Loblolly pine grown under elevated CO2 affects early instar pine sawfly performance.
Seedlings of loblolly pine Pinus taeda (L.), were grown in open-topped field chambers under three CO2 regimes: ambient, 150 μl l-1 CO2 above ambient, and 300 μl l-1 CO2 above ambient. A fourth, non-chambered ambient treatment was included to assess chamber effects. Needles were used in 96 h feeding trials to determine the performance of young, second instar larvae of loblolly pine's principal leaf herbivore, red-headed pine sawfly, Neodiprion lecontei (Fitch). The relative consumption rate of larvae significantly increased on plants grown under elevated CO2, and needles grown in the highest CO2 regime were consumed 21% more rapidly than needles grown in ambient CO2. Both the significant decline in leaf nitrogen content and the substantial increase in leaf starch content contributed to a significant increase in the starch:nitrogen ratio in plants grown in elevated CO2. Insect consumption rate was negatively related to leaf nitrogen content and positively related to the starch:nitrogen ratio. Of the four volatile leaf monoterpenes measured, only β-pinene exhibited a significant CO2 effect and declined in plants grown in elevated CO2. Although consumption changed, the relative growth rates of larvae were not different among CO2 treatments. Despite lower nitrogen consumption rates by larvae feeding on the plants grown in elevated CO2, nitrogen accumulation rates were the same for all treatments due to a significant increase in nitrogen utilization efficiency. The ability of this insect to respond at an early, potentially susceptible larval stage to poorer food quality and declining levels of a leaf monoterpene suggest that changes in needle quality within pines in future elevated-CO2 atmospheres may not especially affect young insects and that tree-feeding sawflies may respond in a manner similar to herb-feeding lepidopterans.


Safety and effectiveness of insulin analogues in type 2 diabetic patients from Algeria: a sub-analysis of the A₁chieve study.
To determine the safety and effectiveness of insulin analogues in type 2 diabetes (T2D) patients in the Algerian cohort of the A₁chieve study and to examine the status of T2D management across different regions in Algeria. Patients starting therapy with biphasic insulin aspart 30, insulin detemir, insulin aspart (IAsp) or IAsp + basal insulin at their physicians' decision were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary outcomes included changes from baseline to Week 24 in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), weight and quality of life (QoL, evaluated using the EQ-5D questionnaire). Overall, 1494 patients (mean ± SD age: 60.1 ± 10.3 years; body mass index: 28.1 ± 4.9 kg/m(2); HbA1c: 9.2 ± 1.8%) were enrolled. Poor baseline glucose control was revealed across the different Algerian regions with mean HbA1c varying from 8.9% to 9.6%. Two SADRs were reported during the study. The proportion of patients reporting major hypoglycaemic events decreased from 1.1% at baseline to 0.2% at Week 24 (p = 0.0017). Significant improvements in mean HbA1c (-1.3 ± 2.0%), FPG (-38.8 ± 79.9 mg/dL) and post-breakfast PPPG (-51.4 ± 97.1 mg/dL) were observed in the entire cohort (all p < 0.001). The mean body weight increased by 0.9 ± 3.8 kg, while QoL increased by 9.2 ± 16.7 points after 24 weeks. Insulin analogue therapy was well-tolerated and significantly improved blood glucose control over 24 weeks in the Algerian cohort.


An economic approach to reducing water pollution: point and diffuse sources.
A review of economic policy towards pollution control is presented which shows that appropriate measures will depend on whether the pollution is of a point or a diffuse nature. Regulation of the former is comparatively straightforward, with command and control and market instruments the tools of pollution control. The advantages and disadvantages of each measure are outlined. However, the inability to monitor emissions at source, precludes the application of point source measures in the case of diffuse source pollution. Instead, methods are required which overcome the need for direct monitoring. Several suggestions that propose ways of achieving this have been put forward and these are described. It is concluded that appropriate measures depend on the particular features of the problem and it is not possible to offer a blanket solution to either point sources or diffuse pollution.


The use of hybridoma cells as a murine model to study tumor immunity.
The secretion of antibody by hybridoma cells allows the growth of individual cells to be measured by a hemolytic plaque assay. Similarly, plaque reduction assays were sensitive indicators of tumor immunity. A series of strains of hybridoma have been isolated from an original isolate which is sensitive to cytotoxic T cells and NK cells. In the derivation of a spleen-seeking variant, the cells appear to have lost immunogenic but not antigenic characteristics. This model lends itself to the quantitative study of immune constraints on tumor growth in vivo. Combined with the selection of tumor variants, the model is of wide application to many fields of tumor biology, particularly where sensitive measurement of tumor cell number and viability is crucial.


Directed differentiation of neural and sensory tissues from embryonic stem cells in vitro.
We have recently identified a stromal cell-derived inducing activity (SDIA), which induces differentiation of neural cells from mouse embryonic stem (ES) cells. Particularly, midbrain TH+ dopaminergic neurons are generated efficiently in this system. These dopaminergic neurons are transplantable and survive well in the 6-OHDA-treated mouse striatum. SDIA induces co-cultured ES cells to differentiate into rostral central nervous system (CNS) tissues containing both ventral and dorsal cells. While early exposure of SDIA-treated ES cells to BMP4 suppresses neural differentiation and promotes epidermogenesis, late BMP4 exposure after the 4th day of co-culture causes differentiation of neural crest cells and dorsal-most CNS cells, with autonomic system and sensory lineages induced preferentially by high and low BMP4 concentrations, respectively. In contrast, Sonic Hedgehog (Shh) suppresses differentiation of neural crest lineages and promotes that of ventral CNS tissues such as motor neurons and HNF3beta+ floor plate cells with axonal guidance activities. Thus, SDIA-treated ES cells generate naïve precursors that have the competence of differentiating into the "full" dorsal-ventral range of neuroectodermal derivatives in response to patterning signals. I also discuss the role of SDIA and the mode of rostral-caudal specification of neuralized ES cells. In addition, I would like to discuss them in the light of control of in vitro neural production for the use in regenerative medicine for parkinsonism and retinal degeneration.


Effect of resiniferatoxin on stimulated gastric acid secretory responses in the rat.
The effect of the capsaicin analogue 'resiniferatoxin' (RTX) was studied on basal and stimulated gastric acid secretory responses following sc bethanechol (1.5 mg/kg), sc pentagastrin (50 micrograms/kg) and sc histamine (0.5 and 2.5 mg/kg) in the 1-h pylorus-ligated plus saline (2 ml ig)-treated rats. Resiniferatoxin applied intragastrically in doses of 0.6 and 1 microgram/kg at time of pylorus-ligation and administration of the above secretagogues reduced acid secretory responses to bethanechol by 18.3 and 26.4%, to 0.5 mg/kg histamine by 39.9 and 44.6%, to 2.5 mg/kg histamine by 21.3 and 40.8% and to pentagastrin by 10.2 and 30.9% respectively. A single sc injection of 0.4 microgram/kg of RTX abolished basal secretion in pylorus ligated rats (which did not receive ig saline). Our results indicate that locally applied RTX is capable of inhibiting basal secretory responses and modifying gastric acid responses stimulated with histamine, bethanechol or pentagastrin in the rat.


Development of early PCLP1-expressing haematopoietic cells within the avian dorsal aorta.
The first haematopoietic stem cells (HSC) develop in the dorsal aorta as haematopoietic intra-aortic clusters (HIAC). To evaluate the initial steps of definitive haematopoiesis, we have studied the emergence and the expression profile of podocalyxin-like protein 1 (PCLP1)-expressing cells in early chick embryos. Here we demonstrate that at embryonic day 2 (E2), the PCLP1+ cells are present in the splanchnic mesoderm and in the ventral lining of the paired dorsal aorta. Following aortic fusion at E3, the PCLP1-expressing cells are exclusively found in the aortic floor and as the development proceeds, both the haematopoietic clusters and the aortic endothelial cells express PCLP1. In parallel with the early PCLP1 expression, bone morphogenetic protein 4 (BMP4) expression was detected in the splanchnopleura and thereafter in the densely packed mesenchymal cells beneath the HIAC. The microarray analyses of early E3 PCLP1+ cells revealed elevated expression of genes known to be involved in the stem cell function. These data suggest that splanchnopleura-derived PCLP1-expressing cells give rise to the earliest definitive haematopoietic progenitors.


Tunnelled haemodialysis catheter insertion into the persistent left superior vena cava.
Persistent left superior vena cava is an uncommon abnormality of the venous system. Most commonly, it is diagnosed incidentally during central vein catheterisation on the left side or pacemaker implantation. We present the case of a patient with persistent left superior vena cava, which was diagnosed after the attempted insertion of tunnelled haemodialysis catheter through the left internal jugular vein. The presence of the persistent left superior vena cava was confirmed by cardiac echography and angio-computed tomography scan. The 19-cm long tunnelled haemodialysis catheter was inserted into persistent left superior vena cava through the left internal jugular vein with good long-term function.


Validation of the Rasch-based Depression Screening in a large scale German general population sample.
The study aimed at presenting normative data for both parallel forms of the "Rasch-based Depression Screening (DESC)", to examine its Rasch model conformity and convergent and divergent validity based on a representative sample of the German general population. The sample was selected with the assistance of a demographic consulting company applying a face to face interview (N = 2509; mean age = 49.4, SD = 18.2; 55.8% women). Adherence to Rasch model assumptions was determined with analysis of Rasch model fit (infit and outfit), unidimensionality, local independence (principal component factor analysis of the residuals, PCFAR) and differential item functioning (DIF) with regard to participants' age and gender. Norm values were calculated. Convergent and divergent validity was determined through intercorrelations with the depression and anxiety subscales of the Hospital Anxiety and Depression Scale (HADS-D and HADS-A). Fit statistics were below critical values (< 1.3). There were no signs of DIF. The PCFAR revealed that the Rasch dimension "depression" explained 68.5% (DESC-I) and 69.3% (DESC-II) of the variance, respectively which suggests unidimensionality and local independence of the DESC. Correlations with HADS-D were rDESC-I = .61 and rDESC-II = .60, whereas correlations with HADS-A were rDESC-I = .62 and rDESC-II = .60. This study provided further support for the psychometric quality of the DESC. Both forms of the DESC adhered to Rasch model assumptions and showed intercorrelations with HADS subscales that are in line with the literature. The presented normative data offer important advancements for the interpretation of the questionnaire scores and enhance its usefulness for clinical and research applications.


Gut microbiota and their metabolite profiles following peripheral nerve xenotransplantation.
Intestinal pathogens are associated with xenotransplantation tolerance and rejection. However, changes in the gut microbiota in patients who have undergone peripheral nerve xenotransplantation and their association with immune rejection have not yet been reported. We aimed to explore intestinal microbes and their metabolites at different time points after peripheral nerve transplantation to provide new insight into improving transplant tolerance. A peripheral nerve xenotransplantation model was constructed by suturing the segmented nerves of Sprague Dawley rats to those of C57 male mice using xenotransplantation nerve bridging. Fecal samples and intestinal contents were collected at three time points: before surgery (Pre group; n = 10), 1 month after transplantation (Pos1 m group; n = 10), and 3 months after transplantation (Pos3 m group; n = 10) for 16S DNA sequencing and nontargeted metabolome detection. Alpha diversity results suggested that species diversity was significantly downregulated after peripheral nerve xenotransplantation. There were six gut flora genera with significantly different expression levels after xenotransplantation: four were downregulated and two were upregulated. A comparison of the Pre vs. Pos1 m groups and the Pos1 m vs. Pos3 m groups revealed that the most significant differentially expressed Kyoto Encyclopedia of Genes and Genomes metabolite pathways were involved in phenylalanine, tyrosine, and tryptophan biosynthesis, as well as histidine metabolism. Metabolites with a strong relationship to the differentially expressed microbial flora were identified. Our study found lower gut microbiome diversity, with increased short-chain fatty acid (SCFA)-producing and sulfate-reducing bacteria at 1 month post peripheral nerve xenotransplantation, and these were decreased at 3 months post-transplantation. The identification of specific bacterial metabolites is essential for recognizing potential diagnostic markers of xenotransplantation rejection or characterizing therapeutic targets to prevent post-transplant infection.


Cap-assisted ERCP in patients with a Billroth II gastrectomy.
ERCP is difficult in patients with a Billroth II gastrectomy because of anatomical changes. Cap-assisted ERCP can improve the cannulation rate and the success rate of stone removal. Case series. A tertiary referral center. Ten consecutive patients with bile-duct stones (9) or a distal common bile duct stricture (1), who had previously undergone Billroth II gastrectomy and were referred for ERCP, were analyzed for the outcome of their ERCP. All procedures were carried out with a cap-fitted regular forward-viewing endoscope. Ability to perform afferent loop intubation and bile-duct cannulation. Of 10 patients in whom ERCP was attempted, afferent loop intubation and selective bile-duct cannulation were achieved in all patients (100%). Endoscopic sphincterotomy (EST) was successful in all 10 patients (100%). All stones were removed by EST alone in 7 patients and by both EST and endoscopic papillary balloon dilation in 2 patients. There were no serious complications in the patients. Small sample size, single-center experience. Diagnostic and therapeutic ERCP with a cap-fitted regular forward-viewing endoscope was successful in all patients with a prior Billroth II gastrectomy. The high rate of successful ERCP was achieved by improving afferent loop intubation and bile-duct cannulation with a cap-fitted endoscope.


Effects of electropolishing surface treatment on the cyclic fatigue resistance of BioRace nickel-titanium rotary instruments.
This study evaluated the influence of electropolishing surface treatment on the number of cycles to fracture of BioRace rotary nickel-titanium endodontic instruments. BioRace size BR5C instruments with or without electropolishing surface treatment were used in an artificial curved canal under rotational speed of 300 rpm until fracture. Fractured surfaces and the helical shafts of fractured instruments were analyzed by scanning electron microscopy (SEM). Polished instruments displayed a significantly higher number of cycles to fracture when compared with nonpolished instruments (P < .001). Actually, the number of cycles to fracture of a polished BR5C instrument was 124% higher than that of a nonpolished instrument. SEM analysis showed that the fractured surface of both polished and nonpolished BR5C instruments had ductile morphologic characteristics. Evaluation of the separated fragments after cyclic fatigue testing showed the presence of microcracks near the fracture surface. Polished instruments exhibited fine cracks that assumed an irregular path (zigzag crack pattern), whereas nonpolished instruments showed cracks running along the machining grooves. Electropolishing surface treatment of BioRace endodontic instruments significantly increased the cyclic fatigue resistance.


Sacral nerve stimulation as an option for the treatment of faecal incontinence in patients suffering from cauda equina syndrome.
Retrospective clinical study with 1-year follow-up. Treatment of faecal incontinence by permanent sacral nerve stimulation (SNS) in patients suffering from cauda equina syndrome (CES). Klosterneuburg, Austria. A flaccid paresis of the sphincter ani muscle and the pelvic floor combined with faecal incontinence can occur in patients suffering from CES as a result of a trauma in the region of the lumbar spine. If the incontinence cannot be managed by the use of laxatives or anal tampons, the patient is restricted in his/her quality of life. Thus, it was our aim to improve sphincter function and anal sensitivity to achieve voluntary rectal defaecation. The functional integrity of at least one sacral root (S2-S4) was determined through percutaneous nerve evaluation (PNE). Following this analysis, a period of external temporary SNS was performed to evaluate the functional effect. If there was a decrease in the number of episodes of faecal incontinence during this evaluation period, a neurostimulation device (InterStim; Medtronic) was implanted. A total of 11 patients suffering from flaccid paresis of the anal sphincter muscle and faecal incontinence caused by CES underwent PNE, which was successful in 8 patients. Two of these patients were eliminated from the procedure at the end of the temporary SNS period, one patient refused the permanent implantation. Therefore, five patients proceeded to permanent implantation, which led to an improved continence in all the cases. In the synopsis of the preoperative proctologic and neurological findings, successful electric stimulation of the sacral roots can be expected in incomplete CES. In the case of flaccid paresis of the anal sphincter muscles caused by an incomplete CES, permanent SNS offers a promising option for the treatment of faecal incontinence. .


Intraosseous hemangioma of the skull with dural tail sign: radiologic features with pathologic correlation.
Osseous hemangiomas of the calvaria account for about 0.2% of bone neoplasms. We report a case of an extensive intraosseous cavernous hemangioma in a 46-year-old woman. MR imaging showed a mass in the right frontal bone with intra- and extracranial extension and a dural tail sign after gadopentetate dimeglumine administration, mimicking a meningioma in which the dural tail sign was due to a direct noninvasive superficial growth of the lesion.


Without the bursary, two thirds would not have chosen nursing.
Two thirds of nurses would not have joined the profession had a bursary not been available during training, a major new survey has revealed.


Orbital character of the spin-reorientation transition in TbMn6Sn6.
Ferromagnetic (FM) order in a two-dimensional kagome layer is predicted to generate a topological Chern insulator without an applied magnetic field. The Chern gap is largest when spin moments point perpendicular to the kagome layer, enabling the capability to switch topological transport properties, such as the quantum anomalous Hall effect, by controlling the spin orientation. In TbMn6Sn6, the uniaxial magnetic anisotropy of the Tb3+ ion is effective at generating the Chern state within the FM Mn kagome layers while a spin-reorientation (SR) transition to easy-plane order above TSR = 310 K provides a mechanism for switching. Here, we use inelastic neutron scattering to provide key insights into the fundamental nature of the SR transition. The observation of two Tb excitations, which are split by the magnetic anisotropy energy, indicates an effective two-state orbital character for the Tb ion, with a uniaxial ground state and an isotropic excited state. The simultaneous observation of both modes below TSR confirms that orbital fluctuations are slow on magnetic and electronic time scales < ps and act as a spatially-random orbital alloy. A thermally-driven critical concentration of isotropic Tb ions triggers the SR transition.


Fine structural studies of the nervous system and the apical organ in the planula larva of the sea anemone Anthopleura elegantissima.
The nervous system of the planula larva of Anthopleura elegantissima consists of an apical organ, one type of endodermal receptor cell, two types of ectodermal receptor cells, central neurons and nerve plexus. Both interneural and neuromuscular synapses are found in the nerve plexus. The apical organ is a collection of about 100 long, columnar cells each bearing a long cilium and a collar of about 10 microvilli. The cilia of the apical organ are twisted together to form an apical tuft. The ciliary rootlets of the apical organ cells are extremely long, reaching to the basal processes of the cells adjacent to the mesoglea. All three types of sensory cells are tall and slender in profile and are identified by the presence of one or more of the following features: microtubules, small vesicles, membrane-bound granules and synapses. The interneurons are bipolar cells with somas restricted to the aboral end, adjacent to the apical organ. All synapses observed are polarized or asymmetrical. A diagram including all the elements of the nervous system is presented and the possible functions of the nervous system are discussed in relation to larval behavior.


Feasibility of chitosan crosslinked with genipin as biocoating for cellulose-based materials.
Crosslinking with genipin increases the acidic stability of chitosan-based materials, opening an opportunity to explore new applications. In this work, the viability of using chitosan-genipin solutions on cellulose-based materials coating was studied. Non-calendered paper and cardboard were used as raw materials. Different number of chitosan-genipin coating layers (1, 3, 6, 20, and 30) were applied and their influence on the materials mechanical, physicochemical, and barrier properties was studied. The small thickness and basis weight of non-calendered paper resulted in an inefficient adhesion of chitosan-genipin coating to the cellulose fibers. However, in cardboard, chitosan-genipin created a dense layer onto the cellulosic-fibers surface without impairing their mechanical properties. It conferred a greenish color, whose intensity increased with the layers number. The chitosan-genipin coating decreased the cardboard air and water vapor permeability up to 71 % and 52 %, respectively, and acted as a physical barrier for cardboard compounds leaching, being suitable for covering cellulose-based materials.


Rationale and design of the AUGUST-AHF Study.
We aim to assess the effect of a lyophilized herbal injection on 90 day mortality and readmission rates in patients with acute heart failure (AHF). The AUGUST-AHF study is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 1270 hospitalized patients for AHF. Patients are randomized to receive YiqiFumai lyophilized injection (5.2 g/day) or placebo for 10 days, in addition to standard therapy, using a 1:1 ratio via an interactive web response system. The primary endpoint is the 90 day all-cause mortality or AHF readmission rates. Secondary endpoints include 180 day all-cause mortality or heart failure readmission rates, length of hospital stay for the indexed AHF, 90 day cardiac-specific mortality rate, occurrence of worsening heart failure through Day 10, changes in the Minnesota Living with Heart Failure Quality of Life scale score through Day 180, and 90 day major adverse cardiac events. Additional secondary endpoints include change in dyspnoea via visual analogue scale (VAS) and Likert 7-point comparator scale, N terminal pro-B-type natriuretic peptide value and New York Heart Association functional class, and the total amount of diuretics for the indexed AHF hospitalization. Study recruitment is expected to be completed by March 2021, and follow-up will end in September 2021. In an optional sub-study, patients will be followed up for 3 years. To our best knowledge, AUGUST-AHF is the first study assessing the efficacy of a Chinese herbal injection in patients with AHF. The results will be valuable to guide clinicians in using YiqiFumai lyophilized injection, which was included in the latest Chinese Health Insurance Catalog.


Synergistic combined effect between CD40-1C>T and CTLA-4+6230G>A polymorphisms in Graves' disease.
The aim of this study was to investigate whether a genetic combined effect exists between CD40-1C>T and CTLA-4+6230G>A (CT60) polymorphisms and whether the combined effect renders susceptibility to Graves' disease (GD). We recruited 260 patients with GD and 248 healthy controls. Single nucleotide polymorphisms were genotyped by polymerase chain reaction-high resolution melting. Genetic polymorphisms related to GD were identified, levels of thyroid stimulating hormone receptor antibodies (TRAb) were measured, and genetic interactions were assessed by logistic regression analysis. Significant difference in allele and genotype frequency of CD40-1C>T polymorphism was observed between the patients and control subjects (P<0.001, 0.002 respectively). As for CTLA-4+6230G>A polymorphism, significant difference was observed only in allele frequencies between the patient and control groups (P=0.014). Moreover, a significant combined effect was presented in CD40-1C>T and CTLA-4+6230G>A polymorphism (P=0.020), and all, but one, combination CC-genotype of CD40-1C>T and GG-genotype of CTLA-4+6230G>A polymorphism has 54% lower risk of GD development than subjects with the CC and GG genotypes (OR=0.46, 95% CI=0.25-0.84). In newly onset GD group, neither single SNP (CD40-1C>T or CTLA-4+6230G>A polymorphism) nor their combined effect was showed a significant association with TRAb concentration (all P>0.05). Our findings suggest a possible additive combined effect between CD40-1C>T and CTLA4+6230G>A polymorphisms in the development of GD.


Recent advances in our understanding of 1,25-dihydroxyvitamin D(3) regulation of intestinal calcium absorption.
Calcium is required for many cellular processes including muscle contraction, nerve pulse transmission, stimulus secretion coupling and bone formation. The principal source of new calcium to meet these essential functions is from the diet. Intestinal absorption of calcium occurs by an active transcellular path and by a non-saturable paracellular path. The major factor influencing intestinal calcium absorption is vitamin D and more specifically the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). This article emphasizes studies that have provided new insight related to the mechanisms involved in the intestinal actions of 1,25(OH)(2)D(3). The following are discussed: recent studies, including those using knock out mice, that suggest that 1,25(OH)(2)D(3) mediated calcium absorption is more complex than the traditional transcellular model; evidence for 1,25(OH)(2)D(3) mediated active transport of calcium by distal as well as proximal segments of the intestine; 1,25(OH)(2)D(3) regulation of paracellular calcium transport and the role of 1,25(OH)(2)D(3) in protection against mucosal injury.


P wave signal-averaged electrocardiogram as a new marker for atrial tachyarrhythmias in postoperative Fontan patients.
This study was undertaken to determine the potential role of P wave signal-averaged electrocardiogram (PSAECG) for risk assessment of atrial tachyarrhythmias (ATs) in patients after Fontan operation. Onset of atrial flutter/fibrillation (AFF) in patients who have undergone Fontan operation for univentricular hearts constitutes an unfavorable clinical event associated with a high risk of cardiovascular complications. There is no data available on PSAECG in postoperative Fontan patients to predict potential susceptibility to ATs. Twenty-four post-Fontan patients and 15 age-matched healthy subjects were prospectively studied with PSAECG, and the following measurements were made: filtered P wave duration (FPWD), P wave vector integrals (PINTs), root-mean-square voltage for the initial 30 ms (RMSi30), and duration of persistent amplitude signals <4 microV from the beginning of the P wave (Di4). The FPWDs were significantly longer in the study group patients with ATs when compared with the study group patients without ATs (p<0.01) and compared with the controls (p < 0.001). An FPWD cut point of 135 ms resulted in a sensitivity of 71% and a specificity of 81% in differentiating patients with ATs from patients without ATs among the postoperative Fontan patients. The PINT was significantly greater in Fontan patients with AFF and also without AFF when compared with controls (p<0.01, p<0.05, respectively). The RMSi30 and the Di4 were not significantly different between study and control groups. Signal-averaged P wave duration is significantly prolonged in postoperative Fontan patients. A prolonged signal-averaged P wave duration may be an effective noninvasive marker to predict risk of development of ATs in this patient group.


Surgical Treatment for Pulmonary Metastasis of Pancreatic Ductal Adenocarcinoma: Study of 12 Cases.
Few studies have reported results with pulmonary metastasectomy for pancreatic ductal adenocarcinoma (PDAC), probably because of their extremely poor outcomes. The aim of this study was to review our institutional experience and analyze the outcomes of pulmonary metastasectomy for PDAC. A retrospective case-control study of patients undergoing pulmonary metastasectomy for isolated lung metastasis of PDAC between 2004 and 2016. Clinicopathological features were analyzed and survival curves were plotted using the Kaplan-Meier method. Twelve patients were included. The median follow-up period after metastasectomy was 33 months. At the time of analysis, five patients had deceased, two were alive with disease, and five were alive without disease. The median survival time after pulmonary metastasectomy was 47 months. The estimated 3- and 5-year overall survival rates were 62.3% (95%CI=27.8-84.0) and 31.2% (95%CI=1.7-71.7). Outcomes were favorable following pulmonary metastasectomy in selected patients with PDAC.


VrMYB90 Functions Synergistically with VrbHLHA and VrMYB3 to Regulate Anthocyanin Biosynthesis in Mung Bean.
Mung bean is an important grain-legume crop and its sprout is an economical and nutrient vegetable for the public, but the genetic regulation of anthocyanin production, which is an antioxidant in mung bean, remains elusive. In our study, we characterized a subgroup (SG) 6 R2R3-MYB anthocyanin activator VrMYB90 and a SG 4 R2R3-MYB anthocyanin repressor VrMYB3, which synergistically function in regulating anthocyanin synthesis with VrbHLHA transcription factor. The overexpressed VrMYB90 protein activates the expression of VrMYB3 and VrbHLHA in mung bean hair roots, and also promotes VrDFR and VrANS transcript levels by directly binding to the corresponding promoters at specific motifs (CAACTG and CCGTTG). VrMYB90 interacts with VrbHLHA to enhance its regulatory activities on VrDFR and VrANS. Furthermore, the interaction between VrMYB3 with VrMYB90 and VrbHLHA could result in the restriction of anthocyanin synthesis to prevent excessive anthocyanin accumulation. Our results demonstrate that the VrMYB90 protein, in conjunction with VrMYB3 and VrbHLHA, forms a key regulatory module to fine-tune anthocyanin synthesis in mung bean.


Influence of spark erosion on the fit of screw-retained Co-Cr fixed complete denture frameworks veneered with different materials.
Spark erosion is a fit corrective technology that can be used even after the veneering material has been applied. The framework does not require sectioning, thus preserving its mechanical resistance. However, the spark erosion effect on veneered Co-Cr fixed complete denture (FCD) frameworks has not been investigated. The purpose of this in vitro study was to evaluate whether spark erosion is effective in improving marginal fit on screw-retained Co-Cr FCD frameworks veneered with different materials. A comparison between ceramic applications and simulated ceramic firing cycles was also investigated. Forty FCD frameworks were fabricated with a Co-Cr alloy. Four groups (n=10) were obtained according to the veneer material used on frameworks: HR (heat-polymerized resin); LR (light-polymerized resin); C (ceramic); and SC (simulated ceramic firing cycle). The spark erosion process was conducted for all groups. The marginal fit was analyzed according to the single-screw test protocol, and the measurements were performed at 3 evaluation times: initial, after veneer material application, and after spark erosion process. The results were submitted to a 2-way repeated measures ANOVA and the Tukey honest significant differences test (α=.05). Poorer marginal fit (in micrometers) was noted after veneer material application, where the HR and C groups presented the worst values (HR: 170; LR: 72; C: 165; SC: 86; P<.05). The spark erosion process was effective in improving the fit for all groups (HR: 109; LR: 52; C: 110; SC: 60; P<.05). Spark erosion improved the fit of Co-Cr FCD frameworks veneered with different materials. An actual ceramic application should be used to assess distortions generated by veneer material application instead of using only simulated ceramic firing cycles.


Synchronous Oligometastatic Non-Small Cell Lung Cancer and Isolated Renal Cell Carcinoma: A Case Report and Literature Review.
A 58-year-old gentleman presenting with a progressive headache, visual disturbance, decreased appetite, and weight loss was found to have a localized clear cell carcinoma of the kidney and synchronous Stage IV non-small cell lung cancer with a solitary brain metastasis. This case illustrates the challenges in distinguishing between primary and metastatic disease in a patient with both renal cell carcinoma and lung cancer. We highlight the uncertainties in the diagnosis and management of this unique clinical scenario and the potential implications on prognosis.


[Chronic obstructive pulmonary disease: an autoimmune disease?].
Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality characterized by irreversible airflow limitation involving a reduced caliber of distal airways (less than 2mm) and alveolar destruction. Exposure to tobacco is a major risk factor for COPD, but all smokers do not develop the disease. In addition, there is continued progression of the disease several years after cessation of the exposure. To explain these phenomena, factors involving innate immunity including the release of neutrophil elastase, macrophage metalloproteases, in combination with pro-apoptotic factors, involved in the worsening of the lesions of emphysema and fibrosis of small airways have been described for many years. More recently, it has been proposed at an advanced stage of the disease that an autoimmune reaction directed mainly at elastin could participate to the pathogenesis of the disease. We here review the immunological processes and currently available data on autoimmunity in COPD.


Changes in the concentration of monocytic chemotaxic protein-1 in patients with unstable angina treated with arixtra.
The time course of inflammatory reaction markers in the blood of patients with unstable angina was studied during therapy including arixtra. Plasma concentration of monocytic chemotaxic protein-1 (MCP-1) decreased on days 2 and 3 in patients receiving arixtra and a trend to an increase in MCP-1 concentration was observed on day 7 after the drug was discontinued. After 1 month, MCP-1 level decreased in all patients. The concentration of highly sensitive C-reactive protein also decreased 1 month after the disease onset; no changes in the concentrations of IL-8 and IL-2 receptor α-subunit were detected during these periods. It seems that arixtra is characterized by an anti-inflammatory effect manifesting by reduction of plasma chemokine MCP-1 concentration.


Comparison of visceral adipose tissue quantification on water suppressed and nonwater-suppressed MRI at 3.0 Tesla.
To systematically evaluate and compare the performance of water-saturated and nonwater-saturated T1-weighted 3.0 T magnetic resonance imaging (MRI) in the application of visceral adipose tissue (VAT) quantification. Forty-five patients underwent abdomen MRI using two different sequences at 3.0 T: 1) a traditional T1-weighted gradient echo sequence, and 2) the same sequence with water presaturation to enhance fat and nonfat contrast. VAT amounts from both water-saturated and nonwater-saturated images were quantified with a manual thresholding technique and an automated segmentation method to study quantification variability and consistency of the two imaging techniques. Nonwater-saturated MRI had significantly larger coefficient of variation than water-saturated MRI in the imaging reproducibility study based on 112 slices from seven subjects (11.4% vs. 2.5%, P < 0.0001). VAT volumes measured from the nonwater-saturation MRI sequence had significantly higher variability than those from water-saturation images even when using a manual quantification method based on images from 38 subjects (1.76% vs. 1.08%, P < 0.001). In addition, the VAT volume amounts from nonwater-saturation images and water-saturated images quantified with the automatic and manual quantification methods were statistically consistent. Water-saturated MRI sequences at 3.0 T for VAT quantification improve reproducibility and decrease variability compared with nonwater saturated sequences, especially with the use of automatic quantification methods.


Efficacy and Safety of a Subanesthetic Dose of Esketamine Combined with Propofol in Patients with Obesity Undergoing Painless Gastroscopy: A Prospective, Double-Blind, Randomized Controlled Trial.
Patients with obesity are more susceptible to hypoxemia. Anesthetic management for patients with obesity undergoing painless gastroscopy presents a severe challenge for anesthesiologists. Esketamine is a NMDA antagonist that has been proven to be beneficial for ameliorating respiratory depression owing to its sympathomimetic effect; however, there are no relevant reports on its use in patients with obesity. We designed a randomized controlled trial to evaluate whether esketamine can be the ideal adjuvant to propofol sedation in patients with obesity undergoing painless gastroscopy. A total of 104 patients with obesity undergoing painless gastroscopy were randomly divided into group C (propofol+saline) and group S (propofol+esketamine 0.25 mg/kg). Anesthesia was induced by 2 mg/kg propofol with saline or esketamine. The consumption of propofol, hemodynamic parameters, duration of procedure, induction time, postoperative awakening time, and orientation recovery time were recorded. Adverse events and satisfaction scores were also recorded. Propofol consumption was 274.4±22.6 mg and 201.3±16.6 mg in groups C and S, respectively. The induction time of groups C and S were 25.4±2.3 s and 17.8±1.9 s, respectively. The postoperative awakening times of groups C and S were 6.2±1.1 min and 4.8±1.3 min, respectively. Hemodynamic parameters were more stable in group S than in group C. The incidence of adverse events such as injection pain, hypoxemia, hypotension, bradycardia, choking, and body movement were significantly lower in group S. The satisfaction scores of the endoscopist and anesthesiologist were (4.58±0.49 vs 3.71±0.83) and (4.75±0.44 vs 3.33±0.92), respectively. The combination of propofol and esketamine (0.25 mg/kg) improves the safety and reduces the incidence of adverse events in patients with obesity during painless gastroscopy. Thus, this method is worthy of clinical application. ChiCTR 2200062547.


Neutrophil mobility during anaesthesia in children. A trial of ascorbate premedication.
In 20 healthy children undergoing elective surgery, mobility of neutrophils, both unstimulated and stimulated by endotoxin, was studied using a millipore filter system with microscopic determination of leading front migration. Paired samples were incubated with 10(-2) mol l-1 calcium ascorbate and ten children also received 10 mg kg-1 ascorbic acid before premedication. Stimulation of mobility was reduced after the opioid premedication (P less than 0.05) in the ascorbate group only, but not significantly during anaesthesia and surgery. A few individuals showed persisting abnormally low values. No effect of ascorbate in vivo or in vitro was demonstrated. There were no infections.


Recurrent severe placenta increta at 8 weeks of gestation in a twin pregnancy following uterus-conserving surgery for prior placenta accreta spectrum disorder.
We describe herein our experience of employing a hysterectomy and prophylactic internal iliac artery balloon occlusion (IIABO) strategy for the management of recurrent severe placenta increta at 8 weeks in a twin pregnancy following uterus-conserving surgery for prior placenta accreta spectrum (PAS) disorder. A 40-year-old woman with a history of uterus-conserving surgery for PAS disorder underwent transvaginal ultrasound evaluation at 8 weeks of pregnancy, which showed a dichorionic/diamniotic pregnancy with viable embryos of a crown-rump length of 1.65 cm and 2.03 cm, respectively. Many irregularly-shaped grade 3+ lacunae were observed, and color Doppler imaging revealed diffuse intraplacental and perihypervascularity. A total abdominal hysterectomy was performed at 10 weeks, with an estimated blood loss of 1275 mL. Placenta increta was confirmed by histopathologic examination. The high rate of recurrence of PAS disorder in a subsequent pregnancy should be discussed following an antenatal diagnosis of PAS disorder with patients who may be considering uterine conservation in order to retain the option of a future pregnancy.


LDL cholesterol estimation using the Anandaraja's and Friedewald's formulas in schizophrenic patients treated with antipsychotic drugs.
The use of new antipsychotic drugs is associated with an increased risk of diabetes and metabolic syndrome, and the routine monitoring of blood lipids during treatment has been recommended. Recently, a new formula for the estimation of low-density lipoprotein (LDL) cholesterol from total cholesterol and triglycerides has been proposed by Anandaraja et al. (Int J Cardiol 2005; 102: 117), and the aim of our study was its evaluation in schizophrenic patients treated with antipsychotic drugs. In 487 serum samples from schizophrenic patients treated with clozapine in polytherapy, the concentrations of LDL cholesterol were determined by agar gel electrophoresis and the formula of Friedewald et al. (Clin Chem 1972; 18: 499), and compared with the results of the Anandaraja's formula. A higher correlation and lower error of the estimate of the electrophoresis results was found with those of Friedewald (r=0.940, ma68=0.17 mmol/L) than those of Anandaraja (r=0.811, ma68=0.31 mmol/L). Similar results were obtained on making a dichotomy of the patients with and without metabolic syndrome lipid profile. A highly significant correlation was found between the high-density lipoprotein (HDL) cholesterol levels and the Anandaraja/Electrophoresis (r=0.817, p<0.001) and Anandaraja/Friedewald (r=0.977, p<0.001) ratios. According to our data, Anandaraja's formula tends towards an overestimation or underestimation of LDL cholesterol levels, depending on whether the HDL cholesterol levels are high or low, which may be clinically significant. These results do not support the proposed better accuracy of the Anandaraja's than the Friedewald's formula.


Prevention of otitis media in children by pneumococcal vaccination.
A total of 3,340 infants, 95 per cent of them 7 to 9 months old, were randomly vaccinated in a double-blind fashion with either the 14-valent pneumococcal (Pn) polysaccharide vaccine or a saline placebo in three urban areas in Finland. The second dose of the vaccine was given 5 months later. Age and sex distribution, recruitment of infants, and their otitis-related treatment and follow-up were similar in the study areas. Side effects after vaccination were mild and fewer than among older children. Antibody responses to vaccine polysaccharides varied from type to type, but were generally poor, especially to types most prevalent in otitis media. After the first dose of vaccine, the occurrence of otitis visits among the Pn-vaccinated, as compared with controls, showed inter-area differences, but ranged from not more than a 30 per cent reduction at its best to an increase in some areas and in some clinical categories. The respective figures for children with acute otitis media were similar between the vaccination groups and the study areas. The effect of the vaccine on acute otitis media caused by specific Pn types/groups represented in the vaccine was variable but generally poor. Group 6 attacks especially seemed to behave problematically. The second dose of the vaccine did not give additional benefit serologically or clinically. The efficacy of currently available pneumococcal vaccine against otitis media seemed poor in infants.


Young adult, geriatric and aphasic group responses to simple analogies.
The efficiency of interactive language processing was compared in three groups: 25 young adults, 25 geriatric subjects, and 25 adult aphasic subjects. The task involved simple analogy completion. Data analysis included six categories of responses which represetned levels of convergence toward the expected relationships. Results of chi-square comparisons between groups were all significant, and indicated substantial reductions in interactive processing for geriatric subjects. The findings suggest that a general aging factor may contribute to the poor prognosis in elderly aphasic patients.


A Rare Secondary Dysmenorrhea Resulted from Separation of Corpus Uteri from Cervix: A Case Report and Literature Review.
Secondary dysmenorrhea is a pain associated with disease such as endometriosis, pelvic inflammatory disease, leiomyomas, and interstitial cystitis. Treatment of secondary dysmenorrhea always focuses on the causative pelvic pathology or medical condition. Here, we found a rare case with secondary dysmenorrhea that resulted from traumatic separation of the uterine corpus from the cervix. In this case, the patient experienced a childhood blunt trauma of the pelvic crush and was successfully diagnosed by magnetic resonance imaging and 3-dimensional ultrasonography. Moreover, laparoscopic anastomosis could be a minimally invasive way to resolve this problem.


Integrating functions at the kinetochore.
Kinetochore components have catalytic as well as structural activities. New evidence illustrates how these proteins integrate spindle morphogenesis with regulation of the timing and accuracy of chromosome segregation.


Noddle Pox: Syphilis and the Conception of Nosomania/Nosophobia (c. 1665-c. 1965).
Hypochondriac or phobic reactions to venereal disease, specifically syphilis, have invited over three centuries of medical reification and nosological reframing. This bibliographic overview establishes that the early specification and psychiatricization of early modern concepts of melancholy and hypochondriasis, imaginary syphilis or syphilophobia, animated the early respective territorializations of venereology, infectiology more broadly, neurology, and mental medicine. Together with mercuriophobia and a wider emergent clinical sensitivity to sexual angst, the diagnosis, while evidently only sporadically made, functioned as a durable soundboard in the confrontation of emergent medical rationale with various confounders and contenders: medically literate and increasingly mobile but possibly deluded patients; charlatans and putative malpractitioners; self-referral laboratory serology (after 1906); and eventually, through psychoanalysis, the patient's unconscious. Requiring medical psychology early on, syphilology became and remained self-conscious and circumspect, attentive to the casualties of overdiagnosis, overtreatment, and iatrogenesis. Finally, patient apprehension led to makeshift forms of "moral treatment," including fear-instilling and placebos.


Evaluation of potential cardiotoxicity of ammonia: l-selenomethionine inhibits ammonia-induced cardiac autophagy by activating the PI3K/AKT/mTOR signaling pathway.
Ammonia is a major harmful gas in the environment of livestock and poultry. Studies have shown that excessive ammonia inhalation has adverse effects in pig heart. However, the mechanism of ammonia-induced cardiac toxicity in pigs has not been reported. L-selenomethionine is a kind of organic selenium (Se) which is easily absorbed by the body. Therefore, in this study, twenty-four 125-day-old pigs were randomly divided into 4 groups: C (control) group, A (ammonia) group, Se group (Se content: 0.5 mg kg-1), and A (ammonia) + Se group. The mechanism of ammonia-induced cardiotoxicity and the alleviating effect of L-selenomethionine were examined. The results in the A group showed as follows: a large number of myocardial fiber edema and cytoplasmic bleakness were observed in the heart; a large number of mitochondrial autophagy were observed; ATP content, ATPase activities and hematological parameters decreased significantly; Endoplasmic reticulum stress (ERS) markers (GRP78, IRE1α, ATF4, ATF6, and CHOP) were significantly induced in the mRNA and protein levels; PI3K/AKT/mTOR signaling pathway was activated; and autophagy key genes and proteins (Beclin-1, LC3, ATG3, and ATG5) were significantly up-regulated. The results of comparison between the A + Se group and the A group were as follows: the degree of edema of cardiac muscle fiber in the A + Se group was somewhat relieved; the level of mitochondrial autophagy decreased; ATP content and ATPase activities increased significantly; the mRNA and protein levels of ERS markers were significantly down-regulated; the expression level of PI3K/AKT/mTOR signaling pathway was decreased; and the mRNA and protein levels of key autophagy genes were decreased. However, the changes of these indexes in the A + Se group were still significantly different from those in the C group. Our results indicated that L-selenomethionine supplementation inhibited ammonia-induced cardiac autophagy by activating the PI3K/AKT/mTOR signaling pathway, which confirmed that L-selenomethionine could alleviate the cardiac injury caused by excessive ammonia inhalation to a certain extent. This study aims to enrich the toxicological mechanism of ammonia and provide valuable reference for future intervention of ammonia toxicity.


Association of resistin with visceral fat and muscle insulin resistance.
Maturing Sprague-Dawley (S-D) rats develop obesity and skeletal muscle insulin resistance. To investigate the relationship between fat mass and insulin responses, we performed surgical removal of the epididymal and retroperitoneal depots of visceral adipose tissue (VF) or sham surgery (SHAM) in male rats aged 4 months. At sacrifice, 30 days later, the mass of visceral fat was 48% lower (p<0.05) in VF- compared to SHAM, while subcutaneous fat was essentially unchanged. VF- animals displayed increased insulin responses in isolated strips of skeletal muscle. Insulin-stimulated glucose transport was increased 28% in soleus muscle (p<0.05), with a trend toward a 31% increase in extensor digitorum longus muscle (p=0.058). Glucose tolerance was not significantly affected by surgical fat removal. In VF- animals, serum resistin was reduced 26% (p<0.05) and serum adiponectin was reduced 30% (p<0.05), with trends for reductions in IL-4 (58% reduction, p=0.084) and IL-6 (56% reduction, p=0.123). TNF-alpha, leptin and free fatty acids (NEFAs) were unchanged. We conclude that in maturing S-D rats, increased visceral adiposity leads to an increase in systemic release in resistin and possibly interleukins. Elevation of circulating cytokines may play a role in the development of muscle insulin resistance.


Diagnosis of acute neurological emergencies in pregnant and post-partum women.
Acute neurological symptoms in pregnant and post-partum women could be caused by exacerbation of a pre-existing neurological condition, the initial presentation of a non-pregnancy-related problem, or a new acute-onset neurological problem that is either unique to or occurs with increased frequency during or just after pregnancy. Pregnant and postpartum patients with headache and neurological symptoms are often diagnosed with pre-eclampsia; however, a range of other causes must also be considered, such as cerebral venous sinus thrombosis and reversible cerebral vasoconstriction syndrome. Precise diagnosis is essential to guide subsequent management. Our ability to differentiate between the specific causes of acute neurological symptoms in pregnant and post-partum patients is likely to improve as we learn more about the pathogenesis of these disorders.


Osteoarthritis and the incidence of fracture in the United Kingdom: a retrospective cohort study of 258,696 patients.
The goal of this study was to analyze the relationship between osteoarthritis and the incidence of fracture in men and women aged ≥18 years followed in general practices in the United Kingdom. This study included patients aged ≥18 years who had received an initial diagnosis of osteoarthritis in one of 256 general practices in the United Kingdom between January 1997 and December 2016 (index date). Patients without osteoarthritis were matched (1:1) to those with osteoarthritis by sex, age, index year, diabetes, dementia, corticosteroid therapy, and practice. For patients without osteoarthritis, the index date was a randomly selected visit date between 1997 and 2016. The association between osteoarthritis and the incidence of fracture was investigated using Kaplan-Meier curves and conditional Cox regression analyses. This retrospective cohort study included 129,348 patients with osteoarthritis and 129,348 patients without osteoarthritis [60.1% women; mean (standard deviation) age 63.7 (14.0) years]. After 10 years of follow-up, 12.1% of individuals with osteoarthritis and 7.7% of those without osteoarthritis had suffered at least one fracture (log-rank P-value<0.001). There was a positive and significant association between osteoarthritis and fracture in the overall sample [hazard ratio (HR) = 1.55, 95% confidence interval (CI) = 1.50-1.60]. These findings were corroborated in all sex, age, and osteoarthritis joint site subgroups. Intervention is urgently needed to reduce the risk of fracture in adults with osteoarthritis, and further research is warranted in order to gain more of an insight into the mediators involved in the relationship between osteoarthritis and fracture.


Prognostic significance of the lymphocyte-to-neutrophil ratio in percutaneous fine-needle aspiration biopsy specimens of advanced nonsmall cell lung carcinoma.
The prognostic significance of tumor-infiltrating lymphocytes (TILs) in surgically resected carcinomas was reported. To apply this to inoperable nonsmall cell lung carcinomas (NSCLC) of Stage IIIB-IV, the authors estimated the occurrence of TILs using percutaneous fine-needle aspiration biopsy specimens, and tested the validity of this method. The authors defined the L-N index as [L(S)/(L(S) + N(S)) - L(B)/(L(B) + N(B))], in which L(S) and N(S) denoted lymphocyte and neutrophil counts in the aspiration smear, and L(B) and N(B) denoted lymphocyte and neutrophil counts in the peripheral blood specimen. The cutoff value was set at twice the standard deviation of the L-N index of 41 smears contaminated with abundant blood. Retrospectively, the authors compared the survival rate of the group with a high L-N index (lymphocyte-dominant group) (n = 12) with the survival rate of the group with a low L-N index (lymphocyte-nondominant group) (n = 60). Then, they performed a prospective study and compared the survival rates of these 2 groups (n = 21 and n = 54). The Cox proportional hazards model was used to determine the effect of the L-N index as a continuous variable and other prognostic factors. The correlation (r) between the L-N index-based grouping (L-N grouping) and the histologic grade of TILs was studied among resected lung tumor specimens (n = 164). In the retrospective and prospective studies, the survival rate was significantly higher in the lymphocyte-dominant group than in the lymphocyte-nondominant group (P = 0.0019 and P = 0.0001). Using multivariate analysis, the L-N index was an independent prognostic factor. A significant correlation was noted between L-N grouping and histologic grade of TILs (r = 0.476). The L-N index of aspiration smears was found to be an independent prognostic factor for patients with advanced-stage NSCLC. L-N grouping was correlated with the histologic assessment of TILs.


The content of non-esterified fatty acids in rat myocardial tissue. A comparison between the Dole and Folch extraction procedures.
Oliver and coworkers hypothesized that under certain circumstances NEFA (non-esterified fatty acids = FFA = free fatty acids) might be toxic for myocardial function. Unambiguous conclusions on the putative detrimental effect of intracellularly localized NEFA are hampered by contradictory values published for the NEFA content in normoxic myocardial tissue. From studies in which the assay procedures were carefully evaluated, one might conclude that the NEFA content in dog and rat myocardial tissue will not exceed 60 and 150 nmol/g wet weight, respectively. However, recently Victor and coworkers found considerably higher NEFA values in rat myocardial tissue and suggested that the low NEFA values as measured, for example, in our laboratory, resulted from incomplete extraction when the Folch medium was applied instead of the Dole mixture. Since Victor and coworkers used a modified Dole procedure as described by Hagenfeldt, we evaluated the Folch procedure as well as the original Dole technique and the modified version. Our findings indicate that the lower values found by the Folch technique are more likely to be correct. Incomplete extraction of NEFA did not occur, whereas hydrolysis and transmethylation of phospholipid fatty acids were observed in case of the (modified) Dole procedures.


Valorization of neem seeds biomass to biofuel via non-catalytic and catalytic pyrolysis process: Investigation of catalytic activity of Co-Mo/Al2O3 and Ni-Mo/Al2O3 for biofuel production.
Biofuel production from neem seeds have been evaluated via non-catalytic and catalytic pyrolysis process. Co-Mo/Al2O3 and Ni-Mo/Al2O3 industrial catalysts have been applied in upgrading process of pyrolysis oil to biofuel. The catalytic activity test revealed that these catalysts succeeded in converting fatty acids content of pyrolysis oil into low oxygen content compounds such as alcohols, alkanes, cyclic compounds, and esters via deoxygenation route. Enhancement of temperature and catalyst loading lead to increase of bio-gas production yield, significantly. The highest yield of pyrolysis oil (60.2%) was obtained at 450 °C, heating rate of 40 °C.min-1 via non-catalytic pyrolysis. Using 40% catalyst loading of Ni-Mo/Al2O3, the content of alcohol, cyclic and alkane compounds in the bio-oil were reached 12.65%, 21.74% and 15%, respectively. The highest selectivity using 40% catalyst loading of Co-Mo/Al2O3 catalyst at 450 °C was related to fatty acids (62.5%), esters (18.2%) and alkanes (6.25). It is inferred that the addition of Ni to Mo causes more progress of decarbonylation and decarboxylation reactions, and the addition of Co to Mo generates more ester compounds. Sensitivity analysis indicated that the effect of Ni-Mo/Al2O3 catalyst through catalytic pyrolysis process was more severe than Co-Mo/Al2O3 catalyst.


Relationship between Dental Caries Experience and Social Capital among Children - A Pilot Study.
The effect of larger and distal environmental and societal factors on oral health is established and the concept of social capital (SC) is gaining importance. The aim of the study is to evaluate the association of dental caries (DC) experience of children with parental social SC. A cross-sectional survey was conducted among 200 pairs of 5-12-year-old children and their parents of Kaloor (65th division), Kerala. A 30-item self-administered neighborhood SC Index questionnaire. DC of children was assessed as per the WHO guidelines. The final analysis included 186 pairs of children and parents, out of which 54.8% were boys. The mean caries experience of children was 3.3 ± 3.7. A significantly higher proportion of parents rated their children as "poor oral health" in caries experienced group than caries-free group (P = 0.006). No other significant differences were found with total SC and demographic variables except for "frequency of having meal together." Regression analysis showed that trust, control, and political domains were significant with carious status. On adjusting the confounders that were significant in bivariate analysis, only control domain of the SC remained significant. The social control domain (family members or neighbors actions that seek to correct deviant behavior) of SC was associated with caries experience of the children. Distal factors such as SC can influence the caries status of children.


HIV replication elicits little cytopathic effects in vivo: analysis of surrogate markers for virus production, cytotoxic T cell response and infected cell death.
Several potential mechanisms for viral destruction of HIV-infected cells have been described. The hypothesis was examined that if HIV were cytopathic, a positive relation between the in vivo virus production or CTL activity and infected cell death should be observed. In a regression analysis no significant relation was found between surrogate markers for in vivo virus production or the virus-specific CTL response and death rates of productively infected cells. In a subgroup of patients the hypothesis is rejected that HIV replication elicits a large (R(2) > 0.25) cytopathic effect (P < 0.05, N = 36). It is concluded that HIV replication elicits little cytopathic effect in productively infected cells and that CD4(+) T lymphocytes are eroded by other mechanisms.


Effect of Peganum harmala Total Alkaloid Extract on Sexual Behavior and Sperm Parameters in Male Mice.
The study was designed to evaluate the effects of the total alkaloid extract of Algerian Peganum harmala seeds on sexual behavior and male reproductive function. After two weeks of acclimatization, the male mice were randomly divided into four groups (seven mice in each group). For 35 days, the extract was administered orally at dose levels of 6.25, 12.5, and 25 mg/kg body weight per day to the respective groups of male mice (n = 7) and normal saline daily to the control group. On day 28, sexual behavior parameters were recorded. At the end of the trial, reproductive organ weights, sperm quality, seminal fructose, and testosterone hormone levels were evaluated. The three treated groups were compared with the control using statistical variance analysis (one-way ANOVA, p < 0.05), followed by Tukey's test. The results of the groups treated with 12.5 and 6.25 mg/kg of P. harmala alkaloid revealed the MF and IF parameters to be the lowest compared to the control group (p < 0.05). However, the male mice treated with 25 mg/kg recorded the highest values. A low significant value of ML was observed in the group treated with 25 mg/kg of the total alkaloid extract of P. harmala compared to the control group (p < 0.01), while a rise was observed in the concentration group treated with 6.25 mg/kg. Regarding IL, the male mice treated with different concentrations of the total alkaloid extract of P. harmala recorded a higher time than the control group. Moreover, an increase in the gonadosomatic index was noticed in all groups compared to the control group. However, there was a significant (p < 0.01) decrease in the sperm counts of the groups treated with 12.5 mg/kg and 6.25 mg/kg. However, there was no significant difference in the motility, membrane integrity, and total antioxidant capacity of sperm cells compared to the control. The extract treatment also brought about a non-significant increase in fructose content of the seminal vesicle and serum testosterone level. The findings of this study demonstrate that the extract acts in a dose-dependent manner, and it has varying effects on the reproductive parameters of male mice.


Structure of cupric bleomycin. Nitrogen and proton couplings from EPR and electron nuclear double resonance spectroscopy.
Low frequency (S-band) EPR and electron nuclear double resonance (ENDOR) data have been used to provide a detailed description of the magnetic environment of the cupric complex of the antitumor antibiotic, bleomycin. S-band EPR spectra show well resolved nitrogen hyperfine structure in both gl and g regions. Computer simulation of these spectra are consistent with binding to four donor nitrogen atoms, three with AN = 10 gauss and one with AN = 15 G. ENDOR data confirm the presence of at least two inequivalent nitrogens with AN approximately 11 and 15 G. In addition, at least six proton couplings were evident in the ENDOR spectrum although these could not be unambiguously assigned. Diminution of the matrix ENDOR signal in D2O relative to that in H2O was found; this demonstrates the accessibility of H2O to the metal site.


Detection of GFAP in vertebral fibrocartilage in human fetal and newborn tissue.
Previously we reported the coexpression of cytokeratin and vimentin in nucleus pulposus cells in fetal life and childhood (Stosiek et al. 1988). In this study, we observed also an unexpected reaction of an antibody against glial fibrillary acidic protein (GFAP) with some chondroblasts in fibrous cartilage, which will here be published using an enlarged panel of mono- and polyclonal antibodies specific for GFAP.


Sex influences the effect of adiposity on arterial stiffness and renin-angiotensin aldosterone system activity in young adults.
Sex influences the cardiovascular risk associated with body mass index (BMI) in older adults. Whether this risk differs by sex in younger adults is unknown. We aimed to evaluate the association between measures of adiposity and arterial stiffness and reninangiotensin-aldosterone system (RAAS) activity in younger adults, stratified by sex. Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and fat mass% (FM%) were measured in healthy participants in a fasting, high-salt state. Arterial stiffness [pulse wave velocity (PWV) and aortic augmentation index (AIx)] were measured at baseline and in response to angiotensin II challenge, a validated marker of RAAS activity. Associations were evaluated using linear regression analysis and stratified by sex. Ninety-five healthy, normotensive, non-diabetic females (n = 67, 37 ± 2 y, BMI 25 ± 1 kg/m2 ) and males (n = 28, 39 ± 3 y, BMI 27 ± 1 kg/m2 ) participated in the study. No association was observed between any measure of adiposity and PWV, either at baseline or in response to angiotensin II challenge in premenopausal females. In contrast, all measures of adiposity except HC were associated with PWV at baseline (BMI r = 0.32; WC r = 0.18; WHtR r = 0.34; FM r = 0.21; all values p < .05) and in response to AngII (BMI r = -0.39; WC r = -0.42; WHR r = -0.39; and WHtR r = -0.55) in males. Most adiposity measures were positively associated with baseline AIx (BMI r = 0.33; WC r = 0.27; WHtR r = 0.35; FM% r = 0.25; p < .05) in females, while only WHtR was associated with baseline AIx (r = 0.39; p = .04) in males. All measures of adiposity were positively associated with a blunted Aix response to Ang II (all values p < .001) in females. BMI, WC, WHR and WHtR were associated with a blunted AIx response to Ang II (ΔAIx: BMI r = -0.37; WC r = -0.31; WHR r = -0.16; and WHtR r = -0.22; all values p < .05) in males. The associations between adiposity measures and cardiovascular risk differ by sex in a young population. These factors should be considered when managing cardiovascular risk.


Incidentalomas of the adrenal gland: 36 operated patients and review of literature.
Incidental discovery of an adrenal mass during radiologic examinations is common. Several recommendations have been made for the management of so-called incidentalomas. It has become clear that not all incidentalomas should be operated, but the criteria for nonoperative treatment have been under continuous debate. In this study 36 operated incidentalomas are presented, and the indications for operative treatment are discussed with a review of the recent literature on the subject. Four pheochromocytomas and three hormonally active cortical adenomas, two producing cortisol and one androgens, were found. In this series there were no malignancies. The operation could have been avoided in most cases, and patients could have been followed up with repeated radiologic examinations. It is suggested that masses smaller than 6 cm in diameter be followed radiologically after 3, 9, and 18 months. Masses between 3 and 6 cm could be further examined using magnetic resonance imaging and fine needle aspiration and then operated if features suggestive of malignancy are found. Masses larger than 6 cm in diameter should be treated operatively.


Pan-Pseudothrombocytopenia in COVID-19: A Harbinger for Lethal Arterial Thrombosis?
Pseudothrombocytopenia in the setting of COVID-19-associated coagulopathy prompts the question whether it is representative of increased platelet aggregation activity in vivo.


Isolation and characterization of a hemagglutinin with affinity for lipopolysaccharides from plasma of the crayfish Pacifastacus leniusculus.
A hemagglutinin with a high specific activity against trypsinized rabbit erythrocytes was identified in plasma of the freshwater crayfish Pacifastacus leniusculus. The activity of this crayfish hemagglutinin could be inhibited by sialoglycoproteins such as porcine stomach mucin, bovine submaxillary mucin, fetuin, and ovalbumin. However, the involvement of sialic acid in its binding specificity could not be unambiguously proven. Furthermore, the hemagglutinating activity in the crayfish plasma could be specifically inhibited by lipopolysaccharide from E. coli K-235, which might indicate a recognition role for this hemagglutinin. This hemagglutinin, which accounts for less than 0.01% of the total plasma protein, was purified to near homogeneity using affinity chromatography on a Fetuin-Sepharose 4B column. The molecular mass of the unreduced protein as revealed by sodium dodecyl sulphate electrophoresis in polyacrylamide gel was found to be 420,000 Da. Upon reduction with dithiothreitol the hemagglutinin dissociated to several subunits with masses ranging from 65,000 to 80,000 Da. Affinoblotting with peroxidase labelled lectins indicated that the hemagglutinin was likely to be a glycoprotein.


Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway.
Fisetin is a naturally occurring flavonoid that has been reported to inhibit the proliferation and to induce apoptotic cell death in several tumor cells. However, the apoptosis-inducing effect of fisetin on tumor cell lines was investigated besides HeLa cells. In this study, we found that fisetin induced apoptosis of HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining of 4'-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI double-labeling. In addition, fisetin triggered the activations of caspases-3 and -8 and the cleavages of poly (ADP-ribose) polymerase, resulting in apoptosis induction. Moreover, treatment of HeLa cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059 (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector significantly abolished the fisetin-induced apoptosis through the activation of caspase-8/-3 pathway. The in vivo xenograft mice experiments revealed that fisetin significantly reduced tumor growth in mice with HeLa tumor xenografts. In conclusion, our results indicated that fisetin exhibited anti-cancer effect and induced apoptosis in HeLa cell lines both in vitro and in vivo.


Selective CB2 agonists with anti-pruritic activity: discovery of potent and orally available bicyclic 2-pyridones.
The CB2 receptor has emerged as a potential target for the treatment of pruritus as well as pain without CB1-mediated side effects. We previously identified 2-pyridone derivatives 1 and 2 as potent CB2 agonists; however, this series of compounds was found to have unacceptable pharmacokinetic profiles with no significant effect in vivo. To improve these profiles, we performed further structural optimization of 1 and 2, which led to the discovery of bicyclic 2-pyridone 18e with improved CB2 affinity and selectivity over CB1. In a mouse pruritus model, 18e inhibited compound 48/80 induced scratching behavior at a dose of 100 mg/kg. In addition, the docking model of 18e with an active-state CB2 homology model indicated the structural basis of its high affinity and selectivity over CB1.


Perspectives of radiologists in Ghana about the emerging role of artificial intelligence in radiology.
The integration of Artificial Intelligence (AI)-based technologies in medicine is advancing rapidly especially in the field of radiology. This however, is at a slow pace in Africa, hence, this study to evaluate the perspectives of Ghanaian radiologists. Data for this cross-sectional prospective study was collected between September and November 2021 through an online survey and entered into SPSS for analysis. A Mann-Whitney U test assisted in checking for possible gender differences in the mean Likert scale responses on the radiologists' perspectives about AI in radiology. Statistical significance was set at P ≤ 0.05. The study comprised 77 radiologists, with more males (71.4%). 97.4% were aware of the concept of AI, with their initial exposure via conferences (42.9%). The majority of the respondents had average awareness (36.4%) and below average expertise (44.2%) in radiological AI usage. Most of the participants (54.5%) stated, they do not use AI in their practices. The respondents disagreed that AI will ultimately replace radiologists in the near future (average Likert score = 3.49, SD = 1.096) and that AI should be an integral part of the training of radiologists (average Likert score = 1.91, SD = 0.830). Although the radiologists had positive opinions about the capabilities of AI, they exhibited an average awareness of and below average expertise in the usage of AI applications in radiology. They agreed on the potential life changing impact of AI and were of the view that AI will not replace radiologists but serve as a complement. There was inadequate radiological AI infrastructure in Ghana.


Transition of MEMS technology to nanofabrication.
The transition of MEMS technology to nano fabrication is a solution to the growing demand for smaller and high-density feature sizes in the nanometer scale. Nanoimprint lithography (NIL) techniques for fabricating micro- and nano-features are discussed including hot embossing lithography (HEL), UV Molding (UVM) and micro contact printing (microCP). Recent results in micro and nano-pattern transfer are presented where features ranged from < 100 nm to several centimeters. We also present a comparative study between standard glass microfluidic chips and their HEL counterparts by metrology. Hot-embossed microfluidic chips are shown to be faithful replicates of their parent stamps. NIL is presented as a promising avenue for low-cost, high throughput micro and nano-device fabrication.


Integration of Inpatient and Residential Care In-Reach Service Model and Hospital Resource Utilization: A Retrospective Audit.
In parts of Australia, Residential In-Reach (RIR) services have been implemented to treat residential aged care (RAC) residents for acute conditions in their place of residence to avoid preventable hospital presentation. Our service was initiated in 2009 and restructured in 2014. We compared acute healthcare resource utilization (RIR activity and emergency hospital presentations) by RAC residents under 2 RIR models of care. Acute RAC RIR service model of care was changed from existing nurse/emergency physician-led service to nurse/geriatrician-led service and incorporate inpatient liaison nurse consultant into the team. RAC episodes and hospital presentations from a single tertiary referral hospital and its associated RAC RIR service. Retrospective audit comparing RIR activity, hospital presentations, and associated costs from 2 12-month periods, prior to and postimplementation. Data were expressed as a proportion of the total number of RAC beds in the hospital RIR catchment. After implementation of the new model of care, RIR episodes of care increased from 589 to 985 (15.3 vs 24.7 episodes/100 RAC beds, P < .001). Emergency department (ED) presentations fell from 1616 to 1478 (41.9 vs 37.2 presentations/100 RAC beds, P < .001). There were fewer unplanned ED presentations by RIR patients (2.4% vs 0.8%, = 0.03) and fewer 28-day ED re-presentations (16.8% vs 13.7%, P = .01) under the new model of care. ED cost [$AUD 30,830 vs $28,030/100 RAC beds ($USD 21,344 vs $19,407), P < .001] and inpatient admission costs [$145,607 vs $117,531/100 RAC beds ($USD 100,814 vs $81,380), P < .001] were each lower in the second period. In the 12 months following implementation of the new model of care, an increase in RIR activity, and a decrease in ED presentations was observed. Further research is necessary to validate these retrospective findings and better evaluate clinical outcomes and consumer satisfaction of the service.


[Schnyder's crystalline dystrophy. II. Association with genu valgum].
The present study describes a family in which Schnyder's crystalline stromal dystrophy coexisted with genu valgum. One member, a woman, exhibited only the corneal dystrophy. She underwent a bilateral corneal graft and the buttons studied by light and electron microscopy were described in another report. Her daughter exhibited only genu valgum and her son had both disorders. It is to our knowledge the fourth report on the combination of Schnyder's dystrophy and genu valgum in the same family. The significance of this association and other associations like hyperlipoproteinaemia and xanthelasma are discussed.


Factors affecting the preparation of 99mTc-sulfur colloid.
Some factors, such as the effect of mannitol as 'stabilizer', increased concentration of thiosulfate, autoclaving conditions, etc., that can affect the preparation of 99mTc-sulfur colloid and consequently its biodistribution into different tissues are discussed. Also discussed are parameters, such as distribution with respect to time, effect of storage, preloading dose, etc., that can influence the uptake of the radiopharmaceutical by the RES in animals and humans.


Evidencing the presence of merkel cell polyomavirus in papillary thyroid cancer.
Merkel cell polyomavirus (MCPyV) infects most people asymptomatically, but recent reports indicate that the virus may be related to carcinogenesis. This study aimed to evaluate the impact of MCPyV on the development of papillary thyroid cancer (PTC). Totally, 1057 samples, including 412 fresh biopsy samples (FBS) and 645 paraffin-embedded PTC biopsy samples (PEBS), and 1057 adjacent non-cancerous samples were assessed for the presence of MCPyV DNA and RNA. MCPyV DNA was positive in 215 (20.3%) of samples, including 126 (30.6%) in FBS and 89 (13.8%) in PEBS. In MCPyV-positive samples, the mean MCPyV copy number was higher in the patients with FBS (2.3 × 10-1 ± 0.5 × 10-1 copies/cell) compared to PEBS (0.7 × 10-4 ± 0.1 × 10-4 copies/cell) and adjacent non-PTC normal samples (0.3 × 10-5 ± 0.02 × 10-5 copies/cell), indicating a statistically significant difference (P < 0.001). The LT-Ag RNA expression was higher in FBS compared to PEBS, while VP1 gene transcript was not detected in any samples. Although our findings showed the presence of MCPyV in a subset of PTC Iranian patients, further research is required to confirm these findings.


Functional and phosphoproteomic analysis of β-adrenergic receptor signaling at excitatory synapses in the CA1 region of the ventral hippocampus.
Activation of β-adrenergic receptors (β-ARs) not only enhances learning and memory but also facilitates the induction of long-term potentiation (LTP), a form of synaptic plasticity involved in memory formation. To identify the mechanisms underlying β-AR-dependent forms of LTP we examined the effects of the β-AR agonist isoproterenol on LTP induction at excitatory synapses onto CA1 pyramidal cells in the ventral hippocampus. LTP induction at these synapses is inhibited by activation of SK-type K+ channels, suggesting that β-AR activation might facilitate LTP induction by inhibiting SK channels. However, although the SK channel blocker apamin enhanced LTP induction, it did not fully mimic the effects of isoproterenol. We therefore searched for potential alternative mechanisms using liquid chromatography-tandem mass spectrometry to determine how β-AR activation regulates phosphorylation of postsynaptic density (PSD) proteins. Strikingly, β-AR activation regulated hundreds of phosphorylation sites in PSD proteins that have diverse roles in dendritic spine structure and function. Moreover, within the core scaffold machinery of the PSD, β-AR activation increased phosphorylation at several sites previously shown to be phosphorylated after LTP induction. Together, our results suggest that β-AR activation recruits a diverse set of signaling pathways that likely act in a concerted fashion to regulate LTP induction.


Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study.
Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration. To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D. Cohort study. The Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis. 1621 white older adults. Serum 25-(OH)D concentration (using a high-performance liquid chromatography-tandem mass spectrometry assay that conforms to National Institute of Standards and Technology reference standards) and associations with time to a composite outcome of incident hip fracture, myocardial infarction, cancer, or death. Over a median 11-year follow-up, the composite outcome occurred in 1018 participants (63%). Defining events included 137 hip fractures, 186 myocardial infarctions, 335 incidences of cancer, and 360 deaths. The association of low 25-(OH)D concentration with risk for the composite outcome varied by season (P = 0.057). A concentration lower than a season-specific Z score of -0.54 best discriminated risk for the composite outcome and was associated with a 24% higher risk in adjusted analyses (95% CI, 9% to 42%). Corresponding season-specific 25-(OH)D concentrations were 43, 50, 61, and 55 nmol/L (17, 20, 24, and 22 ng/mL) in winter, spring, summer, and autumn, respectively. The observational study was restricted to white participants. Threshold concentrations of 25-(OH)D associated with increased risk for relevant clinical disease events center near 50 nmol/L (20 ng/mL). Season-specific targets for 25-(OH)D concentration may be more appropriate than static targets when evaluating health risk. National Institutes of Health.


Measurement of ordered associate of protonated tetraphenylporphine formed at toluene/aqueous H2SO4 interface by attenuated total internal reflection spectroscopy with polarized light.
Attenuated total internal reflection (ATR) spectroscopy with an s- or p-polarized visible light was examined for some species of protonated 5,10,15,20-tetraphenylporphine (tpp) at toluene/aqueous H2SO4 (3-6 mol dm(-3)) interface. Tpp initially dissolved in the toluene phase was diprotonated at the interface to form monomeric H2tpp2+, the absorption peak of which was 438nm. At the same time, a long H2tpp2+ oligomer was formed, the absorption peak of which was 448 nm. The two interfacial species were transient. Just after their disappearance, a rod-shaped H2tpp2+ associate was formed at the interface, the absorption peak of which was 417 and 478 nm. The former and latter wavelengths corresponded to H- and J-bands of the associate, respectively. Theoretical calculation of the strength of electric field of light at the interface allowed one to estimate the interfacial concentration of the three species with measured reflection absorbance (A(R)). The monomeric H2tpp2+ and its oligomer were at sub-monolayer levels, whereas the associate was at a multilayer level. Reflection absorption anisotropy (K(R)), which was calculated from A(R) with the s- and p-polarized lights, was adopted for the evaluation of out-of-plane orientation of the interfacial species for the first time. The K(R) value suggested that the rod-shaped associate lay at the interface.


[Possible use of a sunflower protein isolate in preparing dishes for public catering].
Results derived from an investigation into the possibility of utilizing the proteinic sunflower isolate (PSFI) in cooking meals with minced and comminuted meat are presented. A method of enriching meals with PSFI during their preparation has been devised and their pepsin digestibility investigated.


Extracellular ATP induces fast and transient non-selective cationic currents and cytosolic Ca2+ changes in human umbilical artery smooth muscle cells.
Ionotropic purinergic receptors (P2X) are expressed in endothelial and smooth muscle cells of blood vessels. ATP acting on smooth muscle P2X receptors is able to induce vasoconstriction in different kind of vessels. However, to our knowledge, there are no reports that directly show the activity of these purinergic receptors in native human vascular smooth muscle cells. In this work, we describe for the first time an ATP-induced current in freshly isolated human umbilical artery (HUA) smooth muscle cells. The current was measured by patch-clamp technique in whole-cell condition on cells clamped at -50 mV. At 100 μM of ATP the current showed a rapid activation and desensitization, and was carried by both Na(+) and Ca(2+). The current was completely blocked by suramin (300 μM) and partially blocked by 100 μM of Zn(2+) without affecting the kinetic of desensitization. All these properties suggest that the ATP-induced ionic currents are mediated through P2X(1)-like receptors. Moreover, we show that ATP transiently increased cytosolic Ca(2+) in "in situ" smooth muscle cells of intact HUA segments and that this response is dependent of extracellular and intracellular Ca(2+). These data expand the knowledge of purinergic receptors properties in vascular smooth muscle cells and the probable role of ATP as a paracrine modulator of contractile tone in a human artery which is fundamental for feto-placental blood flow.


No Effect of Return to Sport Test Batteries with and without Psychological PROs on the Risk of a Second ACL Injury: A Critical Assessment of Four Different Test Batteries.
Patients report psychological barriers as important when returning to sport, however, psychological outcome measures are seldom included in return to sport (RTS) assessment. There is a need for clinical trials to integrate psychological patient-reported outcomes (PROs) in return to sport batteries assessing patients treated with ACL reconstruction. The aim of this study was to determine the association between passing clinical tests of muscle function and psychological PROs and sustaining a second ACL injury in patients who RTS after primary ACL reconstruction. Retrospective Cohort study. Patients' sex, age, height and weight, and the results of strength and hop tests, as well as answers to PRO's (including Tegner activity scale, the ACL Return to Sport after Injury scale (ACL-RSI) as well as the Quality of Life (QoL) subscale of the Knee injury and Osteoarthritis Outcome Score [KOOS]), were extracted from a rehabilitation-specific registry. Four different test batteries comprising muscle function tests and PROs were created to assess whether patients were ready to RTS. Passing each of the test batteries (yes/no) was used as an independent variable. A multivariable Cox proportional hazard model analysis was performed, with sustaining a second ACL injury (either ipsi- or contralateral; yes/no) within two years of RTS as the dependent variable. A total of 419 patients (male, n=214; 51%) were included, of which 51 (12.2%) suffered a second ACL injury within the first two years after RTS. There were no differences in passing rates in the different RTS test batteries comprising muscle function tests and PROs for patients who suffered a second ACL injury compared to patients who did not. No association between passing the RTS clinical tests batteries comprising muscle function and psychological PROs used, and the risk of a second ACL injury could be found. 3©The Author(s).


Results of the implementation of a triage system of vascular access performance in haemodialysis patients: experience of a single dialysis centre.
Routine systems for monitoring vascular access (VA) performance are lacking. We developed a vascular access triage system to evaluate the monthly performance of the access, developed a specific score and assessed the association between score improvement and clinical outcomes. Vascular access was triaged (Green, Yellow or Red) according to a score generated by dialytic and clinical parameters in all patients who, from 1/1/2014 to 31/03/2014, had been receiving haemodialysis treatment for at least 3 consecutive months in our Unit and who were then followed up for 4 years. We enrolled 130 patients, 78 with arteriovenous fistula (AVF) and 52 with tunnelled central venous catheter (CVC). During a median of 29 ± 11 months of follow up (range 3-46 months), 28 deaths and 303 hospitalizations (lasting 16 ± 30 days) were recorded. Vascular access triage scores improved over time (2014 vs 2015 vs 2016 vs 2017) in the population with an AVF (Green from 25% to 58% to 77% to 79%, Yellow from 65% to 39% to 18% to 20% and Red from 10% to 3% to 5% to 1%, respectively; χ2 p < 0.01) but not in the CVC group (Green 58% to 57% to 80% to 92%; Yellow 37% to 36% to 20% to 8%; Red 5% to 7% to 0%; χ2 = n.s). Blood pressure and dialysis efficiency improved in the population as a whole and in the two subgroups (AVF and CVC) separately. AVF and CVC populations, stratified separately according to median VA score, had different event-free follow-up, which was higher (p = 0.0085) in patients with lower scores in the AVF population only. The vascular access monitoring system improved the vascular access score as well as some clinical and dialytic parameters. Green triage in AVF patients identify those with better outcomes, in agreement with the commonly recognized clinical value of a well-functioning vascular access.


Multiple injections of anti-mouse β2glycoprotein 1 antibody induce FcRγ-dependent fetal growth restriction (FGR) in mice.
The antiphospholipid syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies (aPLs), is a leading cause for thromboembolic events, repeated miscarriage, fetal loss and is a major risk factor for fetal growth restriction (FGR) and preeclampsia. In human, anti-β2 glycoprotein I (aβ2GPI) antibody is one of the aPLs and considered to be a specific and important marker for APS. However, pathophysiological changes induced by aβ2GPI antibodies in FGR are largely unknown. In the present study, we developed a murine FGR model induced by multiple injections of WBCAL-1, a well-characterized mouse aβ2GPI monoclonal antibody. Administration of WBCAL-1, but not the isotype control antibody and saline, into pregnant mice specifically decreased the size of fetuses and placentas without affecting the number of delivered pups. Also, a significant increase in urinary albumin and electron microscopic changes, such as splitting layers of basal membranes in the placental labyrinth and rearrangement of pores in glomerular endothelial cells, were observed in WBCAL-1 treated mice. WBCAL-1 injection did not induce any changes in blood pressure and typical parameters of blood thromboembolic symptoms. Furthermore, FcRγ deficiency protected the fetuses from aβ2GPI antibody-induced injuries. Our present findings suggest that proteinuria is a symptom associated with APS-related FGR with placental and renal tissue injuries, and that FcRγ might be a molecular target for prevention of aβ2GPI antibody-mediated obstetrical pathologies.


Pirenperone effects on temperature preference and body temperature in maturing mice.
Thermoregulatory effects of the selective 5-HT2 antagonist pirenperone were studied 1 hr after IP injection in mice aged 1, 3, 5, 7 and 10 days postpartum. Compared with vehicle injected littermates, a dose of 0.16 mg/kg decreased temperature preference (T pref) on a thermal gradient at all ages. No significant effects were observed on body temperature (Tb) at any of the ages. An increased dose (0.48 mg/kg) caused no greater effect on T pref and no significant effect on Tb. These results indicate that Tb and T pref are separable on the basis of receptor pharmacology, and are discussed in relation to drug effects on 5-HT2 receptors.


Phosphoprotein phosphatase-2A docks to Dishevelled and counterregulates Wnt3a/beta-catenin signaling.
Wnt3a stimulates cellular trafficking of key signaling elements (e.g., Axin, Dishevelled-2, beta-catenin, and glycogen synthase kinase-3beta) and primitive endoderm formation in mouse F9 embryonic teratocarcinoma cells. The role of phosphoprotein phosphatase-2A in signaling of the Wnt/beta-catenin/Lef-Tcf-sensitive gene activation pathway was investigated. Wnt3a action attenuates phosphoprotein phosphatase-2A activity and stimulates the Lef/Tcf-sensitive gene transcription. Inhibiting phosphoprotein phosphatase-2A by okadaic acid, by treatment with siRNA (targeting the C-subunit of the enzyme), or by expression of SV40 small t antigen mimics Wnt3a action, increasing the cellular abundance of Axin and phospho-glycogen synthase kinase-3beta as well as the trafficking of signaling elements in the Wnt/beta-catenin pathway. Although mimicking effects of Wnt3a on the cellular abundance and trafficking of key signaling elements in the Wnt canonical pathway, suppression of phosphatase-2A alone did not provoke activation of the Lef/Tcf-sensitive transcriptional response, but did potentiate its activation by Wnt3a. Phosphoprotein phosphatase-2A and the scaffold phosphoprotein Dishevelled-2 display similarities in cellular trafficking in response to either Wnt3a or suppression of the phosphatase. A docking site for phosphoprotein phosphatase-2A in the DEP domain of Dishevelled-2 was identified. In current study, we showed new roles of phosphoprotein phosphatase-2A in Wnt/beta-catenin signaling pathway: effect on protein expression, effect on protein trafficking, retention of molecules in subcellular compartments, and regulation of enzymatic activity of several key players. Docking of phosphoprotein phosphatase-2A by Dishevelled-2 suppresses phosphatase activity and explains in part the central role of this phosphatase in the counterregulation of the Wnt/beta-catenin signaling pathway.


The influence of some prostaglandins on DNA synthesis and DNA excision repair in mouse spleen cells in vitro.
In vitro experiments were performed on mouse spleen cells to establish possible influences of some naturally occurring prostaglandins on DNA synthesis and DNA excision repair. The prostaglandins A1, B1, E1, E2 and F2alpha were tested in concentrations of lopg, 5ng and 2.5microgram per ml cell suspension. DNA synthesis was significantly increased by PgF2alpha in all the three concentrations tested, while the other tested prostaglandins were essentially ineffective. DNA excision repair was significantly inhibited by PgE1 and PgE2 at 5ng/ml and at 2.5microgram/ml but increased by PgF2alpha in the two lower concentrations. The rejoining of DNA-strand breaks after gamma-irradiation was slightly reduced by PgE1, PgE2 and PgF2alpha at 2.5microgram/ml.


Cortical 5HT 2A receptor function under hypoxia in neonatal rats: role of glucose, oxygen, and epinephrine resuscitation.
Neonatal hypoxia induces brain injury through alterations in neurotransmitters and its receptors. Molecular processes regulating serotonergic receptors play an important role in the control of respiration under hypoxia. The present study evaluates the serotonergic regulation of neonatal hypoxia and its resuscitation methods. Receptor binding assays and gene expression studies were done to evaluate the changes in 5HT(2A) receptors and its transporter in the cerebral cortex of hypoxic neonatal rats and hypoxic rats resuscitated with glucose, oxygen, and epinephrine. Hypoxic stress increased total 5HT and 5HT(2A) receptor number along with an upregulation of 5HT(2A) receptor and 5HT transporter gene in the cortex. The enhanced cortical 5HT(2A) receptors may act as a modulator of ventilatory response to hypoxia. These alterations were reversed to near control by glucose supplementation. Glucose supplementation helped in managing the serotonergic functional alterations. Hypoxia-induced adenosine triphosphate depletion causes a reduction in blood glucose levels which can be encountered by glucose administration, and oxygenation helps in overcoming the anaerobic condition. The adverse effect of immediate oxygenation and epinephrine supplementation was also reported. This has immense clinical significance in establishing a proper resuscitation for the management of neonatal hypoxia.