A computerized kinematic diagnostic system.
This paper describes the instrumentation developed for a clinical system that measures upper extremity kinematics in normal and cerebral palsied children. The ability to diagnose cerebral palsy during early and midinfancy is influenced by the fact that movement and postural abnormalities become apparent only over time, and are not readily detectable until there is sufficient abnormality so that it can be viewed by gross inspection during clinical examination. The methodology presented here serves to discriminate normal from deviant movement at an earlier age than what is presently possible, and may also result in alternative therapeutic intervention.


Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database.
Considerable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization. The Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018. A total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment. We present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.


[CT guided 125I seeds implantation in treatment of local recurrent rectal cancer after surgery resection: analysis of 21 cases].
To explore the clinical value of CT guided 125I seeds implantation in the treatment of local recurrent rectal cancer after surgery resection. Twenty-one patients with local recurrent rectal cancer after surgery, 12 males and 9 females, aged 47 (35-69), with the longest diameter of 4. 2 cm (3.4 - 6.4 cm), were treated by CT guided 125I radioactive seeds implantation according to treatment planning system (TPS) or Halarism's experienced function: mCi = Da x 5. Totally, 506 seeds, 24.1 for one patient on average, were implanted. All the patients received PET-CT scan 3 months after the treatment and were followed up for 12.5 months (7-22 months). Complete remission, partial remission, and no change were seen in 16, 3, and 2 patients respectively. All patients survived. CT guided 125I seeds implantation is an effective methods in the treatment of local recurrent rectal cancer after surgery resection.


In vivo noninvasive detection and age definition of arterial thrombus by MRI.
The purpose of this study was to evaluate the potential of magnetic resonance (MR) to detect arterial thrombotic obstruction and define thrombus age. BACKGROUND; Arterial thrombi underlie the clinical consequences of atherosclerosis and are not reliably detected by current noninvasive diagnostic techniques. Carotid thrombi were induced in swine (n = 7) by arterial injury. Serial high-resolution in vivo MR images were obtained using black-blood T1-weighted (T1W) and T2-weighted (T2W) sequences in a clinical 1.5T MR system at 6 h, 1 day and at 1, 2, 3, 6 and 9 weeks. At each time point one animal was sacrificed and the occluded carotid artery processed for histopathology. Thrombus signal intensity (SI) was normalized to that of the adjacent muscle. Thrombus age was assessed based on MR appearance by two blinded independent observers. Thrombus appearance and relative SI revealed characteristic temporal changes in multicontrast-weighted MR images, reflecting histologic changes in the composition. Acute thrombus appeared very bright on the T2W images, facilitating the detection. Signal intensity was 197 +/- 25% at 6 h, peaking at 1 week (246 +/- 51%), reaching a plateau by 6 weeks (120 +/- 15%). At six weeks, complete thrombus organization was confirmed histologically. The T1W images had similar pattern with lower SI than T2W. Age definition using visual appearance was highly accurate (Pearson's chi-square with 4 df ranging from 96 to 132 and Cohen's kappa at 0.81 to 0.94). Agreement between observers was substantial (Pearson chi-square with 4 df = 91.5, kappa = 0.79). Magnetic resonance imaging is a promising tool to noninvasively detect arterial thrombosis. Measurement of SI and the characteristic visual appearance of the thrombus have the potential to define thrombus age.


Application of liquid chromatography with on-line radiochemical detection to metabolism studies on a novel class of analgesics.
Vanilloids are a class of compounds structurally related to capsaicin, the pungent principle of hot peppers, which are under development as a novel class of analgesics. Vanilloids undergo extensive first-pass metabolism when dosed orally to rats and mice. These compounds, as well as capsaicin, would be anticipated to be susceptible to three major routes of metabolism: (omega, beta)-oxidation of the alkyl side chain, hydrolysis of the amide bond and conjugation of the phenolic group. Olvanil [N-(3-methoxy-4-hydroxybenzyl)oleamide], radiolabelled with either 14C at the benzylic carbon or 3H in the oleyl side chain, was studied in various in vitro, in situ and in vivo metabolism models to determine the major route(s) of intestinal and hepatic metabolism in rats for this new class of compounds. Models used in metabolism studies included isolated hydrolytic enzymes, cell-free intestinal and liver supernatants, hepatocytes, enterocytes, perfused intestine and whole animal studies. Reversed-phase liquid chromatography (LC) with on-line radiochemical detection was used to examine the metabolic profiles from the different models. The major metabolic route for olvanil in both the intestine and the liver was found to be hydrolysis of the amide bond. The benefits of selective 14C and 3H labels in conjunction with LC with on-line radiochemical detection are discussed.


Sulfated Metabolites of Luteolin, Myricetin, and Ampelopsin: Chemoenzymatic Preparation and Biophysical Properties.
Authentic standards of food flavonoids are important for human metabolic studies. Their isolation from biological materials is impracticable; however, they can be prepared in vitro. Twelve sulfated metabolites of luteolin, myricetin, and ampelopsin were obtained with arylsulfotransferase from Desulfitobacterium hafniense and fully characterized by high-performance liquid chromatography, MS, and NMR. The compounds were tested for their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and N,N-dimethyl-p-phenylenediamine radicals, to reduce ferric ions and Folin-Ciocalteu reagent, and to inhibit tert-butyl hydroperoxide-induced lipid peroxidation of rat liver microsomes. The activity differed considerably even between monosulfate isomers. The parent compounds and myricetin-3'-O-sulfate were the most active while other compounds displayed significantly lower activity, particularly luteolin sulfates. No mutagenic activity of the parent compounds and their main metabolites was observed; only myricetin showed minor pro-mutagenicity. The prepared sulfated metabolites are now available as authentic standards for future in vitro and in vivo metabolic studies.


Agomir miRNA-150-5p alleviates pristane-induced lupus by suppressing myeloid dendritic cells activation and inflammation via TREM-1 axis.
Triggering receptors expressed on myeloid cells-1 (TREM-1) has been shown to participate in inflammatory autoimmune diseases. Nevertheless, the detailed underlying mechanisms and therapeutic benefits by targeting TREM-1 remain elusive, especially in myeloid dendritic cells (mDCs) and systemic lupus erythematosus (SLE). Disorders of epigenetic processes including non-coding RNAs give rise to SLE, resulting in complicated syndromes. Here, we aim to address this issue and explore the miRNA to inhibit the activation of mDCs and alleviate the progress of SLE by targeting TREM-1 signal axis. Bioinformatics methods were used to analyze the differentially expressed genes (DEGs) between patients with SLE and healthy individuals by four mRNA microarray datasets from Gene Expression Omnibus (GEO). Then we identified the expression of TREM-1 and its soluble form (sTREM-1) in clinical samples by ELISA, quantitative real-time PCR and Western blot. Phenotypic and functional changes of mDCs elicited by TREM-1 agonist were determined. Three databases of miRNAs target prediction and a dual-luciferase reporter assay were used to screen and verify miRNAs that can directly inhibit TREM-1 expression in vitro. Moreover, pristane-induced lupus mice were injected with miR-150-5p agomir to evaluate the effects of miR-150-5p on mDCs in lymphatic organs and disease activity in vivo. We screened TREM-1 as one of the hub genes closely correlated with the progression of SLE and identified sTREM-1 in serum as a valuable diagnostic biomarker for SLE. Moreover, activation of TREM-1 by its agonist promoted activation and chemotaxis of mDCs and increased the production of inflammatory cytokines and chemokines, showing higher expression of IL-6, TNF-α, and MCP-1. We showed that lupus mice displayed a unique miRNA signature in spleen, among which miR-150 was the most significantly expressed miRNA that targeting TREM-1 compared with wild type group. Transfection of miRNA-150-5p mimics directly suppressed the expression of TREM-1 by binding to its 3' UTR. Our in vivo experiments first indicated that administration of miR-150-5p agomir effectively ameliorated lupus symptoms. Intriguingly, miR-150 inhibited the over activation of mDCs through TREM-1 signal pathway in lymphatic organs and renal tissues. TREM-1 represents a potentially novel therapeutic target and we identify miR-150-5p as one of the mechanisms to alleviate lupus disease, which is attributable for inhibiting mDCs activation through TREM-1 signaling pathway.


Nomogram Predicting the Prognosis of Patients with Surgically Resected Stage IA Non-small Cell Lung Cancer.
The American Joint Committee on Cancer (AJCC) 8th stage system was limited in accuracy for predicting prognosis of stage IA non-small cell lung cancer (NSCLC) patients. This study aimed to establish and validate two nomograms that predict overall survival (OS) and lung cancer-specific survival (LCSS) in surgically resected stage IA NSCLC patients. Postoperative patients with stage IA NSCLC in SEER database between 2004 and 2015 were examined. Survival and clinical information according to the inclusion and exclusion criteria were collected. All patients were randomly divided into the training cohort and validation cohort with a ratio of 7:3. Independent prognosis factors were evaluated using univariate and multivariate Cox regression analyses, and predictive nomogram was established based on these factors. Nomogram performance was measured using the C-index, calibration plots, and DCA. Patients were grouped by quartiles of nomogram scores and survival curves were plotted by Kaplan-Meier analysis. In total, 33,533 patients were included in the study. The nomogram contained 12 prognostic factors in OS and 10 prognostic factors in LCSS. In the validation set, the C-index was 0.652 for predicting OS and 0.651 for predicting LCSS. The calibration curves for the nomogram-predicted probability of OS and LCSS showed good agreement between the actual observation and nomogram prediction. DCA indicated that the clinical value of the nomograms were higher than AJCC 8th stage for predicting OS and LCSS. Nomogram scores related risk stratification revealed statistically significant difference which have better discrimination than AJCC 8th stage. The nomogram can accurately predict OS and LCSS in surgically resected patients with stage IA NSCLC. The online version contains supplementary material available at 10.1007/s13193-022-01700-w.


Deep learning-based inverse design of microstructured materials for optical optimization and thermal radiation control.
Microstructures with engineered properties are critical to thermal management in aerospace and space applications. Due to the overwhelming number of microstructure design variables, traditional approaches to material optimization can have time-consuming processes and limited use cases. Here, we combine a surrogate optical neural network with an inverse neural network and dynamic post-processing to form an aggregated neural network inverse design process. Our surrogate network emulates finite-difference time-domain simulations (FDTD) by developing a relationship between the microstructure's geometry, wavelength, discrete material properties, and the output optical properties. The surrogate optical solver works in tandem with an inverse neural network to predict a microstructure's design properties that will match an input optical spectrum. As opposed to conventional approaches that are constrained by material selection, our network can identify new material properties that best optimize the input spectrum and match the output to an existing material. The output is evaluated using critical design constraints, simulated in FDTD, and used to retrain the surrogate-forming a self-learning loop. The presented framework is applicable to the inverse design of various optical microstructures, and the deep learning-derived approach will allow complex and user-constrained optimization for thermal radiation control in future aerospace and space systems.


In-vitro toxicity assessment of Eucalyptus robusta Smith extracts via whole-cell bioreporter.
Eucalyptus is widely planted in China for wood industries, and there are increasing concerns about its ecotoxicity in the environment. This study explored the in-vitro toxicity of Eucalyptus extracts by assessing the impacts of water-soluble and dimethylsulfoxide (DMSO)-soluble fractions via a whole-cell bioreporter, Acinetobacter baylyi ADPWH_recA. Compounds identified in Eucalyptus extracts included one tannin, two phenolic acids, four terpenoids, four glycosides, and five flavonoids. The leaf extracts contained more biological-active components than barks and roots. Genotoxicity induced by Eucalyptus extracts was mainly associated with water extracts (e.g., flavonoids, phenolic acids) instead of DMSO extracts. The significant cytotoxicity was explained by programmed cell death (PCD), suggested by the results of propidium iodide (PI) and 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assays. Generally, water-soluble fractions contributed more toxicities than DMSO-soluble fractions, particularly at high concentrations. A robust linear regression was built between the compromised toxicity and PCD index (Compromised toxicity = -2.192 × PCD index + 2.219; R2 = 0.8886), suggesting a PCD-dependent compromised toxicity which was greatly underestimated. Our results implied non-neglectable ecotoxicological risks of Eucalyptus extracts, hinting at the possible magnified ecological impacts of its large-scale plantation and the potential adverse outcomes to the surrounding ecosystems.


Prevalence of asthma, local risk factors and agreement between written and video questionnaires among Turkish adolescents.
There is currently no standard tool for the measurement of asthma in epidemiological studies. The objectives of this study were to determine the prevalence of asthma, to describe the potential local risk factors, and to assess the agreement between written and video questionnaires in 13- to 14-year-old schoolchildren. We performed a cross-sectional study involving 5427 adolescents in 26 schools. Prevalence of asthma symptoms were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) written and video questionnaire. The adolescents were asked additional questions for risk factors of asthma. The prevalence of lifetime wheeze, wheeze in the last 12 months and doctor-diagnosed asthma with written questionnaire were found as 13.5%, 6.3% and 11.2% respectively. Prevalence of lifetime wheeze, wheeze in the last 12 months, wheeze after exercise in the last 12 months, with video questionnaire were found as 9.6%, 5.5%, 11.9% and 1.9% respectively. The proportion of total agreement between the two questionnaires was high (0.77-0.81) with poor kappa value (0.25-0.50). In multivariate analysis, family history of atopy, stuffed toys and accompaniment of children to their parents after school hours in textile industry were found as risk factors for asthma. In addition kind of bird, such as canary was found as a risk factor. Prevalence of asthma is moderate in Turkey. Agreement between the two questionnaires was high. Accompaniment of children to their parents in textile industry is a newly-described risk factor for asthma.


Chemical Probing of RNA Structure In Vivo Using SHAPE-MaP and DMS-MaP.
The functional roles of RNAs are often regulated by their structure. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) and dimethyl sulfate (DMS) base reactivity can be employed to investigate the flexibility of nucleotides and correlate it to the constraints imparted by base-pairing and/or protein-binding. In vivo, a multitude of proteins could bind an RNA molecule, regulating its structure and function. Hence, to obtain a more comprehensive view of the RNA structure-function relationship in vivo, it may be required to characterize both the RNA structure and the RNA-protein interaction network. In this chapter, we describe methods for characterizing the in vivo nucleotide flexibility of RNA in cells by SHAPE-MaP (SHAPE by Mutational Profiling) and DMS-MaP. In another chapter, we will discuss the characterization of RNA-protein interaction network by RNP-MaP.


Incorporation of inhomogeneous ion diffusion coefficients into kinetic lattice grand canonical monte carlo simulations and application to ion current calculations in a simple model ion channel.
To deal with inhomogeneous diffusion coefficients of ions without altering the lattice spacing in the kinetic lattice grand canonical Monte Carlo (KLGCMC) simulation, an algorithm that incorporates diffusion coefficient variation into move probabilities is proposed and implemented into KLGCMC calculations. Using this algorithm, the KLGCMC simulation method is applied to the calculation of ion currents in a simple model ion channel system. Comparisons of ion currents and ion concentrations from these simulations with Poisson-Nernst-Planck (PNP) results show good agreement between the two methods for parameters where the latter method is expected to be accurate.


Validation of ethnopharmacological uses of Murraya paniculata in disorders of diarrhea, asthma and hypertension.
Murraya paniculata is traditionally used for management of gut, air way and cardiovascular disorders. The study was conducted for provision of pharmacological rationalization for folkloric uses of Murraya paniculata in gut, air way and cardiovascular problems. Aqueous-ethanolic extract of Mp.Cr was tested using in vitro techniques on isolated tissue of rabbit (jejunum, trachea and aorta) to detect the possible presence of spasmolytic activity. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system. Application of the extract of Mp.Cr relaxed spontaneous and high K(+) (80mM)-induced contraction in rabbit jejunum preparation. Because it shifted the CRCs (Calcium response curve) towards the right side so the possible blockade was of calcium channel similar to verapamil. In rabbit trachea, extract of Mp.Cr produced relaxation of carbachol and high K(+) induced contractions. When plant extract was checked further on isolated aorta for its possible vasodilator effect, it caused relaxation of phenylephrine and high K(+)-induced spastic contractions at different doses. These results indicate that Murraya paniculata shows anti-spasmodic, bronchodilator and vasodilator activity facilitated through Ca(++) antagonist mechanisms.


Bilateral Proprioceptive Evaluation in Individuals With Unilateral Chronic Ankle Instability.
Despite extensive research on chronic ankle instability, the findings regarding proprioception have been conflicting and focused only on the injured limb. Also, the different components of proprioception have been evaluated in isolation. To evaluate bilateral ankle proprioception in individuals with unilateral ankle instability. Cohort study. Research laboratory center in a university. Twenty-four individuals with a history of unilateral ankle sprain and chronic ankle instability (mechanical ankle instability group, n = 10; functional ankle instability [FAI] group, n = 14) and 20 controls. Ankle active and passive joint position sense, kinesthesia, and force sense. We observed a significant interaction between the effects of limb and group for kinesthesia (F = 3.27, P = .049). Increased error values were observed in the injured limb of the FAI group compared with the control group (P = .031, Cohen d = 0.47). Differences were also evident for force sense (F = 9.31, P < .001): the FAI group demonstrated increased error versus the control group (injured limb: P < .001, Cohen d = 1.28; uninjured limb: P = .009, Cohen d = 0.89) and the mechanical ankle instability group (uninjured limb: P = .023, Cohen d = 0.76). Individuals with unilateral FAI had increased error ipsilaterally (injured limb) for inversion movement detection (kinesthesia) and evertor force sense and increased error contralaterally (uninjured limb) for evertor force sense.


Maximal exercise testing and gas exchange in patients with chronic atrial fibrillation.
To evaluate the response of patients with chronic atrial fibrillation to exercise, 50 men (mean age 65 +/- 8 years) with atrial fibrillation underwent a maximal exercise test using respiratory gas exchange techniques. Patients were classified by the presence (n = 29) or absence ("lone atrial fibrillation," n = 21) of underlying heart disease. Responses were evaluated at a standard submaximal work load (3.0 mph, [4.8 km/h] 0% grade), at the gas exchange anaerobic threshold and at maximal exercise. For all 50 patients, the mean maximal oxygen uptake was 20.6 ml/kg per min, which approximates 85% of the aerobic capacity predicted for age-matched normal individuals. Patients with lone atrial fibrillation demonstrated normal exercise capacity in contrast to patients with atrial fibrillation and known heart disease (22.7 +/- 5 versus 19.1 +/- 5.0 ml/kg per min, p less than 0.05). The mean maximal heart rate (176 +/- 30 beats/min) was approximately 20 beats/min higher than that expected for age, was extremely variable and accounted for only 8% of the variance in maximal oxygen uptake. Maximal heart rate in subjects with lone atrial fibrillation was higher than that of subjects with atrial fibrillation and known heart disease (189 +/- 32 versus 166 +/- 24 beats/min, p less than 0.01). Stepwise regression analysis revealed that maximal systolic blood pressure accounted for 19% of the variance in maximal oxygen uptake (VO2 max), suggesting that systolic function is an important determinant of exercise performance in atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)


Fibroid volume, location and symptoms in women undergoing uterine artery embolization: does size or position matter?
To investigate the relationship between MRI-determined uterine fibroid size and their location, and fibroid-related symptoms, including quality of life and sexual function, in women with symptomatic fibroids before uterine artery embolization (UAE). Forty-six women underwent pelvic MRI within four weeks prior to UAE. The MRIs were analyzed and fibroid size and fibroid location were recorded. Women also completed a comprehensive self-report questionnaire within the four weeks prior to the procedure. The questionnaire (Short Form-36 (SF-36) and Female Sexual Function Index (FSFI), respectively, investigated the frequency of fibroid-related symptoms, as well as quality of life and sexual function. Pearson product moment correlation coefficients were used to examine relationships among variables, and ANOVAs were used to determine between-group difference. At baseline, women with symptomatic fibroids had worse quality of life and sexual function scores than healthy controls (p < .05). No fibroid-related symptoms, or aspects of quality of life or sexual function, were significantly correlated with either total uterine volume or largest fibroid volume. No significant differences with respect to fibroid-related symptoms were found between patients with or without subserosal or submucosal fibroids. Women with symptomatic fibroids pre-UAE had impaired quality of life and sexual function, but size and location of fibroids as determined by MRI were not related to fibroid-related symptoms, health-related quality of life, or sexual function.


Baveno VII criteria for recompensation predict transplant-free survival in patients with hepatitis B-related decompensated cirrhosis.
The latest Baveno VII consensus has provided guidance for identifying patients who have truly recompensated from those with hepatic decompensation. This study aimed to evaluate patients' transplant-free survival in three different stages of cirrhosis. All patients with chronic HBV infection and liver cirrhosis treated with oral nucleos(t)ide analogues from March 2006 to December 2022 were identified from a territory-wide database in Hong Kong. Patients with follow-up duration of <1 year were excluded. Participants were classified into three mutually exclusive groups: (1) no decompensated events (i.e. compensated group); (2) decompensated events occurred (i.e. decompensated group); or (3) decompensated events occurred followed by recompensation according to Baveno VII criteria (i.e. recompensated group). A time-dependent Cox proportional hazard model was adopted for evaluation. The follow-up period was 5 years. A total of 4,701 patients with cirrhosis and HBV who were treated with entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) were identified. During a median follow-up of 5 years (interquartile range 3.7, 5 years), 3,327 (70.8%), 1,347 (29.2%), and 265 (5.6%) patients had compensated, decompensated, and recompensated cirrhosis, respectively, at least once before the end of the study. In the time-dependent multivariable model, the recompensated group had similar transplant-free survival compared with the compensated group (adjusted hazard ratio 1.16; 95% CI 0.72-1.86; p = 0.536). The 5-year transplant-free survival rate was 89.3% for the compensated group, whereas it was 76.0% for the recompensated group, reflecting a minimal difference between the two groups. The clinical significance of recompensation of cirrhosis in improving patient outcomes for individuals with CHB infection was highlighted in this study. Early identification and treatment with nucleos(t)ide analogues might promote hepatic recompensation and thus reduce mortality in patients with CHB. The latest Baveno VII consensus introduces the new concept of hepatic recompensation, which refers to the reversal of the structural and functional changes of cirrhosis after removal, cure, or suppression of the aetiology of cirrhosis. It is essential to investigate the transplant-free survival rates of patients who are able to achieve hepatic recompensation, as this has significant implications for the medical resources required to manage liver failure and transplantation. This study features the clinical significance of hepatic recompensation by comparing patient outcomes of those who achieve it to those who do not. The early identification and use of antiviral treatment with nucleos(t)ide analogues is a pivotal strategy to promote hepatic recompensation, which has the potential to significantly reduce mortality rates in patients with chronic HBV infection and ultimately aid in the elimination of hepatitis.


Dominant genomic structures: detection and potential signal functions in the interferon-beta domain.
Eukaryotic genomes are divided into chromatin domains, which are thought to represent independent regulatory units. Typically, these domains are flanked by bordering elements that insulate the transcription unit from outside influences. Borders also demarcate the range of action for enhancer-like elements within the domain as they are formed around dominant genomic structures such as DNAse I hypersensitive sites (HS). Here we describe an efficient strategy to localize these elements. Our procedure is based on a computational method and predictions are verified by classical in vivo and in vitro procedures. Exemplified by the interferon-beta (IFN-beta) domain it proves its potential to provide novel insights into remote control principles of transcription. Sites with secondary-structure forming potential are localized by the analysis of stress-induced duplex destabilization (SIDD) properties and the associating factors are characterized by electrophoretic mobility shift assays (EMSA). These studies reveal far upstream factor binding sites within the IFN-beta domains of both humans and mice. A prominent example is YY1, a transcription factor that not only recognizes a core consensus motif, ATGG, but, in addition, the structural context, which is evident from characteristic imprints in the respective SIDD-profiles.


Role of adenosine in cerebral hypoxic hyperemia in the unanesthetized rabbit.
The present study was undertaken to determine the importance of adenosine in the cerebrovascular response to hypoxia. The mass spectrometry method was used to investigate local blood flow, tissue pO2 and pCO2 in 3 cerebral structures: caudate nucleus (n = 8), thalamus (n = 5) and hippocampus (n = 5) in unanesthetized, spontaneously breathing rabbits. After having tested the reproducibility of the hypoxic response each animal was exposed twice to moderate hypoxia. I.v. theophylline (10 mg/kg) was administered between the first and second exposures to hypoxia. The principal finding is that in each cerebral region, the vasodilatation induced by hypoxia was significantly decreased by pretreatment with theophylline despite the low theophylline dose used. It is concluded that adenosine is partly responsible for the cerebral vasodilatation observed during hypoxia. Several other mechanisms possibly involved in this cerebrovascular response are discussed.


The treatment of plantar warts using microwave-A review of 85 consecutive cases in the United States.
Plantar warts (verrucae plantaris) are a common source of pain for patients and are often refractory to treatment. Previous work has shown a high clearance rate of verrucae using a surface-based microwave device (Swift®). To assess the efficacy, defined as the complete visible clearance of warts, in patients with verrucae plantaris receiving microwave treatment. We undertook a retrospective review and identified records of 85 patients who underwent a course of microwave treatment at a single US-based podiatry centre. Efficacy was analyzed on the basis on intention-to-treat. In patients who received ≥1 session there was a complete clearance rate of 60.0% (51/85) (intention-to-treat; 59 patients completed treatment, 26 lost to follow-up) and 86.4% (51/59) per treatment completion; no significant differences in clearance rates of children and adults were observed (61.0% [25/41] vs. 59.1% [26/44]). There were 31 patients who received three sessions of microwave therapy with a clearance rate of 71.0% (22/31) as per intention-to-treat (27 patients completed treatment, 4 lost to follow-up). An average of 2.3 sessions (SD: 1.1; range: 1-6) was required for the complete clearance of plantar warts. Complete clearance was also observed in some patients with recalcitrant warts following additional treatment sessions (42.9% [3/7]). A significant reduction in wart related pain was reported for all patients undergoing treatment. Some patients continued to report a reduced amount of pain post-therapy compared with pretherapy. Microwave treatment of verrucae plantaris appears to be a safe and effective procedure.


Methods for determinging carbohydrates, hydroxymethylfurfural, and proline in honey: collaborative study.
A modification of the official selective absorption method for honey carbohydrates, 31.124--31.133, was studied collaboratively; the determinations of sucrose, total monosaccharides, disaccharides, and higher sugars by this procedure were satisfactory and were adopted by the AOAC. High pressure liquid chromatography of glucose, fructose, and sucrose in honey showed better precision than the modified official method and gave concordant results; it was also adopted. Two methods for hydroxymethylfurfural do not qualify. A method for proline was also adopted.


Alcohol-Related Liver Disease Including New Developments.
The prevalence of alcohol consumption, alcohol use disorder (AUD), and alcohol-related liver disease (ALD) has exponentially increased over the last several years and rates continue to increase. Significant alcohol use can cause progression from steatosis in the liver to inflammation, fibrosis, and eventually cirrhosis. Additional risk factors for the progression of ALD disease include gender, race, and genetic predisposition. As such, it is essential for clinicians to understand and implement screening tools for early diagnosis of both AUD and ALD and be aware of emerging novel treatment options.


The intertidal midge Clunio marinus is distributed along the European coast-line. Stocks from distinct locations differ in the programming of their emergence time. They represent ecological races. The crossability between 7 stocks was examined.Between some stocks a non-reciprocal cross sterility has been found, characterized by fertile hybrids in one cross direction, and no offspring in the reciprocal crosses.The cross Jean ♀xSan ♂ was fertile, while the cross San ♀xJean ♂ was sterile. After three backcrosses of the hybrid females to San males, the sterility in the reciprocal crosses with San females had not been changed. The maternal inheritance of this non-reciprocal sterility is compared with similar studies in Culex pipiens by Laven.According to aspects of population genetics, the non-reciprocal cross sterility is considered in view of elimination of crossing types, of gene flow and reproductive isolation. With regard to the significance of the non-reciprocal cross sterility in the field, three hypotheses are discussed: 1. by-product of evolutionary divergence in ecological races, 2. unilateral reproductive isolation which blocks the gene flow between adjacent populations only in one direction, and 3. speciation.


Co-activation is not altered in the contra-lateral limb of individuals with moderate knee osteoarthritis compared to healthy controls.
Contra-lateral knee joint function in individuals with moderate knee osteoarthritis is not well understood, despite the functional burden of bilateral osteoarthritis on end stage clinical management. The purpose of this study was to determine whether co-activation and joint biomechanics are altered in the contra-lateral limb compared to age-matched controls. 20 Individuals with moderate knee osteoarthritis and 20 asymptomatic individuals walked on an instrumented dual belt treadmill at a self-selected speed. Surface electromyography of the knee joint musculature, including quadriceps, hamstrings and gastrocnemius muscles, normalized to maximum voluntary isometric contractions, as well as sagittal plane motion and sagittal and frontal plane moments were collected. Co-contraction indices were calculated and discrete variables from motion and moment data were extracted. Two-sample t-tests and 2-sample mixed model ANOVAs were performed with alpha <0.05. Contra-lateral knee muscle co-activation differences were not found between groups (p > 0.65). Peak knee adduction moment (0.41 Nm/kg vs. 0.32 Nm/kg) and knee adduction moment impulse (0.14 Nm s/kg vs. 0.10 Nm s/kg) were higher in the contra-lateral limb compared to the asymptomatic group respectively, whereas the sagittal motion (9.8° vs. 14.4°) and moment ranges (0.66 Nm/kg vs. 0.86 Nm/kg) during stance were less dynamic (p < 0.03). The contra-lateral limb was functioning differently biomechanically despite no changes present in muscle co-activation. Findings suggest biomechanical changes are occurring without greater demand on the neuromuscular system to preserve contra-lateral joint function in moderate knee osteoarthritis gait. A greater focus should be made to address biomechanical abnormalities in both knees of individuals with moderate unilateral symptomatic knee osteoarthritis.


Effects of sodium butyrate on 1,25-dihydroxyvitamin D3 receptor activity in primary chick kidney cells.
The genomic effects of the steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by high affinity nuclear associated specific receptors that belong to the superfamily of ligand induced transcription factors. The carboxylic acid, sodium butyrate--a potent inhibitor of histone deacetylase--is known to modulate gene expression in a variety of systems. Specific binding of 1,25(OH)2D3 to its receptor was examined in primary chick kidney cells, the chick macrophage cell line HD-11, and other mammalian cell lines such as ROS 17/2.8, HT-29 and CV-1 cells, that were all cultured in the presence or absence of 1 mM sodium butyrate. Treatment with n-butyrate resulted in significant (4.0-4.5-fold) increases in 1,25(OH)2D3 receptor binding without changing binding affinity only in the primary cultures of chick renal epithelial cells and the chick macrophage cell line but not in the other heterologous receptor-positive cell lines. The maximum increase in receptor binding was evident at 1 mM butyrate concentration. This effect reached a maximum at 15 h treatment, beyond which there was slow attenuation in increased binding until 24 h. The butyrate induced increases in receptor activity was associated with increases in the 1,25(OH)2D3-mediated induction of calbindin-D28K protein only in primary chick kidney cultures but not in the macrophage cell line (HD-11). Similarly, calbindin-D28K promoter activity was enhanced only in butyrate-treated primary chick kidney cultures, transfected with chimeric plasmids containing the 5' flanking sequence of the calbindin-D28K promoter fused to the chloramphenicol acetyl transferase (CAT) reporter gene but not in HD-11 cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Unravelling and engineering an operon involved in the side-chain degradation of sterols in Mycolicibacterium neoaurum for the production of steroid synthons.
Harnessing engineered Mycolicibacteria to convert cheap phytosterols into valuable steroid synthons is a basic way in the industry for the production of steroid hormones. Thus, C-19 and C-22 steroids are the two main types of commercial synthons and the products of C17 side chain degradation of phytosterols. During the conversion process of sterols, C-19 and C-22 steroids are often produced together, although one may be the main product and the other a minor byproduct. This is a major drawback of the engineered Mycolicibacteria for industrial application, which could be attributed to the co-existence of androstene-4-ene-3,17-dione (AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (HBC) sub-pathways in the degradation of the sterol C17 side chain. Since the key mechanism underlying the HBC sub-pathway has not yet been clarified, the above shortcoming has not been resolved so far. The key gene involved in the putative HBC sub-pathway was excavated from the genome of M. neoaurum by comparative genomic analysis. Interestingly, an aldolase- encoding gene, atf1, was identified to be responsible for the first reaction of the HBC sub-pathway, and it exists as a conserved operon along with a DUF35-type gene chsH4, a reductase gene chsE6, and a transcriptional regulation gene kstR3 in the genome. Subsequently, atf1 and chsH4 were identified as the key genes involved in the HBC sub-pathway. Therefore, an updated strategy was proposed to develop engineered C-19 or C-22 steroid-producing strains by simultaneously modifying the AD and HBC sub-pathways. Taking the development of 4-HBC and 9-OHAD-producing strains as examples, the improved 4-HBC-producing strain achieved a 20.7 g/L production titer with a 92.5% molar yield and a 56.4% reduction in byproducts, and the improved 9-OHAD producing strain achieved a 19.87 g/L production titer with a 94.6% molar yield and a 43.7% reduction in byproduct production. The excellent performances of these strains demonstrated that the primary operon involved in the HBC sub-pathway improves the industrial strains in the conversion of phytosterols to steroid synthons.


Arthropathic and amyloidogenic Enterococcus faecalis infections in brown layers: A study on infection routes.
Intravenous, intra-articular and intraperitoneal inoculation of 6-week-old brown-layer pullets with an arthropathic and amyloidogenic strain of Enterococcus faecalis resulted in amyloid arthropathy, while intramuscular, oral and intratracheal inoculation did not. Oral inoculation of 1-day-old chickens did not cause any pathology. However, intramuscular inoculation with 106 colony forming units resulted in severe growth retardation and arthritis in 60% of the birds, and amyloid arthropathy in approximately 40%. In egg transmission studies, neither egg dipping nor inoculation of the air chamber with E. faecalis reproduced the condition, although a few chicks became septicaemic. Yolk sac inoculation of 6-day-old embryos caused embryonic death within 2 days. In contrast, egg albumen inoculation with E. faecalis led to arthritis in one of six of the progeny, indicating the possibility that vertical transmission of E. faecalis by the oviductal route could lead to arthritis. The presence of antibodies to E. faecalis was confirmed by enzyme-linked immunosorbent assay in 14/15 of experimental birds that had developed arthritis.


Methane preconcentration in a microtrap using multiwalled carbon nanotubes as sorbents.
The GC monitoring of green house gases is a challenging task because the concentration of organic species such as methane are relatively low (ppm to ppb) and their analysis requires some level of preconcentration. Since methane is highly volatile, it is not easily retained on conventional sorbents. In this paper we present multiwalled carbon nanotubes (MWNTs) as an effective sorbent for a microtrap designed for methane preconcentration. Its performance was compared to other commercially available carbon based sorbents, and it was found to be the most effective sorbent in terms of breakthrough volume and enthalpy of adsorption.


Correlation between clinical parameters characterising peri-implant and periodontal health: a practice-based research in Spain in a series of patients with implants installed 4-5 years ago.
To explore peri-implant health (and relation with periodontal status) 4-5 years after implant insertion. A practice-based dental research network multicentre study was performed in 11 Spanish centres. The first patient/month with implant insertion in 2004 was considered. Per patient four teeth (one per quadrant) showing the highest bone loss in the 2004 panoramic X-ray were selected for periodontal status assessment. Bone losses in implants were calculated as the differences between 2004 and 2009 bone levels in radiographs. A total of 117 patients were included. Of the 408 teeth considered, 73 (17.9%) were lost in 2009 (losing risk: >50% for bone losses ≥7 mm). A total of 295 implants were reviewed. Eight of 117 (6.8%) patients had lost implants (13 of 295 implants installed; 4.4%). Implant loss rate (quadrant status) was 1.4% (edentulous), 3.6% (preserved teeth), and 11.1% (lost teeth) (p=0.037). The percentage of implant loss significantly (p<0.001) increased when the medial/distal bone loss was ≥3 mm. The highest (p≤0.001) pocket depths were found in teeth with ≥5 mm and implants with ≥3 mm bone losses, with similar mean values (≥4 mm), associated with higher rates of plaque index and bleeding by probing. The significant bi-directional relation between plaque and bone loss, and between each of these two parameters/signs and pocket depths or bleeding (both in teeth and implants, and between them) together with the higher percentage of implants lost when the bone loss of the associated teeth was ≥3 mm suggest that the patient's periodontal status is a critical issue in predicting implant health/lesion.


Cuproptosis-Related Genes MTF1 and LIPT1 as Novel Prognostic Biomarker in Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) is a life-threatening hematologic malignant disease with high morbidity and mortality in both adults and children. Cuproptosis, a novel mode of cell death, plays an important role in tumor development, but the functional mechanisms of cuproptosis-related genes (CRGs) in AML are unclear. The differential expression of CRGs between tumors such as AML and normal tissues in UCSC XENA, TCGA and GTEx was verified using R (version: 3.6.3). Lasso regression, Cox regression and Nomogram were used to screen for prognostic biomarkers of AML and to construct corresponding prognostic models. Kaplan-Meier analysis, ROC analysis, clinical correlation analysis, immune infiltration analysis and enrichment analysis were used to further investigate the correlation and functional mechanisms of CRGs with AML. The ceRNA regulatory network was used to identify the mRNA-miRNA-lncRNA regulatory axis. Cuproptosis-related genes LIPT1, MTF1, GLS and CDKN2A were highly expressed in AML, while FDX1, LIAS, DLD, DLAT, PDHA1, SLC31A1 and ATP7B were lowly expressed in AML. Lasso regression, Cox regression, Nomogram and calibration curve finally identified MTF1 and LIPT1 as two novel prognostic biomarkers of AML and constructed the corresponding prognostic models. In addition, all 12 CRGs had predictive power for AML, with MTF1, LIAS, SLC31A1 and CDKN2A showing more reliable results. Further analysis showed that ATP7B was closely associated with mutation types such as FLT3, NPM1, RAS and IDH1 R140 in AML, while the expression of MTF1, LIAS and ATP7B in AML was closely associated with immune infiltration. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) revealed that biological functions such as metal ion transmembrane transporter activity, haptoglobin binding and oxygen carrier activity, pathways such as interferon alpha response, coagulation, UV response DN, apoptosis, hypoxia and heme metabolism all play a role in the development of AML. The ceRNA regulatory network revealed that 6 lncRNAs such as MALAT1, interfere with MTF1 expression through 6 miRNAs such as hsa-miR-32-5p, which in turn affect the development and progression of AML. In addition, APTO-253 has the potential to become an AML-targeted drug. The cuproptosis-related genes MTF1 and LIPT1 can be used as prognostic biomarkers in AML. A total of six lncRNAs, including MALAT1, are involved in the expression and regulation of MTF1 in AML through six miRNAs such as hsa-miR-32-5p.


Nurse Practitioner Employment in Relation to Nursing Staff Turnover and Resident Care Outcomes in US Nursing Homes.
A growing number of nurse practitioners (NPs) are employed in nursing homes (NHs) through various NP staffing mechanisms. The purpose of this study was to examine if having NH-employed NPs was associated with nursing staff turnover and resident care outcomes measured as hospital utilization, infection control citations, and substantiated complaints in NHs in 2021-2022. A cross-sectional, retrospective study. A total of 13,966 NHs from payroll-based journal (PBJ) and claim-based quality measures published by the Centers for Medicare and Medicaid Services in 2021-2022. Facilities were identified as having NH-employed NPs if at least 1 employed NP with paid working hours ≥10 per week was reported through the PBJ. We examined if having NH-employed NPs was associated with nursing staff turnover rates, unplanned hospital utilization, infection control citations, and substantiated complaints using doubly robust estimation that combined inverse probability weight representing the NH's likelihood of employing NPs and outcome regression. Approximately, 2.8% of NHs had employed NPs. Facilities with NH-employed NPs tended to be larger, hospital affiliated, and not for profit with greater medical and nursing staff availability. In addition, a significantly higher proportion of facilities with NH-employed NPs were in metropolitan areas or states with full NP practice independence. We found that facilities with NH-employed NPs had significantly lower registered nurse (adjusted β, -5.40; 95% CI, -9.50 to -1.30) and certified nursing assistant turnover rates (adjusted β, -3.35; 95% CI, -6.29 to -0.40). Facilities with NH-employed NPs also had significantly fewer long-stay resident hospitalizations, infection control citations, and substantial complaints compared with those with no NH-employed NPs. This study highlights the value of NH-employed NPs to improve registered nurse and certified nursing assistant staff retention and NH resident outcomes. NH stakeholders and policymakers may consider various strategies to incentivize NP employment in NHs such as removing regulatory barriers to NP practice.


Solid phase synthesis of oligoribonucleotides using the o-nitrobenzyl group for 2'-hydroxyl protection and H-phosphonate chemistry.
Oligoribonucleotides with chain length of 7, 11, 15, 17, 24 and 34 were synthesized on long chain alkylamine controlled pore glass beads (LCA-CPG) using o-nitrobenzyl protection of 2'-hydroxyls via a H-phosphonate approach either manually or by using an automatic synthesizer. The oligoribonucleotides were obtained in yields of 0.6 0.6-20%, based on initial nucleoside bound to the LCA-CPG support.


Glial cell-derived neurotrophic factor gene delivery enhances survival of human corneal epithelium in culture and the overexpression of GDNF in bioengineered constructs.
This paper evaluates the effects of adenoviral vector-mediated glial cell-derived neurotrophic factor (GDNF) gene delivery on survival of primary human corneal epithelial cells (PHCEC) established from limbal explants in vitro and the overexpression of GDNF gene in bioengineered human corneal constructs on substrate of corneal stromal discs followed by autograft ex vivo. In vitro, the overexpression of GDNF in the supernatant of PHCEC peaked at day 4, but lasted for at least 4 weeks after the transduction mediated by adenoviral vector. At day 10, the cell viability was 2-fold greater (P < 0.001), the number of terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL)-positive cells was more than 50% lower (P < 0.01) in the GDNF transduction group than the non-transduction group. 5 weeks after the transduction, the living cell population was greater in the GDNF transduction group than the non-transduction group (P < 0.01). In the ex vivo autograft of the bioengineered human corneal constructs, outgrowth of enhanced green fluorescent protein (eGFP) positive cells on the recipient corneoscleral tissue was observed. Overexpression of GDNF in the supernatant peaked at day 2, but was observed for at least 4 weeks after transplantation. At day 5, immunofluorescent staining showed expression of GDNF by all layers of epithelial cells on the graft. Our findings revealed that GDNF is a survival growth factor for cultured human corneal epithelium. The use of bioengineered human corneal constructs containing GDNF-transduced epithelial cells represents a novel method for delivering of this gene to promote survival of transplanted corneal epithelium to treat various corneal surface diseases.


Impact of Oocyte Extract Supplement on Quality of Life after Hepatectomy for Liver Tumours: A Prospective, Multicentre, Double-Blind Randomized Clinical Trial.
Previous studies on oocyte extract supplementation showed benefits in patients with liver tumours. In this trial, we hypothesized that the oocyte extract supplement impacted the QoL after hepatectomy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. This was a multicentre, double-blind, randomized clinical trial designed to assess the QoL of patients receiving a supplement of oocyte extract or placebo postoperatively. QoL was assessed using the Short Form-36 questionnaire in participants randomly assigned to treatment (Synchrolevels) or placebo. All study personnel and participants were masked to treatment assignment. The endpoint was the change in the QoL score. Between June 2018 and September 2022, 66 of 128 expected patients were considered as per interim analysis, of which 33 were assigned to the treatment and 33 to the placebo group. Baseline and clinicopathological characteristics were similar between the two groups. In the treatment group, the health, mental and psychological status improved for many of the items considered, reaching statistical significance, while in the placebo group, those items either did not change or were impaired in comparison with the corresponding baseline. Supplementation with oocyte extract modifies QoL after liver surgery by enhancing functional recovery. Further in-depth studies are required to confirm this evidence.


Low incidence of UPD in spontaneous abortions beyond the 5th gestational week.
Approximately 15-20% of all clinically recognised pregnancies abort, most commonly between 8-12 gestational weeks. While the majority of early pregnancy losses is attributed to cytogenetic abnormalities, the aetiology of approximately 40% of early abortions remains unclear. To determine additional factors causing spontaneous abortions we retrospectively searched for uniparental disomies (UPD) in 77 cytogenetically normal diploid spontaneous abortions. In all cases an unbalanced chromosome anomaly was ruled out by cytogenetic investigation of chorionic/amniotic membranes and/or chorionic villi. For UPD screening microsatellite analyses were performed on DNA of abortion specimens and parental blood using highly polymorphic markers showing UPD in two cases. The distribution of markers analysed indicated maternal heterodisomy for chromosome 9 (UPhD(9)mat) in case 1 and paternal isodisomy for chromosome 21 (UPiD(21)pat) in case 2. The originating mechanism suggested was monosomy complementation in UPiD(21)pat and trisomy rescue in UPhD(9)mat. In the case of UPhD(9)mat purulent chorioamnionitis was noted and a distinctly growth retarded embryo of 3 cm crown-rump length showing no gross external malformations. Histological analysis in the case of UPiD(21)pat suggested a primary anlage defect. Our results indicate that less than 3% of genetically unexplained pregnancy wastage is associated with total chromosome UPD. UPD may contribute to anlage defects of human conception. Chromosome aneuploidy correction can occur in very early cleavage stages. More research, however, ought to be performed into placental mosaicism to further clarify timing and mechanisms involved in foetal UPD.


Spreading of non-transformed and transformed cells.
Mechanisms of cellular reactions responsible for the spreading of non-transformed cultured tissue cells on the surface of various substrata and relationships of these reactions to the control of cell proliferation are reviewed; the special role of the membrane-cytoskeleton interactions leading to extension and attachment of pseudopods is stressed. Transition of cells from non-transformed to transformed phenotype is characterized by decreased spreading and by decreased dependence of proliferation on spreading. Manifestations of both of these spreading-associated changes are reviewed and their possible mechanisms are discussed. It is suggested that cell transition to transformed phenotype involves shift of an equilibrium between the reactions induced by the two groups of membrane-bound ligands: those attached and those not attached to the substratum.


Composite MR image reconstruction and unaliasing for general trajectories using neural networks.
In rapid parallel magnetic resonance imaging, the problem of image reconstruction is challenging. Here, a novel image reconstruction technique for data acquired along any general trajectory in neural network framework, called "Composite Reconstruction And Unaliasing using Neural Networks" (CRAUNN), is proposed. CRAUNN is based on the observation that the nature of aliasing remains unchanged whether the undersampled acquisition contains only low frequencies or includes high frequencies too. Here, the transformation needed to reconstruct the alias-free image from the aliased coil images is learnt, using acquisitions consisting of densely sampled low frequencies. Neural networks are made use of as machine learning tools to learn the transformation, in order to obtain the desired alias-free image for actual acquisitions containing sparsely sampled low as well as high frequencies. CRAUNN operates in the image domain and does not require explicit coil sensitivity estimation. It is also independent of the sampling trajectory used, and could be applied to arbitrary trajectories as well. As a pilot trial, the technique is first applied to Cartesian trajectory-sampled data. Experiments performed using radial and spiral trajectories on real and synthetic data, illustrate the performance of the method. The reconstruction errors depend on the acceleration factor as well as the sampling trajectory. It is found that higher acceleration factors can be obtained when radial trajectories are used. Comparisons against existing techniques are presented. CRAUNN has been found to perform on par with the state-of-the-art techniques. Acceleration factors of up to 4, 6 and 4 are achieved in Cartesian, radial and spiral cases, respectively.


Maybe the various forms of kidney disease are not so mechanistically different?
Sieckmann and colleagues provide evidence of a common abnormality in polyamine metabolism in 11 different rodent models of acute kidney injury and chronic kidney disease, and in human renal transplantation. The abnormality is characterized by downregulation of enzymes involved in polyamine synthesis and/or upregulation of enzymes involved in polyamine metabolism. Therefore, polyamine metabolism is a potential target for development of pharmacotherapies for a broad range of kidney diseases.


Polycystic liver disease in golden hamsters.
Seven cases of multiple hepatic cysts of varying sizes and shapes were recorded in a closed colony of golden hamsters. Ante-mortem examination failed to show any clinical signs except for abdominal enlargement in one hamster. Multiple, thin-walled cysts of varying sizes (0.25 to 3.0 cm) and shape were observed in the liver. The larger cysts protruded from the liver surfaces and contained a colourless, clear, serous fluid and caused pathological change in 5-60 per cent of the hepatic parenchyma. Microscopically, the cysts were uni- or multilocular and lined by low cuboidal or flattened epithelial cells. The hepatic parenchyma around cysts showed pressure atrophy, necrosis, engorged sinusoids or other blood vessels or even haemorrhages, mild to extensive fatty or vacuolar degenerative changes and occasionally proliferation of biliary ducts.


Vegetation patches improve the establishment of Salvia mexicana seedlings by modifying microclimatic conditions.
Human disturbance has disrupted the dynamics of plant communities. To restore these dynamics, we could take advantage of the microclimatic conditions generated by remaining patches of vegetation and plastic mulch. These microclimatic conditions might have great importance in restoring disturbed lava fields located south of Mexico City, where the rock is exposed and the soil is shallow. We evaluated the effects of both the shade projected by vegetation patches and plastic mulch on the mean monthly soil surface temperature (Tss) and photosynthetic photon flux density (PPFD) and on the survival and growth of Salvia mexicana throughout the year. This species was used as a phytometer of microsite quality. Shade reduced the T ss to a greater extent than mulch did. Both survival and growth were enhanced by shade and mulch, and the PPFD was related with seedling growth. During the dry season, plant biomass was lost, and there was a negative effect of PPFD on plant growth. At micro-meteorological scales, the use of shade projected by patches of vegetation and mulch significantly reduced the mortality of S. mexicana and enhanced its growth. Survival and growth of this plant depended on the environmental quality of microsites on a small scale, which was determined by the environmental heterogeneity of the patches and the landscape. For plant restoration, microsite quality must be evaluated on small scales, but on a large scale it may be enough to take advantage of landscape shade dynamics and the use of mulch to increase plant survival and growth.


Anemia in pediatric renal transplant recipients.
The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.


Growth and aflatoxin production ofaspergillus flavus on some spices marketed in Turkey.
Growth and aflatoxin production byAspergillus flavus (MAM-268 C17, TNS=98) on autoclaved coconut, black pepper, crushed red pepper, red pepper powder were studied. Coconut were found to be a better substrate for fungal growth, as well as aflatoxin production. Red pepper powder could be considered as a poor substrate for fungal growth. The amount of aflatoxin found in crushed red pepper under laboratory conditions is much less compared with coconut, black pepper and red pepper powder.


Inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol in mouse spleen cells: a potential mechanism for cannabinoid-mediated immunosuppression.
The ability of delta 9-Tetrahydrocannabinol (delta 9-THC) to modulate adenylate cyclase activity in mouse spleen cells was investigated. These studies were prompted by the recent identification and cloning of a G-protein coupled cannabinoid receptor localized in certain regions of the brain and the potential for a common mechanism between cannabinoid-mediated CNS effects and immunosuppression. Temporal addition studies were initially performed to identify the period of time when spleen cells in culture were most susceptible to the inhibitory effects of delta 9-THC, as measured by the day 5 IgM antibody forming cell response. delta 9-THC was only inhibitory when added to spleen cell cultures during the first 2 hr following antigen sensitization. In light of this time course, adenylate cyclase activity was measured in spleen cells incubated in the presence of 22 microM delta 9-THC for 5 min and subsequently stimulated with forskolin. delta 9-THC treated spleen cells demonstrated a 33% inhibition and a 66% inhibition in intracellular cAMP after a 5 or 15 min stimulation with forskolin, respectively. These studies suggest that inhibition of immune function by delta 9-THC may be mediated through the inhibition of intracellular cAMP early after antigen stimulation.


Yohimbine potentiates cold-water swim analgesia: re-evaluation of a noradrenergic role.
Continuous cold-water swims (CCWS) elicit a nonopioid and neurohormonal analgesia which displays adaptation. The norepinephrine (NE) system has been implicated since parallel alterations in NE occur following acute and repeated CCWS exposure, and since CCWS analgesia is reduced by locus coeruleus lesions and is potentiated by clonidine and desipramine. The present study evaluated the effects of the alpha-2 NE receptor antagonist, yohimbine upon CCWS (2 degrees C for 3.5 min) analgesia on the jump and tail-flick tests, CCWS hypothermia, and basal nociceptive and thermoregulatory measures in rats. Yohimbine (0.1-2.0 mg/kg, IP) dose-dependently increased basal jump thresholds and potentiated CCWS analgesia: these effects appeared to be additive. Yohimbine potentiated CCWS analgesia on the tail-flick test without altering basal latencies. Yohimbine failed to alter either CCWS hypothermia or basal thermoregulation. Since yohimbine and clonidine, an alpha-2 NE receptor antagonist and agonist respectively, similarly potentiate CCWS analgesia, it appears that NE effects are orthoganol to the intrinsic system mediating CCWS.


Computer simulation of the dynamics of a spatial susceptible-infected-recovered epidemic model with time delays in transmission and treatment.
In this work, we analyze the spatial-temporal dynamics of a susceptible-infected-recovered (SIR) epidemic model with time delays. To better describe the dynamical behavior of the model, we take into account the cumulative effects of diffusion in the population dynamics, and the time delays in both the Holling type II treatment and the disease transmission process, respectively. We perform linear stability analyses on the disease-free and endemic equilibria. We provide the expression of the basic reproduction number and set conditions on the backward bifurcation using Castillo's theorem. The values of the critical time transmission, the treatment delays and the relationship between them are established. We show that the treatment rate decreases the basic reproduction number while the transmission rate significantly affects the bifurcation process in the system. The transmission and treatment time-delays are found to be inversely proportional to the susceptible and infected diffusion rates. The analytical results are numerically tested. The results show that the treatment rate significantly reduces the density of infected population and ensures the transition from the unstable to the stable domain. Moreover, the system is more sensible to the treatment in the stable domain. The density of infected population increases with respect to the infected and susceptible diffusion rates. Both effects of treatment and transmission delays significantly affect the behavior of the system. The transmission time-delay at the critical point ensures the transition from the stable (low density) to the unstable (high density) domain.


Loss of heterozygosity on chromosome 22q and 17p correlates with aggressiveness of meningiomas.
According to reported cytogenetic studies, there is a significant association between chromosomal aberrations and aggressiveness in meningiomas. With the method of restriction fragment length polymorphism analysis (RFLP), we examined tumor specific LOH on chromosome 17p and 22q in 30 cases of intracranial meningiomas. There were eight cases of meningiomas with aggressive characteristics, such as invasive meningioma, malignant meningioma, hemangiopericytic meningioma, and multiple meningiomas with central neurofibromatosis. Twenty-five of 30 cases (83%) were constitutionally heterozygous for at least one of the chromosome 22q DNA markers and sixteen of 25 informative cases (64%) displayed loss of heterozygosity (LOH). All of the 8 informative cases (100%) of meningiomas with aggressive characteristics, showed LOH on chromosome 22q whereas non-aggressive cases revealed LOH in eight of 17 informative cases (47%). At the loci on chromosome 17p, only two cases of malignant meningionas showed LOH. Our results suggest that the inactivations of putative tumor suppressor genes on chromosome 22q and 17p may correlate with aggressiveness and malignant transformation of meningiomas.


Low-molecular-weight heparins for the treatment of acute coronary syndrome and venous thromboembolism in patients with chronic renal insufficiency.
The clinical management of patients with renal insufficiency who develop an acute coronary syndrome or venous thromboembolism is a common clinical scenario that is problematic because of the lack of well-designed randomized trials assessing management strategies in such patients. Impaired renal function is common in patients who develop thromboembolic disorders, particularly in elderly patients in whom renal insufficiency is under-recognized. Low-molecular-weight heparins (LMWHs), which are the most widely used anticoagulant for the treatment of patients with an acute coronary syndrome or venous thromboembolism, are eliminated primarily by the kidney and, therefore, pose treatment challenges in patients with impaired renal function. However, there is emerging evidence regarding the use of LMWHs in patients with impaired renal function suggesting that some preparations may be safe in such patients. The objective of this review is to discuss the clinical management of patients with renal insufficiency who develop an acute coronary syndrome or venous thromboembolism, and to explore similarities and differences of LMWHs when used in this clinical setting.


Leveraging high-throughput hyperspectral imaging technology to detect cadmium stress in two leafy green crops and accelerate soil remediation efforts.
Cadmium (Cd) is a toxic metal that can accumulate in soils and negatively impact crop as well as human health. Amendments like biochar have potential to address these challenges by reducing Cd bioavailability in soil, though reliance on post-harvest wet chemical methods to quantify Cd uptake have slowed efforts to identify the most effective amendments. Hyperspectral imaging (HSI) is a novel technology that could overcome this limitation by quantifying symptoms of Cd stress while plants are still growing. The goals of this study were to: 1) determine whether HSI can detect Cd stress in two distinct leafy green crops, 2) quantify whether a locally sourced biochar derived from hardwoods can reduce Cd stress and uptake in these crops, and 3) identify vegetative indices (VIs) that best quantify changes in plant stress responses. Experiments were conducted in a tightly controlled automated phenotyping facility that allowed all environmental factors to be kept constant except Cd concentration (0, 5 10 and 15 mg kg-1). Symptoms of Cd stress were stronger in basil (Ocimum basilicum) than kale (Brassica oleracea), and were easier to detect using HSI. Several VIs detected Cd stress in basil, but only the anthocyanin reflectance index (ARI) detected all levels of Cd stress in both crop species. The biochar amendment did reduce Cd uptake, especially at low Cd concentrations in kale which took up more Cd than basil. Again, the ARI index was the most effective in quantifying changes in plant stress mediated by the biochar. These results indicate that the biochar evaluated in this study has potential to reduce Cd bioavailability in soil, and HSI could be further developed to identify rates that can best achieve this benefit. The technology also may be helping in elucidating mechanisms mediating how biochar can influence plant growth and stress responses.


Characterization of starch Pickering emulsions for potential applications in topical formulations.
The aim of this work has been to characterize starch based Pickering emulsions as a first step to evaluate their possible use as vehicles for topical drug delivery. A minor phase study of emulsions with high oil content has been performed. Emulsion stability against coalescence over eight weeks and after mild centrifugation treatment has been studied. The particle size, rheological properties and in vitro skin penetration of emulsions containing three different oils (Miglyol, paraffin and sheanut oil) was investigated. It was shown that it is possible to produce oil in water starched stabilised Pickering emulsions with oil content as high as 56%. Furthermore, this emulsions show good stability during storage over eight weeks and towards mild centrifugation. The particle size of the systems are only dependent on the ratio between oil and starch and for liquid oils the type of oil do not affect the particle size. The type of oil also affects the cosmetic and rheological properties of the creams but did not affect the transdermal diffusion in in vitro tests. However, it seems as if the Pickering emulsions affected the transport over the skin, as the flux was twice that of what has been previously reported for solutions.


The association between major dietary patterns and severe mental disorders symptoms among a large sample of adults living in central Iran: Baseline data of YaHS-TAMYZ cohort study.
The diet's role in developing psychological disorders has been considered by researchers in recent years. To examine the association between major dietary patterns and severe mental disorders symptoms in a large sample of adults living in Yazd city, central Iran. This cross-sectional study used the baseline data of a population-based cohort study (Yazd Health study: YaHS). Dietary intakes were assessed by a multiple-choice semi-quantitative food frequency questionnaire (FFQ, Yazd nutrition survey called TAMYZ). Psychological assessments were also done by using the depression, anxiety, and stress scale-21 (DASS-21) questionnaire. Major dietary patterns were identified using principal component analysis (PCA). Analysis of covariance (ANCOVA) and logistic regression analyses were used to evaluate the relationship between dietary patterns and mental disorders symptoms. A total of 7574 adults were included in the current analysis. Four major dietary patterns were identified: "Sugar and Fats", "Processed Meats and Fish", "Fruits" and "Vegetables and Red Meat". After adjustment for all confounding variables, participants in the fifth quintile of "Fruits" dietary pattern which was highly correlated with dried fruits, canned fruits, fruit juice, olive, hydrogenated fats and fruits intake, had a lower odds of severe depression (OR=0.61, 95% CI: 0.45-0.81, p for trend=0.057), anxiety (OR=0.64, 95% CI: 0.50-0.80, p for trend=0.007), and stress, (OR=0.45, 95% CI: 0.30-0.68, p for trend=0.081). The intake of a dietary pattern high in dried fruits, canned fruits, fruit juice, olive, hydrogenated fats, and fruits might be inversely associated with depression, anxiety, and stress symptoms. Future prospective studies are needed to warrant this finding.


Brighter yellow blue tits make better parents.
Whether or not bird ornaments are a signal for direct (e.g. good parents) or indirect (e.g. good genes) benefits to prospective partners in sexual selection is controversial. Carotene coloration in Parus species is directly related to the ingestion of caterpillars, so that a brightly carotene-coloured tit may be signalling its ability to find caterpillars, a main high-quality food source for good fledgling development, and hence its parental abilities. If carotene-based plumage coloration is related to the good-parent hypothesis, we predict that yellow plumage brightness of tit fathers should be positively correlated to their investment in offspring provisioning. Here, we use cross-fostering experiments in blue tits (Parus caeruleus) to show that chick development (as measured by tarsus length) is related to yellowness of the foster father, but not to that of the genetic parents. Using these data, we were able to measure, for the first time to our knowledge, the separate contribution of genetic and environmental factors (i.e. parental plumage coloration) to chick development, and hence parental investment. Our data, which relate carotenoid coloration to models of good parents, and data from other authors, which relate ultraviolet coloration to good-genes models, stress that different kinds of coloration within an individual may provide different units of information to prospective females.


Experience with use of recombinant activated factor VII.
Recombinant activated factor VII (rFVIIa) has recently been introduced for improving haemostasis in haemophiliac patients developing alloantibodies (inhibitors) to factor VIII (FVIII) or factor IX (FIX). We describe the successful management of haemorrhagia with rFVIIa in five different situations: an episode of surgical bleeding in a patient with haemophilia A and non-surgical haemorrhages in four patients with haemophilia A, acquired haemophilia, congenital severe FV defect and pseudo-acquired haemophilia, respectively. In each case, rFVIIa was effective and safe. There is no doubt that rFVIIa is useful in the therapeutic management of patients with antibodies to FVIII or FIX. However, the treatment is expensive and a cost-effectiveness analysis would be useful.


Review and Updates in Regenerative and Personalized Medicine, Preclinical Animal Models, and Clinical Care in Cardiovascular Medicine.
The goal of this paper is to provide an updated review for scientists and clinicians on the major areas in cardiovascular medicine published in the Journal. Leading topics in regenerative and personalized medicine are presented along with a critical overview of the field. New standards in large preclinical animal models of pulmonary hypertension and left bundle branch block are highlighted. Finally, clinical care in the areas of atherosclerosis, the aortic valve, platelet biology, and myocarditis is discussed as well as autonomic modulation therapies.


Advances in diarylpyrimidines and related analogues as HIV-1 nonnucleoside reverse transcriptase inhibitors.
HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been playing an important role in the fight against acquired immunodeficiency syndrome (AIDS). Diarylpyrimidines (DAPYs) as the second generation NNRTIs, represented by etravirine (TMC125) and rilpivirine (TMC278), have attracted extensive attention due to their extraordinary potency, high specificity and low toxicity. However, the rapid emergence of drug-resistant virus strains and dissatisfactory pharmacokinetics of DAPYs present new challenges. In the past two decades, an increasing number of novel DAPY derivatives have emerged, which significantly enriched the structure-activity relationship of DAPYs. Studies of crystallography and molecular modeling have afforded a lot of useful information on structural requirements of NNRTIs, which contributes greatly to the improvement of their resistance profiles. In this review, we reviewed the discovery history and their evolution of DAPYs including their structural modification, derivatization and scaffold hopping in continuous pursuit of excellent anti-HIV drugs. And also, we discussed the prospect of DAPYs and the directions of future efforts.


Production and characterization of neglect in rats with unilateral lesions of ventrolateral orbital cortex.
Neglect is a clinical syndrome characterized by an inability to orient, report, or respond to novel or meaningful stimuli presented to one side of the body or in one hemispace. Neglect in humans and monkeys most often results from damage to one of several interconnected cortical areas, including limbic cortex. In rats damage to only one cortical area, medial agranular cortex (AGm), has been found to produce neglect. Thus, it remains to be determined if there is a cortical circuitry related to neglect in rodents. AGm has extensive bilateral reciprocal connections with the paralimbic area ventrolateral orbital cortex (VLO). The current study was conducted to determine if lesions of VLO also result in neglect in the rat. Male Long-Evans hooded rats with lesions of right VLO (n = 7), left VLO (n = 7), and sham operates (n = 23) were tested for a minimum of 4 weeks on the following: (i) motor asymmetry based on assessment of rotational behavior during a 2-minute period, (ii) neglect based on the degree of orientation to visual, tactile, and auditory stimuli presented in each hemispace, and (iii) tactile extinction based on the tendency to touch the ipsilesional tab first when adhesive tabs were attached to each wrist. Lesions of VLO resulted in no obvious motor asymmetry. Both right and left VLO operates showed significant overall contralesional neglect relative to shams. However, whereas left VLO operates showed significant contralesional neglect relative to shams in the auditory and visual modalities, right VLO operates showed significant neglect in the tactile modality. On the extinction measure only right VLO operates demonstrated an asymmetry, left VLO operates were unimpaired.


Conservative management of patients with early endometrial carcinoma: a systematic review.
To know the characteristics of endometrial adenocarcinoma in young patients and to review the published experience in patients with endometrial adenocarcinoma that were conservatively managed with hormonal therapy to spare their fertility. We carried out a search in the Survey conducted by the Section of Oncologic Gynecology of SEGO (Spanish Society of Gynecologists) to identify the characteristics of young patients with endometrial adenocarcinoma. In addition we searched MEDLINE and other databases for English-language articles describing patients with endometrial adenocarcinoma who were treated with hormonal therapy. The search included articles published between January 1966 and January 2007. Endometrial carcinoma in patients under 45 years old is an unusual condition that shows a more favourable pattern than in older patients. One hundred and thirty-three patients were found in the search. The average duration of hormonal therapy was approximately six months. The average response time was 12 weeks; 76% of patients treated with hormonal therapy had a complete response and the other 24% never responded to treatment. Of those who initially responded, 66% percent did not show recurrence of disease. The other 34% had a relapse. There have been 4 published deaths of conservatively managed patients. A conservative approach in these patients can offer reasonable oncological security and the opportunity of fulfilling their maternal desires in selected cases. However, consideration should be taken regarding the potential adverse outcomes that have been recently published in the literature.


Role of oxidative stress in thuringiensin-induced pulmonary toxicity.
To understand the effect of thuringiensin on the lungs tissues, male Sprague-Dawley rats were administrated with thuringiensin by intratracheal instillation at doses 0.8, 1.6 and 3.2 mg/kg of body weight, respectively. The rats were sacrificed 4 h after treatment, and lungs were isolated and examined. Subsequently, an effective dose of 1.6 mg/kg was selected for the time course study (4, 8, 12, and 24 h). Intratracheal instillation of thuringiensin resulted in lung damage, as evidenced by increase in lung weight and decrease in alkaline phosphatase (10-54%), an enzyme localized primarily in pulmonary alveolar type II epithelial cells. Furthermore, the administration of thuringiensin caused increases in lipid peroxidation (21-105%), the indices of lung injury. In addition, the superoxide dismutase (SOD) and glutathione (GSH) activities of lung tissue extracts were measured to evaluate the effect of thuringiensin on antioxidant defense system. The SOD activity and GSH content in lung showed significant decreases in a dose-related manner with 11-21% and 15-37%, respectively. Those were further supported by the release of proinflammatory cytokines, as indicated by increases in IL-1beta (229-1017%) and TNF-alpha (234%) levels. Therefore, the results demonstrated that changes in the pulmonary oxidative-antioxidative status might play an important role in the thuringiensin-induced lung injury.


Photothermal Effect-based Cytotoxic Ability of Melanin from Mytilus edulis Shells to Heal Wounds Infected with Drug-resistant Bacteria in vivo.
Owing to antibiotic abuse and the subsequent development of antibiotic resistance, bacterial infection has become one of the most persistent unresolved problems. New antibacterial agents, especially those that are environmental-friendly, are urgently needed. Melanin extracted by filtration centrifugation and acid and proteolytic hydrolysis was characterized using UV, FTIR, TEM, and XPS. Photothermal conversion was calculated, and the bacteriostatic effects, in vitro and in vivo, were assessed by plate counting and ratios (%) of wound areas. Natural melanin hydrolyzed by trypsin had good photothermal conversion effects, which resulted in superior bacteriostatic activities. The extracted melanin along with laser NIR irradiation at 808 nm promoted the healing of wounds infected by drug-resistant bacteria in vivo and was biocompatible according to toxicity tests in vivo and in vitro. The present findings indicated a safe and efficient method of developing natural antibacterial agents.


Older men and older women in the arms of criminal law: offending patterns and sentencing outcomes.
This study examines whether older defendants receive more lenient sentences compared with their younger counterparts and whether the effects of aging on sentencing outcomes manifests itself similarly across male and female offenders. Using statewide data from Pennsylvania for 1990-94, logit models were used to assess the effects of aging on the in/out or incarcerative decision, and, ordinary least squares models were used to assess the effects on the length-of-term decision. Results show that older offenders of both genders were sentenced less harshly-they are less likely to be imprisoned than their younger counterparts and, if imprisoned, elderly defendants receive shorter prison terms. However, the elderly advantage was diminished in the case of drug offending, and the within-gender elderly advantage was found to be greater for males than for women. While these age differences in sentence outcomes appear to thwart norms of judicial impartiality, they also might reflect legitimate sentencing concerns of judges (in areas such as crime propensity, blameworthiness, and even the extra costs needed tojail older defendants). Therefore, an overall pattern of less severe punishment of older defendants (and/or female defendants) may still be warranted.


[Physiokinesitherapeutic management of traumatic lesions of the brachial plexus. Indications and results].
An account is given of the indications and results of physical and rehabilitative management of brachial plexus lesions when used electively or as a complement to surgery. Material from the Florence Traumatological and Orthopaedics Centre and the V. Putti Mutilated Patients Centre, Bologna (formerly directed by Prof. O. Scaglietti) dating from 1940 to 1980 is used to explain the indications for conservative and surgical management, in the conviction that sound results depend on exact indication. A selected sample of 51 patients treated conservatively and 194 surgically is presented. The results were satisfactory in about 50% of each group, with a slight advantage in favour of physiotherapy, this being obviously employed when lesions were less severe.


Overall bacterial community composition and abundance of nitrifiers and denitrifiers in a typical macrotidal estuary.
Coupled nitrogen cycling processes can alleviate the negative effects of eutrophication caused by excessive nitrogen load in estuarine ecosystems. The abundance and diversity of nitrifiers and denitrifiers across different environmental gradients were examined in the sediment of Hangzhou Bay. Quantitative PCR and Pearson's correlation analyses suggested that the bacterial ammonia-oxidizers (AOB) were the dominant phylotypes capable of ammonia oxidation, while the nirS-encoding denitrifiers predominated in the denitrification process. Simultaneously, nitrite and pH were found to be the two major factors influencing amoA and nir gene abundances, and the distribution of bacterial communities. Moreover, the ratio of nirS/AOB amoA gene abundance showed negative correlation with nitrite concentration. Fluorescence in situ hybridization further demonstrated that AOB and acetate-denitrifying cells were closely connected and formed obvious aggregates in the sediment. Together, all these results provided us a preliminary insight for coupled nitrification-denitrification processes in the sediment of Hangzhou Bay.


[A new surgical technique in congenital cataracts for prevention of regenerated cataract. Controlled central excision of capsular leaves with endodiathermy coagulation of the capsular sac periphery].
Inherent in all operative methods of congenital cataract surgery with the aim of preserving the posterior leaf of the capsule is the risk of recurrence. Even after phakectomy of the pars plicata, secondary cataract can occur in the peripheral remains of the capsule, and this method also entails the risk of retinal detachment and loss of the capsule diaphragm, which would otherwise allow subsequent IOL implantation. We developed a new surgical technique to preserve the peripheral capsular sac and to avoid secondary cataract within the optical axis. Unipolar diathermy coagulation was applied to the anterior peripheral leaf of the capsule, provided that both leaves of the capsule were touching when slight pressure was applied to the probe. In preliminary studies of autopsy eyes, fusion of the capsular leaves was clearly apparent, even if the lens epithelium was not morphologically destroyed by diathermy coagulation. These were 42 eyes with congenital cataract (12 children with bilateral cataract, 9 eyes with mild anterior PHPV syndrome). Their ages were between 4 weeks and 8.5 years and the period from April 1988 to December 1992; follow-up was 1 to 4.5 years: 36 eyes, 6 eyes with PHPV. The following operation was undertaken in the children. After central anterior capsulectomy and aspiration of the lens, the anterior and posterior leaves of the capsular sac were fused circularly at the periphery by unipolar endodiathermy coagulation. The posterior chamber was deepened by viscoelastic substance allowing diathermy application at the anterior capsule with risk.(ABSTRACT TRUNCATED AT 250 WORDS)


Kinetics of the superoxide reductase catalytic cycle.
The steady state kinetics of a Desulfovibrio (D.) vulgaris superoxide reductase (SOR) turnover cycle, in which superoxide is catalytically reduced to hydrogen peroxide at a [Fe(His)4(Cys)] active site, are reported. A proximal electron donor, rubredoxin, was used to supply reducing equivalents from NADPH via ferredoxin: NADP+ oxidoreductase, and xanthine/xanthine oxidase was used to provide a calibrated flux of superoxide. SOR turnover in this system was well coupled, i.e. approximately 2O*2 reduced:NADPH oxidized over a 10-fold range of superoxide flux. The reduction of the ferric SOR active site by reduced rubredoxin was independently measured to have a second-order rate constant of approximately 1 x 10(6) m-1 s-1. Analysis of the kinetics showed that: (i) 1 microM SOR can convert a 10 microM/min superoxide flux to a steady state superoxide concentration of 10(-10) m, during which SOR turns over about once every 6 s, (ii) the diffusion-controlled reaction of reduced SOR with superoxide is the slowest process during turnover, and (iii) neither ligation nor deligation of the active site carboxylate of SOR limits the turnover rate. An intracellular SOR concentration on the order of 10 microM is estimated to be the minimum required for lowering superoxide to sublethal levels in aerobically growing SOD knockout mutants of Escherichia coli. SORs from Desulfovibrio gigas and Treponema pallidum showed similar turnover rates when substituted for the D. vulgaris SOR, whereas superoxide dismutases showed no SOR activity in our assay. These results provide quantitative support for previous suggestions that, in times of oxidative stress, SORs efficiently divert intracellular reducing equivalents to superoxide.


Assessment of dental practitioners in the secondary and tertiary prevention of eating disorders.
A questionnaire based upon the transtheoretical model and the health belief model was utilized to investigate dental practitioners' involvement in the secondary and tertiary prevention of eating disorders. Findings indicate that respondents are in the precontemplation or contemplation stages in identification, oral treatment, referral, and case management behaviors. Many are not completely aware of the health implications and oral manifestations of disordered eating and barriers were identified which may stand in the way of secondary and tertiary prevention. This pilot study provides a framework for the development of effective programming to increase the proportion of dental practitioners involved in prevention of eating disorders. To move the dental professionals toward assessment, referral, and case management, barriers to action must be removed.


Target-specific yield rate and clinical utility of percutaneous tissue sampling in spinal infection.
Percutaneous tissue sampling in spondylodiscitis is frequently performed but with highly variable yield in literature and unclear clinical impact. Factors that influence the culture success rate are not well established. To determine target specific yield and clinical impact of percutaneous biopsy in clinically and imaging diagnosed spinal infection and factors that may influence the yield rate. Institutional review board approved single center retrospective chart review from 2015 to 2019 analyzing imaging findings, clinical notes, procedural reports, and laboratory results on cases of concurrent imaging and clinically diagnosed spondylodiscitis that underwent percutaneous tissue sampling. A total of 111 patients and 189 specimens were analyzed. The overall culture yield in spondylodiscitis was approximately 27%, 9% affecting management. Abscess/fluid and septic arthritis aspirations had higher yield rates compared to soft tissue/phlegmon aspirations. Core sampling of the bone and disc yielded positive culture 12% of the time, 2% resulted in change in management. Upper thoracic spine biopsies were more frequently positive and associated with change in management. Positive culture elsewhere in the body represented the major reason underlying lack of clinical impact. Lack of prior antibiotic treatment and diabetes mellitus demonstrated a trend toward higher culture positivity, although a larger sample size is needed to confirm these findings. No repeat biopsy yielded positive culture. Staphylococcus spp. accounted for approximately half of the microorganisms cultured. In positive biopsies where infection was also found elsewhere in the body, the organism was nearly always congruent (96%).


Protection against hydrogen peroxide-induced cell death in cultured human retinal pigment epithelial cells by 17beta-estradiol: a differential gene expression profile.
It has been demonstrated that estrogen receptors are present in the retinal pigment epithelium (RPE)-choroids complex regardless of sex. This suggests that estrogen could play a functional role in the outer retina, especially the RPE. To gain further insights on the molecular mechanisms differentially activated by 17beta-estradiol (betaE2) in RPE cells, we investigated gene expression changes in response to betaE2 in cultured RPE cells using cDNA microarray technology. A total of 47 genes among 21,329 human genes are significantly altered in response to betaE2 treatment in RPE cells. Among these 47 altered genes, 34 are up-regulated and 13 are down-regulated by betaE2. The products of 34 genes have a known or suspected function. These functions belong to various categories, including caspases; extracellular matrix proteins; metabolism pathway components; GTP/GDP exchangers and G-protein GTPase activity modulators; transcription activators and repressors. Six genes which may contribute to the unique functions of the RPE cells have been validated by both quantitative real-time reverse transcription (RT)-PCR and semi-quantitative RT-PCR. In addition, we also demonstrated that betaE2 quenches H2O2-induced up-regulation of apoptosis-related protein, and protects RPE cell degeneration. These results indicate that estrogen regulates functions of RPE cells and is involved in the maintaining and survival of RPE cells during oxidative stress, and its deficiency during menopause period may be a factor contributing to the development of age-related macular degeneration in elderly women.