A small dose of somatostatin inhibits the secretin stimulated secretion of bicarbonate, amylase, and chymotrypsin in man.
The effects of a small dose of somatostatin (0.025 mg/h) on the pancreatic secretion of bicarbonate, amylase, and chymotrypsin during stepwise increasing doses of secretin was examined in six healthy volunteers. The secretion of bicarbonate, amylase, and chymotrypsin in response to secretin was significantly reduced by somatostatin. Both output and concentration of pancreatic enzymes were reduced, whereas the concentration of bicarbonate remained unchanged. The pattern of inhibition suggests that somatostatin is a competitive inhibitor of secretin in the stimulation of pancreatic secretion of bicarbonate, which supports the hypothesis of a direct effect of somatostatin on the exocrine secretory cells of the pancreas. The pattern of inhibition of amylase and chymotrypsin secretion is different and difficult to interpret from the present study, but somatostatin may inhibit also the secretin stimulated pancreatic secretion of enzymes completely, as the inhibitory effect seemed to decline when larger doses of secretin were applied.


[Progress of problems related to the reconstruction of aortic arch in acute type A aortic dissection].
Aortic arch reconstruction is one of the most challenging operations in aortic surgery. Anatomical abnormalities of the aortic arch, including bovine aortic arch, aberrant right subclavian artery, and single vertebral artery have direct impact on the choice of surgical procedures and methods of brain protection.The risk of aortic arch reconstruction and the difficulty of operation, it is possible to avoid the injury of patients by strictly grasping the indication of operation. Intraoperative arterial cannulation and brain protection strategies are directly related to the success of the operation. This article makes a brief review of the above problems in the reconstruction of the aortic arch, hoping to be helpful to the cardiovascular surgeon.


[Establishment of a Method of Hepatocyte Differentiation from Human Pluripotent Stem Cells for Innovative Drug Development].
Hepatocyte-like cells differentiated from human pluripotent stem cells (such as human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells) are expected to be utilized in drug screening. However, the hepatocyte differentiation efficiency and hepatic functions of hepatocyte-like cells were not sufficient to perform ES/iPS cell-based drug discovery. Therefore, we decided to improve the method of hepatocyte differentiation from human ES/iPS cells. To enhance this hepatocyte differentiation efficiency, hepatocyte-related transcription factors, such as forkhead box protein A2 (FOXA2) and hepatocyte nuclear factor 1 alpha (HNF1α), were overexpressed during the hepatocyte differentiation process. In addition, to enhance the functions of hepatocyte-like cells, these cells were cultured in three dimensional (3D) conditions using a Nanopillar plate. By FOXA2 and HNF1α overexpression, human ES/iPS cells could efficiently (more than 80%) differentiate into albumin-positive hepatocyte-like cells. Various hepatic functions, including albumin secretion and drug metabolism capacities, of the hepatocyte-like cells were significantly enhanced by performing 3D cell culture. These results suggest that the method of hepatocyte differentiation could be improved by using gene transfer and 3D cell culture technologies. We believe that these new hepatocyte-like cells would be useful tools in drug development.


Urea and thiourea modified polypropyleneimine dendrimers clear intracellular α-synuclein aggregates in a human cell line.
Synucleinopathies are neurodegenerative pathologies in which disease progression is closely correlated to brain accumulation of insoluble α-synuclein, a small protein abundantly expressed in neural tissue. Here, two types of modified polypropyleneimine (PPI) dendrimers having either urea or methylthiourea (MTU) surface functional groups were investigated in a cellular model of synucleinopathy. Dendrimers are synthetic macromolecules that may be produced in a range of well-defined molecular sizes. Using cellomics array scan high-content screening, we show that both types of dendrimers are able to significantly reduce intracellular levels of α-synuclein aggregates dependent on the concentration, the type and molecular size of the dendrimer with the bigger size MTU-dendrimers having the highest potency. The intracellular clearance of α-synuclein aggregates by dendrimers was achieved at noncytotoxic concentrations.


Stopping Biologics in IBD-What Is the Evidence?
Biologic treatments have revolutionized the way we treat inflammatory bowel disease patients (IBD). Anti-tumor necrosis factor (anti-TNF) antibodies are superior to conventional therapies to achieve sustained remission without steroids and mucosal healing. The objective of IBD treatment has evolved from symptom alleviation to a combination of absence of symptoms and intestinal healing. Nevertheless, biologics are expensive and are associated with an increased risk of infections and possibly skin cancers. Therefore, the duration of these treatments may be questioned, and stopping them may be contemplated by some patients and clinicians, while it is sometimes even imposed by some jurisdictions across the world. In the present paper, I highlight the recent literature about outcomes after biologics withdrawal, patients' profiles associated with these outcomes, monitoring after withdrawal, and results of retreatment. We also introduce the concept of biologic treatment cycles in IBD.


Comparative Performance Analysis of Intel Xeon Phi, GPU, and CPU: A Case Study from Microscopy Image Analysis.
We study and characterize the performance of operations in an important class of applications on GPUs and Many Integrated Core (MIC) architectures. Our work is motivated by applications that analyze low-dimensional spatial datasets captured by high resolution sensors, such as image datasets obtained from whole slide tissue specimens using microscopy scanners. Common operations in these applications involve the detection and extraction of objects (object segmentation), the computation of features of each extracted object (feature computation), and characterization of objects based on these features (object classification). In this work, we have identify the data access and computation patterns of operations in the object segmentation and feature computation categories. We systematically implement and evaluate the performance of these operations on modern CPUs, GPUs, and MIC systems for a microscopy image analysis application. Our results show that the performance on a MIC of operations that perform regular data access is comparable or sometimes better than that on a GPU. On the other hand, GPUs are significantly more efficient than MICs for operations that access data irregularly. This is a result of the low performance of MICs when it comes to random data access. We also have examined the coordinated use of MICs and CPUs. Our experiments show that using a performance aware task strategy for scheduling application operations improves performance about 1.29× over a first-come-first-served strategy. This allows applications to obtain high performance efficiency on CPU-MIC systems - the example application attained an efficiency of 84% on 192 nodes (3072 CPU cores and 192 MICs).


Diagnosis of pulmonary fungal infections.
The diagnosis of pulmonary fungal infections is reviewed. An overview of the major endemic and opportunistic fungal infections is followed by a brief discussion of the available diagnostic tools. These include: (1) direct microscopic examination of secretions or body fluids; (2) histopathologic examination of tissue biopsies; (3) cultures of secretions, body fluids, or ground-up tissue; and (4) immunological tests ("fungal serologies"). In the final section, a current diagnostic approach is given that identifies the diagnostic tests more likely to be helpful for each infection.


A new hemostatic procedure for percutaneous transhepatic portal vein catheterization.
To avoid major complications, such as intraperitoneal bleeding after percutaneous transhepatic catheterization, a new technique has been developed. In this procedure, a stick-like gelfoam sponge compressed manually and loaded in a cartridge, is inserted through an outer sheath catheter after the removal of the catheter, and the puncture hole is plugged. No bleeding has been experienced in 56 patients with various hepatic diseases since using this method.


[Rigid ureteroscopy in the case of suspected tumor of the upper urinary tract: report of 63 cases].
This retrospective study was designed to determine the place of rigid ureteroscopy in the diagnosis of upper urinary tract tumours. 63 patients (45 males and 18 females) with a mean age of 60 years, were investigated by rigid ureteroscopy for suspected upper urinary tract tumour. The Wolf 8-9.8 F ureteroscope was used in the case of suspected upper urinary tract tumour in a context of ureteric obstruction on the IVU in 29 cases, haematuria in 23 cases, a defect on retrograde ureteropyelography in 5 cases, suspicious CT scan in 5 cases and positive cytology with normal cystoscopy in 2 cases. The ureteroscope was able to be advanced as far as the suspicious zone in 89% of cases. The mean operating time was 48 minutes and the mean hospital stay was 3.2 days. Diagnostic rigid ureteroscopy has a Sensitivity of 58% (95% confidence interval CI95: +/- 28), a Specificity of 100%, a Positive Predictive Value of 100%, a Negative Predictive Value of 91% (+/- 7) and a low morbidity (3%). Rigid ureteroscopy does not appear to be the examination of choice for the diagnosis of upper urinary tract tumours, as it cannot investigate the renal pelvis or calices and the ureteroscope cannot always be advanced to the suspicious zone. The flexible ureteroscope now appears to be a more reliable diagnostic tool.


The Predictive Validity of the National Board of Osteopathic Medical Examiners' COMLEX-USA Examinations With Regard to Outcomes on American Board of Family Medicine Examinations.
To examine the predictive validity of the National Board of Osteopathic Medical Examiners' Comprehensive Osteopathic Medical Licensing Examination of the United States of America (COMLEX-USA) series with regard to the American Board of Family Medicine's (ABFM's) In-Training Examination (ITE) and Maintenance of Certification for Family Physicians (MC-FP) Examination. A repeated-measures design was employed, using test scores across seven levels of training for 1,023 DOs who took the MC-FP for the first time between April 2012 and November 2014 and for whom the ABFM had ITE scores for each of their residency years. Pearson and disattenuated correlations were calculated; Fisher r to z transformation was performed; and sensitivity, specificity, and positive and negative predictive values for the COMLEX-USA Level 2-Cognitive Evaluation (CE) with regard to the MC-FP were computed. The Pearson and disattenuated correlations ranged from 0.55 to 0.69 and from 0.61 to 0.80, respectively. For MC-FP scores, only the correlation increase from the COMLEX-USA Level 2-CE to Level 3 was statistically significant (for Pearson correlations: z = 2.41, P = .008; for disattenuated correlations: z = 3.16, P < .001). The sensitivity, specificity, and positive and negative predictive values of the COMLEX-USA Level 2-CE with the MC-FP were 0.90, 0.39, 0.96, and 0.19, respectively. Evidence was found that the COMLEX-USA can assist family medicine residency program directors in predicting later resident performance on the ABFM's ITE and MC-FP, which is becoming increasingly important as graduate medical education accreditation moves toward a single aligned model.


Development of Intrinsically Labeled Eggs and Poultry Meat for Use in Human Metabolic Research.
Stable isotope amino acids are regularly used as tracers to examine whole-body and muscle protein metabolism in humans. To accurately assess in vivo dietary protein digestion and absorption kinetics, the amino acid tracer is required to be incorporated within the dietary protein food source (i.e., intrinsically labeled protein). We assessed the practicality of producing eggs and poultry meat intrinsically labeled with l-[5,5,5-(2)H3]leucine through noninvasive oral tracer administration. A specifically formulated diet containing 0.52% leucine was supplemented with 0.3% l-[5,5,5-(2)H3]leucine and subsequently fed to 3 laying hens (Lohmann LSL Whites) for 55 d. On day 55, the hens were slaughtered and their meat, bones, and organs were harvested to determine tissue labeling. In Expt. 1, 2 healthy young men [mean ± SEM age: 22 ± 1.5 y; mean ± SEM body mass index (BMI; in kg/m(2)): 23.7 ± 0.5] ingested 18 g l-[5,5,5-(2)H3]leucine-labeled egg protein. In Expt. 2, 2 healthy young men (mean ± SEM age: 20.0 ± 0.0 y; mean ± SEM BMI: 26.4 ± 3.1) ingested 28 g l-[5,5,5-(2)H3]leucine-labeled poultry meat protein. Plasma samples (Expts. 1 and 2) and muscle biopsies (Expt. 1) were collected before and after labeled-food ingestion. High tracer labeling [>20 mole percent excess (MPE)] in the eggs was obtained after 7 d and maintained throughout the feeding protocol (P < 0.05). Over a 55-d period, ∼850 g egg protein (145 eggs) was produced, with a mean ± SEM tracer enrichment of 22.0 ± 0.8 MPE. Mean ± SEM l-[5,5,5-(2)H3]leucine enrichment in the meat was 9.6 ± 0.1 MPE. In Expts. 1 and 2, the consumption of labeled eggs and poultry meat protein increased plasma l-[5,5,5-(2)H3]leucine enrichment, with mean ± SEM peak values of 6.7 ± 0.1 MPE and 4.0 ± 0.9 MPE, respectively. The mean ± SEM 5-h postprandial increase in myofibrillar l-[5,5,5-(2)H3]leucine enrichment after egg ingestion in healthy young men was 0.051 ± 0.008 MPE (Expt. 1). We demonstrated the feasibility of producing intrinsically labeled eggs and poultry meat for use in human metabolic research.


Anorectal myectomy in adult Hirschsprung's disease: a report of six cases.
The presentation and management of six adult patients with proven aganglionosis of the rectum are reported. Rectal mucosal biopsy combined with enzyme histochemistry was used to establish the diagnosis and it is recommended as the first investigative procedure. Conservative surgery either with anterior resection and anorectal myectomy or myectomy alone was found to be simple and relatively complication-free and to give very satisfactory results.


Connective tissue responses to some heavy metals. II. Lead: histology and ultrastructure.
Lead loaded ion exchange resin beads implanted into the loose connective tissue of the rat pinna induced local lesions which differed widely from those of the control (sodium loaded) beads (Ellender & Ham 1987). These lesions were characterized by changes in the granulation tissue and the approximating connective tissue. Granulation tissue contained mononuclear phagocytes in various guises, and some cells with intranuclear inclusion bodies. The matrix of the granulation tissue contained collagen fibrils having a wide range of diameters suggestive of altered collagen biosynthesis. Foci of collagen mineralization occurred in zones of combined trauma and lead impregnation. Once mineralized they became enveloped by giant cells and epithelioid cells. Lead in damaged tissues is thought to modify the protective mechanism of calcification inhibition and the biosynthesis of the matrix.


What do we know about direct-to-consumer advertising of prescription drugs?
Two papers, by Joel Weissman and colleagues and by Robert Dubois, add to our limited knowledge of the effects of direct-to-consumer (DTC) advertising of prescription drugs. Their results reinforce the largely positive findings from consumer surveys, while adding valuable new data and insights. These suggest that DTC ads probably improve patients' health outcomes and do not tend to lead to inappropriate prescribing. DTC advertising is emerging as a positive force in health care markets, consistent with what is known about the effects of advertising in many other markets.


Symmetrical peripheral gangrene complicating ventricular pseudoaneurysm: a report of an unusual case and a brief review of the literature.
Symmetrical peripheral gangrene is an ischemic necrosis simultaneously involving the distal portions of two or more extremities without any proximal arterial obstruction or vasculitis. It may occur as a result of a large number of infectious and non-infectious causes. A few cases of symmetrical peripheral gangrene associated with cardiac disease have been described in the literature. We describe a case of symmetrical peripheral gangrene complicating ventricular pseudoaneurysm, probably a hitherto unreported occurrence. In this report, we sought to emphasize the importance of cardiac evaluation while dealing with a case of symmetrical peripheral gangrene.


Cutoff radius effect of isotropic periodic sum method for transport coefficients of Lennard-Jones liquid.
Molecular dynamics simulations of a Lennard-Jones (LJ) liquid were applied to compare the isotropic periodic sum (IPS) method [X. Wu and B. R. Brooks, J. Chem. Phys. 122, 044107 (2005)], which can reduce the calculation cost of long-range interactions, such as the Lennard-Jones and Coulombic ones, with the cutoff method for the transport coefficients which includes the self-diffusion coefficient, bulk viscosity, and thermal conductivity. The self-diffusion coefficient, bulk viscosity, and thermal conductivity were estimated with reasonable accuracy if the cutoff distance of the LJ potential for the IPS method was greater than 3sigma. The IPS method is an effective technique for estimating the transport coefficients of the Lennard-Jones liquid in a homogeneous system.


Charging-free electrochemical system for harvesting low-grade thermal energy.
Efficient and low-cost systems are needed to harvest the tremendous amount of energy stored in low-grade heat sources (<100 °C). Thermally regenerative electrochemical cycle (TREC) is an attractive approach which uses the temperature dependence of electrochemical cell voltage to construct a thermodynamic cycle for direct heat-to-electricity conversion. By varying temperature, an electrochemical cell is charged at a lower voltage than discharge, converting thermal energy to electricity. Most TREC systems still require external electricity for charging, which complicates system designs and limits their applications. Here, we demonstrate a charging-free TREC consisting of an inexpensive soluble Fe(CN)6(3-/4-) redox pair and solid Prussian blue particles as active materials for the two electrodes. In this system, the spontaneous directions of the full-cell reaction are opposite at low and high temperatures. Therefore, the two electrochemical processes at both low and high temperatures in a cycle are discharge. Heat-to-electricity conversion efficiency of 2.0% can be reached for the TREC operating between 20 and 60 °C. This charging-free TREC system may have potential application for harvesting low-grade heat from the environment, especially in remote areas.


Epidemiology of Surgical Site Infections Considering the NHSN Standardized Infection Ratio in Hip and Knee Arthroplasties.
Introduction Surgical site infections (SSIs) are a predominant form of hospital-acquired infections in surgical wards. The objective of the study was analysis of the incidence of SSI in, both primary and revision, hip and knee arthroplasties. The study was conducted in 2012-2018 in a Trauma and Orthopedics Ward in Tarnów according to the methodology of the Healthcare-Associated Infections Surveillance Network (HAI-Net), European Centre for Disease Prevention and Control (ECDC). The surveillance comprised 2340 surgery patients, including: 1756 Hip Arthroplasties (HPRO) and 584 Knee Arthroplasties (KPRO). In the group of patients under study, 37 cases of SSI were detected, including: 26 cases of SSI after HPRO and 11 cases in KPRO. The average incidence of SSI amounted to 1.6% (1.5% HPRO and 1.9% KPRO) and in-hospital incidence density rates were 1.23 and 1.53 per 1000 patient-days, respectively. Median age of surgical patients in both HPRO and KPRO was 70 years. Women were undergoing arthroplasty surgery more often than men, HPRO (p < 0.05) and KPRO (p < 0.001). Patients with SSI stayed in the ward longer (SSI-HPRO, p < 0.001) (SSI-KPRO p < 0.01). In KPRO operations, the incidence of SSI was higher than expected, calculated according to the Standardized Infection Ratio (SIR). The most common etiologic agents isolated from SSIs in both HPRO and KPRO were coagulase-negative staphylococci. Establishing a thorough surveillance of hospital-acquired infections that takes into consideration epidemiological indicators is indispensable to properly assess the epidemiological situation in the ward. The optimal solution is to carry out long-term and multi-center surveillance in the framework of a uniform program, however, even results of single-center studies provide valuable data indicating challenges and needs in improving patient safety.


Tunable bimetallic Au-Pd@CeO2 for semihydrogenation of phenylacetylene by ammonia borane.
The fabrication of a bimetallic core and ceria shell nanostructure is considered a promising way to promote catalytic performance and stability. Here, we report an Au-Pd@CeO2 core-shell structure with a tunable Au/Pd ratio through a self-assembly autoredox reaction approach. This process involves the sequence reduction of Au and Pd precursors and then self-assembly of CeO2 nanoparticles to encapsulate the noble metal core. The as-obtained samples exhibit excellent activity and selectivity towards the ammonia borane initiated hydrogenation of phenylacetylene with an enhanced stability owing to the protection from outside CeO2 nanoparticles. Through the construction of an Au-Pd bimetallic structure, an electron modification of Pd due to charge transfer between Au and Pd results in an enhanced catalytic performance. Such a strategy is promising for the synthesis of other bimetallic noble core and ceria shell structures for further applications.


Neonatal diabetes mellitus: Insulin pump as an alternative management strategy.
Neonatal diabetes mellitus (hyperglycaemia within the first month of life, with an insulin requirement) may be transient or permanent. Management is complex, due to lack of subcutaneous fat and the need for small doses of insulin, and may be complicated by additional medical problems. Three cases are presented, the first of which was treated with conventional insulin therapy. The latter two were successfully treated with subcutaneous insulin pump therapy. We present suggested guidelines for treatment of neonatal diabetes, using this novel approach to management.


Compounding Effects of Agricultural Land Use and Water Use in Free-Flowing Rivers: Confounding Issues for Environmental Flows.
Defining the ecological impacts of water extraction from free-flowing river systems in altered landscapes is challenging as multiple stressors (e.g., flow regime alteration, increased sedimentation) may have simultaneous effects and attributing causality is problematic. This multiple-stressor context has been acknowledged in environmental flows science, but is often neglected when it comes to examining flow-ecology relationships, and setting and implementing environmental flows. We examined the impacts of land and water use on rivers in the upper Ringarooma River catchment in Tasmania (south-east Australia), which contains intensively irrigated agriculture, to support implementation of a water management plan. Temporal and spatial and trends in river condition were assessed using benthic macroinvertebrates as bioindicators. Relationships between macroinvertebrate community structure and environmental variables were examined using univariate and multivariate analyses, focusing on the impacts of agricultural land use and water use. Structural changes in macroinvertebrate communities in rivers in the catchment indicated temporal and spatial declines in the ecological condition of some stretches of river associated with agricultural land and water use. Moreover, water extraction appeared to exacerbate impairment associated with agricultural land use (e.g., reduced macroinvertebrate density, more flow-avoiding taxa). The findings of our catchment-specific bioassessments will underpin decision-making during the implementation of the Ringarooma water management plan, and highlight the need to consider compounding impacts of land and water use in environmental flows and water planning in agricultural landscapes.


An automated framework to quantify areas of regional ischemia in retinal vascular diseases with OCT angiography.
In this observational and cross-sectional study, capillary nonperfusion (CNP) and vascular changes in branch retinal vein occlusion (BRVO, sample size [n] = 26) and choroidal neovascularization (CNV, n = 29) were evaluated. Subjects underwent imaging using Optical coherence tomography angiography (Angiovue OCTA, RTVue XR, Optovue Inc., Fremont, California). Local fractal analysis was applied to the OCTA images of superficial, deep and choriocapillaris layer. CNP area (BRVO eyes) and vascular parameters were computed using local fractal-based method. Sensitivity and specificity of vascular parameters were assessed with receiver operating characteristics curve. Automated CNP area showed excellent agreement with manually quantified CNP areas in both superficial (intraclass coefficient [ICC] = 0.96) and deep (ICC = 0.96) layers. BRVO eyes showed significantly altered (P < .05) vascular parameters in both superficial and deep layer as compared to normal eyes (n = 30). CNVM eyes had significantly higher capillary free zones (P < .001) as compared to normal eyes. In normal vs BRVO eyes, vessel density and spacing between the large vessels had similar area under the curve (AUC) (P > .05) in both superficial (0.97 and 0.97, respectively) and deep layer (0.99 and 0.98, respectively). Further, capillary free zones showed high AUC (0.92) in differentiating CNV eyes from normal eyes.


Repeat selective visceral angiography in patients with gastrointestinal bleeding of obscure origin.
In the past 9 years, we have operated on 56 patients with gastrointestinal bleeding of obscure origin. Selective visceral angiography demonstrated the bleeding lesions in 24 of the 30 patients who underwent this investigation. Six of these 24 patients, however, had a negative angiogram initially and the lesions were only demonstrated on a repeat angiogram. The negative initial angiograms were due to: (1) slow bleeding from lesions in two patients; (2) a small bleeding tumour that caused only intermittent jejunojejunal intussusception in one patient; (3) technical fault in one patient; and (4) spasm of the bleeding vascular lesions and their feeding arteries in two patients. We advocate repeat angiography the following day in all patients in whom profuse bleeding continues, and during the next intestinal bleeding in those whose bleeding stops after the initial negative angiography. In patients who have repeated episodes of massive bleeding, and in whom full investigations fail to reveal the bleeding source, repeat angiography carried out 4 weeks after the bleeding has stopped can sometimes demonstrate the vascular lesions.


Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation.
Artemisinin is a natural product used as an alternative drug in the treatment of severe and multidrug-resistant malaria. In the present work we show that artemisinin shares with other sesquiterpene lactones the ability to inhibit the activation of the nuclear factor NF-kB: by this mechanism, artemisinin, as well as parthenolide, inhibits nitric oxide synthesis in cytokine-stimulated human astrocytoma T67 cells. These results suggest that artemisinin, in addition to its antiparasitic properties, could also exert a therapeutic effect on neurological complications of malaria.


Juvenile dermatomyositis and polymyositis.
Myositis in childhood is characterized by elevated serum levels of muscle-derived enzymes, proximal symmetrical muscle weakness, abnormal EMG and a muscle biopsy which frequently documents an inflammatory process. In the paediatric age group, JDMS is much more common than PM and occurs more frequently among females. Mortality has been reduced from 33 per cent to 7 per cent following the use of steroids. The development of calcifications (33 per cent) can be the most debilitating consequence of JDMS . It is our premise that JDMS is a distinct disease entity and that the increase in HLA-B8 and -DR3 in JDMS places this disease in the company of other immunopathic disorders. There are conflicting data concerning immunological abnormalities in JDMS , but there appears to be impairment of natural killing and evidence of complement activation. The frequent positive ANA in JDMS raises the speculation of its relationship to the antinuclear antibody, Jo-1, found in some adults with PM, which has specificity for tRNAHis. Most newly diagnosed JDMS patients have antibodies to Coxsackie B which may be related to the pathogenesis of this disease. Specific pathological findings of endothelial cells containing reticulotubular inclusions are associated with vessel occlusion, subsequent obliteration and increased Factor VIII levels in clinically active disease. In addition to physical therapy, prednisone is the drug most used, but immunosuppressive agents and plasmapheresis have been tried in severely ill children. Rigorous evaluation of the efficacy of these modalities is needed.


Mineral content of the honey produced in Zulia state, Venezuela.
The mineral content of the honey produced in five zones of the Zulia state, Venezuela, during dry and rainy seasons was determined. The analyzed elements were: sodium, potassium (by emission spectroscopy), calcium, magnesium, copper, iron, manganese (by atomic absorption spectroscopy), phosphorus (phosphate ions, by colorimetric method), and ash content of raw honey samples directly collected from different beekeepers. The mean values for Na, K, Ca, Mg, Cu, Fe, Mn, and P were 353+84; 1774+138; 237+66; 52+24; 0.76+0.43; 13.5+10.23; 0.92+0.42 and 1642+323 mg/kg respectively. The mean ash content was 0.431+0.15%. Potassium was the most abundant of the elements determined. This results confirm that Zulian honey can be considered a good source of minerals.


Daemonorops draco Blume Induces Apoptosis Against Acute Myeloid Leukemia Cells via Regulation of the miR-216b/c-Jun.
Daemonorops draco Blume (DD), also called dragon's blood, has been used as a traditional Korean medicine, especially for relieving pain caused by wound infection. Recently, it has been described that DD has antibacterial and analgesic effects. In this study, the underlying anticancer effect of DD associated with apoptosis was investigated in acute myeloid leukemia cell lines U937 and THP-1. DD exhibited cytotoxic effects and induced apoptosis in U937 and THP-1 cells. Moreover, DD treatment significantly reduced mitochondrial membrane potential (ΔΨ). The protein expression of cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, p-H2A.X, CCAAT/enhancer-binding protein (CHOP), and activating transcription factor 4 was upregulated by DD treatment. Consistently, DD-treated cells had increased reactive oxygen species (ROS) level in a concentration-dependent manner via miR-216b activation in association with c-Jun inhibition. N-acetyl-L-cysteine pretreatment reversed the cytotoxic effect of DD treatment as well as prevented ROS accumulation. Collectively, the results of this study suggest that the anticancer effect of DD in AML was mediated by CHOP-dependent apoptosis along with ROS accumulation and included upregulation of miR-216b followed by a decrease in c-Jun.


A functional tool to differentiate nasal valve collapse from other causes of nasal obstruction: the FRIED test.
Nasal valve collapse is a dynamic abnormality that is currently diagnosed purely on the basis of clinical features and thus subject to certain interpretation. The aim of this study was to develop a new and reliable functional test to objectively characterize nasal valve collapse. This was an observational prospective study including consecutive patients referred to our center for exploration of chronic nasal congestion. The patients were classified into two groups according to their symptoms and clinical abnormalities: the nasal valve collapse (NV+) group when nasal valve collapse was clinically detected during moderate forced inspiration and/or when the feeling of nasal congestion improved during passive nasal lateral cartilage abduction (n = 32); and the no-nasal valve collapse (NV-) group for the others (n = 23). All patients underwent nasal functional tests (posterior rhinomanometry and acoustic rhinometry) before and after topical nasal decongestion. We compared the difference between the pressure flow of the inspiratory and expiratory phases during posterior rhinomanometry [flow rate inspiratory-expiratory difference (FRIED) test] between the two groups. The difference between the absolute value of inspiratory and expiratory flow was significantly higher in the NV+ group than in the NV- group both before and after topical decongestion. The cutoff value for the FRIED test was -0.008 l/s with a good sensitivity (82%) and a specificity of 59%. We suggest that the FRIED test constitutes an objective and easy-to-apply technique to diagnose nasal valve collapse in daily practice.


Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities.
Hormone-activated nuclear receptors (NR) bind to specific regulatory DNA elements associated with their target genes and recruit coactivator proteins to remodel chromatin structure, recruit RNA polymerase, and activate transcription. The p160 coactivators (e.g., SRC-1, GRIP1, and ACTR) bind directly to activated NR and can recruit a variety of secondary coactivators. We have established a transient-transfection assay system under which the activity of various NR is highly or completely dependent on synergistic cooperation among three classes of coactivators: a p160 coactivator, the protein methyltransferase CARM1, and any of the three protein acetyltransferases, p300, CBP, or p/CAF. The three-coactivator functional synergy was only observed when low levels of NR were expressed and was highly or completely dependent on the methyltransferase activity of CARM1 and the acetyltransferase activity of p/CAF, but not the acetyltransferase activity of p300. Other members of the protein arginine methyltransferase family, which methylate different protein substrates than CARM1, could not substitute for CARM1 to act synergistically with p300 or p/CAF. A ternary complex of GRIP1, CARM1, and p300 or CBP was demonstrated in cultured mammalian cells, supporting a physiological role for the observed synergy. The transfection assay described here is a valuable new tool for investigating the mechanism of coactivator function and demonstrates the importance of multiple coactivators, including CARM1 and its specific protein methyltransferase activity, in transcriptional activation.


Polarization rotation locking of vector solitons in a fiber ring laser.
Polarization rotation of vector solitons in a fiber ring laser was experimentally studied. It was observed that the period of vector soliton polarization rotation could be locked to the cavity roundtrip time or multiple of it. We further show that multiple vector solitons can be formed in a fiber laser, and all the vector solitons have the same group velocity in cavity, however, their instantaneous polarization ellipse orientations could be orthogonal.


Microglia: Key Players in Retinal Ageing and Neurodegeneration.
Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in maintaining the normal function of the retina and brain. During early development, microglia migrate into the retina, transform into a highly ramified phenotype, and scan their environment constantly. Microglia can be activated by any homeostatic disturbance that may endanger neurons and threaten tissue integrity. Once activated, the young microglia exhibit a high diversity in their phenotypes as well as their functions, which relate to either beneficial or harmful consequences. Microglial activation is associated with the release of cytokines, chemokines, and growth factors that can determine pathological outcomes. As the professional phagocytes in the retina, microglia are responsible for the clearance of pathogens, dead cells, and protein aggregates. However, their phenotypic diversity and phagocytic capacity is compromised with ageing. This may result in the accumulation of protein aggregates and myelin debris leading to retinal neuroinflammation and neurodegeneration. In this review, we describe microglial phenotypes and functions in the context of the young and ageing retina, and the mechanisms underlying changes in ageing. Additionally, we review microglia-mediated retinal neuroinflammation and discuss the mechanisms of microglial involvement in retinal neurodegenerative diseases.


[Laboratory and clinical studies on biapenem (L-627) in the field of pediatrics].
Laboratory and clinical studies on biapenem (L-627), a new carbapenem antibiotic, were carried out in the field of pediatrics. 1. Antibacterial activities of L-627 against clinically isolated organisms in our department were generally high. 2. After 30 minutes intravenous infusion of L-627 at a dose of 10 mg/kg in 3 and of 12 mg/kg in 2 children, peak plasma levels of L-627 ranged from 25.6 to 44.6 micrograms/ml at the end of the infusion. The half-lives were from 0.68 to 0.94 hours. The cumulative urinary recovery rates in the first 6 hours after the start of drip infusion ranged from 11.4 to 47.5%. 3. 14 patients with various bacterial infections were treated with L-627. The clinical efficacy rate was also 92.9% and the bacteriological efficacy rate was also 92.9%. 4. No side effects were observed. A few abnormal laboratory test results were obtained, but they were mild with slight elevation of GOT/GPT and platelets in 1 each.


Cytosolic Delivery of Proteins Using Amphiphilic Polymers with 2-Pyridinecarboxaldehyde Groups for Site-Selective Attachment.
Protein-based drugs are a promising class of therapeutics, but poor membrane permeability typically limits their application to extracellular receptors. Delivery strategies that can transport functional proteins to reach intracellular targets are needed, but with many current approaches, biomolecules become entrapped in the endosomes. This greatly reduces the effective concentrations of therapeutic agents at the target sites. Herein, we report a bioconjugation-based approach for intracellular protein delivery by site-selectively attaching amphiphilic polymers to the N-terminal positions of proteins using 2-pyridinecarboxaldehyde groups. The reaction is simple and features mild, aqueous conditions with no required genetic engineering of the proteins. Imaging studies demonstrate that the polymer-protein conjugates are successfully delivered into the cytosol of various cancer cell lines, likely through a membrane fusion mechanism. When conjugated to the delivery polymers, the activity of modified RNase A was retained and notably promoted cytotoxicity in cancer cells upon delivery to the cytosol. This work therefore provides a promising platform for protein-based material delivery for therapeutic applications.


Knowledge about and preventive practices against neonatal tetanus among young Nigerian women.
The objective of this study was carried out to determine the knowledge about and preventive practices against neonatal tetanus (NNT) in young women of reproductive age. Descriptive cross-sectional study design of 380 randomly selected consenting young women of child-bearing age at a Nigerian tertiary educational institution. They completed a semi-structured questionnaire on knowledge about and risk factors for NNT, willingness to receive the vaccine, and uptake of tetanus toxoid vaccine. The mean age (standard deviation) of the women was 22.4 (4.6) years ranging from 15 to 30 years. The majority (64.5%) had poor knowledge of the causes of and risk factors for NNT with only 31% knowing that immunizing women against tetanus prevents NNT. Most of the women (58%) were unwilling to receive tetanus immunization. A total of 15.5% had received tetanus toxoid, but only 0.5% had completed the required dosage. A higher proportion of respondents with good knowledge about tetanus had tetanus toxoid immunization (28.1% vs. 8.6%; P < 0.0001). Knowledge about NNT, willingness to receive the vaccine, and uptake of tetanus toxoid were unacceptably poor among respondents. There is a need for continuous education targeting young women on the link between the tetanus immunization status of women and the occurrence of NNT.


Coexpression of interleukin-2 enhances the immunization effect of a DNA vaccine expressing herpes simplex 1 glycoprotein D.
In this study, DNA vaccines consisting of vector IRES-gD expressing Herpes simplex virus 1 (HSV-1) glycoprotein D (gD) and vector IRES-gD-IL-2 coexpressing HSV-1 gD and interleukin-2 (IL-2), respectively, were constructed. After intramuscular inoculation, both vaccines induced in BALB/c mice antibodies as assayed by ELISA and virus neutralization. However, IRES-gD-IL-2 elicited significantly higher levels of IgG (ELISA) and neutralizing antibodies than IRES-gD. Isotyping of sera from mice injected with IRES-gD-IL-2 revealed predominantly IgG2a antibodies. IRES-gD-IL-2 also elicited a higher delayed-type sensitivity (DTH) reaction. However, there was no difference in the protection against lethal challenge with HSV-1 between the two vaccines (P>0.05). The results suggest that the vaccination with IRES-gD-IL-2 can efficiently enhance the immune response of mice to HSV-1, particularly through increased cellular immunity.


Advances in Spine Surgery.
Technological advances in the field of spine surgery have most often involved instrumentation. In recent years, a great deal of attention has been focused on variable hookscrew-rod systems, the prototype of which is the Cotrel-Dubousset instrumentation (CDI). This French-designed system and similar ones such as the Texas-Scottish Rite (TSRH), or the Isola, provide significantly better fixation and rigidity than has ever been possible, and they allow many patients to be spared the discomfort and inconvenience of post-operative brace or cast support. These features are particularly important for older and chronically ill patients, whose often difficult problems can also be addressed more safely and effectively with this new technology.


The Effects of Social Rank and Neighborhood and School Environment on Adolescent Depression and Suicidal Ideation: A Structural Equation Modeling Approach.
Depression and suicide constitute major public health problems, and their prevalence has been increasing among adolescents in the United States. More research is needed to understand the association between multilevel risk factors and depression and suicidal ideation in adolescents, particularly factors related to perceived social rank and environmental stress. The present study examined relationships among family mental history of mental illness, in-utero and perinatal complications, social rank factors, environmental factors, and depression and suicidal ideation in the past month in a clinical population of adolescents. A cross-sectional survey was administered in outpatient clinics to 197 adolescents ages 12-18 who were primarily Black and female. Findings from structural equation modeling showed the largest effects for the social rank factor on depression and suicidal ideation in the past month. These findings highlight the importance of preventive interventions for coping with social hierarchies to prevent depression and suicidal ideation.


General and disease-specific use of outcomes scores for the shoulder: a survey of AOSSM, AANA, and ISAKOS members.
To report on the knowledge and use of both general and disease-specific shoulder outcomes scores among orthopedic surgeons. A 22-question Internet survey was administered to members of the American Orthopaedic Society for Sports Medicine, the Arthroscopy Association of North American, and the International Society of Arthroscopy, Knee Surgery, and Orthopedic Sports Medicine via voluntary e-mail participation. Questions targeted demographic information, preferred surgical management of shoulder conditions, and the preferred use of shoulder outcomes instruments in clinical practice. Excluding defunct and duplicate e-mails among membership societies, a total of 3892 unique e-mails were sent, from which 1129 surveys were returned and were fully completed (29%). The largest number of respondents were in private practice (52%); 21% were in academia; and 26% were in a mix of settings. As for location, 74% practiced in the United States, 10% in Europe, 8% in Mexico/South America, and 6% in Asia. A total of 31% total respondents used scores all or most of the time, and 30% used scores at least some of the time. Respondents felt that the 3 most commonly utilized shoulder scores were the American Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) score, and the Constant score. The majority of respondents (76%) performed all-arthroscopic instability repairs. The ASES and Western Ontario Shoulder Instability Index (WOSI) scores were the most preferred measures to monitor instability patients, whether or not the scores were actually implemented in their practice. Most perform between 10 and 25 superior labrum anterior-posterior repairs per year and preferred the ASES, UCLA, and Constant scores for these repairs; rotator cuff repair preferred outcomes instruments were similar. When asked to choose 1 score for all shoulder conditions, the ASES was the clear favorite. This study reports the knowledge and utilization of shoulder scores for both general and disease-specific conditions. Most respondents preferred the ASES score for most shoulder conditions; however, other scores, such as the WOSI, the Constant, and the Short-Form (SF)-36/12, were popular. This information offers insight into the current and future use of shoulder outcomes both for general and disease-specific use.


Meta-analysis of the association of the HTRA1 polymorphisms with the risk of age-related macular degeneration.
HTRA1 was considered as one of important age-related macular degeneration (AMD) candidate genes. However, due to population heterogeneity and bias from case-control study, the association between HTRA1 and AMD needs further confirmation across different studies in different population. In this study, a meta-analysis was performed in 14 case-control studies which were published before August 31, 2008. Effect of HTRA1 polymorphism with AMD was synthetically evaluated. The pooled odds ratio (OR) for heterozygous genotype GA versus wild homozygous genotype GG is 2.13 (95% CI: 1.90, 2.39), the OR of homozygous genotype AA versus GG is 6.92 (95% CI: 5.74, 8.34) and the OR of allele A carrier (GA+AA) versus GG is 3.02 (95% CI: 2.57, 3.53). Sub-analysis indicated that the risk of HTRA1 rs11200638 on wet AMD was stronger than dry AMD, and it seems that HTRA1 rs11200638 could increase the risk of AMD in all races. This study strengthens the hypothesis of association between rs11200638 in the promoter of HTRA1 polymorphism and AMD. The variant of HTRA1/625G-->A could be a potentially promising genetic biomarker of AMD.


Isolated native tricuspid valve Candida endocarditis in a non-drug-addicted patient: case report and review of the literature.
A case is reported of isolated native tricuspid calve Candida parapsilosis endocarditis (INTVCE) in a male patient with no history of drug abuse or heart disease. The patient had received hyperalimentation and antibiotics for four months via a central venous catheter after abdominal surgery. He underwent successful treatment with tricuspid valve debridement, liposomal amphotericin (AmBisome) and fluconazole, and remained without relapse during an eight-year follow up. A literature review of 12 similar cases (including the present patient) without history of drug abuse or heart disease, dating from 1970, is included.


Treatment of Clostridium difficile infection: recent trial results.
Clostridium difficile is a major cause of infection worldwide and is associated with increasing morbidity and mortality in vulnerable patient populations. Metronidazole and oral vancomycin are the currently recommended therapies for the treatment of C. difficile infection (CDI) but are associated with unacceptably high rates of disease recurrence. Novel therapies for the treatment of CDI and prevention of recurrent CDI are urgently needed. Important developments in the treatment of CDI are currently underway and include: novel antibacterial agents with narrower antimicrobial spectra of activity, manipulation of the gut microbiota and enhancement of the host antibody immune response.


Mechanism of immune interferon production in vitro: interaction between immune interferon-producing cells and antigenic cells.
Various processes of in vitro immune interferon production by sensitized spleen cells stimulated with allogeneic cells were investigated. When L cells, an interferon-inducing antigen, were fixed with methyl alcohol or paraformaldehyde, the ability to induce immune interferon disappeared. In this immune interferon production system, the majority of sensitized spleen cells adhered to target cells within 1 h of cocultivation. Adherence of immune interferon-producing cells to target cells was observed only when L cell-sensitized spleen cells were cocultured with L cells or with mouse embryo cells derived from C3H mice. Fixation of antigenic cells with methyl alcohol or paraformaldehyde significantly reduced cell adherence. When L cells alone or sensitized spleen cells alone were pretreated separately with cytochalasin D, neither cell type could bind to partner cells. Specific adherence did not take place at 4 degrees C, nor in the presence of dinitrophenol or sodium azide. Continuous protein synthesis in both cells was not required for immune cell adherence. Divalent cations, Ca2+ or Mg2+, were required for this immune specific adherence to take place. However, once stable adherence was established, treatment with cytochalasin D, ethylenediaminetetraacetic acid, or sodium azide, or simple reduction of temperature, did not disrupt the binding. Interaction between immune interferon-producing cells and antigenic cells can be subdivided into two phases according to the requirement for divalent cations: (i) lymphocytes and antigenic cells interact transiently, and divalent cations are required to maintain the binding; (ii) lymphocytes and antigenic cells form a stable interaction, and deprivation of divalent cations does not disrupt the binding. Colchicine showed an inhibitory effect in the period after cell-to-cell adherence. Colchicine did not inhibit the release of interferon. On the other hand, vinblastine, another antimicrotubule agent inhibited the secretion of immune interferon. Since interferon synthesis was not stopped immediately after addition of cycloheximide, continued protein synthesis of sensitized spleen cells was not required for interferon secretion. The present study showed that adherence of immune interferon-producing cells to antigenic cells was a complex phenomenon involving a series of successive events.


Growth hormone binding protein correlates strongly with leptin and percentage body fat in GH-deficient adults, is increased by GH replacement but does not predict IGF-I response.
GH-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor (GHR) and has been shown to be closely related to body fat. This study aimed to examine the inter-relationship between GHBP, leptin and body fat, and to test the hypothesis that GHBP is modified by GH replacement in GH-deficient adults and predicts IGF-I response. Twenty adults, mean age 47 years (range 20-69) with proven GH deficiency were randomly allocated to either GH (up to 0.25 U/kg/week in daily doses) or placebo for 3 months before cross-over to the opposite treatment. Plasma GHBP and leptin were measured at baseline and 2, 4, 8 and 12 weeks after each treatment. Whole body composition was measured at baseline by dual-energy X-ray absorptiometry (DEXA). There was a strong correlation between baseline leptin and GHBP (r = 0.88, P < 0.0001) and between baseline GHBP and percentage body fat, (r = 0.83, P < 0.0001). Mean GHBP levels were higher on GH compared with placebo, 1.53 +/- 0.28 vs 1.41 +/- 0.25nM, P = 0.049. There was no correlation between baseline IGF-I and GHBP (r = -0.049, P = 0.84), and GHBP did not predict IGF-I response to GH replacement. The close inter-relationship between GHBP, leptin and body fat suggests a possible role for GHBP in the regulation of body composition. GHBP is increased by GH replacement in GH-deficient adults, but does not predict biochemical response to GH replacement.


[Photodynamic therapy in treatment of chorioid neovascularization].
The authors studied the effectiveness of photodynamic therapy (PDT) with Photosence, a Russian photosensitizer, in treatment of chorioid neovascularization (CNV) in cases of age-related macular degeneration (ARMD) and pathological myopia (PM). The subjects were 73 patients with CNV suffering from ARMD and PM. The efficiency of PDT and complex conservative therapy was compared using vision acuity measurement, retinal morphometry, and fluorescent eye ground angiography (FEGA), performed before treatment, immediately after treatment, and 1, 3, 6, and 12 months later. The study showed that PDT in patients with CNV, ARMD and PM was more efficient than pharmacotherapy. Vision acuity improved or stabilized, and the parameters of retinal morphometry and FEGA improved as well. The results of the study evidence high efficiency of PDT with Photosence in treatment of CNV with ARMD and PM.


Targeted therapy for Epstein-Barr virus-associated gastric carcinoma using low-dose gemcitabine-induced lytic activation.
The constant presence of the viral genome in Epstein-Barr virus (EBV)-associated gastric cancers (EBVaGCs) suggests the applicability of novel EBV-targeted therapies. The antiviral nucleoside drug, ganciclovir (GCV), is effective only in the context of the viral lytic cycle in the presence of EBV-encoded thymidine kinase (TK)/protein kinase (PK) expression. In this study, screening of the Johns Hopkins Drug Library identified gemcitabine as a candidate for combination treatment with GCV. Pharmacological induction of EBV-TK or PK in EBVaGC-originated tumor cells were used to study combination treatment with GCV in vitro and in vivo. Gemcitabine was found to be a lytic inducer via activation of the ataxia telangiectasia-mutated (ATM)/p53 genotoxic stress pathway in EBVaGC. Using an EBVaGC mouse model and a [125I] fialuridine (FIAU)-based lytic activation imaging system, we evaluated gemcitabine-induced lytic activation in an in vivo system and confirmed the efficacy of gemcitabine-GCV combination treatment. This viral enzyme-targeted anti-tumor strategy may provide a new therapeutic approach for EBVaGCs.


Call for nurses to share experiences.
Former emergency nurse and whistleblower Helene Donnelly, who brought more than 100 incidents to light while working at Stafford Hospital, has said it is 'vital' nurses share their experiences of raising concerns.


Polygamy: the possibly significant behavior of Aedes aegypti and Aedes albopictus in relation to the efficient transmission of dengue virus.
The polygamous behavior of male Aedes aegypti (L.) and Ae. albopictus (Skuse) was investigated by co-habiting a newly-emerged male and females in a 30 cm3 cage (1 male: 20 females) for up to 5 consecutive days. As determined by insemination rates, the results indicated that one Ae. aegypti and Ae. albopictus male could successfully mate with 1.10 (0-4), 4.10 (1-8), 5.40 (4-8), 5.10 (2-8), 5.15 (3-9) and 0.20 (0-3), 1.70 (0-3), 2.35 (1-4), 2.30 (0-4), 2.35 (1-4) Ae. aegypti and Ae. albopictus females, respectively on day 1,2,3,4 and 5 consecutively. The possibly significant role of their polygamy in relation to dengue virus transmission is discussed.


Effect of private insurance incentive policy reforms on trends in coronary revascularisation procedures in the private and public health sectors in Western Australia: a cohort study.
The Australian federal government introduced private health insurance incentive policy reforms in 2000 that increased the uptake of private health insurance in Australia. There is currently a lack of evidence on the effect of the policy reforms on access to cardiovascular interventions in public and private hospitals in Australia. The aim was to investigate whether the increased private health insurance uptake influenced trends in emergency and elective coronary artery revascularisation procedures (CARPs) for private and public patients. We included 34,423 incident CARPs from Western Australia during 1995-2008 in this study. Rates of emergency and elective CARPs were stratified for publicly and privately funded patients. The average annual percent change (AAPC) in trend was calculated before and after 2000 using joinpoint regression. The rate of emergency CARPs, which were predominantly percutaneous coronary interventions (PCIs) with stenting, increased throughout the study period for both public and private patients (AAPC=12.9%, 95% CI=5.0,22.0 and 14.1%, 95% CI=9.8,18.6, respectively) with no significant difference in trends before and after policy implementation. The rate of elective PCIs with stenting from 2000 onwards remained relatively stable for public patients (AAPC=-6.0, 95% C= -16.9,6.4), but increased by 4.1% on average annually (95% CI=1.8,6.3) for private patients (pdifference=0.04 between groups). This rate increase for private patients was only seen in people aged over 65 years and people residing in high socioeconomic areas. The private health insurance incentive policy reforms are a likely contributing factor in the shift in 2000 from public to privately-funded elective PCIs with stenting. These reforms as well as the increasing number of private hospitals may have been successful in increasing the availability of publicly-funded beds since 2000.


Sequential occurrence of toxic nodular goiter followed by Graves' disease.
To present the first case of Graves' disease occurring after toxic nodular goiter in a patient who had not received radioiodine therapy. We describe the clinical, laboratory, and radiologic findings in a 65-year-old woman with toxic nodular goiter followed by Graves' disease and review related reports in the literature. Although isolated case reports have documented the sequential occurrence of toxic nodular goiter or toxic adenoma and Graves' disease, no definite connection currently exists between these two types of hyperthyroidism. In cases previously described, Graves' disease appeared after the use of radioiodine for the treatment of the toxic nodular goiter. In our current patient, toxic nodular goiter was treated surgically, followed by the occurrence of Graves' disease 3 years later. This is the first published case of sequential toxic nodular goiter and Graves' disease in which radioiodine was not used for treatment of the goiter and thus cannot be implicated as the inciting event for the subsequent development of Graves' disease.


Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases.
To investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus (HBV) and C virus (HCV)-related liver diseases. We generated a new monoclonal Nup88 antibody to investigate the Nup88 protein expression by immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising all stages of hepatocellular carcinogenesis. In addition, in cell culture experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma cell lines were tested for the Nup88 expression by Western-immunoblotting to test data obtained by IHC. Specific Nup88 expression was found in chronic HCV hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88 expression was detected in normal liver. The Nup88 expression was markedly reduced or missing in mild chronic HBV infection and inversely correlated with HBcAg expression. Irrespective of the HBV- or HCV-status, increasing Nup88 expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly expressed in hepatocellular carcinomas. The intensity of Nup88 expression significantly increased during carcinogenesis (P<0.0001) and correlated with dedifferentiation (P<0.0001). Interestingly, Nup88 protein expression was significantly downregulated in HBV-positive HepG2.2.15 (P<0.002) and HB611 (P<0.001) cell lines as compared to HBV-negative HepG2 cells. Based on our immunohistochemical data, HBV and HCV are unlikely to influence the expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an interaction of HBV with the nuclear pore in chronic hepatitis. The expression of Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non-neoplastic and neoplastic conditions of the liver.


Irreverent Nature of Dissymmetry Factor and Quantum Yield in Circularly Polarized Luminescence of Small Organic Molecules.
Recently, a rational modification of small organic molecules has attracted considerable attention for designing advanced materials with enhanced circularly polarized luminescence (CPL) activity. A particular emphasis has been placed on fully allowed π-π* transition of rigid aromatic systems, due to their relatively superior emission properties or quantum yields of luminescence (Φlum). However, their dissymmetry factors (g lum), differential left and right CPL intensities, are typically disappointingly low at least in one to two orders of magnitude. Truly useful organic CPL materials, rated by a circular polarization luminosity index (ΛCPL) per single molecule, possess both |g lum| and Φlum values high. However, how to improve these two factors simultaneously with a proper molecular design is an open question. Here, we addressed this issue by theoretical and statistical inspection on a possible relation of the g lum and Φlum values. According to the analysis, we propose simple, unpretentious, yet pertinent guidelines for designing superior organic CPL materials for the future with large ΛCPL values.


Nutrition and newly emerging viral diseases: an overview.
Infectious diseases are on the increase worldwide. When discussing interactions of nutrition and infection, nutritionists have traditionally considered only the effects of diet on the host. Recent data, however, indicate that, at least for an RNA virus, host nutriture can influence the genetic make-up of the pathogen and thereby alter its virulence. This symposium was organized to alert the nutrition community to this discovery and its possible implications for the investigation of nutrition-infection interrelationships. Topics covered in the symposium include the following: the public health threat of emerging viral diseases; the rapid evolution of viral RNA genomes; oxidants and antioxidants in viral diseases-disease mechanisms and metabolic regulation; and increased virulence of coxsackievirus B3 due to vitamin E or selenium deficiency. If the findings with coxsackievirus are more broadly applicable to other RNA viruses, the results could be of great public health significance because RNA viruses constitute the majority of all plant, animal and human viruses.


Comparison of Extended-Spectrum β-Lactamase (ESBL) CTX-M Genotypes in Franklin Gulls from Canada and Chile.
Migratory birds have been suggested to contribute to long-distance dispersal of antimicrobial resistant bacteria, but tests of this hypothesis are lacking. In this study we determined resistance profiles and genotypes of ESBL-producing bacteria in randomly selected Escherichia coli from Franklin´s gulls (Leucophaeus pipixcan) at breeding sites in Canada and compared with similar data from the gulls' wintering grounds in Chile. Resistant E. coli phenotypes were common, most notably to ampicillin (30.1%) and cefadroxil (15.1%). Furthermore, 17.0% of the gulls in Canada carried ESBL producing bacteria, which is higher than reported from human datasets from the same country. However, compared to gulls sampled in Chile (30.1%) the prevalence of ESBL was much lower. The dominant ESBL variants in Canada were blaCTX-M-14 and blaCTX-M-15 and differed in proportions to the data from Chile. We hypothesize that the observed differences in ESBL variants are more likely linked to recent exposure to bacteria from anthropogenic sources, suggesting high local dissemination of resistant bacteria both at breeding and non-breeding times rather than a significant trans-hemispheric exchange through migrating birds.


Notes from the field: Human Salmonella infantis infections linked to dry dog food--United States and Canada, 2012.
CDC is collaborating with public health and agriculture officials in multiple states, the Public Health Agency of Canada, and the Food and Drug Administration (FDA) to investigate an outbreak of human Salmonella Infantis infections linked to direct or indirect contact with dry dog food. Multiple brands of dry dog food produced by Diamond Pet Foods at a single manufacturing facility in Gaston, South Carolina, have been linked to human illnesses.


A role for the hypoblast (AVE) in the initiation of neural induction, independent of its ability to position the primitive streak.
The mouse anterior visceral endoderm (AVE) has been implicated in embryonic polarity: it helps to position the primitive streak and some have suggested that it might act as a "head organizer", inducing forebrain directly. Here we explore the role of the hypoblast (the chick equivalent of the AVE) in the early steps of neural induction and patterning. We report that the hypoblast can induce a set of very early markers that are later expressed in the nervous system and in the forebrain, but only transiently. Different combinations of signals are responsible for different aspects of this early transient induction: FGF initiates expression of Sox3 and ERNI, retinoic acid can induce Cyp26A1 and only a combination of low levels of FGF8 together with Wnt- and BMP-antagonists can induce Otx2. BMP- and Wnt-antagonists and retinoic acid, in different combinations, can maintain the otherwise transient induction of these markers. However, neither the hypoblast nor any of these factors or combinations thereof can induce the definitive neural marker Sox2 or the formation of a mature neural plate or a forebrain, suggesting that the hypoblast is not a head organizer and that other signals remain to be identified. Interestingly, FGF and retinoids, generally considered as caudalizing factors, are shown here to play a role in the induction of a transient "pre-neural/pre-forebrain" state.


Simplified method for DNA and protein staining of human hematopoietic cell samples.
A rapid reproducible method yielding high resolution analysis of DNA and protein in human hematopoietic cell samples has been developed by modification of the propidium iodide and fluorescein isothiocyanate procedure. Cell staining involves sequential addition of each reagent (RNase, fluorescein isothiocyanate and propidium iodide) to ethanol-fixed cells and requires no centrifugation steps. Stained cells are analyzed in the reagent solutions. Analysis of bone marrow samples from multiple myeloma patients showed mixed normal and aneuploid populations with a major portion of the aneuploid cells having a significantly higher protein content. This approach permitted differential cell cycle analysis of normal and the aneuploid populations.


Presentation of occult Chiari I malformation following spinal anesthesia.
Chiari I malformation (CM-I) manifests with tonsillar herniation below foramen magnum. These patients are at high risk of respiratory depression and bulbar dysfunction in the perioperative period with underlying obstructive sleep apnea. However, the safe use of both general and regional anaesthesia has been documented in a known CM-I parturients. We describe the successful management of a patient who had hypercapnic respiratory failure in the post-anaesthetic care unit following an uneventful subarachnoid block for left knee replacement surgery. This patient was retrospectively diagnosed with occult CM-I and moderate to severe obstructive sleep apnea in the postoperative period.


MR diffusion-weighed imaging of rabbit liver.
To study the techniques of MR diffusion-weighed imaging (DWI) for normal rabbit liver. After 15 normal New Zealand white rabbits and one New Zealand white rabbit implanted with VX-2 tumor were anesthetized with 3% soluble pentobarbitone, DWI was performed respectively for different b values, repetition times (TR) or thicknesses, when other parameters were the same and magnetic resonance imaging (MRI) was performed respectively, or with different field of views (FOV) or coil when other parameters were the same. The distinction between groups was analyzed by SPSS10.0 with apparent diffusion coefficient (ADC), quality index (QI) or signal-noise ratio (SNR). As b value increased, liver ADC, QI and SNR of DWI became smaller and simultaneously (F = 292.87, 156.1, 88.23, P<0.01). QI of DWI was high, when b value was 10, 50 or 100 respectively, but the distinction between them was insignificant; when b value was 800, QI and SNR of DWI were low. QI and SNR of DWI had no significant difference between TR = 4 000, 6 000 and 8 000. QI of DWI with 2 mm thickness was bigger than that with 5 mm thickness (t = 3.04, P<0.01), but SNR of DWI with 2 mm thickness was significantly smaller (t = -17.86, P<0.01). SNR of MRI with knee joint coil was obviously bigger than that with cranium coil (t = -5.77 (T1WI) or -4.02 (T2WI), P<0.01), but QI of MRI was smaller on the contrary (t = 7.10 (T1WI) or 3.97 (T2WI), P<0.01). When FOV was enlarged gradually, SNR of MRI increased (F = 85.81 (T1WI) or 221.96 (T2WI), P<0.01), but QI firstly increased, then decreased (F = 68.67 (T1WI) or 69.46 (T2WI), P<0.01) and QI of MRI was the biggest when FOV was 20 cm x 15 cm. The scanning technique is very important in DWI of rabbit liver and the overall quality of DWI with b (100 s/mm2), thickness (2 mm), cranium coils and FOV (20 cm x 15 cm) was best in our study, when other parameters were the same.


Bone marrow infiltration patterns and their prognostic significance in chronic lymphocytic leukemia: correlations with clinical, immunologic, phenotypic, and cytogenetic data.
Bone marrow biopsies were prospectively performed on 75 patients with chronic lymphocytic leukemia (CLL). There was a highly significant relationship (p less than 0.002) between clinical stages and bone marrow infiltration patterns. Ten (50%) of 20 patients with diffuse patterns died; the estimated median survival time for these patients was 87 months. In contrast, only six (11%) of 55 patients with nondiffuse patterns died; the estimated median survival time for these patients could not be computed. When both clinical stage and infiltration pattern were evaluated for survival, a highly significant association between clinical stage and survival time was still observed (p less than 0.003) whereas bone marrow infiltration pattern was no longer significant. A significant association was also observed between bone marrow infiltration patterns and absolute lymphocyte counts (p less than 0.0005), Fc-receptor-positive cells (p less than 0.002), 3H-thymidine uptake of leukocytes (p less than 0.01), serum alkaline phosphatase levels (p less than 0.05), monoclonal urinary-free light chain status (p less than 0.05), and cytogenetics of leukemic cells (p less than 0.05). These observations lead to the conclusion that in an overall prognostic evaluation of patients with CLL, although bone marrow histopathology may have no additional value over a well-established clinical staging system, as a whole, it may be of clinically predictive value in disease progression of patients with stage I and II.


Stretch--induced inhibition of spontaneous EMG activity in extensor muscles of the rat caused by chronic deafferentation.
Stretching the chronically deafferented soleus muscle has recently been found to inhibit spontaneous EMG activity recorded by silicone-plate electrodes in this muscle. In order to ascertain whether this stretch-induced inhibition (SII) of EMG activity is not restricted exclusively to the soleus, a study was made of SII in the gastrocnemius muscle employing either concentric EMG needles or bipolar "fish-hook" electrodes. The results showed that SII of spontaneous EMG activity can be demonstrated in the soleus and gastrocnemius muscles (both extensor muscles) several days after dorsal rhizotomy L1-S1, employing all three modes of EMG recording in awake rats (namely, silicone-plate electrodes, concentric electrodes and bipolar "fish-hook" electrodes). It is suggested that ventral root afferents may be involved in this phenomenon.


Cationic liposomes bearing IL-2 on their external surface induced mice leukocytes to kill human cervical cancer cells in vitro, and significantly reduced tumor burden in immunodepressed mice.
Tumor cells are known to modify their surroundings in order to escape immunologic detection, and IL-2, a killer cell activator, is one of the factors known to overcome this escape mechanism. In this regard, when we cocultured cells from the human cervical cancer cell line INBL with mice blood leukocytes, no inhibition of tumor cell growth was observed, but when a similar coculture was done in the presence of cationic liposomes bearing IL-2 on their external surface (CL-IL-2), all the INBL cells were killed. In order to evaluate whether this in vitro property of CL-IL-2 to overcome tumor cell detection by lymphocytes could also be reproduced in vivo, INBL cells were intraperitoneally (i.p.) inoculated into immunodepressed mice to produce solid tumors. We observed that the subsequent i.p. delivery of CL-IL-2 rendered the tumor masses significantly smaller. The presence of a large number of infiltrating lymphocytes on those tumors, and the fact that many had a cytotoxic CD8(+) phenotype suggests that these lymphocytes were responsible for the observed antitumor effect. Finally, the possible formation of a bridge between the IL-2R receptors on both, the lymphocytes and the INBL cells, mediated by the IL-2-bearing liposomes, and its possible effect on the activation of antitumor cytotoxic lymphocytes is discussed.


Thermally triggered frame-guided assembly.
We report a thermally triggered frame-guided assembly (FGA) strategy for the preparation of vesicles. We employ thermally responsive poly(propylene oxide) (PPO) to make the leading hydrophobic groups (LHGs) thermally responsive, so that they are hydrophilic below the low critical solution temperature (LCST) and the frame forms in a homogeneous environment. When the temperature is increased above the LCST, the LHGs become hydrophobic and the assembly process is triggered, which drives DNA-b-PPO to assemble around the LHGs, forming vesicles. This work verified that FGA is a general strategy and can be applied to polymeric systems. The thermally triggered assembly not only provides more controllability over the FGA process but also promotes an in-depth understanding of the FGA strategy and in a broad view, the formation mechanism and functions of cell membrane.


Modification of practice-dependent plasticity in human motor cortex by neuromodulators.
Practice-dependent plasticity underlies motor learning in everyday life and motor relearning after lesions of the nervous system. Previous studies showed that practice-dependent plasticity is modifiable by neuromodulating transmitters such as norepinephrine (NE), dopamine (DA) or acetylcholine (ACh). Here we explored, for the first time comprehensively and systematically, the modifying effects of an agonist versus antagonist in each of these neuromodulating transmitter systems on practice-dependent plasticity in healthy subjects in a placebo-controlled, randomized, double-blind crossover design. We found that the agonists in all three neuromodulating transmitter systems (NE: methylphenidate; DA: cabergoline; ACh: tacrine) enhanced practice-dependent plasticity, whereas the antagonists decreased it (NE: prazosin; DA: haloperidol; ACh: biperiden). Enhancement of plasticity under methylphenidate and tacrine was associated with an increase in corticomotoneuronal excitability of the prime mover of the practice, as measured by the motor evoked potential amplitude, but with a decrease under cabergoline. Our findings demonstrate that agonists and antagonists in various neuromodulating transmitter systems produce significant and oppositely directed modifications of practice-dependent plasticity in human motor cortex. Enhancement of plasticity occurred through different strategies that either favoured extrinsic (NE, ACh) or intrinsic (DA) modulating influence on the motor cortical output network.


Recruiting and retaining minority women: findings from the Women on the Move study.
To describe the recruitment, enrollment, and retention of women participating in the Women on the Move study, a physical activity validation study targeting urban minority women aged 40 to 70 years. The intensive 15-day validation protocol included ingestion of doubly labeled water (2H2 18O), collection of 9 urine samples, completion of multiple physical activity surveys, including selected questions from the BRFSS and NHANES III, wearing an accelerometer, and completing a detailed diary of physical activity for 7 days. The follow-up interview included completion of more questionnaires, followed by measurement of resting metabolic rate. In planning for recruitment, enrollment, and retention of participants, investigators consulted with a community advisory board and conducted focus groups with members of the target communities and with key community leaders. Recruitment methods included print, television, and radio advertisements and presentations at community health fairs, churches, and health clinics. Of the 656 women who expressed interest in the study, 386 (59%) met eligibility criteria, and 260 were enrolled (130 Latina, 130 African-American). To retain participants in the study, investigators had intensive telephone contact with the participants, scheduled meetings at times and locations convenient for the participants, used bilingual and bicultural staff, and offered participants staged monetary payments. Of the women enrolled, the retention for the meetings that could happen at more convenient locations was 98.8% and for the required meeting at a central location it was 85.4%. Experience from the Women on the Move study suggests that by working with community members, Latina and African-American women can be successfully recruited and, through extensive contact, retained, even in research studies with demanding protocols.


Structural analysis of the Ss sialoglycoprotein specific for Henshaw blood group from human erythrocyte membranes.
The N-terminal structures of the MN and Ss erythrocyte membrane sialoglycoproteins (glycophorins A, B) from two Henshaw (He) blood-group heterozygotes were determined by manual sequencing of tryptic glycopeptides and various secondary fragments. No structural alteration of the MN glycoprotein could be detected. The He-specific portion of the Ss glycoprotein was found to exhibit the N-terminal sequence Trp-Ser+-Thr+-Ser+-Gly-(+ = glycosylation). Thus it differs at three positions from its normal counterpart which possesses 'N' activity and exhibits the N-terminal structure Leu-Ser+-Thr+-Thr+-Glu-. Analysis of the Ss glycoprotein from 15 He-negative erythrocyte samples did not reveal any of the three He-specific structural alterations. The presence of a glycine residue at the fifth position of the blood-group-M-active MN glycoprotein as well as in the He-specific Ss glycoprotein provides an explanation for the occurrence of antisera (anti-Me) reacting with the M and He antigens.


Effect of smoking on maternal glucose metabolism.
Maternal smoking, studied in late pregnancy, was found to be associated with lower blood glucose values, both during fasting and after an intravenous glucose load. As a correlation between blood glucose levels and infant birth weight has been reported, it is possible that smoking during pregnancy might reduce fetal growth through an effect on maternal glucose metabolism.


Immunomodulatory drugs (natalizumab), worsening of multiple sclerosis, rebound effect and similitude.
Homeopathic treatment is based on the principle of similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the paradoxical or biphasic action of the organism as therapeutic response. This homeostatic, vital or secondary action of the organism is scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after enantiopathic treatment withdrawal. Natalizumab reduces relapses in patients with active multiple sclerosis (MS), but recent studies report severe worsening of MS after suspension of treatment, as a consequence of the rebound effect. Extending this source of evidence, this work reviews research that demonstrates secondary worsening of MS after discontinuation of natalizumab, a human monoclonal antibody that suppresses the disease inflammatory activity as primary action. Several studies refer to the immune reconstitution inflammatory syndrome (IRIS) as a plausible explanation of reactivation of MS after withdrawal of natalizumab: a rebound effect or secondary action of the organism in response to the primary immunosuppression caused by the drug. Relapses of MS after discontinuation of natalizumab treatment indicate rebound of disease activity, supporting the homeopathic principle and warning healthcare professionals about this serious iatrogenic event.


EMG and fatigue of human voluntary and stimulated contractions.
During a 60s maximal voluntary isometric contraction (MVC) of the adductor pollicis muscle the loss of force is accompanied by a parallel decline in both the integrated surface electromyogram (EMG) and the single muscle fibre spike counts recorded intramuscularly. This decline is not due to neuromuscular block since the muscle mass action potential (M wave) evoked by single maximal shocks to the nerve is well maintained; nor does the size of the single fibre spike change. It must, therefore, reflect a decline in the firing pattern of the motor neuron pool. The force of a sustained MVC continues to match that from maximal tetanic nerve stimulation; thus, all motor units remain active. Continuous nerve stimulation at the frequency required to match the voluntary force of unfatigued muscle leads to a progressive failure of the M wave, and a more rapid force loss than in an MVC. Both are largely restored by reducing the stimulus frequency. The decline in neural firing rate correlates well with the rate of muscle contractile slowing. It thus optimizes force by maintaining a relatively constant degree of tetanic fusion, while avoiding peripheral failure of electrical propagation.


Posttranslational regulation of cell-surface colony-stimulating factor-1.
Colony-stimulating factor-1 (CSF-1) plays a central role in the survival, proliferation, differentiation, and function of monocytes and macrophages. CSF-1 is synthesized as both a soluble and a membrane-spanning growth factor. The membrane-spanning isoform is biologically active, but it can also be proteolytically cleaved to generate a soluble growth factor. A recent study revealed that the TNF-alpha-converting enzyme is involved in this activity, and, moreover, that membrane-spanning CSF-1 undergoes internalization. These findings may have important implications for the posttranslational regulation and the functions of cell-surface CSF-1.


Targeted gene approach with biochemical assay confirms ABCD1 mutation of X-linked adrenoleukodystrophy in a 62-year-old man with gait imbalance.
X-linked adrenoleukodystrophy is a peroxisomal disorder caused by a mutation in ABCD1 gene. The three main phenotypes of X-linked adrenoleukodystrophy include cerebral adrenoleukodystrophy, adrenomyeloneuropathy, and isolated primary adrenal insufficiency. More than 750 non-recurrent mutations exist throughout the coding region of the ABCD1 gene. We report a 62-year-old man with a 17-year history of progressive gait imbalance and numb feet. He had noted difficulty rising from a chair for 3 years. Examination revealed proximal lower limb weakness and length-dependent sensory loss with preservation of reflexes and unilateral Babinski sign. Electrodiagnostic evaluation confirmed a length-dependent sensorimotor peripheral neuropathy and proximal myopathy. Family history was remarkable for similar symptoms in 6 siblings. A targeted gene approach for 102 known peripheral neuropathy genes led to discovery of ABCD1 mutation confirmed by kindred evaluation and biochemical assay. This case highlights the importance of combining targeted gene approaches with functional assay confirmation especially for atypical clinical presentations.


Expression of connexin 43 protein in cardiomyocytes of heart failure mouse model.
Heart failure (HF) is the end stage of various cardiovascular diseases, with high morbidity and mortality, and is associated with a poor prognosis. One of the primary causes of HF is aortic valve disease, manifested by progressive aortic valve stenosis (AVS), resulting in increased left ventricular load, ventricular hypertrophy, ultimately ventricular dysfunction, and HF. Early assessment of the degree of cardiomyopathy and timely intervention is expected to improve patients' cardiac function and delay or even avoid the occurrence of HF. The Wnt signaling pathway is mainly involved in regulating myocardial insufficiency after valve stenosis. Connexin 43 protein (Cx43) is an essential target of Wnt signaling pathway that forms gap junction (GJ) structures and is widely distributed in various organs and tissues, especially in the heart. The distribution and transformation of Cx43 among cardiac cells are crucial for the development of HF. To specifically label Cx43 in vivo, we established a new Cx43-BFP-GFP mouse model with two loxp sites on both sides of the tag BFP-polyA box, which can be removed by Cre recombination. This double-reporter line endowed us with a powerful genetic tool for determining the area, spatial distribution, and functional status of Cx43. It also indicated changes in electrical conduction between cells in a steady or diseased state.


Streaming the beautiful game: exploring big tech's growing presence in the soccer industry.
This study investigates the evolving role of major technology corporations-namely, Amazon, Apple, Microsoft, Facebook, Netflix, and Google-in the sports industry, with a specific focus on soccer. By employing a qualitative content analysis of media reports, scientific literature, and annual reports from 2000 to 2021, the research scrutinizes the varying approaches and investments of these tech giants in the domain of sports. The findings classify these companies into three distinct categories: (1) those actively securing broadcast rights for major competitions and leagues (Google, Facebook, Amazon); (2) those primarily producing and disseminating soccer documentaries (Netflix); and (3) those not directly engaging in media rights but advancing the technological aspects of clubs and leagues (Apple and Microsoft). This study underscores the escalating significance of Big Tech in reshaping the sports media landscape and calls for further research to comprehend the broader implications of their presence in sports broadcasting and fan engagement.


Isc1 regulates sphingolipid metabolism in yeast mitochondria.
The Saccharomyces cerevisiae inositol sphingolipid phospholipase C (Isc1p), a homolog of mammalian neutral sphingomyelinases, hydrolyzes complex sphingolipids to produce ceramide in vitro. Epitope-tagged Isc1p associates with the mitochondria in the post-diauxic phase of yeast growth. In this report, the mitochondrial localization of Isc1p and its role in regulating sphingolipid metabolism were investigated. First, endogenous Isc1p activity was enriched in highly purified mitochondria, and western blots using highly purified mitochondrial membrane fractions demonstrated that epitope-tagged Isc1p localized to the outer mitochondrial membrane as an integral membrane protein. Next, LC/MS was employed to determine the sphingolipid composition of highly purified mitochondria which were found to be significantly enriched in alpha-hydroxylated phytoceramides (21.7 fold) relative to the whole cell. Mitochondria, on the other hand, were significantly depleted in sphingoid bases. Compared to the parental strain, mitochondria from isc1Delta in the post-diauxic phase showed drastic reduction in the levels of alpha-hydroxylated phytoceramide (93.1% loss compared to WT mitochondria with only 2.58 fold enrichment in mitochondria compared to whole cell). Functionally, isc1Delta showed a higher rate of respiratory-deficient cells after incubation at high temperature and was more sensitive to hydrogen peroxide and ethidium bromide, indicating that isc1Delta exhibits defects related to mitochondrial function. These results suggest that Isc1p generates ceramide in mitochondria, and the generated ceramide contributes to the normal function of mitochondria. This study provides a first insight into the specific composition of ceramides in mitochondria.


Elective penicillin skin testing in a pediatric outpatient setting.
Adverse reactions associated with penicillin-type antibiotics are common in pediatric practice, leading to the subsequent unnecessary use of alternative antibiotics. IgE-mediated penicillin allergy represents only a fraction of these adverse reactions. To examine (1) the trend of penicillin skin test reactivity during a recent 10-year interval, (2) the relative distribution of specific reagents related to a positive skin test result, and (3) skin test reactivity as a function of reaction history. Penicillin testing using 3 reagents--benzylpenicilloyl polylysine, penicillin G, and sodium penicilloate (penicillin A)--was conducted in a prospective study of 359 consecutive patients referred to an outpatient pediatric allergy clinic between January 1, 1993, and May 31, 2003. We also retrospectively reviewed penicillin skin test results for 562 children previously tested between January 1, 1979, and December 31, 1992. Between 1993 and 2003, the prevalence of penicillin skin test sensitivity markedly declined. Of all the positive skin test results between 1979 and 2002, either penicillin G or sodium penicilloate or both identified 34%, with sodium penicilloate alone responsible for 8.5%. The rate of positive skin test reactions was not significantly different between patients with vs without a history of suggestive IgE-mediated reactions. A marked decline in penicillin skin test sensitivity in the pediatric age group is identified. The minor determinant reagents penicillin G and sodium penicilloate are both necessary for determining potential penicillin allergy. Relating history alone to potential penicillin sensitivity is unreliable in predicting the presence or absence of a positive skin test result.


[The spectrum of drug eruptions].
Drug eruptions are frequently encountered and they represent "diseases of medical progress". They are expected in about 2% of treated patients. Their putative diagnosis is based on a set of imputability factors. Several distinct drug-induced skin disorders are identified. They are initially recognized from personal experience, but the implication to a specific drug derives from the collective experience of published evidence. Their histopathological aspect is often evocative or demonstrative for the nature of the dermatosis. Some drug eruptions follow an indolent course, while others are life-threatening.


No evidence of early head circumference enlargements in children later diagnosed with autism in Israel.
Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder. We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy. The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life. These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.


Evaluation of tropical plants containing tannin on in vitro methanogenesis and fermentation parameters using rumen fluid.
Methane (CH(4)) produced during ruminal fermentation represents a loss of 10-11% of gross energy intake. The use of browse species containing tannin as feed supplement for ruminants tends to increase in order to reduce CH(4) production. The present study was conducted to evaluate some tropical plants containing tannin as feed supplement (200 g kg(-1)) on in vitro CH(4) production and fermentation parameters. The crude protein (CP) content ranged from 87 to 390 g kg(-1) dry matter (DM) and was highest in Sesbania grandiflora (L.) Poiret. The neutral detergent fibre (NDF) concentration was highest in Pennisetum purpureum Schumach (725 g kg(-1) DM) and lowest in S. grandiflora (330 g kg(-1) DM). The ranking order of plants based on their total tannin content was Acacia mangium Willd. > Biophytum petersianum Klotzch > Jatropa curcas Linnaeus > Psidium guajava Linnaeus > Phaleria papuana > Persea americana Mill. > S. grandiflora. Methane gas production after 48 h of incubation was significantly (P < 0.05) lower with inclusion of A. mangium (PP + AM), B. petersianum (PP + BP), J. curcas (PP + JC) or P. guajava (PP + PG) as compared to control feed (PP). There was negative correlation between total tannin content and CH(4) production at 48 h of incubation (r = - 0.76). Concentration NH(3)-N was significantly (P < 0.01) higher with inclusion of S. glandiflora. Inclusion of P. guajava significantly (P < 0.05) suppressed protozoa population by 49.7% relative to control feed (PP). It was concluded that A. mangium, B. petersianum, J. curcas and P. guajava have potential to be used as a feed supplement to reduce CH(4) production in ruminants.


Demonstration of atomic frequency comb memory for light with spin-wave storage.
We present a light-storage experiment in a praseodymium-doped crystal where the light is mapped onto an inhomogeneously broadened optical transition shaped into an atomic frequency comb. After absorption of the light, the optical excitation is converted into a spin-wave excitation by a control pulse. A second control pulse reads the memory (on-demand) by reconverting the spin-wave excitation to an optical one, where the comb structure causes a photon-echo-type rephasing of the dipole moments and directional retrieval of the light. This combination of photon-echo and spin-wave storage allows us to store submicrosecond (450 ns) pulses for up to 20 mus. The scheme has a high potential for storing multiple temporal modes in the single-photon regime, which is an important resource for future long-distance quantum communication based on quantum repeaters.


Beyond Mean Arterial Pressure and Lactate: Perfusion End Points for Managing the Shocked Patient.
Patients in shock present frequently to the emergency department. The emergency physician must be skilled in the resuscitation of both differentiated and undifferentiated shock. Early, aggressive resuscitation of patients in shock is essential, using macrocirculatory, microcirculatory, and clinical end points to guide interventions. Therapy should focus on the restoration of oxygen delivery to match tissue demand. This article reviews the evidence supporting common end points of resuscitation for common etiologies of shock and limitations to their use.