The polysialylated neural cell adhesion molecule promotes neurogenesis in vitro.
A characteristic feature of neurogenic sites in the postnatal brain is the expression of the polysialylated forms of the neural cell adhesion molecule (PSA-NCAM). To investigate the role of PSA-NCAM in generation of neuronal populations, we developed an in vitro model where neurogenesis occurs in primary cortical cultures following serum withdrawal. We show that removal or inactivation of the PSA tail of NCAM in these cultures leads to a significant decrease in the number of newly generated neurons. Similarly, cultures prepared from NCAM knock-out mice exhibit a significantly reduced neurogenesis. Pulse-chase experiments using the proliferation marker BrdU reveal that the lack of PSA does not affect the mitotic rate of neural progenitors but rather, it reduces the early survival of newly generated neurons. These results suggest that, in addition to its role in the migration of neuronal progenitors, PSA-NCAM is required for the adequate survival of these cells.


The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) Study: Rationale, Design and Methods.
Mild cognitive impairment (MCI), also termed mild neurocognitive disorder, includes a heterogeneous group of conditions characterized by declines in one or more cognitive domains greater than that expected during "normal" aging but not severe enough to impair functional abilities. MCI has been associated with an increased risk of developing dementia and even considered an early stage of it. Therefore, noninvasively accessible biomarkers of MCI are highly sought after for early identification of the condition. Systemic inflammation, metabolic perturbations, and declining physical performance have been described in people with MCI. However, whether biological and functional parameters differ across MCI neuropsychological subtypes is presently debated. Likewise, the predictive value of existing biomarkers toward MCI conversion into dementia is unclear. The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) study was conceived as a multi-dimensional investigation in which multi-marker discovery will be coupled with innovative statistical approaches to characterize patterns of systemic inflammation, metabolic perturbations, and physical performance in older adults with MCI. The ultimate aim of ODINO is to identify potential biomarkers specific for MCI subtypes and predictive of MCI conversion into Alzheimer's disease or other forms of dementia over a three-year follow-up. Here, we describe the rationale, design, and methods of ODINO.


Nuclear factor erythroid 2-related factor 2 protects bovine mammary epithelial cells against free fatty acid-induced mitochondrial dysfunction in vitro.
Bovine mammary epithelial cells undergo an increase in metabolic rate, mitochondrial dysfunction, and oxidative stress after calving. Nuclear factor erythroid 2-related factor 2 (NFE2L2), a master regulator of cellular redox homeostasis, plays crucial roles in the regulation of mitochondrial function. The objective of this study was to investigate the role of NFE2L2 on mitochondrial function in bovine mammary epithelial cells under hyperlipidemic conditions. Three experiments were conducted as follows: (1) the immortalized bovine mammary epithelial cell line MAC-T was treated with various concentrations of free fatty acids (FFA; 0, 0.6, 1.2, or 2.4 mM) for 24 h to induce stress; (2) MAC-T cells were transfected with small interfering RNA targeting NFE2L2 (si-NFE2L2) and scrambled nontarget negative control (si-Control) for 48 h; and (3) MAC-T cells were pretreated with 10 μM sulforaphane (SFN), an activator of NFE2L2, for 24 h followed by treatment with 1.2 mM FFA for an additional 24 h. Results indicated that exogenous FFA challenge induced linear and quadratic increases in concentrations of mitochondrial reactive oxygen species (ROS). Compared with 0 mM FFA, mitochondrial membrane potential, mRNA abundance of oxidative phosphorylation complexes (CO I-V), protein abundance of nuclear respiratory factor 1 (NRF1), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), mitochondrial transcription factor A (TFAM), and NFE2L2 along with the contents of ATP, mitochondrial DNA (mtDNA), and total mitochondria were greater in the MAC-T challenged with 0.6 mM FFA group, but lower in the 1.2 and 2.4 mM FFA cultures. Knockdown of NFE2L2 via small interfering RNA led to greater mitochondrial ROS content and lower mitochondrial membrane potential along with contents of ATP, mtDNA, and total mitochondria. The SFN pretreatment upregulated protein abundance of NFE2L2 and attenuated the downregulation of NFE2L2 induced by FFA. Pretreatment with SFN attenuated the downregulation induced by FFA of PGC-1α, NRF1, and TFAM protein abundance along with contents of mtDNA and total mitochondria. Furthermore, SFN pretreatment attenuated the upregulation of mitochondrial ROS content, the downregulation of mitochondrial membrane potential, and the decreases in ATP, mtDNA, and mitochondrial content induced by FFA. Overall, data indicated that FFA inhibit NFE2L2, resulting in mitochondrial dysfunction and ROS production in bovine mammary epithelial cells. Thus, NFE2L2 may be a promising therapeutic target against metabolic challenge-driven mitochondrial dysfunction and oxidative stress in bovine mammary epithelial cells.


[Effects of no-tillage on soil water content and physical properties of spring corn fields in semiarid region of northern China].
Field experiments were conducted in 2006-2008 to study the effects of no-tillage on the spatiotemporal dynamics of soil water content and related soil physical properties in spring corn fields in Beijing region during growth season. In study period, the water storage in 0-100 cm soil layer in tillage and no-tillage treatments had the same variation trend with time and precipitation, but the water storage at different time periods and under different precipitations was 2.7%-30.3% higher in no-tillage treatment than in tillage treatment. When the precipitation was relatively abundant, the increment of soil water storage was somewhat increased, but no-tillage was still worth to be popularized in the regions relatively deficit in precipitation. Under no-tillage, the average water storage in 0-100 cm soil layer during the three growth seasons in 2006-2008 was 3.4%-12.8% higher than that under conventional tillage, and the increment of the water storage in 0-20 cm and 80-100 cm soil layers under no-tillage was higher than that in intermediate layer, with the highest increment reached 22.2%. No-tillage improved soil water-holding capacity and water use efficiency via decreasing soil bulk density, increasing soil porosity, and promoting the formation of soil water-stable aggregates, and thereby, promoted crop yielding. After 3 years no-tillage, the soil water use efficiency and spring corn yield were increased by 13.3% and 16.4%, respectively, compared with those under conventional tillage.


[Changes in passive left ventricular pressure-volume relations in acute volume expansion].
The passive left ventricular pressure-volume relationship characterises left ventricular distensibility. However, it has recently been shown that acute pharmacological intervention can significantly change the position of the diastolic pressure-volume curve. We studied the effects of acute volumic expansion on the passive left ventricular pressure-volume relationship. In fact, the interpretation of left ventricular function curves during acute volumic expansion assumes that the left ventricular pressure-volume relationship remains unchanged. We measured the heart rate, cardiac output, left and right ventricular pressures with micromanometers, ventricular volumes by cineangiography 50 frames/sec (n = 6) or ventricular diameters by M mode echocardiography (n = 6) in 12 patients without valvular or coronary heart disease during rapid volumic expansion, and calculated stroke volumes and indices of left ventricular performance; the passive left ventricular pressure-volume or pressure-diameter relationship was adjusted to an exponential function P = a.ekp.V or P = a'.ek'p.De. After volumic expansion the cardiac output rose due to an increase in heart rate and stroke volume. The increase in stroke volume was related to that of end diastolic volume, the end systolic volume remaining unchanged: there was little difference in the indices of left ventricular performance. The pressure-volume and pressure-diameter curves were considerably shifted upwards and to the left during acute volumic expansion: this seemed to be due mainly to an increased intrapericardial pressure secondary to the increase in intrapericardial content. The relationship obtained by subtracting the simultaneous right ventricular from the instantaneous left ventricular pressure after volumic expansion was identical to the basal left ventricular pressure-volume curve. These observations demonstrate the importance of external factors of left ventricular compression in the changes in the passive left ventricular diastolic relationship during acute volumic expansion and invalidate the use of function curves obtained under these conditions for the assessment of left ventricular systolic function. The end diastolic pressure cannot be considered to reflect end diastolic volume and the function curves, in fact, illustrate changes in diastolic distensibility.


T cell-mediated rejection is a major determinant of inflammation in scarred areas in kidney allografts.
Inflammation in fibrosis areas (i-IF/TA) of kidney allografts is associated with allograft loss; however, its diagnostic significance remains to be determined. We investigated the clinicohistologic phenotype and determinants of i-IF/TA in a prospective cohort of 1539 kidney recipients undergoing evaluation of i-IF/TA and tubulitis in atrophic tubules (t-IF/TA) on protocol allograft biopsies performed at 1 year posttransplantation. We considered donor, recipient, and transplant characteristics, immunosuppression, and histological diagnoses in 2260 indication biopsies performed within the first year posttransplantation. Nine hundred forty-six (61.5%) patients presented interstitial fibrosis/tubular atrophy (IF/TA Banff grade > 0) at 1 year posttransplant, among whom 394 (41.6%) showed i-IF/TA. i-IF/TA correlated with concurrent t-IF/TA (P < .001), interstitial inflammation (P < .001), tubulitis (P < .001), total inflammation (P < .001), peritubular capillaritis (P < .001), interstitial fibrosis (P < .001), and tubular atrophy (P = .02). The independent determinants of i-IF/TA were previous T cell-mediated rejection (TCMR) (P < .001), BK virus nephropathy (P = .007), steroid therapy (P = .039), calcineurin inhibitor therapy (P = .011), inosine-5'-monophosphate dehydrogenase inhibitor therapy (P = .011), HLA-B mismatches (P = .012), and HLA-DR mismatches (P = .044). TCMR patients with i-IF/TA on posttreatment biopsy (N = 83/136, 61.0%) exhibited accelerated progression of IF/TA over time (P = .01) and decreased 8-year allograft survival (70.8% vs 83.5%, P = .038) compared to those without posttreatment i-IF/TA. Our results support that i-IF/TA may represent a manifestation of chronic active TCMR.


Raman spectroscopic imaging for quantification of depth-dependent and local heterogeneities in native and engineered cartilage.
Articular cartilage possesses a remarkable, mechanically-robust extracellular matrix (ECM) that is organized and distributed throughout the tissue to resist physiologic strains and provide low friction during articulation. The ability to characterize the make-up and distribution of the cartilage ECM is critical to both understand the process by which articular cartilage undergoes disease-related degeneration and to develop novel tissue repair strategies to restore tissue functionality. However, the ability to quantitatively measure the spatial distribution of cartilage ECM constituents throughout the tissue has remained a major challenge. In this experimental investigation, we assessed the analytical ability of Raman micro-spectroscopic imaging to semi-quantitatively measure the distribution of the major ECM constituents in cartilage tissues. Raman spectroscopic images were acquired of two distinct cartilage tissue types that possess large spatial ECM gradients throughout their depth: native articular cartilage explants and large engineered cartilage tissue constructs. Spectral acquisitions were processed via multivariate curve resolution to decompose the "fingerprint" range spectra (800-1800 cm-1) to the component spectra of GAG, collagen, and water, giving rise to the depth dependent concentration profile of each constituent throughout the tissues. These Raman spectroscopic acquired-profiles exhibited strong agreement with profiles independently acquired via direct biochemical assaying of spatial tissue sections. Further, we harness this spectroscopic technique to evaluate local heterogeneities through the depth of cartilage. This work represents a powerful analytical validation of the accuracy of Raman spectroscopic imaging measurements of the spatial distribution of biochemical components in a biological tissue and shows that it can be used as a valuable tool for quantitatively measuring the distribution and organization of ECM constituents in native and engineered cartilage tissue specimens.


Subacute sclerosing panencephalitis: experimental infection in primates.
Measles virus isolated from the brain of a 12-year-old boy with subacute sclerosing panencephalitis caused a chronic, progressive encephalitis in experimentally infected rhesus monkeys. The infection was eventually fatal in spite of pre-existing measles immunity and a vigorous secondary antibody response in serum and cerebrospinal fluid of the infected animals. The findings provide a basis for studies into the pathogenesis and possible treatment of the human disease.


New perspectives in aspiration community acquired Pneumonia.
Introduction: Aspiration pneumonia is a subclass of community-acquired pneumonia that is expected to have an increasing contribution in mortality and morbidity, particularly in the elderly population over the next coming decades. While studies have revealed significant progress in identifying risk factors for aspiration pneumonia, the clinical presentation and diagnosis remain challenging to healthcare providers. Areas covered: We conducted a broad literature review using the MeSH heading in PubMed/MEDLINE of 'aspiration pneumonia' from January 1970 to July 2019. The understanding of the microbiology of aspiration pneumonia has evolved from a possible shift in the causative organisms away from anaerobes to traditional community-acquired pneumonia organisms. The importance of this shift is not yet known, but it has questioned the pathogenic role of anaerobes, appropriate anaerobic testing and the role of these pathogens in the pulmonary microbiome in patients with pneumonia. The identification of risk factors led to strategies to prevent or minimize the risk of aspiration pneumonia with moderate success. Expert opinion: Our expert opinion is that further research is needed to determine the role of the microbiome with aspiration pneumonia and patient risk factors. There is also a great need to develop clinical tools to help providers diagnose, treat, and prevent aspiration pneumonia.


Use of temporalis muscle flaps in complicated defects of the head and face.
Large defects in the upper two thirds of the face, skull, and skull base pose challenging reconstructive problems. There are a number of applicable reconstructive techniques, all with various advantages and disadvantages, available to otolaryngologists-head and neck surgeons. One method, originally described in the late 1800s, was evaluated by us. Applications of the technique included reconstruction of large defects of the forehead, dura, and anterior skull base, closure of orbital defects, and soft-tissue augmentation of the face. Advantages of this reconstructive technique are the flap's proximity to the defects and its simplicity of execution.


Does family history of alcohol problems influence college and university drinking or substance use? A meta-analytical review.
Family history of alcohol use problems is a reliable determinant of alcohol use and problems in the population at large, but findings are inconsistent when this issue is examined in college and university students. No quantitative summary of this literature has been reported to date. The purpose of this study was to conduct a meta-analysis on the effects of family history on substance use and abuse in college and university students. A two-group contrast meta-analysis was conducted to evaluate the differences in substance use and abuse between family history-positive and -negative students pursuing higher education. The studies that contributed data to this meta-analysis were conducted in five countries, with the majority of studies from the United States. A total of 65 published papers (53 samples) contributed data from 89 766 participants attending university or college. Effect sizes were coded for alcohol consumption, problems and use disorder symptoms, as well as other illegal drug use and abuse. Two independent coders calculated effect sizes and coded descriptive content about the papers, and discrepancies were reconciled. Family history was used as the grouping variable. Family history had a minimal effect on alcohol consumption, with stronger effects on alcohol consequences (Cohen's d: 0.21-0.25), alcohol use disorder symptoms (Cohen's d: 0.24) and other drug involvement (Cohen's d: 0.37-0.86). Relative to students without a family history of alcohol problems, students with positive family histories do not drink more, but may be at greater risk for difficulties with alcohol and drugs.


Cholinergic and nitrergic interneurones in the myenteric plexus of the human colon.
Myenteric interneurones are involved in the reflexes that control the motility of the human colon. The distribution of choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity in myenteric interneurones was investigated in this study. DiI (1,1'- didodecyl 3,3,3',3'-indocarbocyanine perchlorate) was applied to the myenteric plexus of the human colon followed by organotypic culture. Retrogradely labelled neurones, with projections longer than motor neurones (>10 mm), were studied to exclude motor neurone populations. ChAT and NOS immunoreactivity was then determined in the interneurones. We found that 90% of interneurones projecting orally contained ChAT and none contained NOS. Ninety five per cent of descending interneurones were labelled with ChAT and/or NOS antisera; 46% contained NOS immunoreactivity alone, 20% contained ChAT immunoreactivity alone, and 29% contained both ChAT and NOS. Anally directed interneurones had significantly longer projections than orally projecting interneurones. Nearly all interneurones contain either NOS or ChAT immunoreactivity. Orally projecting interneurones are of two types: 90% contain ChAT alone and the remainder contain immunoreactivity for neither ChAT nor NOS. There are three main types of anally projecting interneurones: the largest, which contains NOS but not ChAT, and the two smaller classes which contain ChAT and NOS, and CHAT alone.


[Accelerated determination of blood bacteriostatic activity in patients with tuberculosis by using the semiliquid culture medium].
Blood bacteriostatic activity (BBA) was studied in 87 patients with respiratory tuberculosis. Clinical Mycobacterium tuberculosis (MBT) strains and different culture media, such as solid (Löwenstein-Jensen and Middlebrook), liquid (modified Soton) and semiliquid (SM developed for accelerated determination of drug resistance in MBT) media were used. With isoniazid-resistance of MBT, the use of solid media yielded underestimated BBA. The SM medium based on the Soton medium added by 0.35% of culture agar and 25% equine serum was optimal, which provided evidence for BBA on day 7 (visual recording of MBT growth). Examination of BBA by means of SM revealed a clear inverse correlation between the degree of BBA and the bacteriological parameters of sputum study. The small numbers of sputum MBT cultures (a high correlation, r = -0.88; p = 0.01) and short bacterial isolation (average correlation, r = -0.65; p = 0.01) corresponded to the high values of BBA.


Catalysis as an Enabling Science for Sustainable Polymers.
The replacement of current petroleum-based plastics with sustainable alternatives is a crucial but formidable challenge for the modern society. Catalysis presents an enabling tool to facilitate the development of sustainable polymers. This review provides a system-level analysis of sustainable polymers and outlines key criteria with respect to the feedstocks the polymers are derived from, the manner in which the polymers are generated, and the end-of-use options. Specifically, we define sustainable polymers as a class of materials that are derived from renewable feedstocks and exhibit closed-loop life cycles. Among potential candidates, aliphatic polyesters and polycarbonates are promising materials due to their renewable resources and excellent biodegradability. The development of renewable monomers, the versatile synthetic routes to convert these monomers to polyesters and polycarbonate, and the different end-of-use options for these polymers are critically reviewed, with a focus on recent advances in catalytic transformations that lower the technological barriers for developing more sustainable replacements for petroleum-based plastics.


Homogeneous and efficient production of a bacterial nanocellulose-lactoferrin-collagen composite under an electric field as a matrix to promote wound healing.
BNC was functionalized with collagen (COL) and lactoferrin (LF) to form three different composites: BNC/COL, BNC/LF and BNC/LF/COL using a novel electrophoresis-based technology. The technology is less time-consuming than traditional immersion-adsorption methods and offers the additional advantages of greater protein loading, better homogeneity and a lower requirement for processing solution. Significantly, it has general applicability and great potential for fabricating other similar composites. The water-holding capability and water vapor transmission rate (WVTR) of BNC composites were significantly improved, particularly in the case of BNC/LF/COL, with a WVTR of 2600 g m-2 d-1, indicating that the composite maintains a moderately moist environment over the wound bed, which would enhance epithelial cell migration during the healing process. Compared with BNC and BNC/COL, the LF-impregnated composites mediated a reduction in bacterial viability of at least 77%. Impregnation with COL significantly improved the cytocompatibility of BNC composites to promote the adhesion and proliferation of fibroblast cells. Furthermore, a greater therapeutic effect of BNC/LF/COL was observed in a rat model of wound healing, with a new epithelium formed within 9 days and without any significant adverse reactions. These results suggest that BNC/LF/COL obtained using the electrophoresis method represents a promising wound dressing for use in practical applications.


[Effect of exogenous selenium on soybean yield and its total N and P contents and on soil enzyme activities].
Based on pot experiment with black soil, the effects of various concentrations and various valence of exogenous selenium on soybean yield and its N and P contents and on soil enzyme activities were studied. The results showed that applying 0.25 microgram.g-1 soil and 0.5 microgram.g-1 soil of both Se4+ and Se6+ could increase soybean yield and its N content and promote soil urease activity, but decrease the P content of soybean and soil phosphatase activity. When the concentration of Se6+ was 0.5 microgram.g-1 soil, there was a significantly parabola relationship between the N content of soybean and soil urease activity; and when the concentration of Se6+ was 0.25 microgram.g-1 soil, there was a significantly parabola relationship between the P content of soybean and soil phosphatase activity. There were no significant relationships between the N and P contents of soybean and the activities of test soil enzymes when Se4+ was applied.


Uncoupled hydrogen and volatile fatty acids generation in a two-step biotechnological anaerobic process fed with actual site wastewater.
Among agro-wastes, olive mill wastewater (OMW) truly qualifies as a high impact organic residue due to its biochemical-rich composition and high annual production. In the present investigation, dephenolized OMW (OMWdeph) was employed as the feedstock for a biotechnological two-stage anaerobic process dedicated to the production of biohydrogen and volatile fatty acids (VFAs), respectively. To this end, two identically configured packed-bed biofilm reactors were operated sequentially. In the first, the hydraulic retention time was set to 1 day, whereas in the second it was equal to 5 days. The rationale was to decouple the hydrolysis of the organic macronutrients held by the OMWdeph, so as to quantitatively generate a biogas enriched in H2 (first stage aim), for the acidogenesis of the residual components left after hydrolysis, to then produce a highly concentrated mixture of VFAs (second stage aim). Results showed that the generation of H2 and VFAs was effectively split, with carbohydrates and lipids, respectively, being the main substrates of the two processes. About 250 ml H2 L(-1) day(-1) was produced, corresponding to a yield of 0.36 mol mol(-1) of consumed carbohydrates (expressed as glucose equivalents). The overall concentration of VFAs in the acidogenic process was 13.80 g COD L(-1), so that 2.76 g COD L(-1) day(-1) was obtained. Second generation biorefineries use a selected fraction of an organic waste to conduct a microbiologically-driven pathway towards the generation of one target molecule. With the proposed approach, a greater value of the waste was attained, since the multi-purpose two-stage process did not entail competition for substrates between the first and the second steps.


Pontocerebellar volume deficits and ataxia in alcoholic men and women: no evidence for "telescoping".
Brain volume shrinkage is common in treatment-seeking patients with alcohol use disorders. Whether women are more vulnerable to brain dysmorphology than men despite lower alcohol consumption levels or shorter dependency ("telescoping effect") remains controversial and has not been considered with respect to infratentorial structures or their potential contribution to ataxia. The 200 participants included 64 men and 31 women with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence and 105 controls. An infratentorial region (pons, cerebellar hemispheres, vermis (anterior, posterior, and inferior sectors), fissures, cisterns, fourth ventricle) was quantified with atlas-based parcellation. To enable comparison of men and women, regional tissue volumes were expressed as ratios of tissue in the volume. Participants also completed quantitative ataxia testing. Total infratentorial and vermian tissue ratios were significantly smaller in alcoholics than controls; alcoholic women did not show disproportionately greater volume deficits than alcoholic men. A re-analysis including alcoholic men and women matched in alcohol consumption, onset age, abstinence duration, and age revealed again that alcoholic women did not have disproportionately greater regional vermian volume deficits than alcoholic men. Alcoholic men and women were impaired in all measures of ataxia, which correlated with low infratentorial tissue ratios in men. Alcoholic men showed deficits of pontocerebellar volume ratios, yet alcoholic women did not display signs of "telescoping". Further, alcoholic men and women both showed signs of ataxia of gait and balance, related to affected pontocerebellar systems in the men but not the women, suggesting the need to consider other neural substrates for ataxia in women.


Conjugative transfer of Tn916 in Enterococcus faecalis: trans activation of homologous transposons.
Tn916 [carries tet(M)] is a 16.4-kb conjugative transposon that can establish itself in multiple copies in Enterococcus faecalis. To study the interaction of coresident homologous transposons during conjugation, an E. faecalis mutant defective in homologous recombination was utilized for construction of strains harboring Tn916 delta E (a derivative in which erm is substituted for tet) on the chromosome and Tn916 on a nonconjugative plasmid. When these strains were used as donors, the two transposons were able to transfer independently; however, they were found to transfer and become coestablished in the recipient up to 50% of the time. In contrast, cotransfer of a plasmid marker located outside the transposon occurred at a frequency of no greater than 0.5%. Separate experiments showed that mobilization of the nonconjugative plasmids pAM401 and pVA749 by chromosome-borne copies of Tn916 occurred only at low frequencies (generally less than 2% cotransfer). The data imply that the initiation of transposition of Tn916 results in a trans activation that is specific for homologous transposons present in the same cell.


Strengths and weaknesses in team communication processes in a UK emergency department setting: findings using the Communication Assessment Tool-Team.
Identifying weaknesses in emergency department (ED) communication may highlight areas where quality improvement may be beneficial. This study explores whether the Communication Assessment Tool-Team (CAT-T) survey can identify communication strengths and weaknesses in a UK setting. This study aimed to determine the frequency of patient responses for each item on the CAT-T survey and to compare the proportion of responses according to patient and operational characteristics. Adults presenting to the minors area of a semi-urban ED between April and May 2015 were included. Those lacking capacity or in custody were excluded. Multivariate analysis identified associations between responses and demographic/operational characteristics. A total of 407/526 eligible patients responded (77.3%). Respondents were mostly White British (93.9%), with a median age of 45 years. Most responses were obtained during daytime hours (84.2% between 08 : 00 and 18 : 00). The median reported times to triage, assessment and disposition were 15, 35 and 90 min, respectively. Items most frequently rated as 'very good'/'excellent' (strengths) were 'ambulance staff treated me with respect' (86.7%), ED staff 'let me talk without interruptions' (85%) and 'paid attention to me' (83.7%). Items most frequently rated as 'poor'/'fair' (weaknesses) were 'encouraged me to ask questions', 'reception treated me with respect' (10.4%) and 'staff showed an interest in my health' (6.8%). Arrival time, analgesia at triage and time to assessment were associated with significantly increased odds of positive perception of team communication for a range of items. The CAT-T survey may be used within a UK setting to identify discrete strengths and weaknesses in ED team communication.


Electron microscopic localization of the chloroplast DNA replicative origins in Chlamydomonas reinhardii.
Chloroplast DNA, isolated from a synchronized culture of Chlamydomonas reinhardii, was digested with restriction endonucleases and examined in the electron microscope. Restriction fragments containing displacement loops (D-loop) were photographed and measured to determine the position of replicated sequences in relation to the restriction enzyme sites. D-loops were located at two positions on the physical map of chloroplast DNA. One replication origin was mapped at about 10 kb upstream of the 5' end of a 16s rRNA gene. The second origin was spaced 6. 5kb apart from the first origin and was about 16.5 kb upstream of the same 16s rRNA. Initiations at those two sites were not always synchronized. Replication initiated with the formation of a D-loop resulting from the synthesis of one daughter strand. After a short initial lag phase, corresponding to the synthesis of 350 +/- 130 bp of one daughter strand, DNA synthesis then proceeded in both directions. Both D-loop regions were preferred binding sites of undetermined protein complexes.


[Differential therapy of Gilles de la Tourette's syndrome].
The previous works of the author demonstrated the clinical heterogeneity of Gilles de la Tourette's syndrome (GTS). Based on statistical treatment of the efficacy of 138 courses of the treatment with benzodiazepine tranquilizers, neuroleptics, antidepressants, and anticonvulsants, methods of the individualized treatment of GTS were elaborated. It is recommended that low doses of neuroleptics (orap, haloperidol) be applied in patients with typical GTS. Schizophrenia associated with Tourette-like disorders requires the use of higher doses of neuroleptics and, in some cases, of the combined therapy. In encephalopathy accompanied by Tourette-like disorders, the treatment with anticonvulsants and benzodiazepine tranquilizers turned out most effective.


Deep near-term mitigation of short-lived climate forcers in Oman: grand challenges and prospects.
Over time, short-lived climate forcers (SLCFs) have gradually gained prominence as a rationale in the international global mitigation strategy to preserve temperature below 1.5 °C by the end of this century. Scientists cite the short-term gains in air quality and health co-benefits associated with reducing SLCFs as grounds for raising the pressure on governments to eliminate SLCFs rapidly and aggressively. There is little research on whether deep SLCF mitigation during the next decade is feasible in low- and middle-income nations, particularly the hydrocarbon-based economy. This study estimates current and future emissions of potent SLCFs as methane (CH4) hydrofluorocarbons (HFCs) in Oman using the basic tier 1 approach of the Intergovernmental Panel on Climate Change (IPCC) greenhouse gases (GHG) inventory Guidelines of 2006. Current and future emission of black carbon (BC) was also quantified using specific emission factors. A total of 38,268 Gg of SLFCs were released into the atmosphere in Oman in 2015, accounting for 38.8% of the country's total GHG emissions, and is expected to rise significantly over the next decade to reach 67,777 Gg by 2030. The analysis reveals that the source of Oman's highly potent SLCF emissions is associated with key and critical economic sectors such as the oil and gas industry, heavy road transportation, residential air conditioning (RAC), and industrial refrigeration. These vital economic sectors impose a "Grand Challenge" on the immediate reduction of SLCFs in Oman and the Gulf Cooperation Council (GCC). Accomplishing a rapid, significant reduction in highly potent SLCFs from the three challenging sectors over a 5- to 10-year time period does not appear feasible or realistic in the context of international market mechanisms, socioeconomic factors, and mitigation targets. Achieving a significant reduction in SLCFs for a hydrocarbon-based economy requires a profound economic shift. Creating an effective long-term vision for a post-oil economy over the next two decades provides a sound foundation for implementing economic and societal transformation policies incorporating near-zero-emission measures for the potent SLCFs.


The dinoponeratoxin peptides from the giant ant Dinoponera quadriceps display in vitro antitrypanosomal activity.
The crude venom of the giant ant Dinoponera quadriceps is a cocktail of polypeptides and organic compounds that shows antiparasitic effects against Trypanosoma cruzi, the causative agent of Chagas disease. In order to investigate the venom-derived components responsible for such antitrypanosomal activity, four dinoponeratoxins (DnTxs) were identified, namely M-PONTX-Dq3a, -Dq3b, -Dq3c and -Dq4e, that are diverse in size, net charge, hydrophobicity and propensity to interact with eukaryote cell membranes. These peptides were tested against epimastigote, trypomastigote and amastigote forms of benznidazole (Bz)-resistant Y strain of T. cruzi and in mammalian host cells. The M-PONTX-Dq3a and -Dq4e inhibited all developmental forms of T. cruzi, including amastigotes, the responsible form for the maintenance of infection on chronic phase of the disease. The M-PONTX-Dq3a showed the highest selectivity index (SI) (80) and caused morphological alterations in T. cruzi, as observed by scanning electron microscopy (SEM), and induced cell death through necrosis, as seen by multiparametric flow cytometry analysis with specific biochemical markers. Altogether, the D. quadriceps venom appears as a source for the prospection of trypanocidal peptides and the M-PONTX-Dq3a arises as a candidate among the dinoponeratoxin-related peptides in the development of compounds against Chagas disease.


Repeated hypothesis testing on a growing data set.
In many problems, especially when data are collected over a long period of time, hypothesis testing is done repeatedly as new data arrive. It is shown both for one particular problem and for a more general class of problems that if testing is performed each time on the total amount of data accumulated, the true simple null hypothesis will be rejected at least once as the number of tests approaches infinity. Furthermore, it is conjectured that the conclusion holds for most problems of interest in which the null hypothesis is simple.


Internet delivered images for exposure in specific phobia, design considerations for self-directed therapy.
Exposure to phobic stimuli in subjects with specific phobia typically results in increased anxiety, ranging from mild to severe, followed by gradual habituation. The Internet is a candidate medium for the delivery of phobic stimuli to phobic subjects, such as pictures, video clips or computer animations. Delivery of such images in home settings warrants careful attention to the range and time course of anxiety responses elicited, and to tailoring of progression through hierarchies of images. The agency of the user is paramount, they need to have the final say at all stages of exposure as to whether to proceed or not. We have incorporated solutions to these requirements in the design of an internet-based exposure program (FEARDROP). This employs a database repository of pictures and videos of phobic stimuli. Images are called up by the user engaging a tracking circle with their mouse and following it around the screen. The image fades out if the circle is not followed, a form of 'dead man's brake'. Anxiety responses are measured at intervals on a visual analogue scale and graphed for the user. Initial results show substantial habituation to spider pictures within minutes, with a controlled comparison to video images in progress.


Experiences with care co-ordination among people with cerebral palsy, multiple sclerosis, or spinal cord injury.
To describe the experiences with care co-ordination of people with cerebral palsy, multiple sclerosis, or spinal cord injury; to determine barriers to effective care co-ordination; and to compare experiences across disability and health plan types. Qualitative, semi-structured telephone interviews with 30 people with cerebral palsy, multiple sclerosis, or spinal cord injury. Interviews focused on the care co-ordination experience of individuals in managed care and traditional indemnity health insurance plans in the USA and were analysed using NVivo. Half of the respondents reported that they had a health professional who co-ordinated their care. Participants identified barriers that prevented effective care co-ordination, including a lack of disability specific knowledge, providers' limited time and effort related to care, and insufficient communication among providers. There were few differences between managed care and fee-for-service respondents with regard to these barriers. Study findings reveal few differences in the care co-ordination experiences amongst people with cerebral palsy, multiple sclerosis, or spinal cord injury in both plan types. All providers need to become more literate about the health care needs of people with physical disabilities, and health plans need to reward communication among providers and the time and effort invested in care co-ordination.


New Paradigm in Treating Cancer: Right on Target.
Cancer prevalence is increasing every year and now cancer is the third highest cause of death in developing countries. Effective anticancer treatment can prolong life and improve the patient's quality of life. Targeted therapy is a new therapeutic modality which targets specific molecules in the cancer cell and disrupts dysregulated signaling pathways involved in carcinogenesis. Since targeted therapy does not attack normal cells, its side effects are considered low compared to chemotherapy. More than 15 drugs have been approved for treatment in various human cancers. These drugs can largely be grouped into tyrosine kinase inhibitors and monoclonal antibodies. This review will focus on the most common agents within both groups.


Suicide--the other side. The factor of reality among suicidal motivations.
A prevalent feature of many investigations of suicide is a degree of recoil from true empathic closeness to a suicidal person. The motives for this lie within the investigator's own dynamics--they are anxiety over one's own suicide proneness, together with guilt, shame, contempt, and the avoidance of medicolegal involvement. These motives are not altogether unrelated to the suicidal motives themselves, and they hamper the capacity of objective, neutral assessment. With a recognition of these resistances, the seldomly mentioned realistic determinant of suicide becomes discernible, the act sometimes being a clever, courageous choice of death, and not, as usually diagnosed, a pathologically generated escape from life. All suicidal motives should be evaluated according to several concomitant ratings simultaneously, while emphasizing the realistic rating. A neutral, unbiased approach to suicide should reduce the dangerous false glory sometimes attributed to the act, thus contributing to the discrimination of sickness, therapy, and health.


Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumors with poor prognosis due to extremely high malignancy, low rate of eligibility for surgical resection and chemoradiation resistance. Increasing evidence indicate that the interaction between activated pancreatic stellate cells (PSCs) and PDAC cells plays an important role in the development of PDAC. By producing high levels of cytokines, chemotactic factors, growth factors and excessive extracellular matrix (ECM), PSCs create desmoplasia and a hypoxic microenvironment that promote the initiation, development, evasion of immune surveillance, invasion, metastasis and resistance to chemoradiation of PDAC. Therefore, targeting the interaction between PSCs and PDAC cells may represent a novel therapeutic approach to advanced PDAC, especially therapies that target PSCs of the pancreatic tumor microenvironment.


[Effect of diuretic agents on central and intracardiac hemodynamics in hypertension].
Echocardiography and the method of dye dilution (Evans blue) were used to study parameters of the central and intracardiac haemodynamics in 28 men with uncomplicated essential hypertension during treatment with diuretics. Tests were undertaken thrice: after a 5-6 day control period, after a 3-day furosemide load (120 mg per 24 hrs), after 2-3 weeks course of treatment with hypothiazide (50-100 mg per 24 hrs). As a result there was a decrease of end-systolic, end-diastolic and stroke volumes of the left ventricle. In patients with hypotensive effect minute volume did not diminish. In the group without effect there was no significant decrease of arterial pressure, minute volume and general peripheral resistance but an increase in the heart rate. The initial volumes of the circulating blood and plasma in both groups were indistinguishable and decreased significantly as a result of treatment.


Visual potentiation of vestibular responses in lamprey reticulospinal neurons.
The lamprey normally swims with the dorsal side up. Illumination of one eye shifts the set-point of the vestibular roll control system, however, so that the animal swims with a roll tilt towards the source of light (the dorsal light response). A tilted orientation is often maintained for up to 1 min after the stimulation. In present study, the basis for this behaviour was investigated at the neuronal level. The middle rhombencephalic reticular nucleus (MRRN) is considered a main nucleus for the control of roll orientation in lampreys. Practically all MRRN neurons receive vestibular and visual input and project to the spinal cord. Earlier extracellular experiments had shown that optic nerve stimulation potentiates the response to vestibular stimulation in the ipsilateral MRRN. This most likely represents a neural correlate of the dorsal light response. Experiments were carried out in vitro on the isolated brainstem of the silver lamprey (Ichthyomyzon unicuspis). MRRN cells were recorded intracellularly, and the overall activity of descending systems was monitored with bilateral extracellular electrodes. The responses to 10 Hz optic nerve stimulation and 1 Hz vestibular nerve stimulation, and the influence of optic nerve stimulation on the vestibular responses, were investigated. In most preparations, optic nerve stimulation excited practically all ipsilateral MRRN cells. After stimulation, the cell was typically depolarized and showed an increased level of synaptic noise for up to 80 s. In contralateral MRRN neurons, optic nerve stimulation usually evoked hyperpolarization or no response. Vestibular nerve stimulation evoked compound excitatory postsynaptic potentials (EPSPs) or spikes in approximately 90% of the cells, both ipsilaterally and contralaterally. A smaller subpopulation of MRRN cells (approximately 10%) received vestibular inhibition. In 26 of 48 recorded MRRN cells, the response to vestibular stimulation was potentiated after ipsilateral optic nerve stimulation. The potentiation was seen in cells receiving either excitatory or inhibitory vestibular input as an increase in EPSP amplitude/spiking (85%) and a decrease in inhibitory postsynaptic potential amplitude (15%) respectively. In most cases the vestibular responses did not return to control levels during the testing period (10-30 min), and thus the visual stimulation most likely induced long-lasting changes in the functional connectivity of the role control network, in addition to the short-lasting afteractivity. In four of the 11 cells recorded contralateral to the stimulated optic nerve, a depression of the vestibular response could be seen. In potentiated cells, single vestibular pulses often evoked longer episodes of large synaptic noise and sometimes spiking. In the latter case, the action potentials appeared with highly variable latency after each stimulation pulse. This indicates that an important mechanism underlying the potentiation may be a long-lasting increase in excitability in a pool of unidentified interneurons located either upstream of the MRRN cells, relaying vestibular and visual inputs, or downstream, providing positive feedback.


Characterization of Klebsiella pneumoniae isolates from a mother-child cohort in Madagascar.
To define characteristics of Klebsiella pneumoniae isolated from carriage and infections in mothers and their neonates belonging to a paediatric cohort in Madagascar. A total of 2000 mothers and their 2001 neonates were included. For each mother, vaginal and stool samples were collected at the birth. Additionally, upon suspicion of infection, samples were collected from suspected infected body sites in 121 neonates. Genomic sequences of all isolated K. pneumoniae were used for phylogenetic analyses and to investigate the genomic content of antimicrobial resistance genes, virulence genes and plasmid replicon types. Five percent (n = 101) of mothers were K. pneumoniae positive. Of 251 collected K. pneumoniae isolates, 102 (40.6%) were from mothers and 149 (59.3%) were from neonates. A total of 49 (19.5%; all from infants except 1) isolates were from infected body sites. MLST identified 108 different STs distributed over the six K. pneumoniae phylogroups Kp1 to Kp6. We found 65 (25.8%) ESBL producers and a total of 101 (40.2%) MDR isolates. The most common ESBL gene was blaCTX-M-15 (in 99.3% of isolates expressing ESBL). One isolate co-harboured blaCTX-M-15 and blaNDM-1 genes. Three isolates from infected body sites belonged to hypervirulent-associated ST23 (n = 1) and ST25 (n = 2). We observed two cases of mother-to-child transmission and sustained K. pneumoniae carriage was identified in 10 neonates, with identical isolates observed longitudinally over the course of 18 to 115 days. This study revealed substantial genetic diversity and a high rate of antimicrobial resistance among K. pneumoniae isolated from both carriage and infections in Madagascar.


Effects of CO2/N2 dilution on laminar burning velocity of stoichiometric DME-air mixture at elevated temperatures.
The laminar burning velocity of CO2/N2 diluted stoichiometric dimethyl ether (DME) air mixtures is determined experimentally at atmospheric pressure and elevated mixture temperatures using a mesoscale high aspect-ratio diverging channel with inlet dimensions of 25mm×2mm. In this method, planar flames at different initial temperatures (Tu) were stabilized inside the channel using an external electric heater. The magnitude of burning velocities was acquired by measuring the flame position and initial temperature. The mass conservation of the mixture entering the inlet and the stationary planar flame front is applied to obtain the laminar burning velocity. Laminar burning velocity at different initial mixture temperatures is plotted with temperature ratio (Tu/Tu,o), where a reference temperature (Tu,o) of 300K is used. Enhancement in the laminar burning velocity is observed with mixture temperature for DME-air mixtures with CO2 and N2 dilutions. A significant decrease in the burning velocity and slight increase in temperature exponent of the stoichiometric DME-air mixture was observed with dilution at same temperatures. The addition of CO2 has profound influence when compared to N2 addition on both burning velocity and temperature exponent.


Natural killer cell precursor acute lymphoma/leukemia presenting in an infant.
Lymphoma/leukemia derived from immature natural killer (NK) cells occur most commonly in adults and are characterized by blastic cytologic features and an aggressive outcome. Predilection for extranodal sites and absence of the Epstein-Barr virus associated with mature NK cell malignancies further distinguish this entity. We present a NK precursor acute lymphoma presenting with multiple masses in an infant without circulating blasts or marrow replacement by disease. The diagnostic difficulty arose from several factors, including young age, presentation with multiple masses, blastic cytologic features mistaken for a small, round, blue cell tumor, and the absence of lineage-specific markers. The CD56+, CD34+, CD33+, MPO-, cytoplasmic CD3+, CD45-, CD7-, HLA-DR-, and TdT- immunophenotype of this neoplasm overlaps with previously reported cases of myeloid/NK precursor acute leukemia and blastic NK cell lymphoma/leukemia. This case emphasizes the need for a strong index of suspicion to recognize this rare entity and to distinguish it from solid tumors and other hematolymphoid neoplasms that occur in infancy.


Diagnosis of pulmonary embolism: planar images generated from V/Q SPECT are not a reliable substitute for traditional planar V/Q scan.
The use of summed planar images generated from single-photon emission computed tomography (SPECT) ventilation/perfusion (V/Q) scintigraphy has been proposed as a substitute for planar V/Q scans in order to use the revised PIOPED interpretation criteria when only SPECT acquisition is performed in patients with suspected pulmonary embolism. The aim was to evaluate the accuracy of angular summed planar scans in comparison with true planar images. Patients included in the 'SPECT study' assessing the diagnostic performance of V/Q SPECT were analysed. Angular summed planar images were generated from SPECT acquisition data and compared with true planar scans. Angular summed planar images were successfully generated for 246 patients. Regarding interobserver variability, the interpretation result was different for 15 (6%) summed planar scans with an excellent degree of agreement (κ=0.92; 95% confidence interval 0.88-0.96). With regard to intermodality interpretation variability between conventional planar and angular summed images, the result was different for 63 (26%) of 246 patients with an intermodality degree of agreement of κ=0.66 (95% confidence interval 0.58-0.73). Planar images generated from SPECT V/Q scintigraphy are not a reliable substitute for true planar V/Q images.


FlgM is a primary regulator of sigmaD activity, and its absence restores motility to a sinR mutant.
We have used mini-Tn1O mutagenesis to identify negative regulators of sigmaD activity. Nine independent insertions were mapped to five genes: flgM, flgK, fliD, fliS, and fliT, suggesting that FlgM export is regulated similarly in Bacillus subtilis and Salmonella typhimurium. We show that a deletion of flgM can restore sigmaD activity to a sinR null mutant of B. subtilis, although fla/che operon expression is affected by neither SinR nor FlgM.


The biocompatibility of glass-fibre reinforced composites (GFRCs) - a systematic review.
Fiber-reinforced composites (FRCs) have received considerable attention, owing to their potential use in dental prostheses or bone fracture fixation applications. The aim of this systematic review was to analyze and report the biological properties of FRCs reported in the existing literature. A systematic search of four databases (PubMed/MEDLINE, Scopus, Web of Science, and Cochrane library) was performed to identify all relevant studies published between 1962 and 2019. The search was limited to laboratory-based studies published in English. Citation mining was also performed through cross-referencing of included studies and hand searching of relevant journals. A total of 1283 potentially relevant articles were initially identified, and thirty-three articles were full-text screened. In the final ten studies included for review, four investigated bacterial adhesion and growth abilities on FRCs, four investigated the fibroblastic cytotoxicity of different surface-treated FRCs, and two investigated the osseointegration between bone and FRCs. Owing to the heterogeneity of fiber types, FRC-coating, and lack of standardized testing protocols, a meta-analysis was not feasible. The included studies indicated that glass fibers, and in particular E-glass fibers, are superior to ceramics and other FRCs in terms of bacterial adherence, fibroblast cytotoxicity, and cell viability. Glass-fiber-reinforced composites are cytocompatible materials that possess satisfactory biological properties and can be used in dental prosthesis and craniofacial implants. Further research is necessary to regulate the matrix ion release/degradation of FRCs to prolong the initially demonstrated properties.


Indicator for Success of Obesity Reduction Programs in Adolescents: Body Composition or Body Mass Index? Evaluating a School-based Health Promotion Project after 12 Weeks of Intervention.
Obesity in adolescence is the strongest risk factor for obesity in adulthood. This study aimed to evaluate the effects of a comprehensive lifestyle intervention on different anthropometric indices in 12-16-year-old boy adolescents after 12 Weeks of Intervention. A total of 96 male adolescents from two schools participated in this study. The schools were randomly assigned to intervention (53 students) and control school (43 students). Height and weight of students were measured and their body mass index (BMI) was calculated. Body fat percent (BF) and body muscle percent (BM) was assessed using a bioimpedance analyzer considering the age, gender, and height of students at baseline and after intervention. The obesity reduction intervention was implemented in the intervention school based on the Ottawa charter for health promotion. Twelve weeks of intervention decreased BF percent in the intervention group in comparison with the control group (decreased by 1.81% in the intervention group and increased by 0.39% in the control group, P < 0.01). However, weight, BMI, and BM did not change significantly. The result of this study showed that a comprehensive lifestyle intervention decreased the body fat percent in obese adolescents, although these changes was not reflected in the BMI. It is possible that BMI is not a good indicator in assessment of the success of obesity management intervention.


Subjective Cognitive Impairment Is a Predominantly Benign Condition in Memory Clinic Patients Followed for 6 Years: The Gothenburg-Oslo MCI Study.
In the quest for prevention or treatment, there is a need to find early markers for preclinical dementia. This study observed memory clinic patients with subjective cognitive impairment (SCI) and normal cognitive function at baseline. The primary aim was to address SCI as a potential risk factor for cognitive decline. The secondary aim was to address a potential relation between (1) baseline cerebrospinal fluid biomarkers and (2) a decline in memory performance over the first 2 years of follow-up, with a possible cognitive decline after 6 years. Eighty-one patients (mean age 61 years) were recruited from university memory clinics and followed up for 6 years. Eighty-six percent of the cohort remained cognitively stable or improved, 9% developed mild cognitive impairment, and only 5% (n = 4) developed dementia. Regression analysis revealed that low levels of Aβ42 at baseline and memory decline during the first 2 years predicted dementia. When combined, these variables were associated with a 50% risk of developing dementia. Cognitive stability for 86% of the cohort suggests that SCI is predominantly a benign condition with regard to neuropathology. The low number of individuals who developed dementia limits the generalizability of the results and discussion of progression factors.


Prevention of cardiovascular disease after renal transplantation.
After renal transplantation, cardiovascular disease (CVD) is the leading cause of death with a functioning graft. Guidelines for prevention of CVD are mainly based on data from the general population. The purpose of this review is to give a practical approach on prevention of CVD in renal transplant recipients. New epidemiological data have shown that in addition to traditional risk factors for CVD, other risk factors may influence cardiovascular risk in renal transplant recipients. Recently, a specific risk calculator for CVD in renal transplant recipients has been developed. Prevention of CVD in renal transplant recipients should include lifestyle modifications, such as prevention of overweight, smoking cessation and physical exercise. Optimal treatment of hypertension, lipid disturbances and posttransplant diabetes should be encouraged. Accumulating evidence indicates that declining graft function and graft loss are potentially modifiable risk factors in this population, which make strategies for preserving graft function important. This situation may include individual tailoring of immunosuppression and use of new immunosuppressive medications with a more favorable effect on cardiovascular risk factors and graft function. To prevent CVD in renal transplant recipients, cardiovascular risk assessment should be performed regularly. Prevention should include both lifestyle modifications, optimal treatment of cardiovascular risk factors and strategies to preserve graft function.


Differential release of substance P and somatostatin in the rat spinal cord in response to noxious cold and heat; effect of dynorphin A(1-17).
Dynorphin A(1-17), the proposed endogenous ligand for the kappa receptor, has been reported to demonstrate no antinociceptive activity when tested in analgesic assays involving noxious (heat (e.g., tail-flick and hot-plate assays). By using a rat tail-flick analgesic assay that utilizes extreme cold as its noxious stimulus (an ethylene glycol-water mixture maintained at -10 degrees C), we have recently reported a dose-related and naloxone-reversible antinociceptive effect for i.c.v. administered dynorphin A(1-17). To elucidate the biochemical mechanism of this antinociception, we designed a push-pull perfusion system which would allow us to measure changes in neuropeptide release in the spinal cord during exposure to noxious heat or cold. Male Sprague-Dawley rats were implanted surgically with two lengths of PE-10 tubing inserted into the spinal subarachnoid space via the cisterna magna, with the push cannula at the level of T-1, and the pull cannula at the rostral edge of the lumbar enlargement. At the time of testing, samples of cerebrospinal fluid were collected both in the presence and absence of a noxious stimulus. Substance P (SP) and somatostatin (SST) levels were measured by radioimmunoassay. Exposing the animal's tail to the noxious cold (30 sec/min for 20 min) resulted in a significant elevation in SP release (69% above base-line levels), but no change in the level of SST release. Conversely, exposure to noxious heat (50 degrees C, 20 sec/min for 20 min) produced a significant increase in SST release (56% above base line), but no change in the level of SP release.(ABSTRACT TRUNCATED AT 250 WORDS)


T lymphocytes.
T cells are major players in the adaptive immune response to pathogens. They express clonally distributed, highly polymorphic antigen receptors that enable them to recognize cell-associated antigen. Upon antigen recognition, T cells undergo clonal amplification and progressively acquire effector functions, ranging from the production of paracrine soluble factors that provide "help" to other immune cells to the ability to kill pathogen-infected cells with surgical precision. A pool of antigen-reactive T cells reverts to a state of quiescence and maintains a long-lasting memory of antigen encounter. T cells develop in the thymus through a rigorous selection process that recapitulates Darwinian phylogenesis: only the "fittest" survive, i.e. those that can efficiently recognize infectious non-self-antigens but ignore, or are silenced, by non-infectious self-antigens. Due to their ability to discriminate between self and non-self, T cells are the major effectors of allograft rejection. T cells are involved in the pathogenesis of several human disorders, resulting from their defective or dysregulated function. The former leads to a severe state of immunodeficiency, the latter to organ-specific or systemic autoimmunity.


Medical abortion alternatives to mifepristone.
Social and political constraints have prohibited the use of mifepristone in most countries. As a result, researchers, clinicians, and women throughout the world have pushed for the development of alternative medical abortion regimens. Methotrexate (both oral and intramuscular) combined with misoprostol has been under investigation since 1993, with complete abortion rates similar to mifepristone regimens for pregnancies up to 49 days' gestation. Thousands of women have had safe medical abortions in their own homes using these medications. The overall abortion process using methotrexate and misoprostol takes longer, however, with 20% to 30% of women waiting up to five weeks for the abortion to occur. More recently, misoprostol-only regimens have been proposed for medical termination of pregnancy. The efficacy of these misoprostol regimens has been reported in the same range as those combining mifepristone or methotrexate with misoprostol, although other investigators have been unable to confirm these results. Additionally, a few small studies have tested tamoxifen combined with misoprostol, with mixed results. Continued research is necessary to ensure that reported efficacy rates for all proven medical abortion regimens are true for various populations of women.


Early events in ovarian oncogenesis.
Ovarian cancer represents the most lethal of the gynecological neoplasms. The molecular and genetic events associated with early ovarian oncogenesis are still largely unknown, thus contributing to the lack of reliable biomarkers for disease detection. Since the majority of ovarian tumors are diagnosed at an advanced stage, the availability of early ovarian cancer tissue samples for molecular analyses is very limited. In this review, problems encountered in the study of early ovarian cancer are presented, along with the controversies concerning precursor lesions and stepwise progression towards ovarian malignancy. Experimental modeling in the development of ovarian cancer is also described, as well as genetic and epigenetic alterations associated with early ovarian cancer. Lastly, examples of technological advances in the study of early ovarian cancer are discussed. Hopefully, the increasing knowledge about molecular and genetic events involved in the early stages of ovarian tumorigenesis will provide the basis for management of ovarian cancer in the future.


Reversible C-C bond formation at a triply cyclometallated platinum(iv) centre.
The oxidation of the tribenzylphosphine derivative of the doubly cylcometallated platinum(ii) complex of diphenylpyridine, 1, with PhICl2 led, as a first step, to the formation of a highly electrophilic metal centre which attacked the benzyl phosphine to give a triply cyclometallated species as the arenium ion. The highly acidic arenium ion protonated unreacted starting 1, a reaction that could be supressed by the addition of water, and gave the neutral species 2(t). Octahedral complex 2(t) was induced to reductively couple, with two five-membered rings coupling to give square planar complex 5 containing a nine-membered ring. The crystal structure of 5 showed the nine-membered ring to span trans across the square planar metal accompanied by considerable distortion: the P-Pt-N bond angle is 155.48(5)°. Oxidation of 5 with PhICl2 resulted in the addition of two chlorides and a change of the nine-membered ring ligand coordination to cis at an octahedral centre, still with considerable distortions: the P-Pt-N bond angle in the crystal structure of 6 is 99.46(5)°. Treatment of 2(t) with AgBF4 also induced a coupling to give a nine-membered ring, and the fluxional three coordinate complex 7. A mono-methylated version of 1, Me-1, was prepared and similar reactions were observed. The presence of the methyl group allowed us to observe selectivity in the coupling reaction to give the nine-membered ring, with two products (a-Me-7 and b-Me7) being initially formed in the ratio 7 : 1. The concentrations of two products changed with time giving a final ratio of 1 : 8 at room temperature (half-life 48 hours), the equilibration being made possible by a reversible C-C bond forming reaction. Reaction of complexes 7 with CO or hydrogen left the nine-membered ring intact, though oxidative degradation resulted in decomplexation of the phosphine donor, accompanied by formation of a P[double bond, length as m-dash]O group.


The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins.
The present study was undertaken to determine the relationship between the hyaluronate receptor and CD44 (H-CAM), cell-surface glycoproteins of similar molecular weights that have been implicated in cell adhesion. In initial experiments, a panel of monoclonal antibodies directed against CD44 were tested for their ability to cross react with the hyaluronate receptor. These antibodies immunoprecipitated [3H]hyaluronate binding activity from detergent extracts of both mouse and human cells, indicating that the hyaluronate receptor is identical to CD44. In addition, one of these antibodies (KM-201 to mouse CD44) directly blocked the binding of labeled hyaluronate to the receptor and inhibited hyaluronate dependent aggregation of SV-3T3 cells. CD44 has also been implicated in lymphocyte binding to high endothelial venules during lymphocyte homing. Interestingly, the monoclonal antibody Hermes-3, which blocks lymphocyte binding to the high endothelial venules of mucosal lymphoid tissue, had no effect on the binding of labeled hyaluronate. Furthermore, the binding of lymphocytes to high endothelial cells of lymph nodes and mucosal lymphoid tissue was not significantly affected by treatment with agents that block the binding of hyaluronate (hyaluronidase, excess hyaluronate and specific antibodies). Thus, CD44 appears to have at least two distinct functional domains, one for binding hyaluronate and another involved in interactions with mucosal high endothelial venules.


Hospital mortality over time in patients with specific complications of cirrhosis.
Hospital mortality secondary to cirrhosis is high. To evaluate hospital mortality in patients admitted for specific complications of cirrhosis over time. Registry-data from Administrative Inpatient Dataset of acute care hospitals were collected at discharge from 2003 to 2010. Inclusion criteria were as follows: hospital admissions where one of the diagnoses was cirrhosis and the reason for admission was a specific complication of cirrhosis (ascites, encephalopathy, hepatorenal syndrome and haemorrhage from varices, bacterial spontaneous peritonitis). Analysis of variance was used for comparisons of quantitative variables and Chi-square for qualitative variables. Logistic regression was performed to identify the risk factors associated with hospital mortality; the Hosmer and Lemeshow test was applied to evaluate calibration and the ROC curve for discrimination respectively. A total of 12,671 hospital admissions were analysed; 67.7% were men. Mean hospitalization stay was 10.9 (SD 9.2) days and the most frequent causes were encephalopathy (44.2%) and ascites (30.9%). Global hospital mortality was 11.6%. Logistic regression showed that once all factors had been adjusted, hepatorenal syndrome conveyed the highest risk for death (49.2%; OR = 8.1(95%CI:6.6-9.9). Risk of death was also increased by associated comorbidities and older age. Hospital mortality in the period 2006-2010 was 27% inferior to the period 2003-2005. The area under the ROC curve (AUROC) was 0.77 (95%CI 0.76-0.78). Hospital mortality as a result of specific complications of cirrhosis is high, but has been declining in recent years.


Retinoic acid receptors α and γ are involved in antioxidative protection in renal tubular epithelial cells injury induced by hypoxia/reoxygenation.
Renal interstitial fibrosis (RIF) is a common outcome in various chronic kidney diseases. Injury to renal tubular epithelial cell (RTEC) is major link in RIF. Hypoxia is one of the common factors for RTEC damage. Retinoic acid receptors (RARs), RARα, RARβ and RARγ, are evolutionary conserved and pleiotropic proteins that have been involved in various cellular functions, including proliferation, differentiation, apoptosis, and transcription. Recently, we discovered that aberrant expression of RARs was involved in the development of RIF in rats. Here, we investigated the role of RARs in the hypoxia/reoxygenation (HR) damage model in RTEC with virus-based delivery vectors to knockdown or overexpress RARs. Relevant indicators were detected. Our results showed that HR inhibited RARα and RARγ expressions in a time-dependent manner in RTECs; however, the expression of RARβ was not changed obviously. RARα and RARγ overexpression could protect cells from oxidative stress-induced injury by inhibiting HR-induced intracellular superoxide anion (O2-) generation, cell viability and mitochondria membrane potential (MMP) decrease and transforming growth factor β1 (TGF-β1) expression and promoting endogenous antioxidant defense components, superoxide dismutase (SOD) and glutathione (GSH). Meanwhile, inhibition of RARα and RARγ expressions by small interference RNAs (siRNA) resulted in a less resistance of RTEC to HR as shown in increased O2- production and TGF-β1 expression and decreased cell viability, MMP, SOD and GSH levels. These data indicates that RARα and RARγ act as positive regulators to offset oxidative damage and profibrosis cytokine accumulation and therefore has an antioxidative effect.


Detecting lateral gene transfers by statistical reconciliation of phylogenetic forests.
To understand the evolutionary role of Lateral Gene Transfer (LGT), accurate methods are needed to identify transferred genes and infer their timing of acquisition. Phylogenetic methods are particularly promising for this purpose, but the reconciliation of a gene tree with a reference (species) tree is computationally hard. In addition, the application of these methods to real data raises the problem of sorting out real and artifactual phylogenetic conflict. We present Prunier, a new method for phylogenetic detection of LGT based on the search for a maximum statistical agreement forest (MSAF) between a gene tree and a reference tree. The program is flexible as it can use any definition of "agreement" among trees. We evaluate the performance of Prunier and two other programs (EEEP and RIATA-HGT) for their ability to detect transferred genes in realistic simulations where gene trees are reconstructed from sequences. Prunier proposes a single scenario that compares to the other methods in terms of sensitivity, but shows higher specificity. We show that LGT scenarios carry a strong signal about the position of the root of the species tree and could be used to identify the direction of evolutionary time on the species tree. We use Prunier on a biological dataset of 23 universal proteins and discuss their suitability for inferring the tree of life. The ability of Prunier to take into account branch support in the process of reconciliation allows a gain in complexity, in comparison to EEEP, and in accuracy in comparison to RIATA-HGT. Prunier's greedy algorithm proposes a single scenario of LGT for a gene family, but its quality always compares to the best solutions provided by the other algorithms. When the root position is uncertain in the species tree, Prunier is able to infer a scenario per root at a limited additional computational cost and can easily run on large datasets.Prunier is implemented in C++, using the Bio++ library and the phylogeny program Treefinder. It is available at: http://pbil.univ-lyon1.fr/software/prunier.


Vasopressin, not octreotide, may be beneficial in the treatment of hepatorenal syndrome: a retrospective study.
Hepatorenal syndrome (HRS) is a severe complication of cirrhosis and is associated with high mortality. Ornipressin and terlipressin are effective in treatment of HRS, but are not available in the USA. The efficacy of vasopressin (AVP) and octreotide (OCT) infusions, commonly utilized in the USA, in the treatment of HRS is unknown. This study aims to evaluate the effects of AVP and OCT on renal function, systemic haemodynamics and clinical outcomes in HRS. This observational study evaluated patients receiving AVP or OCT therapy for HRS from January 2000 to December 2003. Recovery from HRS was defined as a decrease in the serum creatinine (SCr) to a value < or =1.5 mg/dl. Forty-three patients were identified: eight received AVP, 16 received OCT and 19 received both AVP and OCT. Patients who received AVP alone or in combination with OCT had significantly greater recovery rates than those receiving OCT monotherapy (42 vs 38 vs 0%, respectively, P = 0.01). The average time to response in serum creatinine (SCr) was 7+/- 2 days. The mean AVP doses were 0.23+/-0.19 U/min in patients demonstrating clinical response. Therapy with AVP was an independent predictor of recovery (odds ratio 6.4, 95% confidence interval 1.3-31.8). Patients who responded to therapy had significantly lower mortality (23 vs 67%, P = 0.008) and higher rates of liver transplantation (23 vs 0%, P = 0.005). No adverse effects related to AVP therapy were observed. When compared with OCT, HRS patients treated with AVP had significantly higher recovery rates, improved survival and were more likely to receive a liver transplant.


Oxidative stress and Nrf2 signaling in McArdle disease.
McArdle disease (MD) is a metabolic myopathy due to myophosphorylase deficiency, which leads to a severe limitation in the rate of adenosine triphosphate (ATP) resynthesis. Compensatory flux through the myoadenylate deaminase > > xanthine oxidase pathway should result in higher oxidative stress in skeletal muscle; however, oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) mediated antioxidant response cascade in MD patients have not yet been examined. We show that MD patients have elevated muscle protein carbonyls and 4-hydroxynonenal (4-HNE) in comparison with healthy, age and activity matched controls (P < 0.05). Nuclear abundance of Nrf2 and Nrf2-antioxidant response element (ARE) binding was also higher in MD patients compared with controls (P < 0.05). The expressions of Nrf2 target genes were also higher in MD patients vs. controls. These observations suggest that MD patients experience elevated levels of oxidative stress, and that the Nrf2-mediated antioxidant response cascade is up-regulated in skeletal muscle to compensate.


2023 International Consensus Meeting on Musculoskeletal Infection: Summary from the Treatment Workgroup and Consensus on Treatment in Preclinical Models.
In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location and implants used, there are also a wide range of animal models described modelling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to 1) animal model considerations, 2) outcome measurements, and 3) imaging. This article is protected by copyright. All rights reserved.


Cytostatic and cytotoxic effects of alkylglycerols (Ecomer).
Shark liver oil, with a standardized concentration of alkylglycerols and their methoxyderivates, has been widely used in Scandinavian countries as complementary medicine in the treatment of different forms of cancer. The aim of our study was to verify the hypothesized antiproliferative effect of alkylglycerols in different human cancer cell lines. The plating efficiency method was used to assay the effect of alkylglycerols on the plating efficiency of human ovarian carcinoma (OVP-10), mammary carcinoma (MCF-7), and prostate cancer (DU-145, PC-3 and PCa-2b) cell lines. Tumor colonies containing more than 20 cells were scored as positive. Flow cytometry was applied to identify necrotic vs. apoptotic mode of cell death. The cells were exposed to Ecomer shark liver oil containing 20% alkylglycerols and 3% methoxyderivates in a dose of 0.1 mg/ml, up to a concentration corresponding to LD-50. Apoptotic and necrotic cells were stained with Anexin V and propidium iodine respectively. The prostate cells from DU-145, PC-3 and PCa-2B showed a dramatic reduction in the colony number even after relatively small doses of 0.5 and 0.1 mg/ml medium. Flow cytomery showed an increased percentage of apoptotic cells of ovarian and prostate carcinoma, while mammary carcinoma cells showed predominantly necrotic cells after exposure to Ecomer. The alkylglycerols and their methoxyderivates present in Ecomer shark liver oil showed a clear apoptotic/necrotic effect on human prostate and mammary carcinoma cell lines.


The role of experience in prioritizing hippocampal replay.
During sleep, recent memories are replayed by the hippocampus, leading to their consolidation, with a higher priority given to salient experiences. To examine the role of replay in the selective strengthening of memories, we recorded large ensembles of hippocampal place cells while male rats ran repeated spatial trajectories on two linear tracks, differing in either their familiarity or number of laps run. We observed that during sleep, the rate of replay events for a given track increased proportionally with the number of spatial trajectories run by the animal. In contrast, the rate of sleep replay events decreased if the animal was more familiar with the track. Furthermore, we find that the cumulative number of awake replay events occurring during behavior, influenced by both the novelty and duration of an experience, predicts which memories are prioritized for sleep replay, providing a more parsimonious neural correlate for the selective strengthening of memories.


The load/deflection characteristics of thermally activated orthodontic archwires.
The objective of the study was to investigate the load/deflection characteristics of three commercially available thermally active nickel-titanium orthodontic archwires using a standard nickel-titanium archwire as a control. The thermally active wires were Regency Thermal, Orthoform, and Eurotherm and the control was Memory. Round 0.4 mm and rectangular 0.4 x 0.56 mm wires were subjected to 2 and 4 mm of deflection in a water bath at temperatures of 20, 30, and 40 degrees C and forces were measured in three-point bend and phantom head situations. Analysis of variance revealed that, irrespective of the test set up and wire type, wire size had a significant effect (P < 0.001) on the forces produced. An increase in size from 0.4 mm round to 0.4 x 0.56 mm rectangular wire approximately doubled the force values for a given deflection. The effect of wire deflection on the force values varied according to the test system, forces being much higher in the phantom head tests than in the beam tests. In the beam tests, an increase in wire deflection from 2 to 4 mm had no significant effect on the forces exerted, but in the phantom head tests the forces produced by each wire at 4 mm deflection were four to five times greater than those at 2 mm deflection. Each of the thermally active wires produced less force that the non-thermally active wire. However, there was a large variation between the three types of thermally active wire. In the beam tests each 10 degrees C rise in temperature from 20 to 40 degrees C had a highly significant effect on the force produced by each thermoelastic wire (P < 0.001). In the phantom head tests there were significant force increases between 20 and 30 degrees C (P < 0.001), but between 30 and 40 degrees C the forces did not change significantly.


Osteoporosis: gender differences and similarities.
Although osteoporosis has traditionally been considered a disease of women, men also incur substantial bone loss with aging, and elderly men have age-specific hip fracture incidence rates and vertebral fracture prevalence rates that are at least half those in women. Early postmenopausal bone loss (which results in the syndrome of type I osteoporosis) is due to the direct skeletal consequences of estrogen deficiency, manifested by an increase in bone resorption without an adequate increase in bone formation. Recent evidence indicates that even late postmenopausal bone loss (type II or 'smile' osteoporosis) in women may be due to estrogen deficiency. In particular, the late consequences of estrogen deficiency in elderly women result in abnormalities in calcium homeostasis and increases in parathyroid hormone secretion, leading to increased bone resorption and bone loss. The etiology of bone loss in aging men has remained relatively unclear. Recent evidence from a male deficient in estrogen receptor-alpha and in two males with aromatase deficiency indicate that estrogen may play a significant role in bone metabolism in men. Moreover, several large epidemiologic studies have found that bone mineral density correlates better with serum estrogen than testosterone in aging men. Thus estrogen deficiency may lead to bone loss in men.


Platelets, inflammation and atherosclerosis.
An expanding body of evidence continues to build on the role of platelets as initial actors in the development of atherosclerotic lesions. Platelets bind to leukocytes and endothelial cells, and initiate monocyte transformation into macrophages. Platelets internalize oxidized phospholipids and promote foam cell formation. Platelets also recruit progenitor cells to the scene that are able to differentiate into foam cells or endothelial cells depending on conditions. Platelets tip the scales in the initiation, development and total extent of atherosclerotic lesions.


Synaptic Variability Introduces State-Dependent Modulation of Excitatory Spinal Cord Synapses.
The relevance of neuronal and synaptic variability remains unclear. Cellular and synaptic plasticity and neuromodulation are also variable. This could reflect state-dependent effects caused by the variable initial cellular or synaptic properties or direct variability in plasticity-inducing mechanisms. This study has examined state-dependent influences on synaptic plasticity at connections between excitatory interneurons (EIN) and motor neurons in the lamprey spinal cord. State-dependent effects were examined by correlating initial synaptic properties with the substance P-mediated plasticity of low frequency-evoked EPSPs and the reduction of the EPSP depression over spike trains (metaplasticity). The low frequency EPSP potentiation reflected an interaction between the potentiation of NMDA responses and the release probability. The release probability introduced a variable state-dependent subtractive influence on the postsynaptic NMDA-dependent potentiation. The metaplasticity was also state-dependent: it was greater at connections with smaller available vesicle pools and high initial release probabilities. This was supported by the significant reduction in the number of connections showing metaplasticity when the release probability was reduced by high Mg(2+) Ringer. Initial synaptic properties thus introduce state-dependent influences that affect the potential for plasticity. Understanding these conditions will be as important as understanding the subsequent changes.


Self-rated health and factors influencing responses among young Egyptian type 1 diabetes patients.
Patients diagnosed with type 1 diabetes mellitus (T1DM) face major daily challenges. Self-rated health (SRH) is a global measure of an individual's health related quality of life (HRQoL) and is based on the question, "In general, how would you rate your health?" Subjects rate their health as excellent, very good, good, poor or very poor. Our objective was to determine the HRQoL using the SRH measure and determine factors influencing responses. We hypothesized that better SRH responses were associated with shorter diabetes duration, better compliance and better glycemic control. The standardized SRH measure was the instrument used for health related quality of life assessment. Logistic regression analysis was used to examine the association between SRH responses and selected variables. 124 subjects, 64 females (51.6%) and 60 males (48.4%) were included. Average age was 13.08 (± 3.19) and average diabetes duration was 5.82 (± 1.60), while the mean HbA1C was 8.02 (± 1.60). The majority rated their health as good (31%), 29% rated it as excellent, 11% as very good, 14% as poor and 15% as very poor. Regression analysis showed that regular exercise was the only predictor that was independently and significantly associated with a "better" self-health rating, with an OR of 12.84, CI of 1.425-115.727 and a p value of 0.023. Regular exercise among Egyptian children with T1DM is strongly associated with a "better" overall health related quality of life and should be repeatedly encouraged.


On the rate-distortion performance and computational efficiency of the Karhunen-Loève transform for lossy data compression.
We examine the rate-distortion performance and computational complexity of linear transforms for lossy data compression. The goal is to better understand the performance/complexity tradeoffs associated with using the Karhunen-Loeve transform (KLT) and its fast approximations. Since the optimal transform for transform coding is unknown in general, we investigate the performance penalties associated with using the KLT by examining cases where the KLT fails, developing a new transform that corrects the KLT's failures in those examples, and then empirically testing the performance difference between this new transform and the KLT. Experiments demonstrate that while the worst KLT can yield transform coding performance at least 3 dB worse than that of alternative block transforms, the performance penalty associated with using the KLT on real data sets seems to be significantly smaller, giving at most 0.5 dB difference in our experiments. The KLT and its fast variations studied here range in complexity requirements from O(n(2)) to O(n log n) in coding vectors of dimension n. We empirically investigate the rate-distortion performance tradeoffs associated with traversing this range of options. For example, an algorithm with complexity O(n(3/2)) and memory O(n) gives 0.4 dB performance loss relative to the full KLT in our image compression experiments.


Low-Frequency rTMS over Contralesional M1 Increases Ipsilesional Cortical Excitability and Motor Function with Decreased Interhemispheric Asymmetry in Subacute Stroke: A Randomized Controlled Study.
To determine the long-term effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional M1 preceding motor task practice on the interhemispheric asymmetry of the cortical excitability and the functional recovery in subacute stroke patients with mild to moderate arm paresis. Twenty-four subacute stroke patients were randomly allocated to either the experimental or control group. The experimental group underwent rTMS over the contralesional M1 (1 Hz), immediately followed by 30 minutes of motor task practice (10 sessions within 2 weeks). The controls received sham rTMS and the same task practice. Following the 2-week intervention period, the task practice was continued twice weekly for another 10 weeks in both groups. Outcomes were evaluated at baseline (T0), at the end of the 2-week stimulation period (T1), and at 12-week follow-up (T2). The MEP (paretic hand) and interhemispheric asymmetry, Fugl-Meyer motor assessment, Action Research Arm Test, and box and block test scores improved more in the experimental group than controls at T1 (p < 0.05). The beneficial effects were largely maintained at T2. LF-rTMS over the contralesional M1 preceding motor task practice was effective in enhancing the ipsilesional cortical excitability and upper limb function with reducing interhemispheric asymmetry in subacute stroke patients with mild to moderate arm paresis. Significance. Adding LF-rTMS prior to motor task practice may reduce interhemispheric asymmetry of cortical excitabilities and promote upper limb function recovery in subacute stroke with mild to moderate arm paresis.


Inhibition of the fast Na+ inward current by the Ca2+ channel blocker tiapamil.
The inhibitory effect of the phenylalkylamine-type Ca2+-entry blocker, tiapamil, on the fast Na+ inward current was investigated in guinea-pig papillary muscles by measuring the maximum upstroke velocity (dV/dt)max of transmembrane action potentials. Tiapamil inhibited (dV/dt)max at concentrations above 10(-6) M, with an IC50 value of 7 X 10(-5) M (1 Hz stimulation frequency, 5.9 mM extracellular K+). Verapamil was less potent in depressing upstroke velocity. Inhibition of the dV/dtmax strongly depended on the frequency at which the muscles were stimulated ("use-dependent" effect). There was no evidence that tiapamil acts in a potential-dependent manner like local anesthetics. The results indicate that the Ca2+-entry blocker tiapamil has additional pharmacological properties, which may contribute to its usefulness in the treatment of ventricular arrhythmias.


Cost-effectiveness of adjuvant paclitaxel and trastuzumab for early-stage node-negative, HER2-positive breast cancer.
Adjuvant paclitaxel and trastuzumab has been shown to be an effective regimen with low risk of cancer recurrence and treatment-related toxicities in early-stage node-negative, HER2-positive breast cancer. We investigated the cost-effectiveness of this regimen. A Markov-based microsimulation model with six health states is used to simulate four adjuvant therapy options for women with early-stage node-negative, HER2-positive breast cancer at different age groups. The four treatment arms are 1) adjuvant paclitaxel and trastuzumab (TH), 2) doxorubicin, cyclophosphamide, paclitaxel and trastuzumab (ACTH), 3) docetaxel, carboplatin and trastuzumab (TCH), and 4) no adjuvant trastuzumab (NT). Data from randomized trials were used to estimate treatment efficacy. Societal perspective was used in this cost-effectiveness analysis. Costs were measured in 2016 US dollars (US$) and quality-adjusted life-years (QALYs) was used for health outcomes. Sensitivity analyses were performed to evaluate the impact of uncertainty in parameter estimation. We found that 40-year-old women undergoing TH treatment would have an average of 16.17 QALYs for the cost of $178,650 when lifetime horizon is used. Compared to NT, TH has incremental cost-effectiveness ratios ranged from $10,584 (ages 40-49) to $84,981 (age 80+) per additional QALYs. The sensitivity analysis showed that TH is cheaper and leads to higher QALYs compared to both ACTH and TCH for all age groups and time horizons. TH is cost-effective for all age groups in the base case scenario and in the sensitivity analysis. In order to reduce the parameter uncertainty, clinical trials with longer follow-up times are needed.


Neutral mechanical alignment: Is it Necessary?
The cause of dissatisfaction following total knee arthroplasty (TKA) remains elusive. Much attention has been focused on static mechanical alignment as a basis for surgical success and optimising outcomes. More recently, research on both normal and osteoarthritic knees, as well as kinematically aligned TKAs, has suggested that other specific and dynamic factors may be more important than a generic target of 0 ± 3º of a neutral axis. Consideration of these other variables is necessary to understand ideal targets and move beyond generic results.


Dosimetric verification and commissioning for a small animal image-guided irradiator.
In recent years, small animal image-guided irradiators have been widely utilized in preclinical studies involving rodent models. However, the dosimetry commissioning of such equipment involving kilovoltage small-field dosimetry has not received as much interest as the megavoltage small-field dosimetry used clinically. To date, a paucity of measured kilovoltage beam data, especially for field sizes less than 3 mm, can be found in the literature. For improvement of rodent treatments in the future, this work aims to provide comprehensive and accurate beam data for the small animal radiation research platform (SARRP, Xstrahl) using EBT3 Gafchromic films and Monte Carlo calculation, with submillimeter resolution and accuracy. This work includes three primary tasks: (1) establish an optimized film measurement protocol for small field dosimetry of kilovoltage photon beam. (2) Acquire dosimetric data including (a) depth dose curves from the surface to 6 cm depth (b) beam profiles, (c) penumbra, (d) cone factors and (e) 2D dose distribution. These tasks were undertaken for a 220 kVp photon beam with five different small field widths and 33 cm source to surface distance (0.5 mm and 1 mm circular fields, 3 × 3 mm2, 5 × 5 mm2, 10 × 10 mm2 square fields). Beam data was measured with EBT3 films. (3) Provide comparative dosimetry for film measurements, Monte Carlo calculations, and the dose calculations performed with the SARRP treatment planning system, Muriplan. For the majority of parameters, film measurement agreed with Monte Carlo simulation within 1%. There were, however, discrepancies between measured beam data and Muriplan treatment planning data. Specifically, for PDD, Muriplan underestimates the dose for field sizes of 0.5 mm and 1 mm. For beam profiles comparisons, the calculation from Muriplan predicts a smaller lateral distance between the 50% isodose lines compared to film measurement. There is a difference of 0.18, 0.72, 0.6 mm between Muriplan and film for field sizes of 3, 5, 10 mm, respectively. This work demonstrates that accurate and precise kilovoltage small-field dosimetry can be conducted using EBT3 Gafchromic film with an optimized protocol. In addition, discrepancies between measured beam data and Muriplan were identified.