Regulation of expression level of fms-like tyrosine kinase-4 is related to osteoclast differentiation.
The aim of this study is to determine whether regulation of the expression level of fms-like tyrosine kinase-4 (Flt-4) is related to osteoclast differentiation. Osteoclast formation and differentiation of mouse bone marrow cells and RAW264.7 cells were performed. To induce osteoclast differentiation, RANKL (50 ng/ml) with or without vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor-D (VEGF-D) was added to mouse bone marrow cells and RAW264.7 cells. Then cells were examined under a microscope. TRAP-positive cells with 3 nuclei or more were considered as osteoclasts and counted. The Flt-4 gene was knocked down by transfection of siRNAs against Flt-4. Immunoblot analyses were performed. The osteoclast formation assay indicated that VEGF-C resulted in 500 or 450 vs. 100 (p < 0.05) of osteoclasts in mouse bone marrow cells and RAW264.7 cells, respectively. Vascular endothelial growth factor-D resulted in about 600 or 630 vs. 100 (p < 0.05) of osteoclasts for both mouse bone marrow cells and RAW264.7 cells. The knock-down of Flt-4 expression abolished the induction by VEGF-C or VEGF-D, resulting in induction similar to that of the negative control PBS. Both VEGF-C and VEGF-D can induce osteoclast differentiation in the presence of the receptor activator of nuclear factor κB ligand. Down-regulation of expression level of Flt-4 protein abolishes osteoclast differentiation induced by VEGF-C or VEGF-D.


Effect of lipids on a membrane-bound NADH dehydrogenase from Bacillus caldotenax.
NADH dehydrogenase [EC 188.8.131.52] in membranes of Bacillus caldotenax was solubilized with sodium N-lauroylsarcosinate and purified 50-fold from membranes to 75-80% homogeneity, as judged by SDS-polyacrylamide gel electrophoresis. The enzyme was considered to be located on the electron transport chain and to be an FAD-containing protein. The molecular weight of the subunit was estimated to be 44,000. The enzyme (or the enzyme bound to the B. caldotenax membrane lipids) follows a ping-pong mechanism. The enzyme can oxidize NADH, but not NADPH, with 2,6-dichlorophenol indophenol, ferricyanide, menadione, and cytochrome c as electron acceptors. Membrane lipids or Triton X-100 stimulated the enzyme activity, except that with menadione. Lipids decreased the apparent affinity of electron acceptors and NADH to the enzyme, and increased the maximum velocity, except when menadione was used as the electron acceptor. Lipids partially protected the enzyme from thermal inactivation. The enzyme exhibited a continuous Arrhenius plot, while the lipids- or membrane-bound enzyme exhibited a discontinuous plot.


Generalized sensitivity analysis of the minimal model of the intravenous glucose tolerance test.
Generalized sensitivity functions characterize the sensitivity of the parameter estimates with respect to the nominal parameters. We observe from the generalized sensitivity analysis of the minimal model of the intravenous glucose tolerance test that the measurements of insulin, 62 min after the administration of the glucose bolus into the experimental subject's body, possess no information about the parameter estimates. The glucose measurements possess the information about the parameter estimates up to three hours. These observations have been verified by the parameter estimation of the minimal model. The standard errors of the estimates and crude Monte Carlo process also confirm this observation.


Catalytic Reductive N-Alkylations Using CO2 and Carboxylic Acid Derivatives: Recent Progress and Developments.
N-Alkylamines are key intermediates in the synthesis of fine chemicals, dyes, and natural products, and hence are highly valuable building blocks in organic chemistry. Consequently, the development of greener and more efficient procedures for their production continues to attract the interest of both academic and industrial chemists. Reductive procedures such as reductive amination or N-alkylation through hydrogen autotransfer by employing carbonyl compounds or alcohols as alkylating agents have prevailed for the synthesis of amines. In the last few years, carboxylic/carbonic acid derivatives and CO2 have been introduced as alternative and convenient alkylating sources. The safety, easy accessibility, and high stability of these reagents makes the development of new reductive transformations with them as N-alkylating agents a useful alternative to existing procedures. In this Review, we summarize reported examples of one-pot reductive N-alkylation methods that use carboxylic/carbonic acid derivatives or CO2 as alkylating agents.


Substrate Facilitating Roles in Rare-Earth-Catalyzed C-H Alkenylation of Pyridines with Allenes: Mechanism and Origins of Regio- and Stereoselectivity.
Although considerable progress has been achieved in C-H functionalization by cationic rare-earth alkyl complexes, the potential facilitating roles of heteroatom-containing substrates during the catalytic cycle remain highly underestimated. Herein, theoretical studies on the model reaction of C(sp2)-H addition of pyridines to allenes by scandium catalyst were carefully carried out to reveal the detailed mechanism. A coordinating pyridine substrate as a ligand can effectively stabilize some key structures. An obvious facilitating role delivered by the coordinating pyridine was found for allene insertion, while the pyridine-free mechanism prefers to occur for C(sp2)-H activation processes. Importantly, the elusive role of heteroatom-containing substrates was systematically revealed for the C-H activation event by designing a metal/ligand combination of catalysts and substrates. We found that the pyridyl C(sp2)-H activation would be switched to the pyridine-coordinated mechanism in the cases of the designed Y and La catalysts. To date, this is the first time to realize the potential substrate-facilitating role in cationic rare-earth-catalyzed C-H activation processes. Moreover, theoretical predictions show that similar switchable mechanisms also work for other types of C-H bonds and other heteroatom-involved substrates by fine-adjusting the steric surroundings of catalysts. The two C-H activation mechanisms are mainly the result of the delicate balance between electronic and steric factors. In general, the catalytic system with less steric hindrance prefers to undergo the substrate-coordinated mechanism. In contrast, the substrate-free mechanism is favorable due to steric repulsion. These results are helpful for us to better understand the variant mechanisms in rare-earth-catalyzed C-H functionalization at the atomistic level and may help guide the rational design of new catalytic reactions. In addition, the origins of the regio- and stereoselectivity were discussed through geometric parameters and distortion/interaction analysis.


Effect of cyclin D1 (CCND1) polymorphism on gastric premalignant condition.
Cyclin D1 (CCND1) is known to regulate function in G1 arrest and therefore may play an important role in carcinogenesis. The aim of this study was to investigate the effect of G870A polymorphism of the CCND1 gene on gastric precancerous condition, on histological chronic gastritis, and on the risk of peptic ulcer diseases. Restriction fragment length polymorphism analysis was performed for polymorphisms at 870GA in the CCND1 gene in 524 cancer-free subjects, including 111 gastric and 54 duodenal ulcers, and 359 non-ulcer subjects. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system in 384 subjects. CCND1 genotype was significantly associated with the severity of intestinal metaplasia by the Kruskal-Wallis test, and this tendency was especially stronger among older subjects of 61 years or older (overall subjects: p=0.035, 61 years approximately : p=0.007). We also found that the 870AA genotype held a significant high risk of intestinal metaplasia [Helicobacter pylori infection adjusted odds ratio (OR)=1.8, 95% confidence interval (CI)=1.03-3.15, p=0.04]. The same genotype was more closely associated with the risk of intestinal metaplasia in older subjects of 61 years or older (H. pylori infection adjusted OR=3.45, 95% CI=1.48-8.08, p=0.004). A non-significant association was found between CCND1 G870A genotypes and the risk of peptic ulcer diseases as well as histological severity of acute or chronic inflammation. It appears that the G870A polymorphism of CCND1 is associated with gastric premalignant condition especially in older subjects.


A potential role of smooth muscle tone in early hypertension: a theoretical study.
A conspicuous long-term consequence of hypertension is a thickening of the arterial wall, which many suggest returns the circumferential wall stress toward its normal value. This thickening results from an increase in smooth muscle and extracellular matrix, with the associated growth and remodeling processes depending on a host of regulatory signals that likely include the altered mechanical environment. Although the precise mechanotransduction pathways remain unknown, we propose that vasoconstriction may be an early response of the arterial wall to a step-change in pressure. In particular, computations suggest that such a response can decrease the magnitude and transmural gradients of the pressure-induced wall stresses and return the mean wall shear stress toward its homeostatic value. Such an initial 'compensatory vasoconstriction' could also help set into motion subsequent growth and remodeling responses due to growth regulatory characteristics of the vasoactive molecules (e.g., nitric oxide, endothelin-1, angiotensin-II). Although the consequences of growth and remodeling have been the focus of prior biomechanical and histological studies, early responses dictate subsequent developments and therefore deserve increased attention in vascular biomechanics and mechanobiology.


Office hysteroscopy in the management of women with postmenopausal bleeding.
Postmenopausal bleeding (PMB) is a relevant aspect for health-care providers in clinical practice: the first objective is to rule out potential gynecological cancer. The purpose of this narrative review is to evaluate the role of office hysteroscopy in the management of PMB. Office hysteroscopy is a minimally invasive procedure allowing direct visualization of uterine pathology without the need for general anesthesia and the use of an operating room, generating cost savings and greater compliance among patients. Here, we focus on major intrauterine diseases (polyps, submucosal myomas, endometrial hyperplasia, and cancer) as causes of PMB. Office hysteroscopy appears to be safe and feasible, and could allow accurate diagnosis of intrauterine pathologies, especially that with a focal growth pattern, otherwise misdiagnosed with blinded procedures. However, studies focusing exclusively on postmenopausal women are still few, so further research, especially randomized controlled trials, is needed.


PARASHIFT Probes: Solution NMR and X-ray Structural Studies of Macrocyclic Ytterbium and Yttrium Complexes.
Ytterbium and yttrium complexes of octadentate ligands based on 1,4,7,10-tetraazacyclododecane with a coordinated pyridyl group and either tricarboxylate (L1) or triphosphinate (L2) donors form twisted-square-antiprismatic structures. The former crystallizes in the centrosymmetric group P21/c, with the two molecules related by an inversion center, whereas the latter was found as an unusual kryptoracemate in the chiral space group P21. Pure shift NMR and EXSY spectroscopy allowed the dynamic exchange between the (RRR)-Δ-(δδδδ) and (RRR)-Λ-(λλλλ) TSAP diastereomers of the [Y.L2] complex to be detected. The rate-limiting step in the exchange between Δ and Λ isomers involves cooperative ligand arm rotation, which is much faster for [Ln.L1] than for [Ln.L2]. Detailed analysis of NOESY, COSY, HSQC, and HMBC spectra confirms that the major conformer in solution is (RRR)-Λ-(λλλλ), consistent with crystal structure analysis and DFT calculations. The magnetic susceptibility tensors for [Yb.L1] and [Yb.L2], obtained from a full pseudocontact chemical shift analysis, are very different, in agreement with a CASSCF calculation. The remarkably different pseudocontact shift behavior is explained by the change in the orientation of the pseudocontact shift field, as defined by the Euler angles of the susceptibility tensor.


Some aspects of the synchronization in coupled maps.
We numerically study the synchronization behavior of a coupled map lattice consisting of a chain of chaotic logistic maps exhibiting power law interactions. We report two main results. First, we find a practical lower bound in the lattice size in order that this system could be considered in the thermodynamic limit in numerical simulations. Second, we observe the existence of a strong correlation between the Lyapunov dimension and the averaged synchronization time.


Subhertz-linewidth Nd:YAG laser.
Light from a Nd:YAG laser at 1064 nm is independently stabilized to two Fabry-Perot etalons situated on separate vibration-isolation platforms. A heterodyne beat measurement shows their relative frequency stability to be at the part-in-10(15) level at 5 s and the relative linewidth to be less than 1 Hz.


Plasmacytoma of the hyoid.
A case of plasmacytoma arising from the hyoid bone is described, this is a distinctly unusual site, as the marrow-containing flat bones are more commonly affected. On a review of the literature this appears to be the first report of plasmacytoma occurring in the hyoid bone. The patient underwent a CT scan and plain radiographs. Histopathology was diagnostic.


The sensitivity of WRF daily summertime simulations over West Africa to alternative parameterizations. Part 2: Precipitation.
This paper evaluates the performance of the Weather and Research Forecasting (WRF) model as a regional-atmospheric model over West Africa. It tests WRF sensitivity to 64 configurations of alternative parameterizations in a series of 104 twelve-day September simulations during eleven consecutive years, 2000-2010. The 64 configurations combine WRF parameterizations of cumulus convection, radiation, surface-hydrology, and PBL. Simulated daily and total precipitation results are validated against Global Precipitation Climatology Project (GPCP) and Tropical Rainfall Measuring Mission (TRMM) data. Particular attention is given to westward-propagating precipitation maxima associated with African Easterly Waves (AEWs). A wide range of daily precipitation validation scores demonstrates the influence of alternative parameterizations. The best WRF performers achieve time-longitude correlations (against GPCP) of between 0.35-0.42 and spatiotemporal variability amplitudes only slightly higher than observed estimates. A parallel simulation by the benchmark Regional Model-v.3 achieves a higher correlation (0.52) and realistic spatiotemporal variability amplitudes. The largest favorable impact on WRF precipitation validation is achieved by selecting the Grell-Devenyi convection scheme, resulting in higher correlations against observations than using the Kain-Fritch convection scheme. Other parameterizations have less obvious impact. Validation statistics for optimized WRF configurations simulating the parallel period during 2000-2010 are more favorable for 2005, 2006, and 2008 than for other years. The selection of some of the same WRF configurations as high scorers in both circulation and precipitation validations supports the notion that simulations of West African daily precipitation benefit from skillful simulations of associated AEW vorticity centers and that simulations of AEWs would benefit from skillful simulations of convective precipitation.


De Garengeot's Hernia: Report of a Rare Surgical Emergency and Review of the Literature.
This is a report of a case who was admitted and operated on for a strangulated femoral hernia. The hernia sac contained a gangrenous appendix, which was excised and the hernia was repaired with sutures without complication. De Garengeot's hernia, although very rare, should be included in the differential diagnosis of cases with strangulated hernia and should receive the optimal treatment.


Demographic processes of urbanisation in Delhi.
"Metropolitanisation has been observed by experts as one of the main characteristics of Indian urbanisation. Rural to urban migration has been a major player in urban growth of metropolitan cities, particularly Delhi. Not only Delhi but its hinterland [are] urbanising fast as compared to the hinterlands of other major cities of India. There are several processes of urbanization viz. historical, physical, demographic and economic. In this paper the role of demographic processes in urban expansion of Delhi [is examined]."


Parental relationships during childhood in homosexuality, transvestism and transsexualism.
The nature of the relationships of 29 male homosexuals, 34 male transvestites and 29 male transsexuals with their parents, during childhood, was assessed on the basis of the subjects' reports, and on their responses to two tests, namely the Childhood Family Relationship test and a Semantic Differential. If the subjects' reports are valid significantly more mothers of transvestite and transsexual subjects hoped for a girl prior to the subject's birth. During childhood there was a trend for homosexual, transvestite and transsexual subjects to report that their fathers lacked interest in them or were absent from home. There was little evidence to support the view that homosexual, transvestite or transsexual subjects had pathological relationships with their mother. Intrafamilial childhood environmental factors reported by homosexuals, transvestites and transsexuals appear to be non-specific.


Synergistic role of Cul1 and c-Myc: Prognostic and predictive biomarkers in colorectal cancer.
Colorectal cancer (CRC) is one of the most common malignant tumors, and its high rates of recurrence and metastasis are the important causes of treatment failure in CRC. Therefore, the development of valuable molecular markers to accurately predict the prognosis of CRC patients is vital. In the present study, we determined the expression of Cullin1 (Cul1) and c-Myc in a CRC tissue microarray containing 470 cancer and corresponding normal tissues by immunohistochemistry. We found that Cul1 and c-Myc expression was significantly upregulated in the CRC cancer tissues compared with that noted in the adjacent non-cancer tissues. High Cul1 expression in cancer tissues was associated with depth of invasion (P=0.005), lymph node metastasis (P=0.001) and TNM stage (P=0.015). High c-Myc expression in cancer tissues was significantly positively association with age (P=0.004), depth of invasion (P<0.001), lymph node metastasis (P<0.001) and TNM stage (P<0.001). Multivariate Cox regression analysis revealed that Cul1 or c-Myc expression was an independent and unfavorable prognostic factor for CRC patients [hazard ratio (HR), 0.749, 95% confidence interval (CI), 0.563-0.996, P<0.05; and HR, 0.384, 95% CI, 0.257-0.472, P<0.001, respectively]. Furthermore, Cul1 and c-Myc exhibited synergistic potential for the prediction of CRC prognosis, and the patients with low expression of both Cul1 and c-Myc had a favorable survival outcome (P<0.001).


Depletion of hepatocyte nuclear estrogen receptor expression is associated with promotion of tamoxifen induced GST-P foci to tumours in rat liver.
The expression of hepatocyte nuclear estrogen receptor (ER) in putative preneoplastic foci, adenomas and carcinomas, induced by the rat liver carcinogen tamoxifen, has been examined immunohistologically. ER staining of normal rat liver shows between 30-50% of hepatocyte nuclei to be positive, depending on fixation. Depletion of ER was defined as <10% of cells in foci or tumours staining for nuclear ER. A proportion of all but the smallest glutathione-S-transferase, placental form (GST-P) expressing foci had depleted expression of nuclear ER. The percentage of GST-P expressing foci with depletion of nuclear ER increased with the size of the foci. The liver adenomas and carcinomas induced by tamoxifen showed a high incidence (90%) of depletion of ER. This suggests that abnormal expression of the ER is associated with the promotion of putative preneoplastic foci to adenomas and carcinomas in tamoxifen exposed rat livers. Dysfunction of the ER could contribute to selective continued stimulation of initiated cells that would be consistent with a role for modification of the ER in target cells and the promotion stage of liver cancer. Liver tumours induced by other carcinogens in both sexes of rat were also found to have a high incidence of ER depletion, indicating that this could be a general regulatory mechanism for rat liver tumour promotion, irrespective of the possible estrogen like action of individual carcinogens.


The T-loop extension of the tomato protein kinase AvrPto-dependent Pto-interacting protein 3 (Adi3) directs nuclear localization for suppression of plant cell death.
In tomato (Solanum lycopersicum), resistance to Pseudomonas syringae pv. tomato is elicited by the interaction of the host Pto kinase with the pathogen effector protein AvrPto, which leads to various immune responses including localized cell death termed the hypersensitive response. The AGC kinase Adi3 functions to suppress host cell death and interacts with Pto only in the presence of AvrPto. The cell death suppression (CDS) activity of Adi3 requires phosphorylation by 3-phosphoinositide-dependent protein kinase 1 (Pdk1) and loss of Adi3 function is associated with the hypersensitive response cell death initiated by the Pto/AvrPto interaction. Here we studied the relationship between Adi3 cellular localization and its CDS activity. Adi3 is a nuclear-localized protein, and this localization is dictated by a nuclear localization signal found in the Adi3 T-loop extension, an approximately 80 amino acid insertion into the T-loop, or activation loop, which is phosphorylated for kinase activation. Nuclear localization of Adi3 is required for its CDS activity and loss of nuclear localization causes elimination of Adi3 CDS activity and induction of cell death. This nuclear localization of Adi3 is dependent on Ser-539 phosphorylation by Pdk1 and non-nuclear Adi3 is found in punctate structures throughout the cell. Our data support a model in which Pdk1 phosphorylation of Adi3 directs nuclear localization for CDS and that disruption of Adi3 nuclear localization may be a mechanism for induction of cell death such as that during the Pto/AvrPto interaction.


Calcium homeostasis: solving the solubility problem.
This report summarizes the evidence that the control of the concentration of free calcium ions in body fluids is centered at mineralized bone surfaces. This process involves an increase in the solubility of bone mineral produced by the non-collagenous proteins existing in the bone extracellular fluid (ECF) and on the adjacent surfaces of bone. The result is a basic equilibrium level produced in the absence of parathyroid hormone (PTH), which is well above the solubility of bone mineral. The effect of PTH is to increase the solubility of bone mineral still further, but the mechanism by which the hormone acts is unknown. The lining cells of the bone contain receptors for PTH and can be observed to respond to this hormone, but the relationship between this response and the increased solubility of bone remains to be discovered. Further research in this field is strongly urged.


Premature ventricular contractions: Which ones require treatment?
Treatment of ventricular arrhythmias remains a difficult problem owing to our lack of understanding of etiology, prognosis, and efficacy of various antiarrhythmic agents. Lidocaine appears to prevent ventricular fibrillation during the CCU of myocardial infarction. Warning arrhythmias seen in the CCU do not in actuality accurately warn the clinician of risk of fibrillation. Secondary prevention of sudden death following infarction with antiarrhythmic agents may be of some value. There is little to suggest that drugs available in the United States are efficacious for this use. For the most part, treatment of outpatients with ventricular arrhythmias probably should be confined to those patients with symptomatic arrhythmias or to patients with complex ventricular arrhythmias and other objective evidence of cardiac disease.


[A case of long-term survival after hepatic resection for metastatic gastric cancer].
We report a case of long-term survival of a patient who underwent hepatic resection for metastatic gastric cancer. The patient was a 75-year-old man who underwent distal gastrectomy for gastric cancer in 2004. On pathological examination, the tumor was diagnosed as T4a (SE) N0M0, stage IIB. A metastatic lesion was detected in segment 6 of the liver at 2 years after gastrectomy. With regard to radiological findings, a single metastatic lesion and no lymph node metastasis or peritoneal recurrence was observed. The hepatic lesion was curatively resected. Another metachronous liver metastasis was identified in segment 7 of the liver at 3 years after gastrectomy. We resected the remnant liver metastasis, after which the patient has not exhibited any evidence of tumor recurrence for more than 5 years. This case suggests that patients could survive for a long period after undergoing resection of hepatic metastasis because no lymph node metastasis was observed during the operation of the primary gastric cancer, only a single hepatic metastasis without any metastasis to other organs was observed, and the metastatic lesion of the liver could be curatively resected.


Arthroscopically assisted arthrodesis for osteoarthrotic ankles.
Arthroscopically assisted arthrodesis of the ankle was performed in nineteen patients who were selected because they had osteoarthrosis with minimum or no deformity of the ankle. After arthroscopic resection of the synovial membrane, the subchondral bone, and cartilage from the tibial, fibular, and talar articular surfaces, three percutaneous, cannulated, cancellous screws were used for internal fixation. Of these nineteen patients, ten had radiographic evidence of union by the second postoperative month; five, by the third; one, by the fifth; and one, by the sixth. Two patients had a non-union, but a successful open arthrodesis was subsequently performed on one of these patients. At two years, the scoring system of Mazur et al. indicated a poor result in one patient (after a non-union), a fair result in two, a good result in four, and an excellent result in twelve patients. Arthroscopically assisted arthrodesis of the ankle produces good results in patients who have osteoarthrosis of the ankle with minimum or no deformity, and the immediate postoperative morbidity is of very short duration.


Traumatic rupture of the tricuspid valve and multi-modality imaging.
Motor vehicle accident (MVA) account for most cases of traumatic rupture of the tricuspid valve. Valve rupture during an MVA is generated by an abrupt deceleration coupled with an increase in right-side cardiac pressures (Valsalva maneuver and thorax compression). A 39-year-old asymptomatic man was referred for an echocardiogram due to the presence of a systolic murmur. He had no prior significant medical history, except for a remote MVA 3 years ago. Real-time 3D echocardiography (RT3DE) showed a tear in the body of the anterior leaflet and not at the cord, as was suggested by two-dimensional transthoracic echocardiography (2D-TTE). Based on these findings, the mechanism was considered anterior leaflet rupture of the tricuspid valve, secondary to chest blunt trauma. The anterior leaflet was repaired using two polytetrafluoroethylene sutures, and tricuspid annuloplasty with an Edwards ring was performed. Multimodality imaging helps to determine timing of surgery in asymptomatic traumatic tricuspid rupture. The combination of echocardiography and magnetic resonance imaging provide information of volumetric data and contractility of the right ventricle (RV) during follow-up. RT3DE gives information relevant to the morphological and functional characterization of the valve, allowing the planning of appropriate surgical procedure.


Analysis of survival in radical and postoperative radiotherapy for prostate cancer.
To analyze survival and complications in high dose 3D conformal radiotherapy (3DCRT) patients treated with curative and post-operative intent and compare radical surgery + radiotherapy (RT) patients vs. RT only patients. 103 patients were treated curatively (RAD), 94 postoperatively (POST-OP). The mean age was higher in RAD group (72.6 years, range 56.4-85.1) than in POST-OP group (65.4 years, 43.9-77) (p < 0.0001). According to NCCN prognostic classification 13 (12%) patients was low risk, 48 (47%) intermediate risk and 42 (41%) high risk in RAD group. In POST-OP group 13 (14%) patients were low risk, 37 (40%) intermediate risk and 44 (46%) high risk. Hormone Therapy (HT) was administered in 98 patients (95%) in RAD and in 45 patients (47.8%) in POST-OP. Patients were treated with a three-dimensional conformal radiotherapy (3D-CRT). In RAD 15 (15%) were alive with disease (AWD), 5 (5%) dead of disease (DOD) and 10 (10%) dead of other cause (DOC); in POST-OP 14 (14.8%) were AWD, 2 (2%) DOD and 3 (3%) DOC. The prescription dose was 80 Gy in 2-Gy fractions in the RAD group, and 70 Gy in 2-Gy fractions in the POST-OP, respectively. No biochemical or clinical relapse was found in low risk patients in RAD group and 1 relapse in POST-OP group. The largest number of relapses occurred and in intermediate-high risk in RAD (39%) and POST-OP group (33%). In the cause-specific survival analysis no significant differences were found in high risk group between RAD and POST-OP (p = 0.9). In the biochemical relapse-free survival (bRFS) at 5 years analysis no significant differences were found in the high risk group between RAD and POST-OP (p = 0.1020). RT in RAD low- risk is very effectiva. RAD and POST-OP RT were well tolerated with a very low toxicity. The cause-specific survival at 5 years was 95% and 97% for the two groups of treatment, RAD and POST-OP respectively (Log-rank test p = 0.2908).


Design, synthesis, and anticancer activity evaluation of curcumol derivatives.
A new series of C-14 curcumol derivatives as potent anticancer agents were designed and synthesized by click reaction, whose structures were confirmed by 1H NMR,13C NMR, and HRMS analysis. All the synthesized compounds were evaluated for in vitro antitumor activity against colorectal cancer cell lines SW620 and HCT116. Most of them exhibited higher inhibitory activity than curcumol. Especially, compound 3j shows good inhibitory activity against SW620 with IC50 value of 8.10 ± 0.13 μM. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry revealed that compound 3j induced SW620 cells apoptosis by facilitating apoptosis-related proteins expressions. Our findings suggested that fluorine functional group on phenyl ring tended to increase the anticancer activity.


Complications of subclavian catheterization in hemodialysis patients.
Subclavian vein catheterization, the most commonly used temporary vascular access for hemodialysis, is associated with a variety of complications. This retrospective study was done on 96 patients who had 150 percutaneous subclavian vein catheterizations over a one year period using Quinton double lumen polyurethane catheters. A total of 56 complications were seen of which 12 were immediate and 44 delayed. Immediate complications seen were six cases of failure of insertion of catheter and three cases each of subclavian artery puncture and inadvertent entry of the catheter into the jugular vein. Delayed complications seen were infection in 33 cases, thrombosis of subclavian vein in six patients, delayed pneumothorax in four cases and hemothorax in one. One patient, who required repeated catheterizations since he refused creation of AV fistula, died of septicemia. The remaining patients responded well to the treatment of the respective complications.


Alzheimer's disease clinical variants show distinct regional patterns of neurofibrillary tangle accumulation.
The clinical spectrum of Alzheimer's disease (AD) extends well beyond the classic amnestic-predominant syndrome. The previous studies have suggested differential neurofibrillary tangle (NFT) burden between amnestic and logopenic primary progressive aphasia presentations of AD. In this study, we explored the regional distribution of NFT pathology and its relationship to AD presentation across five different clinical syndromes. We assessed NFT density throughout six selected neocortical and hippocampal regions using thioflavin-S fluorescent microscopy in a well-characterized clinicopathological cohort of pure AD cases enriched for atypical clinical presentations. Subjects underwent apolipoprotein E genotyping and neuropsychological testing. Main cognitive domains (executive, visuospatial, language, and memory function) were assessed using an established composite z score. Our results showed that NFT regional burden aligns with the clinical presentation and region-specific cognitive scores. Cortical, but not hippocampal, NFT burden was higher among atypical clinical variants relative to the amnestic syndrome. In analyses of specific clinical variants, logopenic primary progressive aphasia showed higher NFT density in the superior temporal gyrus (p = 0.0091), and corticobasal syndrome showed higher NFT density in the primary motor cortex (p = 0.0205) relative to the amnestic syndrome. Higher NFT burden in the angular gyrus and CA1 sector of the hippocampus were independently associated with worsening visuospatial dysfunction. In addition, unbiased hierarchical clustering based on regional NFT densities identified three groups characterized by a low overall NFT burden, high overall burden, and cortical-predominant burden, respectively, which were found to differ in sex ratio, age, disease duration, and clinical presentation. In comparison, the typical, hippocampal sparing, and limbic-predominant subtypes derived from a previously proposed algorithm did not reproduce the same degree of clinical relevance in this sample. Overall, our results suggest domain-specific functional consequences of regional NFT accumulation. Mapping these consequences presents an opportunity to increase understanding of the neuropathological framework underlying atypical clinical manifestations.


Deep sequencing-based analysis of the Cymbidium ensifolium floral transcriptome.
Cymbidium ensifolium is a Chinese Cymbidium with an elegant shape, beautiful appearance, and a fragrant aroma. C. ensifolium has a long history of cultivation in China and it has excellent commercial value as a potted plant and cut flower. The development of C. ensifolium genomic resources has been delayed because of its large genome size. Taking advantage of technical and cost improvement of RNA-Seq, we extracted total mRNA from flower buds and mature flowers and obtained a total of 9.52 Gb of filtered nucleotides comprising 98,819,349 filtered reads. The filtered reads were assembled into 101,423 isotigs, representing 51,696 genes. Of the 101,423 isotigs, 41,873 were putative homologs of annotated sequences in the public databases, of which 158 were associated with floral development and 119 were associated with flowering. The isotigs were categorized according to their putative functions. In total, 10,212 of the isotigs were assigned into 25 eukaryotic orthologous groups (KOGs), 41,690 into 58 gene ontology (GO) terms, and 9,830 into 126 Arabidopsis Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 9,539 isotigs into 123 rice pathways. Comparison of the isotigs with those of the two related orchid species P. equestris and C. sinense showed that 17,906 isotigs are unique to C. ensifolium. In addition, a total of 7,936 SSRs and 16,676 putative SNPs were identified. To our knowledge, this transcriptome database is the first major genomic resource for C. ensifolium and the most comprehensive transcriptomic resource for genus Cymbidium. These sequences provide valuable information for understanding the molecular mechanisms of floral development and flowering. Sequences predicted to be unique to C. ensifolium would provide more insights into C. ensifolium gene diversity. The numerous SNPs and SSRs identified in the present study will contribute to marker development for C. ensifolium.


Plasmacytoma of the Cervical Spine: A Case Study.
The purpose of this case study is to describe the presentation of a patient with plasmacytoma. A 49-year-old man presented with progressive neck pain, stiffness, and dysphagia to a chiropractic office. A radiograph indicated a plasmacytoma at C3 vertebral body. The lesion was expansile and caused a mass effect anteriorly on the esophagus and posteriorly on the spinal cord. Neurologic compromise was noted with fasciculations and hypesthesia in the right forearm. The patient was referred to a neurosurgeon. Surgical resection of the tumor was performed with a vertebral body spacer and surrounding titanium cage. Bony fusion was initiated by inserting bone grafts from the iliac crests into the titanium cage. Additional laboratory analysis and advanced imaging confirmed that the plasmacytoma had progressed to multiple myeloma and radiation and chemotherapy were also necessary. A chiropractor recognized a large, expansile plasmacytoma in the C3 vertebral body and referred the patient for surgical care. This case suggests that all practitioners of manual medicine should provide a careful analysis of the patient's clinical presentation and, if clinically warranted, radiographic examination to determine neck or back pain is due to an underlying malignant condition.


Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7.
Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic black cohosh rhizome extract and cycloartane-type triterpenoids on the estrogen receptor positive human breast cancer cell line MCF-7. Both extract and purified compounds clearly inhibited cellular proliferation. Gene expression profiling with the extract allowed us to identify 431 regulated genes with high significance. The extract induced expression pattern differed from those of 17beta-estradiol or the estrogen receptor antagonist tamoxifen. We observed a significant enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, as well as an increase of mRNAs coding for gene products involved in several stress response pathways. These functional groups were highly overrepresented among all regulated genes. Also several transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Real-Time RT-PCR analysis of 13 selected genes was conducted after treatment with purified compounds - the cycloartane-type triterpene glycoside actein and triterpene aglycons - showing similar expression levels compared to the extract. No estrogenic but antiproliferative and proapoptotic gene expression was shown for black cohosh in MCF-7 cells at the transcriptional level. The effects may be results of the activation of different pathways. The cycloartane glycosides and - for the first time - their aglycons could be identified as an active principle in black cohosh.


Comparison of the analgesic effect of intrathecal morphine between laparoscopic and open living donor hepatectomy: Propensity score matching analysis.
Laparoscopic donor hepatectomy is being increasingly adopted in transplant programs due to its numerous advantages. However, the role of intrathecal morphine (ITM) in laparoscopic donor hepatectomy has not been thoroughly investigated. This study aimed to compare the analgesic effects and safety of ITM between laparoscopic and open donor hepatectomy. This retrospective study included 742 donors who underwent hepatectomy with ITM between April 2007 and June 2019. Among them, 168 and 574 donors underwent laparoscopic hepatectomy (LH) and open hepatectomy (OH), respectively. Propensity score matching yielded two comparable groups of 168 donors each. The primary endpoint was the incidence of moderate-to-severe pain (maximum numerical rating scale [NRS] pain score ≥ 4) within 24 postoperative hours. The LH group had a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours than the OH group (16.1% vs 64.3%, P < .001). Moreover, the cumulative rescue intravenous opioids (in morphine-equivalent dose) on postoperative day (POD) 1 was lower in the LH group than in the OH group (3.3 [0-8.3] mg vs 10 [3.3-17.3] mg; P < .001). There were no significant between-group differences in the incidence of respiratory depression (2.4% vs 0.6%; P = .371) and prescriptions for pruritus (14.3% vs 15.5%; P = .878). However, the prescriptions for postoperative nausea and vomiting (PONV) was significantly higher in the LH group than in the OH group (64.9% vs 41.7%; P < .001). The predictors of antiemetic agent prescription included the use of laparoscopic procedure (adjusted odds ratio [OR], 2.05; 95% confidence interval [CI], 1.11-3.79; P = .021) and female sex (adjusted OR, 5.63; 95% CI, 3.19-9.92; P < .001). Preoperative ITM administration resulted in a significantly lower incidence of moderate-to-severe pain within 24 postoperative hours after laparoscopic donor hepatectomy than after open donor hepatectomy.


Detection of hydrogen bonds in dynamic regions of RNA by NMR spectroscopy.
NMR spectroscopy is a powerful tool to study the structure and dynamics of nucleic acids. In this unit, we give an overview of important experiments to determine and characterize hydrogen bonds in nucleic acids and provide detailed instructions for setting up recently developed sensitivity-improved NMR pulse sequences, i.e., BEST selective long-range HNN-COSY, selective BEST-TROSY-HNNCOSY, and Py H(CC)NN-COSY. The strengths and limitations of these experiments will also be discussed. Detailed step-by-step protocols are provided for each of the three pulse sequences, with special emphasis on adjusting and setting of delays and shaped pulses. The NMR pulse sequences with example datasets and optimized, nonstandard adiabatic pulse shapes used for selective (15)N magnetization transfer are provided. These experiments enable NMR analysis of a broad variety of RNAs ranging from low to high molecular weight and complexity.


The Leptin Receptor Complex: Heavier Than Expected?
Under normal physiological conditions, leptin and the leptin receptor (ObR) regulate the body weight by balancing food intake and energy expenditure. However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. Leptin, therefore, can act as a metabolic switch connecting the body's nutritional status to high energy consuming processes. We provide an extensive overview of current structural insights on the leptin-ObR interface and ObR activation, coupling to signaling pathways and their negative regulation, and leptin functioning under normal and pathophysiological conditions (obesity, autoimmunity, cancer, … ). We also discuss possible cross-talk with other receptor systems on the receptor (extracellular) and signaling cascade (intracellular) levels.


Correlation Between Testosterone and PSA Kinetics in Metastatic Prostate Cancer Patients Treated With Diverse Chemical Castrations.
To assess total testosterone and prostatic-specific antigen (PSA) kinetics among diverse chemical castrations, advanced-stage prostate cancer patients were randomized into three groups of 20: Group 1, Leuprolide 3.75 mg; Group 2, Leuprolide 7.5 mg; and Group 3, Goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients' levels of serum total testosterone and PSA were evaluated at two time periods: before the treatment and 3 months after the treatment. Spearman's rank correlation coefficient was utilized to verify the hypothesis of linear correlation between total testosterone and PSA levels. At the beginning the patients' age, stage, grade, PSA, and total testosterone were similar within the three groups, with median age 72, 70, and 70 years in Groups 1, 2, and 3, respectively. Three months after the treatment, patients who received Leuprolide 7.5 mg presented significantly lower median total testosterone levels compared with Goserelin 3.6 mg and Leuprolide 3.75 mg (9.5 ng/dL vs. 20.0 ng/dL vs. 30.0 ng/dL, respectively; p = .0072), while those who received Goserelin 3.6 mg presented significantly lower PSA levels compared with Leuprolide 7.5 mg and Leuprolide 3.75 mg (0.67 vs. 1.86 vs. 2.57, respectively; p = .0067). There was no linear correlation between total testosterone and PSA levels. Overall, regarding castration levels of total testosterone, 28.77% of patients did not obtain levels ≤50 ng/dL and 47.80% did not obtain levels ≤20 ng/dL. There was no correlation between total testosterone and PSA kinetics and no equivalence among different pharmacological castrations.


Containment of fluid samples in the hydrothermal diamond-anvil cell without the use of metal gaskets: performance and advantages for in situ analysis.
Metal gaskets (Re, Ir, Inconel, or stainless steel) normally used to contain fluid samples in the hydrothermal diamond-anvil cell (HDAC) are sometimes undesirable due to possible contamination and to gasket deformation at high pressures and temperatures resulting in nonisochoric behavior. Furthermore, in x-ray spectroscopic experiments, metal gaskets may attenuate the incident x-ray beam and emitted fluorescence x-rays, and the interaction of scattered radiation with the gasket may produce fluorescence that interferes with the x-ray spectrum of the sample. New arrangements and procedures were tested for the operation of the HDAC without using the metal gaskets. Distilled, de-ionized water was loaded into the sample chamber, a laser-milled recess 300 microm in diameter and approximately 50 microm deep centered in the 1.0 mm face of the lower diamond anvil, and sealed by pressing the top diamond anvil face directly against the lower one without a metal gasket in between. A maximum sample pressure of 202 MPa at 617 degrees C was maintained for a duration of 10 min without evidence of leakage. A small change in fluid density was observed in one experiment where the sample was held at 266 MPa at 708 degrees C for 10 min. The gasketless HDAC was also employed in x-ray absorption spectroscopy experiments, where, in addition to the sample chamber in the lower diamond, two grooves were milled at a 90 degrees angle to each other around the sample chamber to minimize the attenuation of incident and fluorescent x rays. With a minimum distance between the sample chamber and the grooves of 80 microm, a pressure of 76 MPa at 500 degrees C was maintained for 2 h with no change in the original fluid density.


Multicenter evaluation of synovectomy in the treatment of rheumatoid arthritis. Report of results at the end of five years.
A controlled multicenter evaluation of open surgical synovectomy in the treatment of rheumatoid arthritis (RA) was carried out over a period of 5 years after the operation. There was evidence of benefit in some knees but none in finger joints. Synovectomy performed at a stage of minimal damage did not result in fewer recurrences of disease activity than when done after greater damage had occurred. The results showed little longterm value of surgical synovectomy in the general treatment of RA or in the prevention of recurrences of disease activity or progressive articular damage. These results emphasize the need for controls in trials of this type.


Michael Pittaway.
A widely respected veterinary surgeon and an innovator within the profession, Michael Pittaway was also a man of great charm and huge energy, who applied his skills across a wide range of interests.


Activated whole-body arginine pathway in high-active mice.
Our previous studies suggest that physical activity (PA) levels are potentially regulated by endogenous metabolic mechanisms such as the vasodilatory roles of nitric oxide (NO) production via the precursor arginine (ARG) and ARG-related pathways. We assessed ARG metabolism and its precursors [citrulline (CIT), glutamine (GLN), glutamate (GLU), ornithine (ORN), and phenylalanine (PHE)] by measuring plasma concentration, whole-body production (WBP), de novo ARG and NO production, and clearance rates in previously classified low-active (LA) or high-active (HA) mice. We assessed LA (n = 23) and HA (n = 20) male mice by administering a stable isotope tracer pulse via jugular catheterization. We measured plasma enrichments via liquid chromatography tandem mass spectrometry (LC-MS/MS) and body compostion by echo-MRI. WBP, clearance rates, and de novo ARG and NO were calculated. Compared to LA mice, HA mice had lower plasma concentrations of GLU (71.1%; 36.8 ± 2.9 vs. 17.5 ± 1.7μM; p<0.0001), CIT (21%; 57.3 ± 2.3 vs. 46.4 ± 1.5μM; p = 0.0003), and ORN (40.1%; 55.4 ± 7.3 vs. 36.9 ± 2.6μM; p = 0.0241), but no differences for GLN, PHE, and ARG. However, HA mice had higher estimated NO production ratio (0.64 ± 0.08; p = 0.0197), higher WBP for CIT (21.8%, 8.6 ± 0.2 vs. 10.7 ± 0.3 nmol/g-lbm/min; p<0.0001), ARG (21.4%, 35.0 ± 0.6 vs. 43.4 ± 0.7 nmol/g-lbm/min; p<0.0001), PHE (7.6%, 23.8 ± 0.5 vs. 25.6 ± 0.5 nmol/g-lbm/min; p<0.0100), and lower GLU (78.5%; 9.4 ± 1.1 vs. 4.1 ± 1.6 nmol/g lbm/min; p = 0.0161). We observed no significant differences in WBP for GLN, ORN, PHE, or de novo ARG. We concluded that HA mice have an activated whole-body ARG pathway, which may be associated with regulating PA levels via increased NO production.


Comparative immunohistochemical analysis of WT-1, Syndecan and Snail in Ameloblastoma and odontogenic keratocyst: A retrospective study.
The purpose of this experimental study was to evaluate and compare the degree of expression of Wilm's Tumor Gene-1 (WT-1), Syndecan (CD 138) and Snail in Ameloblastoma and odontogenic keratocyst (OKC) and to analyse their potential role in pathogenesis. Immunohistochemical analysis was performed to evaluate WT-1, Syndecan and Snail expression in Ameloblastoma (n = 20) and OKC (n = 20). Topographical immunoexpression pattern of Ameloblast-like cells, Stellate Reticulum-like cells in Ameloblastoma and basal layer as well as suprabasal layer of cells of OKC were also compared. The results obtained were subjected to ANOVA test and Tukey HSD test through SPSS software 20.0 for Microsoft Windows. WT-1 and Snail overexpression was seen in both Ameloblastoma and OKCs. Syndecan, responsible for maintaining normal cellular morphology, cell-cell adhesion and differentiation was significantly downregulated in both the lesions. The Ameloblasts-like cells and the basal cells showed significantly higher immunopositivity for WT-1 and Syndecan as compared to that of basal cells. An inverse relation was noted for Snail protein. The ANOVA test predicted a statistically significant difference of expression across the lesions with a P value <0.0001 for Syndecan and Snail. The under-expression of epithelial membrane protein Syndecan-1 and upregulation of EMT transcription factor Snail can promote local invasion and is indicative of poor prognosis of these lesions. The overexpression of WT-1 results in tumorigenesis, proliferation and localized aggressiveness of Ameloblastoma and intrabony growth of OKC. Further investigation on the biologic behaviour of OKC is still recommended to arrive at more specific conclusions regarding its nature.


Primary follicular dendritic cell sarcoma of the pleura: A clinicopathological and immunohistochemical study of two cases.
Two cases of primary follicular dendritic cell sarcoma (FDCS) of the pleura are presented. The patients are a woman 76-years-old and a man 64-years-old who presented with nonspecific symptoms including chest pain, dyspnea, and cough. Clinical history did not disclose any pertinent history of previous malignancy. Diagnostic imaging showed the presence of a pleural-based mass in both patients and a thoracotomy with resection of the pleural mass was performed. Both tumors were described as solid, light tan, and with ill-defined borders. Histologically, both tumors showed similar histological features, namely the presence of a spindle cellular proliferation composed of elongated cells with fibrillary cytoplasm, oval nuclei, and conspicuous nucleoli. Mild to moderate cellular atypia was present, while mitotic figures ranged from 3 to 4 per 10 high power fields. Mature lymphocytes and plasma cells were also present dispersed throughout the tumor. Immunohistochemical stains in both cases show positive staining for CD21 and CD35 while focal staining was present for D2-40 and clusterin, while negative for other markers including keratin, desmin, S-100 protein, calretinin, and STAT-6. Clinical follow up shows that both patients have remained alive 12 and 14 months after initial diagnosis. The cases herein described represent an unusual occurrence of FDCS arising in the pleural surface and one that must be kept in mind when dealing with spindle cell tumors of the pleura.


Management of antithrombotic therapy before full-mouth extraction.
The management of antiplatelet and anticoagulant therapy before full-mouth extraction is a major concern for dentists. Approach should vary depending on the risk of bleeding and adverse cardiac events. We have adapted a more conservative approach with continuation of antiplatelet therapy in the majority of patients while implementing local hemostatic measures with good outcomes. Specific recommendations are provided for antiplatelet therapy before mouth extraction.


Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease.
Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR). The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease. Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (t(Na)), although 24-hour urinary Na excretion (U(Na)V) remained constant. Daily urinary angiotensinogen excretion (U(AGT)V, 152±10→82±17 μg/g Cre) reduced (p=0.02). Changes in tubular Na load (r(2)=0.26) and t(Na) (r(2)=0.25) correlated with baseline 24-hour U(AGT)V. Changes in filtered Na load correlated with changes in nighttime systolic BP (r(2)=0.17), but not with changes in daytime systolic BP. The change in the t(Na) to filtered Na load ratio was influenced by the change in daytime U(Na)V (β=-0.67, F=16.8), rather than the change in nighttime U(Na)V. Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of U(AGT)V by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events.


Thromboelastography Profiles of Critically Ill Patients With Coronavirus Disease 2019.
The rate of thromboembolic events among patients with coronavirus disease 2019 is high; however, there is no robust method to identify those at greatest risk. We reviewed thromboelastography studies in critically ill patients with coronavirus disease 2019 to characterize their coagulation states. Retrospective. Tertiary ICU in New York City. Sixty-four patients with coronavirus disease 2019 admitted to the ICU with thromboelastography performed. None. Fifty percent of patients had a clotting index in the hypercoagulable range (clotting index > 3) (median 3.05). Reaction time and K values were below the lower limit of normal in 43.8% of the population consistent with a hypercoagulable profile. The median α angle and maximum amplitude (75.8° and 72.8 mm, respectively) were in the hypercoagulable range. The α angle was above reference range in 70.3% of patients indicative of rapid clot formation. Maximum amplitude, a factor of fibrinogen and platelet count and function, and a measure of clot strength was above reference range in 60.1% of patients. Thirty-one percent had thromboembolic events; thromboelastography parameters did not correlate with events in our cohort. Those with D-dimer values greater than 2,000 were more likely to have shorter reaction times compared with those with D-dimer levels less than or equal to 2,000 (4.8 vs 5.6 min; p = 0.001). A large proportion of critically ill patients with coronavirus disease 2019 have hypercoagulable thromboelastography profiles with additional derangements related to fibrinogen and platelet function. As the majority of patients have an elevated thromboelastography maximum amplitude, a follow-up study evaluating platelet aggregation would be instructive.


An all-digital associated particle imaging system for the 3D determination of isotopic distributions.
Associated particle imaging (API) is a non-destructive nuclear technique for the 3D determination of isotopic distributions. By detecting the alpha particle associated with the emitted neutron in the deuterium-tritium fusion reaction with a position- and time-resolving detector, the direction of the 14.1 MeV neutron and its time of emission can be determined. Employing this method, isotope characteristic gamma rays emitted in inelastic neutron scattering events can be correlated with the neutron interaction location. An API system consisting of a sealed-type neutron generator, gamma detectors, and a position-sensitive alpha detector was designed, constructed, and characterized. The system was tested with common soil elements and shown to be sensitive to 12C, 16O, 28Si, 27Al, and 56Fe. New aspects of our approach are the use of a yttrium-aluminum-perovskite scintillator, using a sapphire window instead of a fiber-optic faceplate for light transport to the photomultiplier, and the all-digital data acquisition system. We present a description of the system with simulations and experimental results that show a position resolution on the alpha detector of 1 mm, a depth resolution using a LaBr3 detector of 6.2 cm, and an angular resolution of 4.5°. Additionally, we present single-element gamma response measurements for the elements mentioned above together with a comparison to Monte Carlo simulations (MCNP6).


Mechanism of adenosine triphosphate catabolism induced by deoxyadenosine and by nucleoside analogues in adenosine deaminase-inhibited human erythrocytes.
The mechanism of the depletion of ATP, recorded in the erythrocytes of adenosine deaminase-deficient children and of leukemia patients treated with deoxycoformycin, was investigated in normal human erythrocytes treated with this inhibitor of adenosine deaminase. Deoxyadenosine, which accumulates in both clinical conditions, provoked a dose-dependent accumulation of dATP, depletion of ATP, and increases in the production of inosine plus hypoxanthine. Concomitantly, there was an increase of AMP and IMP, but not of adenosine, indicating that catabolism proceeded by way of AMP deaminase. A series of nucleoside analogues (9-beta-D-arabinofuranosyladenine, N6-methyladenosine, 6-methylmercaptopurine ribonucleoside, tubercidin, ribavirin, and N-1-ribosyl-5-aminoimidazole-4-carboxamide riboside) also stimulated adenine nucleotide catabolism and increased AMP and IMP to various extents. The effects of deoxyadenosine and of the nucleoside analogues were prevented by 5'-iodotubercidin, an inhibitor of adenosine kinase. Strikingly, they were reversed if the inhibitor was added after the accumulation of nucleotide analogues and initiation of adenine nucleotide catabolism. Further analyses revealed linear relationships between the rate of phosphorylation of deoxyadenosine and nucleoside analogues and the increase in AMP and between the elevation of the latter above a threshold concentration of 10 microM and the rate of adenine nucleotide catabolism. Kinetic studies with purified erythrocytic AMP deaminase, at physiological concentrations of its effectors, showed that the enzyme is nearly inactive up to 10 microM AMP and increases in activity above this threshold. We conclude that the main mechanism whereby deoxyadenosine and nucleoside analogues stimulate catabolism of adenine nucleotides by way of AMP deaminase in erythrocytes is elevation of AMP, secondary to the phosphorylation of the nucleosides.


Single-photon tunneling via localized surface plasmons.
Strong evidence of a single-photon tunneling effect, a direct analog of single-electron tunneling, has been obtained in the measurements of light tunneling through individual subwavelength pinholes in a gold film covered with a layer of polydiacetylene. The transmission of some pinholes reached saturation because of the optical nonlinearity of polydiacetylene at a very low light intensity of a few thousand photons per second. This result is explained theoretically in terms of a "photon blockade," similar to the Coulomb blockade phenomenon observed in single-electron tunneling experiments. Single-photon tunneling may find applications in the fields of quantum communication and information processing.


Adolescent drug addiction treatment and weight gain.
Neurotransmitter release in the nucleus accumbens use has been linked to self-administration and learning following drug use. This endogenous reward system is also activated following food intake or sex. Therefore, rebound hyperphagia following abstinence may be a mechanism to replenish the release of neurotransmitters in this reward system, leading to increased weight gain and a rise in body mass index during recovery from substance abuse. In this report, we examined the relationship between supervised drug abstinence and increased weight gain among adolescents at a residential substance abuse treatment center. Mean weight change over time was followed by repeated analysis of weight and body mass index. Significant weight gain and body mass index increase was observed during supervised and confirmed abstinence from drug use. Furthermore, significant interactions between tobacco use and primary substance use disorder with weight gain was demonstrated by multivariate analysis of variance.


Pulmonary rehabilitation for patients with COPD.
In the UK pulmonary rehabilitation is not a well-recognised therapy for patients with COPD. However, there is evidence to support its effectiveness and therefore a review of literature was undertaken to explore its benefits and limitations in the treatment of this disabling disease. The results showed that an improved quality of life for patients is achievable.


Erythrocytosis due to an erythropoietin-producing large uterine leiomyoma.
Various etiologies of myomatous erythrocytosis syndrome (erythrocytosis associated with a uterine leiomyoma), one of which is altered production of erythropoietin, have been proposed. We report a case of erythrocytosis associated with a large uterine leiomyoma in which erythropoietin activity and immunostaining for erythropoietin in the leiomyoma were found. A 64-year-old woman, gravida 2, para 1, was referred to our department for treatment of a large uterine myoma and erythrocytosis with elevated levels of erythropoietin. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, and the results of the pathological examination confirmed the diagnosis of leiomyoma of the uterus, which weighed 920 g. The patient's postoperative course was satisfactory, and the levels of hemoglobin and erythropoietin were normalized and remained within normal ranges. The level of erythropoietin in the uterine leiomyoma measured by radioimmunoassay was elevated (372 mU/wet gram), and specific immunostaining for erythropoietin was found in the cytoplasm of leiomyoma cells. The levels of erythropoietin extracted from uterine leiomyomas of other patients who did not have erythrocytosis (control patients, n = 5) were lower (65 +/- 15.3 mU/wet gram), but specific immunostaining for erythropoietin was also found in the cytoplasm of leiomyoma cells from those patients. Our case was typical of myomatous erythrocytosis syndrome in which uterine leiomyoma was proved to produce erythropoietin. Our results also suggest that erythropoietin is produced in uterine leiomyomas of patients with and without erythrocytosis. Leiomyoma of the uterus may affect the production of erythropoietin and may develop into myomatous erythrocytosis syndrome when the level of erythropoietin exceeds the normal range.


Sarcomatoid variant of anaplastic large cell lymphoma mimicking a primary breast cancer: a challenging diagnosis.
The sarcomatoid variant of anaplastic large cell lymphoma is one of the rarest histologic variants of this neoplasm. Due to its sarcomatoid features, it is frequently misdiagnosed as a poorly differentiated sarcoma, anaplastic carcinoma, or melanoma. We report the case of a 92-year-old woman with a sarcomatoid anaplastic large cell lymphoma mimicking a primary breast neoplasm. The patient presented with a rapidly enlarging lump in the left breast and nodules in the right axilla. The immunohistochemical profile showed reactivity for leukocyte common antigen, UCHL-1, vimentin, and CD30, but immunoexpression of anaplastic lymphoma kinase was lacking. Anaplastic large cell lymphomas are lymphoid neoplasms of T-cell/null-cell lineage that consistently express the activation marker CD30 and usually carry a gene rearrangement of the anaplastic lymphoma kinase gene. To the best of our knowledge, this is the first reported case of sarcomatoid anaplastic large cell lymphoma presenting as a primary breast neoplasm in which anaplastic lymphoma kinase expression was assessed.


Establishing an Artificial Pathway for De Novo Biosynthesis of Vanillyl Alcohol in Escherichia coli.
Vanillyl alcohol is a phenolic alcohol and is used as a flavoring agent in foods and beverages. In this paper, we propose a novel artificial pathway for microbial production of vanillyl alcohol from simple carbon sources. The pathway extends from 4-hydroxybenzoic acid (4-HBA), and needs only three heterologous enzymes, p-hydroxybenzoate hydroxylase (PobA), carboxylic acid reductase (CAR) and caffeate O-methyltransferase (COMT). First, we examined the promiscuous activity of COMT toward 3,4-dihydroxybenzyl alcohol and found a kcat value of 0.097 s-1. Meanwhile, 499.36 mg/L vanillyl alcohol was produced by COMT in vivo catalysis when fed with 1000 mg/L 3,4-dihydroxybenzyl alcohol. In the following experiment, de novo biosynthesis of vanillyl alcohol was carried out and 240.69 mg/L vanillyl alcohol was produced via modular optimization of pathway genes. This work was to date the first achievement for microbial production of vanillyl alcohol. Additionally, the present study demonstrates the application of enzyme promiscuity of COMT in the design of an artificial pathway for the production of high-value methylated aromatic compounds.


Dietary intake of free-living elderly in northern Greece.
The aim of the present study was to investigate the nutrient intake of a non-institutionalized Greek elderly population. Dietary intake and anthropometric data were investigated in 100 elderly subjects from Grevena, Greece, all belonging to the race of "Hasiotes." According to BMI classification, 48% of the subjects are considered overweight and 20% obese. WHR for women and men was 0.91 and 0.98, respectively. Both genders presented insufficient energy intake (7.27 +/- 3.49MJ/d) in 3 +/- 0.9 feeding sessions daily. Mean protein and fiber intake was 0.82 +/- 0.43 and 0.29 +/- 0.2g/kg BW, respectively. The diet presented insufficient amounts of vitamins A, B6, D, E, K, Biotin, Pantothenic acid, Cu, I, Mg, Mn, and Zn. Female subjects exhibited low dietary intake of vitamins B2, B3 and Ca. The diet had many characteristics of the traditional Mediterranean diet and comprised of a high intake of goat-milk yoghurt, olive oil, goat cheese, traditional alcohol drinks, pies, legumes, fruits and meat. The majority of the sample (70%), reported fasting on Orthodox celebrations. Further research should assess adherence to the Mediterranean diet with the use of scores and compare diet characteristics to other regions in Greece, in order to present regional differences in Greek diet variations.


The action of cabbage-leaf phospholipase D upon lysolecithin.
1. The action of the water-soluble phospholipase D from Savoy cabbage leaves upon an aqueous solution of lysolecithin has been studied. 2. Optimum conditions required the presence of Ca(2+) ions and pH5.8. 3. Equivalence was found between the amounts of lysolecithin hydrolysed and free choline released. The reaction was not accompanied by deacylation. 4. As the enzymic degradation proceeded, an opalescence developed, owing to the insolubility of the reaction product in the presence of Ca(2+) ions. 5. Evidence has been obtained indicating the heterogeneity of this reaction product.


Introns boost transgene expression in Drosophila melanogaster.
Using Drosophila as a host, we have examined the effect that the presence of an intron has on the accumulation of a processed transgene mRNA. To provide a model system that was free from major position effects, two fish antifreeze protein (AFP) transgenes were arranged in divergent transcriptional orientation from a central Drosophila yolk protein promoter/enhancer region and introduced into the flies by P-element transformation and/or mobilization. In this way the organization of both the structural genes and the promoter elements mimicked their natural arrangements. When one member of the fish AFP transgene pair had its single 180 bp intron deleted, there was a 2- to 11-fold (average 5-fold) decrease in its mRNA level compared to that generated from the control gene containing the fish AFP intervening sequence. When the deleted intron was replaced by a 70 bp intervening sequence originating from the yolk protein 1 gene, mRNA accumulation was restored to its original level. Even for the streamlined genome of Drosophila, where the intron number and size are generally reduced compared to mammals, the presence of an intervening sequence appears to facilitate mRNA accumulation.


Accelerated induction regimens of TNF-alpha inhibitors in patients with inflammatory bowel disease: a scoping review protocol.
Tumour necrosis factor (TNF)-alpha inhibitors are commonly used to treat inflammatory bowel disease (IBD). In patients with IBD who are unresponsive to their first induction dose, the implementation of an 'accelerated' induction dose schedule (doses more frequent than recommended in product monographs) is becoming increasingly common. It is unclear whether this practice results in favourable patient outcomes, such as avoidance of surgery and disease remission. As such, there is a need to identify and map the current evidence base on accelerated induction schedules of these medications in the treatment of IBD. A scoping review will be employed to systematically identify and characterise the nature of scientific literature on accelerated induction regimens of TNF-alpha inhibitors. MEDLINE, Embase, International Pharmaceutical Abstracts and grey literature will be searched to identify relevant studies. The titles/abstracts of all records and full text of potentially relevant articles will be independently screened for inclusion by two reviewers. Data will be abstracted from included studies by one reviewer and verified for accuracy by another. The findings will be synthesised descriptively. We intend to report the findings of this scoping review in a peer-reviewed journal and a scientific conference. This research was registered prospectively with the Open Science Framework (https://osf.io/z7n2d/).


Comparative Effects of Isokinetic Training and Virtual Reality Training on Sports Performances in University Football Players with Chronic Low Back Pain-Randomized Controlled Study.
The objective of this study is to find and compare the effects of isokinetic training and virtual reality training on sports performances in university football players with chronic low back pain. This is a randomized, double-blinded controlled study. The study was conducted on 45LBP participants at university hospital. First group (n = 15) received isokinetic training, second group (n = 15) received virtual reality training, and the control group (n = 15) received conventional training exercises for four weeks. Clinical (pain intensity and player wellness) and sports performance (40 m sprint, 4 × 5 m sprint, submaximal shuttle running, countermovement jump, and squat jump) scores were measured at baseline, after 4 weeks, 8 weeks, and 6 months. Four weeks following training VRT group shows more significant changes in pain intensity and player wellness scores than IKT and control groups (p ≤ 0.001). Sports performance variables (such as 40 m sprint, 4 × 5 m sprint, submaximal shuttle running, countermovement jump, and squat jump) scores also show significant improvement in VRT group than the other two groups (p ≤ 0.001). Overall, our study suggests that strength training through virtual reality training protocol improves pain and sports performances than isokinetic training and other conventional trainings in university football players with chronic low back pain.


Pre-eclampsia: overview on the role of biomarkers in 2016.
Preeclampsia which affects approximatively 2% of pregnancies is a major cause of maternal and perinatal morbidity and mortality. Pathogenesis of pre-eclampsia is nowadays increasingly understood. It implies multiple actors and biomarkers appear to be playing a major role. New uses of those biomarkers for risk stratification and diagnosis of predisposed preeclamptic patients followed by obstetricians is an hot topic. The combined approach of biomarkers, medical history and obstetrical ultrasounds enables risk estimation in the first quarter and later on. A better understanding of this risk would enable better monitoring of obstetrical patients and reduce the occurrence of adverse complications for them and for the fetal well-being.


EUROPA: A Case Study for Teaching Sensors, Data Acquisition and Robotics via a ROS-Based Educational Robot.
Robots have become a popular educational tool in secondary education, introducing scientific, technological, engineering and mathematical concepts to students all around the globe. In this paper EUROPA, an extensible, open software and open hardware robotic platform is presented focusing on teaching physics, sensors, data acquisition and robotics. EUROPA's software infrastructure is based οn Robot Operating System (ROS). It includes easy to use interfaces for robot control and interaction with users and thus can easily be incorporated in Science, Technology, Engineering and Mathematics (STEM) and robotics classes. EUROPA was designed taking into account current trends in educational robotics. An overview of widespread robotic platforms is presented, documenting several critical parameters of interest such as their architecture, sensors, actuators and controllers, their approximate cost, etc. Finally, an introductory STEM curriculum developed for EUROPA and applied in a class of high school students is presented.


Highly monodisperse M(III)-based soc-MOFs (M = In and Ga) with cubic and truncated cubic morphologies.
In this work, we carry out an investigation on shape-controlled growth of In(III)- and Ga(III)-based square-octahedral metal-organic frameworks (soc-MOFs). In particular, controllable crystal morphological evolution from simple cubes to complex octadecahedra has been achieved, and resultant highly uniform crystal building blocks promise new research opportunities for preparation of self-assembled MOF materials and related applications.


CRISPR Detection and Research on Screening Mutant Gene TTN of Moyamoya Disease Family Based on Whole Exome Sequencing.
Moyamoya disease (MMD) has a high incidence in Asian populations and demonstrates some degree of familial clustering. Whole-exome sequencing (WES) is useful in establishing key related genes in familial genetic diseases but is time-consuming and costly. Therefore, exploring a new method will be more effective for the diagnosis of MMD. We identified familial cohorts showing MMD susceptibility and performed WES on 5 affected individuals to identify susceptibility loci, which identified point mutation sites in the titin (TTN) gene (rs771533925, rs559712998 and rs72677250). Moreover, TTN mutations were not found in a cohort of 50 sporadic MMD cases. We also analyzed mutation frequencies and used bioinformatic predictions to reveal mutation harmfulness, functions and probabilities of disease correlation, the results showed that rs771533925 and rs72677250 were likely harmful mutations with GO analyses indicating the involvement of TTN in a variety of biological processes related to MMD etiology. CRISPR-Cas12a assays designed to detect TTN mutations provided results consistent with WES analysis, which was further confirmed by Sanger sequencing. This study recognized TTN as a new familial gene marker for moyamoya disease and moreover, demonstrated that CRISPR-Cas12a has the advantages of rapid detection, low cost and simple operation, and has broad prospects in the practical application of rapid detection of MMD mutation sites.


Electrical conductivity measurements of aqueous fluids under pressure with a hydrothermal diamond anvil cell.
Electrical conductivity data of aqueous fluids under pressure can be used to derive the dissociation constants of electrolytes, to assess the effect of ionic dissociation on mineral solubility, and to interpret magnetotelluric data of earth's interior where a free fluid phase is present. Due to limitation on the tensile strength of the alloy material of hydrothermal autoclaves, previous measurements of fluid conductivity were mostly restricted to less than 0.4 GPa and 800 °C. By adapting a Bassett-type hydrothermal diamond anvil cell, we have developed a new method for acquiring electrical conductivity of aqueous fluids under pressure. Our preliminary results for KCl solutions using the new method are consistent with literature data acquired with the conventional method, but the new method has great potential for working in a much broader pressure range.


Synthesis of enantiopure pyrrolidine-derived peptidomimetics and oligo-beta-peptides via nucleophilic ring-opening of beta-lactams.
The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by resolution with D- and L-Boc phenylalanine is described. The potential of these optically active spiro beta-lactams on the synthesis of peptidomimetics as analogues of melanostatin is evaluated. Theoretical studies of several models, at the Becke3LYP/6-31+G* level of theory, together with previous experimental evidences from our group, gathered by NMR, allow us to design structures that can efficiently mimic some biologically active peptide-type molecules. On the other hand, the spiro beta-lactams have shown their utility in the preparation of beta-peptides. As an example, a homo-tetra-beta-peptide was synthesized. This research will continue in the future in order to obtain higher peptides with potential biological activity.


Incidence of secondary vascular complications after stroke.
Stroke is a clinical syndrome characterized by the sudden occurrence of a permanent focal neurological deficit. The most common causes of death are transtentorial herniation, pneumonia, pulmonary embolism and heart disease. According to literature data, pulmonary embolism (PE) is responsible for 5% of deaths after stroke. The aim of this article is to determine the incidence of patients who had secondary vascular complications in the form of PE and deep venous thrombosis (DVT) after stroke and indicate the need for creating and promoting the algorithm for these complications in patients after stroke. The study included 86 patients hospitalized at the Clinic of Physical Medicine and Rehabilitation in the period from October 2008 to October 2009 who have had rehabilitation as a continuation of the treatment immediately after the stroke. Hemorrhagic type was present in 13% of patients, and ischemic in 87%. As a secondary complication after stroke, five patients had pulmonary embolism. Neurological deficit in these patients was in the form of hemiplegia and were with ischemic type. Time from stroke until the appearance of symptoms of pulmonary embolism was in average 25.4 days. Suggested thrombi prophylaxis therapy (which they received before rehabilitation) in patients who have developed PE was Aspirin Protect, while no patient had recommended low molecular heparin. Physical therapy was performed for all patients, and mechanical methods of prophylaxis were used. Different attitudes about prophylaxis effects for these patients should be regulated by a unique algorithm that would reduce the possibility of discrepancy in therapeutic sense. That is why for patients with acute stroke and limited mobility it is recommended to use heparin or low molecular heparin (LMH) in preventive doses, if there are no contraindications for anticoagulants, with physical therapy and mechanical methods of prophylaxis.


[Effects of PSMB5 on proliferation and bortezomib chemo-resistance in human myeloma cells and its related molecular mechanisms].
Objective: To investigate the effects of proteasome beta 5 subunit (PSMB5) on proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and its related molecular mechanisms. Methods: We used two MM cell lines, RPMI 8226 and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of human myeloma cells under the treatment of bortezomib; Apoptosis-related gene expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western blot. Results: ①PSMB5 overexpression and knockdown were successfully constructed in RPMI 8226 and BTZ100 cells. ②PSMB5 expression was positively correlated with cell proliferation of RPMI 8226 and BTZ100 cells (P<0.05) . ③The cell viability was lower after PSMB5 knockdown in RPMI 8226 cells than control cells under the same concentration of BTZ[IC(50) at 24 h: (7.01±0.47) and (9.64±0.55) nmol/L respectively, t=6.289, P=0.003]. The cell viability was higher after PSMB5 overexpression in RPMI 8226 cells than control cells under the same concentration of BTZ[IC(50) at 24 h: (10.99±0.58) and (9.51±0.37) nmol/L respectively, t=3.724, P=0.020) . PSMB5 expression was negatively correlated with the sensitivity of RPMI 8226 cells to BTZ. The results of BTZ100 cells were similar. ④The expression of PSMB5 was negatively correlated with the apoptosis of RPMI 8226 and BTZ100 under the treatment of BTZ. ⑤Meanwhile, PSMB5 knockdown could increase the expression of pro-apoptosis gene Bax and cleaved caspase-3 and decrease the expression of anti-apoptotic gene Bcl-2 and p-Akt. PSMB5 over-expression has the opposite results. Conclusion: PSMB5 knockdown could improve the bortezomib sensitivity of MM cells via activation of apoptosis signaling. PSMB5 may be a potential therapeutic target for MM.


Improving the prognosis of diabetic patients: evaluating the role of intensive versus moderate blood pressure control with selective angiotensin II receptor blocker (ARB) therapy.
The ABCD (Appropriate Blood Pressure Control in Diabetes) and ABCD-2V (Part 2 with Valsartan) are prospective, randomised clinical trials which will provide important data on the impact of intensive vs. moderate blood pressure (BP) control on microvascular and macrovascular complications in normotensive and hypertensive patients with type 2 diabetes mellitus (DM). The ABCD trial was a five-year study that compared the effects of intensive vs. moderate BP control on the endpoints of nephropathy, retinopathy, neuropathy, and cardiovascular disease events using a calcium channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor as the primary antihypertensive agents. The recently published results of the hypertensive cohort of ABCD are reviewed herein. The follow-up study, ABCD-2V, is ongoing and was designed to compare intensive vs. moderate BP control on the same endpoints as the ABCD study, using the highly selective angiotensin II receptor blocker (ARB) valsartan as the primary antihypertensive agent. First results of ABCD-2V are expected in 2004. The baseline characteristics for the patients enrolled thus far in the hypertensive cohort of ABCD-2V are reviewed. These studies will provide insight into the role of intensive vs. moderate BP control in the management of normotensive and hypertensive patients with type 2 DM.


Comparative effects of lidocaine and procainamide on acutely impaired hemodynamics.
Controversy exists regarding the relative safety of intravenously administered lidocaine and procainamide to patients with acutely impaired hemodynamics. Accordingly, their effects were studied in 15 such patients, 14 with acute myocardial infarction and one with cardiomyopathy and severe congestive heart failure. All had elevated levels of pulmonary capillary wedge pressure (greater than 15 mm Hg) and/or low cardiac index (less than 2.5 liters/min/m2). Patients were given lidocaine, a 100 mg bolus followed by a 3 mg/min infusion and, after at least a 30 minute recovery period, procainamide, a 100 mg bolus over 2 minutes followed by a 20 mg/min infusion for 20 to 25 minutes. Hemodynamic measurements were compared early and late in the infusion of each drug. Small, clinically insignificant differences were observed in the hemodynamic responses to the drugs, and no clinically significant deterioration occurred with either. Conventional therapeutic doses of intravenous procainamide can be administered by this regimen, to patients with acute myocardial infarction complicated by cardiac failure or low cardiac output, without producing deleterious hemodynamic effects.


Suspected infection in afebrile patients: Are they septic?
We prospectively evaluated afebrile patients admitted to an emergency department (ED), with suspected infection and only tachycardia or tachypnea.The white blood cell count (WBC) was obtained, and patients were considered septic if leukocyte count was >12,000 μL-1 or <4000 μL-1 or with >10% of band forms. Clinical data were collected to examine whether sepsis could be predicted.Seventy patients were included and 37 (52.86%) met sepsis criteria. Self-measured fever showed an odds ratio (OR) of 5.936 (CI95% 1.450-24.295; P = 0.0133) and increased pulse pressure (PP) showed an OR of 1.405 (CI95% 1.004-1.964; P = 0.0471) on multivariate analysis. When vital signs were included in multivariate analysis, the heart rate showed an OR of 2.112 (CI95% 1.400-3.188; P = 0.0004). Self-measured fever and mean arterial pressure <70 mm Hg had high positive likelihood ratios (3.86 and 2.08, respectively). The nomogram for self-measured fever showed an increase of sepsis chance from 53% (pretest) to approximately 80% (post-test).The recognition of self-measured fever, increased PP, and the intensity of heart rate response may improve sepsis recognition in afebrile patients with tachycardia or tachypnea. These results are important for medical assessment of sepsis in remote areas, crowded and low-resourced EDs, and low-income countries, where WBC may not be readily available.


Contrasting the Role of Mg and Ba Doping on the Microstructure and Thermoelectric Properties of p-Type AgSbSe2.
Microstructure has a critical influence on the mechanical and functional properties. For thermoelectric materials, deep understanding of the relationship of microstructure and thermoelectric properties will enable the rational optimization of the ZT value and efficiency. Herein, taking AgSbSe2 as an example, we first report a different role of alkaline-earth metal ions (Mg(2+) and Ba(2+)) doping in the microstructure and thermoelectric properties of p-type AgSbSe2. For Mg doping, it monotonously increases the carrier concentration and then reduces the electrical resistivity, leading to a substantially enhanced power factor in comparison to those of other dopant elements (Bi(3+), Pb(2+), Zn(2+), Na(+), and Cd(2+)) in the AgSbSe2 system. Meanwhile, the lattice thermal conductivity is gradually suppressed by point defects scattering. In contrast, the electrical resistivity first decreases and then slightly rises with the increased Ba-doping concentrations due to the presence of BaSe3 nanoprecipitates, exhibiting a different variation tendency compared with the corresponding Mg-doped samples. More significantly, the total thermal conductivity is obviously reduced with the increased Ba-doping concentrations partially because of the strong scattering of medium and long wavelength phonons via the nanoprecipitates, consistent with the theoretical calculation and analysis. Collectively, ZT value ∼1 at 673 K and calculated leg efficiency ∼8.5% with Tc = 300 K and Th = 673 K are obtained for both AgSb0.98Mg0.02Se2 and AgSb0.98Ba0.02Se2 samples.


Avoiding early revision rhytidectomy: a biomechanical comparison of tissue plication suture techniques.
Manipulation and suspension of the superficial musculoaponeurotic system (SMAS) is performed by 74% of rhytidectomy surgeons. Multiple variations in suture techniques are employed in this task, but they have never been evaluated for differences in their ability to withstand stress. To compare the biomechanical properties of two different suture techniques that are used in SMAS plications during rhytidectomy: a double-layered running locking (DRL) stitch and multiple horizontal mattress stitches. Fourteen horizontal mattress plications, in rows of six sutures, and comparable lengths of 16 DRL stitch plications of pig skin samples, were stressed using a tensometer with grip displacement increasing at a constant rate of 0.5 cm/Min. The required force to cause plication failure was recorded for each sample at three suture break points. There was no significant difference between the two groups in the force required to cause the initial suture failure. Unlike the horizontal mattress plication, an initial break seemed to cause minimal to no distortion of the DRL tissue plication. When results were normalized by the initial break forces to account for small variations in tissue properties, the force ratio required to cause a second suture break was significantly larger in the DRL group than in the horizontal mattress technique. This is evidenced by the average second to first break force ratios of 1.62 vs. 1.13 for the DRL and horizontal mattress stitches, respectively, with a P-value of .60. The mean ratios of third to first break forces for the DRL and horizontal mattress groups were 2.08 and 0.91, respectively, with a P-value of .08. The DRL stitch requires more force than the horizontal mattress stitch to cause significant failure of tissue plication. This technique may enable plastic surgeons to avoid early revision rhytidectomy due to suture failure, and to create a long-lasting, youthful cosmetic result.


Central nervous system decompression sickness and venous gas emboli in hypobaric conditions.
Altitude decompression sickness (DCS) that involves the central nervous system (CNS) is a rare but potentially serious condition. Identification of early symptoms and signs of this condition might improve treatment. We studied data from 26 protocols carried out in our laboratory over the period 1983-2003; all were designed to provoke DCS in a substantial proportion of subjects. The data set included 2843 cases. We classified subject-exposures that resulted in DCS as: 1) neurological DCS of peripheral and/or central origin (NEURO); 2) a subset of those that involved only the CNS (CNS); and 3) all other cases, i.e., DCS cases that did not have a neurological component (OTHER). For each case, echo imaging data were used to document whether venous gas emboli (VGE) were present, and their level was classified as: 1) any level, i.e., Grade 1 or higher (VGE-1); and 2) high level, Grade 4 (VGE-4). There were 1108 cases of altitude DCS in the database; 218 were classified as NEURO and 49 of those as CNS. VGE-1 were recorded in 83.8% of OTHER compared with 58.7% of NEURO and 55.1% of CNS (both p < 0.001 compared with OTHER). The corresponding values for VGE-4 were 48.8%, 37.0%, and 34.7% (p < 0.001, compared to OTHER). Hyperbaric oxygen (HBO) was used to treat about half of the CNS cases, while all other cases were treated with 2 h breathing 100% oxygen at ground level. Since only about half of the rare cases of hypobaric CNS DCS cases were accompanied by any level of VGE, echo imaging for bubbles may have limited application for use as a predictor of such cases.


Morgagnian cataract resulting from a naturally occurring nonsense mutation elucidates a role of CPAMD8 in mammalian lens development.
To investigate the genetic basis of hereditary lens opacities we analyzed 31 cases of bilateral congenital cataract in Red Holstein Friesian cattle. A genome-wide association study revealed a significant association on bovine chromosome 7 at positions 6,166,179 and 12,429,691. Whole genome re-sequencing of one case and four relatives showed a nonsense mutation (g.5995966C>T) in the PZP-like, alpha-2-macroglobulin domain containing 8 (CPAMD8) gene leading to a premature stop codon (CPAMD8 p.Gln74*) associated with cataract development in cattle. With immunohistochemistry we confirmed a physiological expression of CPAMD8 in the ciliary body epithelium of the eye in unaffected cattle, while the protein was not detectable in the ciliary body of cattle with cataracts. RNA expression of CPAMD8 was detected in healthy adult, fetal and cataractous lenses.


Selective excitation with asymmetric adiabatic pulses for NMR spectroscopy.
Existing selective pulses are mainly constructed in the forms of classically shaped pulses, such as the Gaussian pulses, or generated by using numerical optimization methods. However, all of these pulses are highly sensitive to radiofrequency (RF) intensity variation, which means their performance is highly dependent on the accuracy and stability of the RF intensity. Even a slight RF intensity deviation can cause severe degradation in the excitation profile. To solve this problem, we propose a method for narrow selective excitation by sequential application of a pair of phase-opposite asymmetric adiabatic pulses, all within two scans. By retaining the adiabatic character, the new method is highly robust to RF intensity variation. Moreover, it has flexible excitation bandwidth, ranging from line-selective to narrow-band-selective pulses. The method is tested both in numerical simulations and solution-state NMR experiments.


Lack of immunity against rubella among Italian young adults.
To support the evaluation of the 2010-15 National Plan for Measles and Congenital Rubella Elimination, the authors designed and performed a serosurveillance survey to verify the immunity/susceptibility rate against rubella among Apulian young adults. The study was carried out from May 2011 to June 2012 in the Department of Transfusion Medicine/Blood Bank of Policlinico General Hospital in Bari. Subjects were enrolled by a convenience sampling. For each enrolled patient a 5 ml serum sample was collected and tested for anti-rubella IgG. The geometrical means (GMT) of anti-rubella IgG was calculated. T student test or ANOVA test, when appropriate, was used to compare the means of age per gender and GMT of anti-rubella IgG titres per age classes. Chi-square test was used to compare the proportion of anti-rubella IgG positive subjects per gender and per age classes. For all tests, a p value <0.05 was considered as significant. At the end of the study 1764 subjects were enrolled, 1362 (77.2%) of which were male. The mean age was 38.4 ± 11.7 years (range: 17-65). 86.7% (95% CI = 85.0-88.2) had a positive titre of anti-rubella IgG. GMT of anti-rubella IgG titre was 4.3. The proportion of positive subjects was of 76.8% (n = 279/363; 95% CI = 72.2-81.1) in persons aged 18-26 years; 88.1% (n = 310/352; 95% CI = 84.2-91.3) in 27-35 year-old people; 88.5% (n = 464/524; 95% CI = 85.5-91.1) in 36-45 year-old people; 90.7% (n = 350/386; 95% CI = 87.3-93.4) among people aged 46-55 years and 90.6% (n = 126/139; 95% CI = 84.5-94.9) in 55-65 year-old people (Chi-square = 39.7; p < 0.0001). GMT of anti-rubella IgG titre was 4.3 (4.3 in male and 4.2 in female, t = 2.2; p = 0.03) and seems to differ dividing the enrolled subjects by age group (F = 14.3; p < 0.0001). According to our data, too many women of child-bearing age are still unprotected from rubella in the elimination era and in this scenario the public health efforts should be oriented to catch-up activities.