This update on the diagnosis of carbohydrate metabolism abnormalities focuses on a more rational evaluation of glucose metabolism with a clear line of demarcation between overt diabetes and impaired glucose tolerance levels. This approach has eliminated the confusion over a definition of mild asymptomatic diabetes in contradistinction to overt disease. In addition, there is a limited promise of diagnosis in certain instances by means of hemoglobin 1 AC determinations.


YgfY Contributes to Stress Tolerance in Shewanella oneidensis Neither as an Antitoxin Nor as a Flavinylation Factor of Succinate Dehydrogenase.
YgfY(SdhE/CptB) is highly conserved while has controversial functions in bacteria. It works as an antitoxin and composes a type IV toxin-antitoxin system with YgfX(CptA) typically in Escherichia coli, while functions as an flavinylation factor of succinate dehydrogenase and fumarate reductase typically in Serratia sp. In this study, we report the contribution of YgfY in Shewanella oneidensis MR-1 to tolerance of low temperature and nitrite. YgfY deficiency causes several growth defects of S. oneidensis MR-1 at low temperature, while YgfX do not cause a growth defect or morphological change of S. oneidensis MR1-1 and E. coli. YgfY do not interact with FtsZ and MreB nor with YgfX examined by bacterial two-hybrid assay. YgfY effect on growth under low temperature is not attributed to succinate dehydrogenase (SDH) because a mutant without SDH grows comparably with the wild-type strain in the presence of succinate. The ygfY mutant shows impaired tolerance to nitrite. Transcription of nitrite reductase and most ribosome proteins is significantly decreased in the ygfY mutant, which is consistent with the phenotypes detected above. Effects of YgfY on growth and nitrite tolerance are closely related to the RGXXE motif in YgfY. In summary, this study demonstrates pleiotropic impacts of YgfY in S. oneidensis MR-1, and sheds a light on the physiological versatility of YgfY in bacteria.


Effects of the autonomic antagonists on canine urethral responses to autonomic nerve stimulation.
The effects of the autonomic antagonists on urethral activity was studied in female dogs. Urethral responses produced by autonomic nerve stimulation were measured with pressure and motility changes in control conditions and after administration of autonomic antagonists. Phentolamine and guanethidine reduced both hypogastric and pelvic nerve mediated responses. It seems that urethral smooth muscle function is greatly influenced by adrenergic drugs.


Zeolite Lightweight Repair Renders: Effect of Binder Type on Properties and Salt Crystallization Resistance.
Rendering mortars with lightweight zeolite aggregates were designed and tested. The effect of the type of binder used was also researched. For the hardened mortars, macrostructural parameters, mechanical characteristics, hygric and thermal properties were assessed. Specific attention was paid to the analysis of the salt crystallization resistance of the developed rendering mortars. Quartz sand was fully replaced in the composition of mortars with zeolite gave materials with low density, high porosity, sufficient mechanical strength, high water vapor permeability and high water absorption coefficient, which are technical parameters required for repair rendering mortars as prescribed in the WTA directive 2-9-04/D and EN 998-1. Moreover, the zeolite enhanced mortars exhibit good thermal insulation performance and high sorption capacity. The examined rendering mortars were found to be well durable against salt crystallization, which supports their applicability in salt-laden masonry. Based on the compatibility of the repair materials with those originally used, the lime and natural hydraulic lime zeolite mortars can be used as rendering mortars for the repair of historical and heritage buildings. The cement-lime zeolite render is applicable for repair purposes only in the case of the renewal of masonry in which Portland cement-based materials were originally used.


The high-resolution infrared spectrum of DC4H from 450 to 1100 cm-1: overtone, combination, and hot bands.
The high-resolution infrared spectrum of monodeuterated diacetylene has been recorded in the 450-1100 cm(-1) spectral region by Fourier transform infrared spectroscopy. Seven new bands have been identified: the ν3 fundamental (C-C stretch), and the ν8 + ν9, ν7 + ν8, 2ν7, 2ν8, ν8 + ν9 - ν9, and ν6 + ν9 - ν9 combination, overtone, and hot bands. The assigned transitions, together with those previously reported for the fundamental bands [F. Tamassia, L. Bizzocchi, C. Degli Esposti, L. Dore, M. Di Lauro, L. Fusina, M. Villa, and E. Canè, Astron. Astrophys. 549, A38 (2013)], form a comprehensive data set which comprises more than 2500 ro-vibrational transitions, and involves all singly and most doubly excited vibrational states of DC4H lying below 1000 cm(-1). Rotational and vibrational l-type resonance effects among the sub-levels of excited bending states were considered in the analysis, which also included a careful treatment of the various anharmonic interactions coupling many vibrational states lying above 600 cm(-1). Reliable and unambiguous spectroscopic parameters were obtained for each investigated state, including the rotational and centrifugal distortion constants Bv and Dv, the l-type doubling parameter qt, the anharmonicity constants xL(89), xL(69), and the vibrational l-type terms r89, r69 for the v8 = v9 = 1 and v6 = v9 = 1 bend-bend combination states.


T cell subpopulations after allogeneic bone marrow transplantation.
T-cell subpopulations were studied in six patients after allogeneic bone marrow transplantation for aplastic anemia and acute leukaemia, by means of receptors for IgG (TG-cells) and IgM (TM-cells). Significant modifications of TM-TG levels were found: a 2 to 10 fold increase of TG cells and a 2 to 10 fold decrease of TM cells from pre-transplant levels could be observed. The TM-TG imbalance appeared together with the clinical signs of GVHD: the level of TM-depression (but not the level of TG increase) correlated with the severity of GVHD. The TM-TG modifications were observed as long as 3 years after transplantation, also in the absence of signs of GVHD. In addition, all six patients were found to have severely impaired pokeweed-induced B-cell differentiation. The clinical implications and the possible lack of T-helper activity are discussed.


Endometrioid-like variant of ovarian yolk sac tumor with foci of carcinoid: an ultrastructural study.
The endometrioid-like variant of ovarian yolk sac tumor is a rare neoplasm composed partially or completely of glandular tissue resembling endometrioid carcinoma, but identifiable histologically and immunohistochemically as an extraembryonic endodermally differentiated germ cell tumor. Only nine examples of this neoplasm have been published previously, and none was studied by electron microscopy. One of these rare neoplasms, the first documented to have foci of carcinoid, has recently been observed and studied ultrastructurally. Electron microscopic observations showed that the main component of the neoplasm had glandular epithelial cells with nuclear and cytoplasmic features difficult to distinguish from the cells of Müllerian endometrioid and endometrial adenocarcinoma, but a minor component of mucinous adenocarcinoma was confirmed as intestinal by the epithelial cells having characteristic microvilli with filamentous cores and rootlets. In addition, neuroendocrine cells present in the glands and in nests were readily identified ultrastructurally by their dense-core granules. Electron microscopy may be useful in supplementing light microscopic and immunohistochemical examination of this variant of yolk sac tumor.


On the use of MnO2 cartridges for the plutonium determination in seawater.
To analyze plutonium (Pu) in open ocean waters can be challenging due to the low seawater concentrations. In this study we compared two techniques for Pu determination, one in-situ MnO2 cartridge system and the more commonly used MnO2 precipitation technique. During the pre-pilot GEOTRACES cruise ANT XXX-1 (2005) we tested MnO2 cartridges for the pre-concentration of Pu from seawater at 19 sampling stations on a transect in the southeastern Atlantic Ocean between Vigo (Spain) and Cape Town (South Africa). Our in-situ sampling setup consisted of one particle cartridge followed by three MnO2 cartridges in a series. Through the system we pumped between 956 and 2700 l of surface seawater with a flow rate between 1.6 and 5.2 l/min. We found that the adsorption efficiency of a single MnO2 cartridge to adsorb Pu was rather constant and on average a 58 ± 7%. The adsorption efficiency was also found to be independent of seawater: temperature in the range of 18.3-29.2 °C, salinity range 34.2-37.1‰, and conductivity in the range of 46.8-58.4 mS/cm. In parallel with the in-situ sampling, discrete surface water samples between 259 and 281 l were taken and Pu was pre-concentrated using the MnO2 precipitation method. We find a good agreement between the Pu concentrations determined with the two different techniques. The in-situ pre-concentration technique requires more radiochemical work in the laboratory but has the advantage that large seawater volumes can be sampled without the necessity for radiochemical processing on-board the ship. The much larger volumes sampled with the in-situ technique compared with the precipitation technique, enables accurate determination of Pu-isotopic ratios with a low relative standard deviation. We have shown in this study that in-situ MnO2 cartridge technique can be used in a reliable way for the determination of dissolved Pu seawater concentration in open ocean waters.


On the existence of uncharged molecules with a pyramidally coordinated carbon: the cases of pentacyclo[18.104.22.168(2,9).0(3,8).0(7,9)]non-4-ene and heptacyclo- [184.108.40.206(1,5).0(5,15).0(6,14).0(10,14).0(10,15)]pentadecane.
[reaction: see text] B3LYP/6-31G(d) and MP2 calculations predict interactions between the divalent carbon and one double bond in tricyclo[220.127.116.11(2,4)]nona-6,8-dien-3-ylidene (3). Carbene 3 easily forms the more stable 4, a species with a pyramidal geometry. Moreover, the kinetic stability of 4 has been investigated, and some of its decay products are described. Interestingly, 3,3-dibromotricyclo[220.127.116.11(2,4)]nona-6,8-diene (1), the precursor of carbenoid 3, has already been reported and shown to undergo a formal dimerization to give 2. In addition, 15, a compound structurally related to 4, is expected to have a substantially greater stability toward further rearrangement.


Protonation and Zn(II) coordination by dipyridine-containing macrocycles with different molecular architecture. A case of pH-controlled metal jumping outside-inside the macrocyclic cavity.
The synthesis of the macrocyclic ligand 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridylophane (L3), which contains a pentaamine chain linking the 4,4'-positions of a 2,2'-dipyridine moiety, is reported. Protonation and Zn(II) complexation by L3 and by macrocycle L2, containing the same pentaamine chain connecting the 6,6'-positions of 2,2'-dipyridine, were studied by means of potentiometric, UV-vis, and fluorescent emission measurements. While in L2 all the nitrogen donor atoms are convergent inside the macrocyclic cavity, in L3 the heteroaromatic nitrogen atoms are located outside. Both ligands form mono- and dinuclear Zn(II) complexes in aqueous solution. In the mononuclear Zn(II) complexes with L2, the metal is coordinated inside the macrocyclic cavity, bound to the heteroaromatic nitrogen donors and three amine groups of the aliphatic chain. As shown by the crystal structure of the [ZnL2](2+) complex, the two benzylic nitrogens are not coordinated and facile protonation of the complex takes place at slightly acidic pH values. Considering the mononuclear [ZnL3](2+) complex, the metal is encapsulated inside the cavity, not coordinated by the dipyridine unit. Protonation of the complex occurs on the aliphatic polyamine chain and gives rise to translocation of the metal outside the cavity, bound to the heteroaromatic nitrogens.


Dens invaginatus of a mandibular central incisor: surgical endodontic treatment.
Dens invaginatus is a developmental malformation that mostly affects maxillary lateral teeth and mandibular teeth are rarely affected. In this paper a mandibular central incisor with a dens invaginatus is identified as requiring both endodontic and surgical treatment is presented. At one year recall appointment satisfactory clinical and radiographic healing was evident. This case demonstrates that also periapical surgery should be performed in some cases with dens invaginatus for resolution of periapical tissues.


The electrophysiological actions of neurotensin in the central nervous system.
The endogenous neuropeptide, neurotensin (NT) alters the firing frequencies of certain neurons in the central nervous system (CNS). This is one of the findings that support the hypothesis that NT is a neurotransmitter substance. The direct application of NT on CNS neurons causes predominantly excitatory effects. These effects occur in a dose-related fashion via a calcium-dependent postsynaptic mechanism. The C-terminal hexapeptide fragment, NT 8-13 exerts similar electrophysiological effects to NT, while the N-terminal octapeptide fragment, NT 1-8 is devoid of such activity. NT produces a significant increase in the firing rates of individual neurons in the substantia nigra (SN), ventral tegmental area (VTA), medial prefrontal cortex (MPF), hypothalamus, and periaqueductal grey (PAG). This excitation occurs with a rapid onset and is readily reversible after cessation of NT application. In contrast, NT has no effect or weak inhibitory effects on the firing rates of neurons in the locus coeruleus (LC) and cerebellum. These electrophysiological actions of NT appear to be unique and not shared by other neurotransmitter and neuropeptide receptor antagonists and agonists that have been studied via direct co-application. NT attenuates dopamine (DA)-induced inhibition associated with direct application onto neurons in the SN and VTA both in vivo and in vitro. Intracellular recordings suggest that direct application of higher concentrations of NT appears to produce 'depolarization block' on individual neurons in the SN, VTA, MPF, and hypothalamus. The electrophysiological consequences of NT application not only show similarities to clinically efficacious antipsychotic medications, but also demonstrate the ability of NT to modulate the activity of dopamine (DA) neurons at the cellular level via specific NT binding sites. These findings further underscore the possibility that NT may play a pre-eminent role in the pathogenesis of, and psychopharmacological management of neurological and psychiatric disorders purportedly related to perturbation of CNS DA systems including schizophrenia.


Kinesthetic reference for human orthograde posture.
Humans with occluded vision were subjected to superslow tilts of the supporting platform, producing the inclination of the subject's body in the sagittal plane, but subthreshold for the most vestibular and proprioceptive phasic reactions. Two types of perturbation were used: sinusoidal tilts (frequency 0.007 Hz, amplitude 1.5 degrees) and ramps (amplitude 1.0 and 0.25 degrees, angular velocity 0.04 degrees/s). During slow sinusoidal tilts of the platform, the ankle angle and body position undergo periodical changes, but these changes have significant phase lead relative to the platform movement: 119 +/- 26 for ankle angle and 55 +/- 19 degrees for body sway. Gains were about 0.9 for both parameters. Large phase shift (tens of seconds) indicated a long delay in compensation of body inclination by ankle joint. The ramp tilt produced an initial body deviation followed by a slow (seconds or tens of seconds) approach of body position to a new steady level after the termination of ramp. Large slow body movements were superimposed with small irregular oscillations (about 10% of the amplitude of large displacements) of higher frequency. These oscillations resembled normal stabilograms on a stationary support. Thus, the usual process of stabilization of body gravity center was continued, though not around a fixed set-point but relative to a slowly changing position. Data obtained support the hypothesis that, besides operative control assigned to compensate deviations from a reference position, the system of postural control includes at least one additional level, which elaborates this reference using information about mutual position of body links, muscular torques and interaction with the support on the basis of criteria taking into account the energy cost of standing and demands for stability and security.


A conserved domain regulates interactions of the v-fps protein-tyrosine kinase with the host cell.
All cytoplasmic protein-tyrosine kinases (PTKs) share a noncatalytic domain, termed SH2, which comprises approximately 100 residues located immediately N-terminal to the kinase domain. A linker in the AX9m mutant of Fujinami avian sarcoma virus (FSV) introduces a dipeptide insertion into the SH2 domain of the P130gag-fps PTK, which abolishes its ability to transform Rat-2 cells. However, at 36 degrees C AX9m FSV elicits focus formation and agar colony formation in infected chicken embryo fibroblasts (CEF) with single hit kinetics. At 41.5 degrees C AX9m FSV is nontransforming for CEF, and the mutant is therefore both host and temperature dependent for transforming activity. Both in vitro and in vivo, the specific kinase activity of AX9m FSV P130gag-fps, measured by autophosphorylation and phosphorylation of exogenous substrates, correlated with transforming activity. The consequences of the AX9m mutation for enzymatic function and transforming activity therefore depend on the cellular environment in which the altered v-fps protein is expressed. We conclude that the SH2 domain directs the interaction of the P130gag-fps catalytic domain with cellular proteins such as substrates for phosphorylation or regulators of kinase activity important for its transforming ability.


The thermic effect of food is reduced in older adults.
The thermic effect of food accounts for ~10% of daily energy expenditure. A reduction in the thermic effect of food, which has been variably observed in the older adults, could predispose to fat gain. We tested whether the thermic effect of food is reduced in older adults compared with young adults by analyzing our database of standardized studies conducted at the Mayo Clinic between 1999 and 2009. Data were available from 136 older adult volunteers aged 60-88 (56 females) and 141 young adults aged 18-35 years (67 females). Basal energy expenditure was measured by indirect calorimetry to assess basal metabolic rate. Body fat, fat free mass, and visceral fat were measured using a combination of dual energy X-ray absorptiometry and an abdominal CT scan. The thermic effect of food and postprandial insulinemia were measured in 123 older adults (52 females) and 86 young adults (38 females) of these volunteers. Basal metabolic rate adjusted for fat-free mass was less in older adults (p=0.01) and the thermic effect of food was ~1% (p=0.02) less in the older adults. After controlling for meal size and fat-free mass, body fat and fat distribution did not predict the thermic effect of food. Both basal metabolic rate and the thermic effect of food are less in older adults than young adults, even when they have similar amounts of lean tissue and consume a similar size meal. These factors contribute to lower daily energy expenditure in the older adults.


Finite-Time Fuzzy Bounded Control for Semilinear PDE Systems With Quantized Measurements and Markov Jump Actuator Failures.
This article presents a novel reliable fuzzy output feedback controller for a class of semilinear parabolic partial differential equation systems with Markov jump actuator failures. First, the control strategy's novelties include the following aspects: 1) the considered system is represented by using a fuzzy modeling approach, based on which a new asynchronous fuzzy observer is constructed via utilizing a series of discrete output signals that are induced by samplers and quantizers; 2) a novel Markov jump input model, which is more fit for real applications, is introduced to depict various stochastically occurring actuator faults; and 3) inspired by the above discussion, a reliable mode-dependent fuzzy piecewise control strategy, which only needs limited actuators, is developed. Then, some new conditions, which can ensure that the closed-loop system is finite-time bounded, are established. Furthermore, some slave matrices are introduced to relax the strict constraints caused by asynchronous membership functions. Finally, two simulation examples are provided to support the validity of the proposed method.


Molecular domains of myelinated axons in the peripheral nervous system.
Myelinated axons are organized into a series of specialized domains with distinct molecular compositions and functions. These domains, which include the node of Ranvier, the flanking paranodal junctions, the juxtaparanodes, and the internode, form as the result of interactions with myelinating Schwann cells. This domain organization is essential for action potential propagation by saltatory conduction and for the overall function and integrity of the axon.


Diffusible and Volatile Antifungal Compounds Produced by an Antagonistic Bacillus velezensis G341 against Various Phytopathogenic Fungi.
The aim of this study was to identify volatile and agar-diffusible antifungal metabolites produced by Bacillus sp. G341 with strong antifungal activity against various phytopathogenic fungi. Strain G341 isolated from four-year-old roots of Korean ginseng with rot symptoms was identified as Bacillus velezensis based on 16S rDNA and gyrA sequences. Strain G341 inhibited mycelial growth of all phytopathogenic fungi tested. In vivo experiment results revealed that n-butanol extract of fermentation broth effectively controlled the development of rice sheath blight, tomato gray mold, tomato late blight, wheat leaf rust, barley powdery mildew, and red pepper anthracnose. Two antifungal compounds were isolated from strain G341 and identified as bacillomycin L and fengycin A by MS/MS analysis. Moreover, volatile compounds emitted from strain G341 were found to be able to inhibit mycelial growth of various phytopathogenic fungi. Based on volatile compound profiles of strain G341 obtained through headspace collection and analysis on GC-MS, dimethylsulfoxide, 1-butanol, and 3-hydroxy-2-butanone (acetoin) were identified. Taken together, these results suggest that B. valezensis G341 can be used as a biocontrol agent for various plant diseases caused by phytopathogenic fungi.


[Introduction of the module "Evidence-based Medicine" in Child and Adolescent Psychiatry into the psychiatry block practicum at the University of Ulm].
The essential need for the timely availability of additional relevant information has resulted in a focus on "Evidence-based Medicine" (EBM) in medical practice. In Child and Adolescent Psychiatry (CAP) training it is essential to impart knowledge of how to effectively use the available literature, since the evidence for many therapies is still poor. We modified the "Duke Model" for teaching EBM in CAP to better attune it to the educational needs of a German university. We describe the introduction of the teaching module "Evidence-based Medicine in CAP" in practical clinical training. Integrating EBM into mandatory practical training enables the students to deal with problems that directly pertain to patient treatment, thus motivating them to access and read relevant scientific literature. An initial evaluation of this pilot project shows the successful linkage of research with clinical routine and also the conveyance of improved decision making abilities as well as an attitude of life-long learning. Modifying the EBM-module for practical clinical training is an innovative approach to integrating EBM into medical curricula. In the course of a curricular reform, "EBM cross sectional training" for all medical students was introduced into the new curriculum of the Medical School at the University of Ulm.


Reversible switch between bulk MgCO3·3H2O and Mg(OH)2 micro/nanorods induces continuous selective preconcentration of anionic dyes.
It is still a big challenge to treat large amount of water with low concentration of pollutant. In this study, a hierarchical (micro/nano) structured Mg(OH)2 adsorbent was introduced by the in situ hydration of porous MgO in the dye solution. The adsorbent showed high selective adsorption capacity (Q0 ≈ 155 mg/g for acid alizarine blue) and fast adsorption rate for the removal of anionic dyes down to the mg/L levels. Moreover, the adsorbed dye was successfully desorbed by carbonation, resulting in a ~4000 fold enrichment of the dye solution. It was demonstrated that by establishing a reversible switch between the Mg(OH)2 micro/nanorod and the bulk MgCO3·3H2O, a continuous preconcentration of low-concentration dye wastewater could be achieved.


Ceftriaxone and dexamethasone affecting yeast gut flora in experimental mice.
Crl:CD1 (ICR) BR mice were fed regular food or food containing Candida albicans to induce gastrointestinal (GI) colonization by the yeast. Groups of colonized mice were subsequently treated with either ceftriaxone for 10 days or dexamethasone for 10 or 21 days. Another group of colonized mice was treated with the combination of ceftriaxone, given for 10 days, and dexamethasone given for 21 days. Other colonized mice received normal saline, and non-colonized mice received the same drugs or saline, serving as controls. Candida-colonized mice, treated either with ceftriaxone or with dexamethasone alone, had significantly increased levels of GI colonization by the yeast. Colonized mice treated with the combination of the antibiotic with dexamethasone had stool concentrations of Candida similar to those of mice treated with the antibiotic alone. Saline did not affect Candida stool concentration. Yeasts were not found in the stools of non-colonized mice treated with the study drugs or saline. There was no evidence of Candida dissemination to internal organs in any group.


Clinical, biomechanical and biological aspects of immediately loaded dental implants: a critical review of the literature.
In recent years, the use of immediately loaded implants became more acceptable as a standard protocol for completely edentulous lower jaw and/or partially edentulous upper jaw cases, predominantly in the anterior region, after it was one of the cornerstones of the early protocols to avoid any occlusal loading of the implants for at least 3 months. This technique could potentially provide immediate function and aesthetics to the patient. This review aims to present the clinical indications of the immediately loaded protocol according to the individual cases and the corresponding risk factors and contraindications. The clinical, biomechanical and biological requirements concerning bone quality, occlusal loading and implant primary stability are discussed. Primary stability in immediate loading is determined rather by surgical than biological parameters. Peri-implant osteogenesis leading to secondary stability depends on the same biological factors than in unloaded implant healing. However, specific mechanical effects on the biology of immediate loading osseointegration are yet to be investigated.


Dealing with conflicting information: young children's reliance on what they see versus what they are told.
Children often learn about the world through direct observation. However, much of children's knowledge is acquired through the testimony of others. This research investigates how preschoolers weigh these two sources of information when they are in conflict. Children watched as an adult hid a toy in one location. Then the adult told children that the toy was in a different location (i.e. false testimony). When retrieving the toy, 4- and 5-year-olds relied on what they had seen and disregarded the adult's false testimony. However, most 3-year-olds deferred to the false testimony, despite what they had directly observed. Importantly, with a positive searching experience based on what they saw, or with a single prior experience with an adult as unreliable, 3-year-olds subsequently relied on their first-hand observation and disregarded the adult's false testimony. Thus, young children may initially be credulous toward others' false testimony that contradicts their direct observation, but skepticism can develop quickly through experience.


Role of alpha4 integrin and VCAM-1 in CD18-independent neutrophil migration across mouse cardiac endothelium.
Myocardial damage due to reperfusion of ischemic tissue is caused primarily by infiltrating neutrophils. Although leukocyte beta2 integrins (CD18) play a critical role, significant neutrophil emigration persists when CD18 is neutralized or absent. This study examined the role of leukocyte beta1 integrin (alpha4) and its endothelial ligand VCAM-1 in CD18-independent neutrophil migration across cardiac endothelium. In a mouse model of myocardial ischemia and reperfusion, we show that compared with wild-type mice, neutrophil infiltration efficiency was reduced by 50% in CD18-null mice; in both types of mice, myocardial VCAM-1 staining increased after reperfusion. In wild-type mice, antibodies against CD18, ICAM-1 (an endothelial ligand for CD18), or VCAM-1 given 30 minutes before ischemia did not block neutrophil emigration at 3 hours reperfusion. Although anti-VCAM-1 attenuated neutrophil emigration by 90% in CD18-null mice, it did not diminish myocardial injury. To determine if CD18-independent neutrophil emigration was a tissue-specific response, we used isolated peripheral blood neutrophils from wild-type or CD18-null mice and showed neutrophil migration across lipopolysaccharide-activated cultured cardiac endothelium is CD18-independent, whereas migration across endothelium obtained from inferior vena cava is CD18-dependent. Consistent with our in vivo findings, migration of CD18-deficient neutrophils on cardiac endothelial monolayers is blocked by antibodies against alpha4 integrin or VCAM-1. We conclude tissue-specific differences in endothelial cells account, at least partially, for CD18-independent neutrophil infiltration in the heart.


Modal analysis of human body vibration model for Indian subjects under sitting posture.
Need and importance of modelling in human body vibration research studies are well established. The study of biodynamic responses of human beings can be classified into experimental and analytical methods. In the past few decades, plenty of mathematical models have been developed based on the diverse field measurements to describe the biodynamic responses of human beings. In this paper, a complete study on lumped parameter model derived from 50th percentile anthropometric data for a seated 54- kg Indian male subject without backrest support under free un-damped conditions has been carried out considering human body segments to be of ellipsoidal shape. Conventional lumped parameter modelling considers the human body as several rigid masses interconnected by springs and dampers. In this study, concept of mass of interconnecting springs has been incorporated and eigenvalues thus obtained are found to be closer to the values reported in the literature. Results obtained clearly establish decoupling of vertical and fore-and-aft oscillations. The mathematical modelling of human body vibration studies help in validating the experimental investigations for ride comfort of a sitting subject. This study clearly establishes the decoupling of vertical and fore-and-aft vibrations and helps in better understanding of possible human response to single and multi-axial excitations.


Gene expression profiles of major cytokines in the nucleus tractus solitarii of the spontaneously hypertensive rat.
Since the nucleus of the solitary tract (NTS) is a pivotal region for regulating the set-point of arterial pressure, we proposed a role for it in the development of neurogenic hypertension. Recent studies have suggested that pro-inflammatory molecules are highly expressed in the NTS of an animal model of human essential hypertension--the spontaneously hypertensive rat (SHR), compared to normotensive Wistar-Kyoto rat (WKY). Based on this evidence, we hypothesized that inflammatory mediators such as cytokines are up-regulated in the hypertensive NTS. In the present study, we have assessed the level of gene expression of some cytokines in the NTS of SHR compared to WKY. In addition, for further confirmation of abnormal inflammatory condition within the NTS of SHR, we identified gene expression levels of an inflammatory marker, glycoprotein-39 (gp39) precursor, which is homologous to chitinase 3-like protein 1, human cartilage-gp39 or YKL40. The NTS was micro-dissected from 15-week-old male SHR and WKY rats. Total RNA was extracted and quantitative RT-PCR was performed. Gene expression of gp39 precursor and monocyte chemoattractant protein-1 were higher in the NTS of SHR while inter-leukin-6 was lower in the NTS of SHR compared to the WKY. In contrast, there were no significant differences in the expression of other cytokines including: inter-leukin-1 beta, tumor necrosis factor-alpha and transforming growth factor beta 1. These data together with our previous published finding of an over expression of junctional adhesion molecule-1 suggest that the NTS of the SHR exhibits a specific inflammatory state.


On the regulation of spinach nitrate reductase.
A coupled assay has been worked out to study spinach (Spinacea oleracea L.) nitrate reductase under low, more physiological concentrations of NADH. In this assay the reduction of nitrate is coupled to the oxidation of malate catalyzed by spinach NAD-malate dehydrogenase. The use of this coupled system allows the assay of nitrate reductase activity at steady-state concentrations of NADH below micromolar. We have used this coupled assay to study the kinetic parameters of spinach nitrate reductase and to reinvestigate the putative regulatory role of adenine nucleotides, inorganic phosphate, amino acids, and calcium and calmodulin.


Further Insight into the Lability of MeCN Ligands of Cytotoxic Cycloruthenated Compounds: Evidence for the Antisymbiotic Effect Trans to the Carbon Atom at the Ru Center.
The two MeCN ligands in [Ru(2-C6H4-2'-Py-κC,N)(Phen, trans-C)(MeCN)2]PF6 (1), both trans to a sp(2) hybridized N atom, cannot be substituted by any other ligand. In contrast, the isomerized derivative [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(MeCN)2]PF6 (2), in which one MeCN ligand is now trans to the C atom of the phenyl ring orthometalated to Ru, leads to fast and quantitative substitution reactions with several monodentate ligands. With PPh3, 2 affords [Ru(2-C6H4-2'-Py-κC,N)(Phen, cis-C)(PPh3)(MeCN)]PF6 (3), in which PPh3 is trans to the C σ bound to Ru. Compound 3 is not kinetically stable, because, under thermodynamic control, it leads to 4, in which the PPh3 is trans to a N atom of the Phen ligand. Dimethylsulfoxide (DMSO) can also substitute a MeCN ligand in 2, leading to 5, in which DMSO is coordinated to Ru via its S atom trans to the N atom of the Phen ligand, the isomer under thermodynamic control being the only compound observed. We also found evidence for the fast to very fast substitution of MeCN in 2 by water or a chloride anion by studying the electronic spectra of 2 in the presence of water or NBu4Cl, respectively. An isomerization related to that observed between 3 and 4 is also found for the known monophosphine derivative [Ru(2-C6H4-2'-Py-κC,N)(PPh3, trans-C)(MeCN)3]PF6 (10), in which the PPh3 is located trans to the C of the cyclometalated 2-phenylpyridine, since, upon treatment by refluxing MeCN, it leads to its isomer 11, [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(MeCN)3]PF6. Further substitutions are also observed on 11, whereby N^N chelates (N^N = 2,2'-bipyridine and phenanthroline) substitute two MeCN ligands, affording [Ru(2-C6H4-2'-Py-κC,N)(PPh3, cis-C)(N^N)(MeCN)]PF6 (12a and 12b). Altogether, the behavior of the obtained complexes by ligand substitution reactions can be rationalized by an antisymbiotic effect on the Ru center, trans to the C atom of the cyclometalated unit, leading to compounds having the least nucleophilic ligand trans to C whenever an isomerization, involving either a monodentate or a bidentate ligand, is possible.


A patient with primary adenocarcinoma of the appendix metastasizing to the ovary.
The aim of this work is to draw attention to the difficulty of differential dia-gnosis of rare adenocarcinoma of the appendix and the histological diversity of ovarian tumors. We present a case of a 62-year-old patient sent by an attending gynecologist for the finding of an asymptomatic adnextumor diagnosed during a routine preventive examination. Based on preoperative examinations, a malignant ovarian tumor was suspected. Standard surgery was performed including hysterectomy with bilateral adnexectomy, total omentectomy, appendectomy, pelvic and paraaortic lymphadenectomy. Definitive histopathological analysis revealed a secondary ovarian tumor, with the adenocarcinoma of the appendix appearing to be the primary site. Up to 25% of all ovarian tumors are secondary metastatic tumors. Appendix neoplasia should be considered in the differential diagnosis of right-sided adnextumors. Due to their localization, they can only mimic an ovarian tumor during imaging examinations, or they can be the primary origin of an already metastatic ovary, as in our case.


Factors associated with menopausal symptoms among middle-aged registered nurses in Beijing.
To determine factors related to menopause symptoms among middle-aged registered nurses in Beijing. Self-administered questionnaires that included closed-ended questions on many factors possibly related to menopausal symptoms were distributed to 2100 registered nurses aged 40-55 at 20 hospitals in Beijing, China. Menopausal status was most associated with menopausal symptoms (p < 0.01), including hot flashes and sweating, paresthesiae, insomnia, arthralgia/myalgia, palpitations, skin formication and an unsatisfactory sexual life. The odds ratios (ORs) were highest for hot flashes and sweating. Upsetting events in the past year and being pessimistic were significantly inversely correlated with almost all the symptoms analyzed. Hot flashes and sweating (p < 0.01), paresthesiae (p < 0.01), unsatisfactory sexual life (p < 0.01), irritability (p < 0.05), depression or suspicion (p < 0.05) and dizziness (p < 0.05) were negatively correlated with the frequency of sexual activity. Many factors may influence symptoms of the menopause. We found that menopausal status was most strongly associated with most menopausal symptoms, especially hot flashes and sweating. Psychosocial factors also played an important role. A higher frequency of sexual activity negatively correlated with most menopausal symptoms.


Rare Manifestation of Idiopathic Tracheobronchopathia Osteochondroplastica: Misdiagnosed and Untreated Entity?
Tracheobronchopathia osteochondroplastica (TBPO) is a rare benign disease of unknown cause, in which multiple cartilaginous or bony submucosal nodules project into the trachea and proximal bronchi. It usually occurs in men in their fifth decade and can cause airway obstruction, bleeding and chronic cough; patients are more prone to post-obstructive pneumonia and chronic lung infection in some instances. We report a case of a 69-year-old female who presented with shortness of breath and lower extremity swelling over the past couple of weeks. Echocardiography (ECHO) was consistent with heart failure with preserved ejection fraction, and she was treated with diuretics accordingly. Imaging revealed persistent pleural effusions bilaterally, more pronounced on the right side. During the course of her hospitalization, the patient coded once and had to be resuscitated. She had bronchoscopy done and pathology was consistent with TBPO. In this condition, there are numerous osseous or cartilaginous submucosal nodules in the trachea and the main bronchus and nodules are formed due to the deposition of calcium phosphate that results in the proliferation of osseous and cartilaginous structures resulting in the obstruction of large airways. Treatment for the most part is supportive and resolves around bronchodilators for symptomatic relief.


[Male hypogonadism and its treatment].
Male hypogonadism can be of various etiology and that reflects its clinical manifestation, diagnostics and treatment. Male hypogonadism leads not only to decreased fertility, but influences the cardiovascular system, mood changes, bone fragility, lipids and other metabolic functions. Diagnosis of hypogonadism can be cumbersome, as well as the choice of optimal hormonal supplementation. The aim of this article is to summarize the basics from symptoms, diagnosis and treatment of male hypogonadism.


Toxic shock syndrome caused by Streptococcus dysgalactiae subsp. equisimilis in a Mexican preschool patient.
Severe infections due to Streptococcus dysgalactiae subsp. equisimilis (SDSE) have been identified in adults and may cause toxic shock syndrome, although with a low frequency. A preschool-age female patient, who started with an upper respiratory tract infection developing a gradual deterioration in the following three days, is described. She was admitted to the hospital in severe conditions, with tachypnea, tachycardia (200/min), hypotension (blood pressure 68/40 mmHg), capillary refill of 7 s, and erythematous maculopapular rash in thorax, abdomen and lower extremities. She received intensive management with an inadequate response. Furthermore, she developed multiple organ failure and died 8 h after admission. The blood culture was positive for S. dysgalactiae subsp. equisimilis. SDSE is a rare pathogen in children. In Mexico, cases of SDSE have not been reported probably due to an inaccurate identification. Mexican pediatricians should be alert to this situation..


Streptococcus bovis meningitis associated with colonic diverticulosis and hearing impairment: a case report.
A 75-year-old woman presented to the Tropical Diseases Hospital, Goiania, Brazil, with a two-day history of fever and chills followed by headache and vomiting over the last 24 hours. The cerebrospinal fluid (CSF) showed 270 leukocytes/mmc (30 percent neutrophils); 20 red cells/mmc; undetectable levels of glucose and 232 mg/dL of protein. The Gram stain revealed several Gram-positive cocci, and CSF culture yielded Streptococcus bovis. A colonoscopy showed diverticula in descendent and transverse colon. After a 14-day course of penicillin G, the patient was discharged in a good state of health, with only mild hearing impairment.


Scalable alignment and transfer of nanowires based on oriented polymer nanofibers.
We develop a simple and scalable method based on oriented polymer nanofiber films for the parallel assembly and transfer of nanowires at high density. Nanowires dispersed in solution are aligned and selectively deposited at the central space of parallel nanochannels formed by the well-oriented nanofibers as a result of evaporation-induced flow and capillarity. A general contact printing method is used to realize the transfer of the nanowires from the donor nanofiber film to a receiver substrate. The mechanism, which involves ordered alignment of nanowires on oriented polymer nanofiber films, is also explored with an evaporation model of cylindrical droplets. The simplicity of the assembly and transfer, and the facile fabrication of large-area well-oriented nanofiber films, make the present method promising for the application of nanowires, especially for the disordered nanowires synthesized by solution chemistry.


Inhibition of transthyretin amyloid fibril formation by 2,4-dinitrophenol through tetramer stabilization.
Transthyretin (TTR), a homotetrameric thyroxine transport protein found in the plasma and cerebrospinal fluid, circulates normally as a innocuous soluble protein. In some individuals, TTR polymerizes to form insoluble amyloid fibrils. TTR amyloid fibril formation and deposition have been associated with several diseases like familial amyloid polyneuropathy and senile systemic amyloidosis. Inhibition of the fibril formation is considered a potential strategy for the therapeutic intervention. The effect of small water-soluble, hydrophobic ligand 2,4-dinitrophenol (2,4-DNP) on TTR amyloid formation has been tested. 2,4-DNP binds to TTR both at acidic and physiological pH, as shown by the quenching of TTR intrinsic fluorescence. Interestingly, 2,4-DNP not only binds to TTR at acidic pH but also inhibits amyloid fibril formation as shown by the light scattering and Congo red-binding assay. Inhibition of fibril formation by 2,4-DNP appears to be through the stabilization of TTR tetramer upon binding to the protein, which includes active site. These findings may have implications for the development of mechanism based small molecular weight compounds as therapeutic agents for the prevention/inhibition of the amyloid diseases.


Localization of the transcription factor SP1 gene to human chromosome 12q12-->q13.2.
The cellular transcription factor SP1 binds to critical regulatory elements in a variety of cellular and viral promoters. The gene encoding the approximately 100-kDa SP1 protein contains zinc finger DNA-binding domains and glutamine-activation domains. Since SP1 is involved in the regulation of a variety of cellular genes, we wished to determine its chromosomal localization. Southern blot analysis of genomic DNA from a panel of mouse x human somatic cell hybrids indicated that SP1 was localized to chromosome 12. In situ hybridization allowed the localization of the gene encoding SP1 to human chromosome 12q12-->q13.2, with 12q13.1 being the most probable location.


Deciphering the Allosteric Activation Mechanism of SIRT6 Using Molecular Dynamics Simulations.
As a member of the histone deacetylase protein family, the NAD+-dependent SIRT6 plays an important role in maintaining genomic stability and regulating cell metabolism. Interestingly, SIRT6 has been found to have a preference for hydrolyzing long-chain fatty acyls relative to deacetylation, and it can be activated by fatty acids. However, the mechanisms by which SIRT6 recognizes different substrates and can be activated by small molecular activators are still not well understood. In this study, we carried out extensive molecular dynamic simulations to shed light on these mechanisms. Our results revealed that the binding of the myristoylated substrate stabilizes the catalytically favorable conformation of NAD+, while the binding of the acetyl-lysine substrate leads to a loose binding of NAD+ in SIRT6. Based on these observations, we proposed a reasonable allosteric binding mode for myristic acid, which can enhance the catalytic activity of SIRT6 by stabilizing the binding of NAD+ with His131 as well as the acetylated substrate. Furthermore, our molecular dynamics simulations demonstrated that synthetic SIRT6 activators, such as UBCS039, MDL-801, and 12q, block the flipping of ribose in NAD+ and therefore can stabilize substrate-NAD+-His131 interactions in a manner similar to fatty acids. In summary, our newly proposed activation mechanism of SIRT6 highlights the importance of protein-substrate interactions, which would facilitate the rational design of new SIRT6 activators.


Protein minimization of the gp120 binding region of human CD4.
CD4 is an important component of the immune system and is also the cellular receptor for HIV-1. CD4 consists of a cytoplasmic tail, one transmembrane region, and four extracellular domains, D1-D4. Constructs consisting of all four extracellular domains of human CD4 as well as the first two domains (CD4D12) have previously been expressed and characterized. All of the gp120-binding residues are located within the first N-terminal domain (D1) of CD4. To date, it has not been possible to obtain domain D1 alone in a soluble and active form. Most residues in CD4 that interact with gp120 lie within the region 21-64 of domain D1 of CD4. On the basis of these observations and analysis of the crystal structure of CD4D12, a mutational strategy was designed to express CD4D1 and region 21-64 of CD4 (CD4PEP1) in Escherichia coli. K(D) values for the binding of CD4 analogues described above to gp120 were measured using a Biacore-based solution-phase competition binding assay. Measured K(D) values were 15 nM, 40 nM, and 26 microM for CD4D12, CD4D1, and CD4PEP1, respectively. All of the proteins interact with gp120 and are able to expose the 17b-binding epitope of gp120. Structural content was determined using CD and proteolysis. Both CD4D1 and CD4PEP1 were partially structured and showed an enhanced structure in the presence of the osmolyte sarcosine. The aggregation behavior of all of the proteins was characterized. While CD4D1 and CD4PEP1 did not aggregate, CD4D12 formed amyloid fibrils at neutral pH within a week at 278 K. These CD4 derivatives should be useful tools in HIV vaccine design and entry inhibition studies.


Pediatric case management in the emergency department.
Through coordination of care, pediatric nursing case management improves children's health services and decreases duplication of services and the misuse of the emergency department (ED). This study looks at the effect of pediatric nursing case management on the number of ED visits of chronically ill children before, during and after case management.


Effect of Planned Teaching Program Regarding Knowledge on Detection and Prevention of Postpartum Hemorrhage among B. Sc. Nursing Students in Selected Nursing Colleges, Guwahati, Assam.
Postpartum hemorrhage (PPH) is a leading cause of maternal mortality. According to the World Health Organization, PPH accounts for 127,000 deaths annually out of which India accounted for over 20% in 2015. Health-care professionals, especially the nurse, should play an important role in detection and prevention of PPH. The purpose of the study is to assess the effect of planned teaching program regarding knowledge on detection and prevention of PPH among B. Sc. Nursing students. With an evaluative approach, one group of sixty B. Sc. Nursing 4th-year students were selected and pre- and posttest design was adopted for the study. The study revealed that the mean posttest knowledge score (17.27) was higher than the mean pretest knowledge score (8.92). The calculated t59 = 25.2 was significant at P < 0.05, thus the planned teaching program was effective. There was no significant association between the pretest level of knowledge score with the selected demographic variables, i.e., age, previous clinical exposure with PPH mother, and previous source of information on PPH. The present study concluded that the planned teaching program on detection and prevention of PPH was effective in improving the knowledge of the B. Sc. Nursing students.


Effect of Microbial Fermentation on the Fishy-Odor Compounds in Kelp (Laminaria japonica).
Kelp (Laminaria japonica) is an important marine resource with low cost and rich nutrition. However, its fishy odor has compromised consumer acceptance. In this study, the effects of fermentation with Lactobacillus plantarum FSB7, Pediococcus pentosaceus CICC 21862 and Saccharomyces cerevisiae SK1.008 on fishy notes in kelp was studied using gas chromatography-mass spectrometry (GC-MS), gas chromatography-ion mobility spectrometry (GC-IMS) and odor activity values (OAVs). Forty-four volatile organic compounds (VOCs) were identified in unfermented kelp, most of which were aldehydes, followed by alkanes, alcohols and ketones. Among them were 19 volatile compounds with OAV greater than one. Substances containing α,β-unsaturated carbonyl structure (1-Octen-3-one, (E,Z)-2,6-nonadienal, (E,E)-2,4-decadienal, etc.) are the main contributors to kelp fishy odor. The number of VOCs in kelp samples fermented by L. plantarum, P. pentosaceus and S. cerevisiae were decreased to 22, 24 and 34, respectively. GC-IMS shows that the fingerprint of the S. cerevisiae fermented sample had the most obvious changes. The disappearance of 1-octen-3-one and a 91% decrease in unsaturated aldehydes indicate that S. cerevisiae was the most effective, while L. plantarum and P. pentosaceus only reached 43-55%. The decrease in kelp fishy notes was related to the decrease in α,β-unsaturated carbonyl groups. The experimental results show that odor reduction with fermentation is feasible.


Prevalence and economic consequences of medication adherence in diabetes: a systematic literature review.
A systematic literature review was conducted using a comprehensive list of relevant search terms (1990-2005) to identify studies on adherence among patients with diabetes, and its economic effect. A lack of adequate treatment adherence (36%-87%) among patients with diabetes was confirmed, primarily measured by medication possession ratio (MPR). Adherence varied among oral agent-only (36%-87%) versus concomitant or insulin-only (54%-81%) regimens. Economic consequences of adherence were a decrease in health care costs, ranging from 8.6% to 28.9%, with an approximate 10% increase in MPR, mostly in the form of a 4.1% to 31.0% decrease in hospitalization. Increased cost sharing was associated with a 9% to 23% decline in medication use.


A New LoRa-like Transceiver Suited for LEO Satellite Communications.
LoRa is based on the chirp spread spectrum (CSS) modulation, which has been developed for low power and long-range wireless Internet of Things (IoT) communications. The structure of LoRa signals makes their decoding performance extremely sensitive to synchronization errors. To alleviate this constraint, we propose a modification of the LoRa physical layer, which we refer to as differential CSS (DCSS), associated with an original synchronization algorithm. Based on this modification, we are able to demodulate the received signals without performing a complete frequency synchronization and by tolerating some timing synchronization errors. Hence, our receiver can handle ultra narrow band LoRa-like signals since it has no limitation on the maximum carrier frequency offset, as is actually the case in the deployed LoRa receivers. In addition, in the presence of the Doppler shift varying along the packet duration, DCSS shows better performance than CSS, which makes our proposed receiver a good candidate for communication with a low-Earth orbit (LEO) satellite.


Molecular cloning and characterization of two rat renal kallikrein genes.
Kallikreins compose a multigene family coding for a subgroup of serine proteases, which are involved in the processing of bioactive peptides. Two rat kallikrein-related genes, RSKG-7 (rat submandibular gland kallikrein gene 7) and RSKG-3, have been cloned and their sequences analyzed. RSKG-7 is approximately 4200 bases in length and consists of five exons and four introns. The 5' end region contains the variant CATAT box and TTTAAA box; the 3' end region contains the polyadenylation signal AATAAA. This gene encodes a putative 28,935-dalton preproenzyme of 261 amino acids (aa). The active enzyme consists of 237 aa and is preceded by a deduced signal peptide of 18 aa and a profragment of 6 aa. RSKG-3 is highly homologous to RSKG-7 in terms of its sequence and structure; it encodes a 28,730-dalton prepropeptide consisting of a signal peptide of 18 aa, a profragment of 6 aa, and an active peptide of 235 aa. Sequence comparisons of RSKG-7, RSKG-3, and other kallikrein-related enzymes reveal the key amino acid residues needed for both serine protease activity (His/Asp/Ser) and kallikrein-like cleavage specificity at basic amino acids. Northern blot analyses using specific oligonucleotide probes demonstrate that, among the 12 tissues studied, RSKG-7 and RSKG-3 are expressed in the rat kidney and submandibular gland. Castration of male rats results in a decrease in submandibular gland RSKG-7 mRNA, which can be restored to the normal level by treatment with thyroxine or testosterone. On the other hand, neither castration nor hormonal manipulation affects RSKG-7 mRNA levels in the kidney.


Listener weighting of cues for lateral angle: the duplex theory of sound localization revisited.
The virtual auditory space technique was used to quantify the relative strengths of interaural time difference (ITD), interaural level difference (ILD), and spectral cues in determining the perceived lateral angle of wideband, low-pass, and high-pass noise bursts. Listeners reported the apparent locations of virtual targets that were presented over headphones and filtered with listeners' own directional transfer functions. The stimuli were manipulated by delaying or attenuating the signal to one ear (by up to 600 micros or 20 dB) or by altering the spectral cues at one or both ears. Listener weighting of the manipulated cues was determined by examining the resulting localization response biases. In accordance with the Duplex Theory defined for pure-tones, listeners gave high weight to ITD and low weight to ILD for low-pass stimuli, and high weight to ILD for high-pass stimuli. Most (but not all) listeners gave low weight to ITD for high-pass stimuli. This weight could be increased by amplitude-modulating the stimuli or reduced by lengthening stimulus onsets. For wideband stimuli, the ITD weight was greater than or equal to that given to ILD. Manipulations of monaural spectral cues and the interaural level spectrum had little influence on lateral angle judgements.


Cardiovascular beneficial effects of electroacupuncture at Neiguan (PC-6) acupoint in anesthetized open-chest dog.
Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (p<0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.


MR imaging of a novel NOE-mediated magnetization transfer with water in rat brain at 9.4 T.
To detect, map, and quantify a novel nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) with water at approximately -1.6 ppm [NOE(-1.6)] in rat brain using MRI. Continuous wave MT sequences with a variety of radiofrequency irradiation powers were optimized to achieve the maximum contrast of this NOE(-1.6) effect at 9.4 T. The distribution of effect magnitudes, resonance frequency offsets, and line widths in healthy rat brains and the differences of the effect between tumors and contralateral normal brains were imaged and quantified using a multi-Lorentzian fitting method. MR measurements on reconstituted model phospholipids as well as two cell lines (HEK293 and 9L) were also performed to investigate the possible molecular origin of this NOE. Our results suggest that the NOE(-1.6) effect can be detected reliably in rat brain. Pixel-wise fittings demonstrated the regional variations of the effect. Measurements in a rodent tumor model showed that the amplitude of NOE(-1.6) in brain tumor was significantly diminished compared with that in normal brain tissue. Measurements of reconstituted phospholipids suggest that this effect may originate from choline phospholipids. NOE(-1.6) could be used as a new biomarker for the detection of brain tumor. Magn Reson Med 78:588-597, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Deletion of arylamine N-acetyltransferase 1 in MDA-MB-231 human breast cancer cells reduces primary and secondary tumor growth in vivo with no significant effects on metastasis.
Arylamine N-acetyltransferase 1 (NAT1) is frequently upregulated in breast cancer. Previous studies showed that inhibition or depletion of NAT1 in breast cancer cells diminishes anchorage-independent growth in culture, suggesting that NAT1 contributes to breast cancer growth and metastasis. To further investigate the contribution of NAT1 to growth and cell invasive/migratory behavior, we subjected parental and NAT1 knockout (KO) breast cancer cell lines (MDA-MB-231, MCF-7, and ZR-75-1) to multiple assays. The rate of cell growth in suspension was not consistently decreased in NAT1 KO cells across the cell lines tested. Similarly, cell migration and invasion assays failed to produce reproducible differences between the parental and NAT1 KO cells. To overcome the limitations of in vitro assays, we tested parental and NAT1 KO cells in vivo in a xenograft model by injecting cells into the flank of immunocompromised mice. NAT1 KO MDA-MB-231 cells produced primary tumors smaller than those formed by parental cells, which was contributed by an increased rate of apoptosis in KO cells. The frequency of lung metastasis, however, was not altered in NAT1 KO cells. When the primary tumors of the parental and NAT1 KO cells were allowed to grow to a pre-determined size or delivered directly via tail vein, the number and size of metastatic foci in the lung did not differ between the parental and NAT1 KO cells. In conclusion, NAT1 contributes to primary and secondary tumor growth in vivo in MDA-MB-231 breast cancer cells but does not appear to affect its metastatic potential.


Availability and chemical composition of traditional eye cosmetics ("kohls") used in the United Arab Emirates of Dubai, Sharjah, Ajman, Umm Al-Quwain, Ras Al-Khaimah, and Fujairah.
This study was undertaken in order to determine the availability and chemical composition of potentially lead-toxic traditional eye cosmetics ("kohls") in six of the seven emirates of the United Arab Emirates (UAE). Thus of especial interest was the percentage of the purchased samples that contained the toxic element lead. A total of 53 observably different kohl samples were found to be available overall in the six emirates: Dubai, Sharjah, Ajman, Umm Al-Quwain, Ras Al-Khaimah, and Fujairah. It was found that 19 of these samples had been previously analyzed by us in studies covering Oman, Abu Dhabi (city), and Egypt (Cairo). The techniques of X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM) were used to analyze the remaining 34 samples. Overall, for the 53 kohl samples, it was found that 20 (38%) contained a lead compound (galena, PbS) as the main component. The other main components were found to be one of the following: amorphous carbon, calcite/aragonite (CaCO3), goethite (FeO(OH)), hematite (Fe2O3), sassolite (H3BO3), talc (Mg3Si4O10(OH)2), or zincite (ZnO).


Design of Controlled Release Non-erodible Polymeric Matrix Tablet Using Microwave Oven-assisted Sintering Technique.
The objective of the present study was to evaluate the effect of sintering condition on matrix formation and subsequent drug release from polymer matrix tablet for controlled release. The present study highlights the use of a microwave oven for the sintering process in order to achieve more uniform heat distribution with reduction in time required for sintering. We could achieve effective sintering within 8 min which is very less compared to conventional hot air oven sintering. The tablets containing the drug (propranolol hydrochloride) and sintering polymer (eudragit S-100) were prepared and kept in a microwave oven at 540 watt, 720 watt and 900 watt power for different time periods for sintering. The sintered tablets were evaluated for various tablet characteristics including dissolution study. Tablets sintered at 900 watt power for 8 min gave better dissolution profile compared to others. We conclude that microwave oven sintering is better than conventional hot air oven sintering process in preparation of controlled release tablets.


(+)-7S-Hydroxyxestospongin A from the marine sponge Xestospongia sp. and absolute configuration of (+)-xestospongin D.
The structure of the title compound, (+)-7S-hydroxyxestospongin A was solved by single-crystal X-ray diffraction analysis and the absolute stereochemistry obtained by analysis of the derived R and S Mosher's esters. The absolute configuration of xestospongin D was determined for the first time by analysis of anomalous scattering from the X-ray crystal diffraction data set. Xestospongins A, C, and D, araguspongine C, and demethylxestospongin B exhibited modest antifungal activity (MIC 30-100 g/mL) against various fluconazole-resistant Candida spp., but 7S-hydroxyxestospongin A was inactive.


Myocardial function and effect of serum in isolated heart from hypertriglyceridemic and hypertensive rats.
We evaluated the myocardial function of rats with sugar-induced hypertriglyceridemia (HTG) and hypertension, and the effect of serum on myocardial performance in the isolated heart preparation. Also, the response to reperfusion after 30 minutes of global ischemia was investigated. Hearts from HTG rats developed lower ventricular pressure (VP) and the conduction rate was higher than in hearts from control rats (CR). The recovery of VP after ischemia was significantly lower in HTG than in CR hearts (p < 0.05). The HTG sera produced a higher increase in the VP and in the perfusion pressure. During reperfusion, the incidence of premature beats, ventricular fibrillation and tachycardia in HTG hearts was increased so hypertriglyceridemia caused alterations in the mechanical and electrical conduction of the myocardium and exacerbated the injury produced by ischemia-reperfusion. Also a circulating factor in the HTG serum induced a vasoactive response of the heart which was reflected in its mechanical performance.


Remarkable reactions and intermediates in titanocene(IV) chemistry: migratory insertion reactions of 2,2-disubstituted-1-alkenes, intramolecular 1,5-σ bond metathesis via ε-agostic interactions, and a rare example of a β-agostic alkyltitanocene complex.
The compound Cp(2)TiMe(2) reacts with [Ph(3)C][B(C(6)F(5))(4)] in CD(2)Cl(2) at 205 K to give, inter alia, [Cp(2)TiMe(CD(2)Cl(2))][B(C(6)F(5))(4)]. This solvent-separated ion pair reacts in turn with 2,4-dimethyl-1-pentene (DMP) to give a series of cationic species, the first being the alkene complex [Cp(2)TiMe(DMP)](+), which undergoes ready migratory insertion to form the σ-alkyl complex [Cp(2)Ti(CH(2)CMe(2)CH(2)CHMe(2))](+). The latter, which does not contain a β-hydrogen atom, rearranges rapidly via an unprecedented 1,5-σ bond metathesis reaction involving two isomeric ε-agostic species to give the σ-alkyl species [Cp(2)Ti(CH(2)CHMeCH(2)CMe(3))](+); this does contain a β-hydrogen atom and, in concurrent processes, eliminates H(2) or 2,4,4-trimethyl-1-pentene (a major product) to form respectively the allylic complex [Cp(2)Ti{η(3)-(CH(2))(2)CCH(2)CMe(3)}](+) (a major product) or the hydride complex [Cp(2)TiH](+). The latter reacts reversibly with free DMP to give the insertion product [Cp(2)Ti(CH(2)CHMeCH(2)CHMe(2))](+) (V, a major product), in which the italicized hydrogen atom engages in a β-agostic interaction with the metal atom. Compound V is a rare example of both a β-agostic derivative of a group 4 metallocene and a β-agostic compound of any metal in which the (1)H resonance of the agostic hydrogen can be identified in the (1)H NMR spectrum (δ -3.43). Interestingly, a NOESY experiment on V indicates slow mutual exchange between the agostic hydrogen atom, the hydrogen atoms on C(1), and those of Me(2). These observations are consistent with the intermediacy of the allylic dihydrogen species [Cp(2)Ti(H(2)){η(3)-(CH(2))(2)CCH(2)CHMe(2)}](+), which loses H(2) to form [Cp(2)Ti{η(3)-(CH(2))(2)CCH(2)CHMe(2)}](+) (a minor product). Support for all steps of the proposed reaction scheme comes from product distributions, from labeling studies utilizing [Cp(2)Ti(CD(3))(CD(2)Cl(2))](+), and from extensive DFT calculations. The observed titanocene-based chemistry stands in stark contrast to that of the analogous zirconium system, in which the unusual but well-characterized cationic methyl alkene complex [Cp(2)ZrMe(DMP)](+) does not undergo migratory insertion and subsequent reactions.


Leukaemia inhibitory factor inhibits cardiomyogenesis of mouse embryonic stem cells via STAT3 activation.
The leukaemia inhibitory factor is a cytokine that exhibits pleiotropic activities in a wide range of cell types. There are evidences that leukaemia inhibitory factor-regulated signalling pathways are involved in cardiomyogesis and maintenance of cardiomyocytes. In the present work we studied the effect of leukaemia inhibitory factor on cardiomyogenesis of embryonic stem cells together with the role of serum-born factors. We showed that leukaemia inhibitory factor had an inhibitory effect during both the induction and progression phases of cardiomyogenesis of embryonic stem cells. The leukaemia inhibitory factor-mediated inhibition of cardiomyogenesis was abolished by inhibitors of STAT3 activity. These results suggest that leukaemia inhibitory factor- activated STAT3 is responsible for the inhibition of cardiomyogenesis in embryonic stem cells.


Equity, justice, and social values in priority setting: a qualitative study of resource allocation criteria for global donor organizations working in low-income countries.
There is increasing acceptance of the importance of social values such as equity and fairness in health care priority setting (PS). However, equity is difficult to define: the term means different things to different people, and the ways it is understood in theory often may not align with how it is operationalized. There is limited literature on how development assistance partner organizations (DAP) conceptualize and operationalize equity in their health care prioritization decisions that affect low-income countries (LIC). This paper explores whether and how equity is a consideration in DAP priority setting processes. This was a qualitative study involving 38 in-depth interviews with DAPs involved in health-system PS for LICs and a review of their respective webpages. While several PS criteria were identified, direct articulation of equity as an explicit criterion was lacking. However, the criterion was implied in some of the responses in terms of prioritizing vulnerable populations. Where mentioned, respondents discussed the difficulties of operationalizing equity as a PS criterion since vulnerability is associated with several varying and competing factors including gender, age, geography, and income. Some respondents also suggested that equity could be operationalized in terms of an organization not supporting the pre-existing inequities. Although several organizations' webpages identify addressing inequities as a guiding principle, there were variations in how they spoke about its operationalization. While intersectionalities in vulnerabilities complicate its operationalization, if organizations explicitly articulate their equity focus the other organizations who also have equity as a guiding principle may, instead of focusing on the same aspect, concentrate on other dimensions of vulnerability. That way, all organizations will contribute to achieving equity in all the relevant dimensions. Since most development organizations support some form of equity, this paper highlights a need for an internationally recognized framework that recognizes the intersectionalities of vulnerability, for mainstreaming and operationalizing equity in DAP priority setting and resource allocation. Such a framework will support consistency in the conceptualization of and operationalization of equity in global health programs. There is a need for studies which to assess the degree to which equity is actually integrated in these programs.


Factors impacting volumetric white matter changes following whole brain radiation therapy.
Whole brain radiation therapy (WBRT) is one of the most effective modalities for treatment of brain metastases. With increasing cancer control there is growing concern regarding the long-term effects of treatment. These effects are seen as white matter change (WMC) on brain MRI. Severity of WMC is implicated in cognitive and functional decline in many patient groups. Our objective was to identify clinical factors associated with greater accumulation of WMC following WBRT. Through retrospective review of serial MRIs obtained from 30 patients surviving greater than 1 year after WBRT, treated at a single institution between 2002 and 2007, we calculated volumetric WMC over time using segmentation software. Changes related to tumor, secondary effects, surgery or radiosurgery were excluded. Factors that influenced the rate of WMC accumulation were identified through multivariate analysis. Following WBRT, patients accumulated WMC at an average rate of 0.07% of total brain volume per month. In multivariate analyses, greater rates of accumulation were independently associated with older age (β = 0.004, p < .0001), poor levels of glycemic control (β = 0.048, p < .0001) and hypertension diagnosis (β = 0.084, p < .0001). Long-term survivors of cancer allow assessment of late effects of treatment modalities. Radiation injury appears to be related to a steady rate of white matter damage over time, as indicated by progressive accumulation of WMC. Our results suggest that rate of WMC accumulation is enhanced by parameters such as hyperglycemia and hypertension. This has significant clinical impact by clearly identifying hyperglycemia, steroid-induced hyperglycemia, and other vascular risk factors as targets for intervention to decrease WMC in patients receiving WBRT.


Ability of a Au(III)-N unit to bond two aurophilically interacting gold(I) centers.
The monohapto neutral 2-(diphenylphosphino)aniline (PNH(2)) complexes [Au(C(6)F(5))(2)X(PNH(2))] (X = C(6)F(5) (1), Cl (2)) have been obtained from [Au(C(6)F(5))(3)(tht)] or [Au(C(6)F(5))(2)(micro-Cl)](2) and PNH(2), and the cationic [Au(C(6)F(5))(2)(PNH(2))]ClO(4) (3) has been similarly prepared from [Au(C(6)F(5))(2)(OEt(2))(2)]ClO(4) and PNH(2) or from 2 and AgClO(4). The neutral amido complex [Au(C(6)F(5))(2)(PNH)] (4) can be obtained by deprotonation of 3 with PPN(acac) (acac = acetylacetonate) or by treatment of the chloro complex 2 with Tl(acac). It reacts with [Ag(OClO(3))(PPh(3))] or [Au(OClO(3))(PPh(3))] to give the dinuclear species [Au(C(6)F(5))(2)[PNH(MPPh(3))]]ClO(4) (M = Ag (5), Au (6)). The latter can also be obtained by reaction of equimolar amounts of 3 and [Au(acac)(PPh(3))]; when the molar ratio of the same reagents is 1:2, the trinuclear cationic complex [Au(C(6)F(5))(2)[PN(AuPPh(3))(2)]]ClO(4) (7) is obtained. The crystal structures of complexes 2-4 and 7 have been established by X-ray crystallography; the last-mentioned displays an unusual Au(I)-Au(III) interaction.


[The efficacy of droperidol, metoclopramide, propofol, and ondansetron for the prevention of nausea and vomiting following middle ear surgery].
The efficacy and reliability of prophylactic antiemetic therapy with low dose propofol, droperidol, metoclopramide, and ondansetron were evaluated in a randomized, double-blind, and prospective design. A total of 101 ASA I-II patients (34 females, 67 males; age range 16 to 53 years) undergoing middle ear surgery for chronic otitis media or its sequelae were randomly assigned to receive prophylactic antiemetic therapy with propofol (n=21, 0.5 mg/kg), droperidol (n=19, 20 mg/kg), metoclopramide (n=23, 0.2 mg/kg), ondansetron (n=21, 4 mg), and placebo (n=20, 0.9% NaCl). All drugs were administered intravenously five minutes before extubation. In the early postoperative period (0 to 3 hours), the percentages of patients free from nausea and vomiting were 100% with droperidol, 71.4% with ondansetron and propofol, 52.1% with metoclopramide, and 35% with placebo. Ondansetron (90.4%) was found the most effective to prevent and control nausea and vomiting during the postoperative 3 to 24 hours, followed by droperidol (84.2%), propofol (57.1%), metoclopramide (47.8%), and placebo (40%). Compared with controls, the number of patients without nausea and vomiting was significantly greater in each treatment group but metoclopramide (p<0.05). No significant differences were detected with respect to adverse effects. Droperidol and ondansetron seem to exert the highest efficacy to prevent nausea and vomiting during the postoperative 0 to 3 hours and 3 to 24 hours, respectively.


Characterization of hepatocellular resistance and susceptibility to styrene toxicity in B6C3F1 mice.
Short-term inhalation exposure of B6C3F1 mice to styrene causes necrosis of centrilobular (CL) hepatocytes. However, in spite of continued exposure, the necrotic parenchyma is rapidly regenerated, indicating resistance by regenerated cells to styrene toxicity. These studies were conducted to test the hypothesis that resistance to repeated styrene exposure is due to sustained cell proliferation, with production of hepatocytes that have reduced metabolic capacity. Male mice were exposed to air or 500 ppm styrene (6 h/day); hepatotoxicity was evaluated by microscopic examination, serum liver enzyme levels, and bromodeoxyuridine (BrdU)-labeling index (LI). Metabolism was assessed by measurement of blood styrene and styrene oxide. Both single and repeated exposures to styrene resulted in mortality by Day 2; in mice that survived, there was CL necrosis with elevated BrdU LI at Day 6, and complete restoration of the necrotic parenchyma by Day 15. The BrdU LI in mice given a single exposure had returned to control levels by Day 15. Re-exposure of these mice on Day 15 resulted in additional mortality and hepatocellular necrosis, indicating that regenerated CL cells were again susceptible to the cytolethal effect of styrene following a 14-day recovery. However, in mice repeatedly exposed to styrene for 14 days, the BrdU LI remained significantly increased on Day 15, with preferential labeling of CL hepatocytes with enlarged nuclei (karyomegaly). If repeated exposures were followed by a 10-day recovery period, CL karyomegaly persisted, but the BrdU LI returned to control level and CL hepatocytes became susceptible again to styrene toxicity as demonstrated by additional mortality and acute necrosis after a challenge exposure. These findings indicated a requirement for continued styrene exposure and DNA synthesis in order to maintain this resistant phenotype. Analyses of proliferating-cell nuclear-antigen (PCNA) labeling were conducted to further characterize the cell cycle kinetics of these hepatocytes. The proportion of cells in S-phase was increased by repeated exposure. However, PCNA analysis also revealed an even larger increase in the G1 cell compartment with repeated exposures, without a concurrent increase in G2 phase or in mitotic cell numbers. These data indicate that resistance to styrene-induced necrosis under conditions of repeated exposure is not due to sustained cell turnover and production of new, metabolically inactive cells, but rather is due to some other, as yet unknown, protective phenotype of the regenerated cells.


Atopic phenotypes and their implication in the atopic march.
Eczema, allergic rhinitis, and asthma are traditionally considered atopic (or allergic) diseases. They are complex, multifactorial, and are caused by a variety of different mechanisms, which result in multiple heterogeneous clinical phenotypes. Atopic march is usually interpreted as the sequential development of symptoms from eczema in infancy, to asthma, and then allergic rhinitis. Areas covered: The authors reviewed the evidence on the multimorbidity of eczema, asthma, and rhinitis, and the implication of results of data-driven analyses on the concept framework of atopic march. A literature search was conducted in the PubMed and Web of Science for peer-reviewed articles published until July 2020. Application of Bayesian machine learning framework to rich phenotypic data from birth cohorts demonstrated that the postulated linear progression of symptoms (atopic march) does not capture the heterogeneity of allergic phenotypes. Expert opinion: Eczema, wheeze, and rhinitis co-exist more often than would be expected by chance, but their relationship can be best understood in a multimorbidity framework, rather than through atopic march sequence. The observation of their co-occurrence does not imply any specific relationship between them, and certainly not a progressive or causal one. It is unlikely that a sngle mechanism such as allergic sensitization underpins different multimorbidity manifestations.


Novel in vitro method for identification of individuals at risk for beryllium hypersensitivity.
Beryllium-specific lymphocytes were generated by in vitro immunization of peripheral blood mononuclear cells (PBMC) from healthy unexposed individuals. Measurement of blastogenic responses of PBMC by [3H]thymidine uptake demonstrated that sensitization of PBMC with beryllium salts followed by stimulation with unrelated salts resulted in a negative response, whereas sensitization and restimulation of PBMC with beryllium salts produced a positive response. Flow cytometric and cell depletion analyses showed that all of the responding cells were CD4+ T cells. The in vitro immunization system was used to screen 52 human subjects for susceptibility to beryllium sensitization in vitro. The results show that of the 52 healthy unexposed subjects tested, only 1 (2%) was highly responsive, 4 subjects (8%) were moderately responsive, 20 subjects (39%) were low-level responders, and 27 subjects (52%) were nonresponders. The results showing 2% high-level responsiveness to beryllium sensitization in vitro correlate with the 1 to 5% prevalence of chronic beryllium disease in individuals sensitized to beryllium dust in vivo and thus support the thesis that the in vitro immunization system may permit the identification of individuals at risk for beryllium hypersensitivity.


Constitutive activation of ras in neurons: implications for the regulation of the mammalian circadian clock.
Almost all organisms living on earth exhibit rhythms under the control of autonomous timekeeping mechanisms referred to as circadian clocks. In mammals, peripheral clocks are synchronized (entrained) with high precision in a 24 h periodicity by the master circadian clock located in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus. Light is the strongest phase-adjusting stimulus of the circadian clock. Circadian oscillations are driven by transcription/translation-based feedback/feedforward loops, comprising a set of clock genes and their protein products. The signalling pathways that couple light input to transcriptional, translational, and post-translational changes to ensure precise entrainment of the clock are not yet well characterized. A candidate pathway for transmission of photic information in the SCN is represented by the extracellular signal-regulated kinases ERK1/ERK2. In neurons, the ERK pathway is activated by a large array of stimuli, including trophic factors, neurotransmitters, and modulatory peptides. An upstream element of the ERK signalling route is the small intracellular membrane-anchored G-protein, Ras. In order to study its possible role in the entrainment of the circadian clock we are using transgenic gain-of-function mice expressing constitutively activated Val-12 Ha-Ras selectively in neurons (synRas mice). The Ha-Ras transgene protein is expressed in the SCN of synRas mice neurons serving as a model for interfering with the normal rhythmic changes in Ras activities in the SCN. This will allow us to investigate whether the associated modulation of the downstream targets such as ERK activities will interfere with the mechanisms of entrainment.