Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats.
To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP). A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 +/- 0.42 vs 9.76 +/- 0.45, P < 0.01), pulmonary histological scores (7.1 +/- 0.7 vs 8.4 +/- 1.1, P < 0.01), serum AST (667 +/- 103 vs 1 368 +/- 271, P < 0.01), ALT (446 +/- 91 vs 653 +/- 98, P < 0.01) and Cr (1.2 +/- 0.3 vs 1.8 +/- 0.3, P < 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P < 0.01). Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGB1levels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients.


Transcription-Based Multidimensional Regulation of Fatty Acid Metabolism by HIF1α in Renal Tubules.
Lipid metabolism plays a basic role in renal physiology, especially in tubules. Hypoxia and hypoxia-induced factor (HIF) activation are common in renal diseases; however, the relationship between HIF and tubular lipid metabolism is poorly understood. Using prolyl hydroxylase inhibitor roxadustat (FG-4592), we verified and further explored the relationship between sustained HIF1α activation and lipid accumulation in cultured tubular cells. A transcriptome and chromatin immunoprecipitation sequencing analysis revealed that HIF1α directly regulates the expression of a number of genes possibly affecting lipid metabolism, including those associated with mitochondrial function. HIF1α activation suppressed fatty acid (FA) mobilization from lipid droplets (LDs) and extracellular FA uptake. Moreover, HIF1α decreased FA oxidation and ATP production. A lipidomics analysis showed that FG-4592 caused strong triglyceride (TG) accumulation and increased some types of phospholipids with polyunsaturated fatty acyl (PUFA) chains, as well as several proinflammatory lipids. Nevertheless, the overall FA level was maintained. Thus, our study indicated that HIF1α reduced the FA supply and utilization and reconstructed the composition of lipids in tubules, which is likely a part of hypoxic adaptation but could also be involved in pathological processes in the kidney.


Myelopathy secondary to an intramedullary arteriovenous malformation in a mature dog.
A 2-year-old crossbreed dog was presented for evaluation of a 6-week history of progressive paraparesis. Magnetic resonance imaging and computed tomography angiography of the thoracic and lumbar spinal cord disclosed multifocal, anomalous, small, vascular structures, distributed throughout the subarachnoid space of the included section of the spinal cord. An additional focal intramedullary lesion was identified extending from T9 to T10 to T12. Histopathological examination confirmed the presence of an intramedullary arteriovenous malformation affecting the thoracic spinal cord and leading to diffuse congestion and focal hemorrhages into the affected spinal cord.


Common Variants in 6 Lipid-Related Genes Discovered by High-Resolution DNA Melting Analysis and Their Association with Plasma Lipids.
BACKGROUND: Total cholesterol was among the earliest identified risk factors for coronary heart disease (CHD). We sought to identify genetic variants in six genes associated with lipid metabolism and estimate their respective contribution to risk for CHD. METHODS: For 6 lipid-associated genes (LCAT, CETP, LIPC, LPL, SCARB1, and ApoF) we scanned exons, 5' and 3' untranslated regions, and donor and acceptor splice sites for variants using Hi-Res Melting® curve analysis (HRMCA) with confirmation by cycle sequencing. Healthy subjects were used for SNP discovery (n=64), haplotype determination/tagging SNP discovery (n=339), and lipid association testing (n=786). RESULTS: In 17,840 bases of interrogated sequence, 90 variant SNPs were identified; 19 (21.1%) previously unreported. Thirty-four variants (37.8%) were exonic(16 non-synonymous), 28 (31.1%) in intron-exon boundaries, and 28 (31.1%) in the 5' and 3' untranslated regions. Compared to cycle sequencing, HRMCA had sensitivity of 99.4% and specificity of 97.7%. Tagging SNPs (n=38) explained >90% of the variation in the 6 genes and identified linkage disequilibrium (LD) groups. Significant beneficial lipid profiles were observed for CETP LD group 2, LIPC LD groups 1 and 7, and SCARB1 LD groups 1, 3 and 4. Risk profiles worsened for CETP LD group 3, LPL LD group 4. CONCLUSIONS: These findings demonstrate the feasibility, sensitivity, and specificity of HRMCA for SNP discovery. Variants identified in these genes may be used to predict lipid-associated risk and reclassification of clinical CHD risk.


A comparative study of Mini-Mental Test, Clock Drawing task and Cognitive-FIM in evaluating functional outcome of elderly hip fracture patients.
To compare the clock drawing task with other cognitive tests used for the prediction of discharge functional outcome, in elderly hip fracture patients. Cohort study. A department of geriatric-orthopaedic rehabilitation of a tertiary hospital. One hundred and forty-three consecutive patients undergoing inpatient comprehensive rehabilitation following hip fracture. Cognitive status was assessed by the Clock Drawing Task, Mini-Mental State Examination (MMSE) and the Cognitive-FIM (cognFIM). Functional status outcome was evaluated by the Functional Independence Measure (FIM), using absolute and relative parameters of efficacy and efficiency. Correlation coefficients (Pearson correlation) between the three cognitive tests resulted in values ranging from 0.607 to 0.732 (p < 0.001). Similar correlation coefficients were observed for all cognitive tests when correlated with relative efficacy and efficiency outcome parameters (p < 0.001), but not with absolute outcome parameters. Clock Drawing Test is similar to Mini-Mental and Cognitive-FIM with respect to the evaluation of functional status outcome following rehabilitation of hip fractures. The similar correlations with functional outcome parameters as well as the simplicity of administration favour the use of either Clock Drawing Task or MMSE in the initial assessment of elderly patients with hip fractures.


Regularized binormal ROC method in disease classification using microarray data.
An important application of microarrays is to discover genomic biomarkers, among tens of thousands of genes assayed, for disease diagnosis and prognosis. Thus it is of interest to develop efficient statistical methods that can simultaneously identify important biomarkers from such high-throughput genomic data and construct appropriate classification rules. It is also of interest to develop methods for evaluation of classification performance and ranking of identified biomarkers. The ROC (receiver operating characteristic) technique has been widely used in disease classification with low dimensional biomarkers. Compared with the empirical ROC approach, the binormal ROC is computationally more affordable and robust in small sample size cases. We propose using the binormal AUC (area under the ROC curve) as the objective function for two-sample classification, and the scaled threshold gradient directed regularization method for regularized estimation and biomarker selection. Tuning parameter selection is based on V-fold cross validation. We develop Monte Carlo based methods for evaluating the stability of individual biomarkers and overall prediction performance. Extensive simulation studies show that the proposed approach can generate parsimonious models with excellent classification and prediction performance, under most simulated scenarios including model mis-specification. Application of the method to two cancer studies shows that the identified genes are reasonably stable with satisfactory prediction performance and biologically sound implications. The overall classification performance is satisfactory, with small classification errors and large AUCs. In comparison to existing methods, the proposed approach is computationally more affordable without losing the optimality possessed by the standard ROC method.


Forearm hair density and risk of keratinocyte cancers in Australian adults.
Evidence suggests that progenitor cells of keratinocyte cancers (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) may originate from epidermal stem cells including hair follicle stem cells. We hypothesised that, therefore, a relatively higher density of hair follicles on human skin may increase keratinocyte cancer risk. To evaluate this, we assessed density of mid-forearm hair in Australian adults who were randomly selected participants in a community-based cohort study of skin cancer. Hair density was assessed clinically against a set of four standard photographs showing grades of hair density, and incidence data on histologically confirmed BCC and SCC across a 20-year period were collected. Incidence rate ratios were calculated for categories of forearm hair density using multivariable regression analysis with adjustment for age, sex, phenotypic characteristics and markers of chronic sun exposure. Among the 715 participants (43 % male, average age 61 years), 237 developed at least one BCC and 115 persons developed at least one SCC. Participants with dense forearm hair (n = 169, all male) had a higher incidence of BCC (IRR = 2.24, 95 % CI 1.20, 4.18, P = 0.01) and SCC (IRR = 2.80, 95 % CI 1.20, 6.57, P = 0.02) compared to individuals with sparse forearm hair after multivariable adjustment. Stratified analyses showed that among men, those with dense versus sparse hair developed SCC more commonly (IRR = 3.01, 95 % CI 1.03, 8.78, P = 0.04). Women with moderate versus sparse hair density were more likely affected by BCC (IRR = 2.29, 95 % CI 1.05, 5.00, P = 0.038). Thus, our study suggests that in both men and women, a higher density of body hair may be associated with increased BCC and SCC risk.


Effect of strategic deworming on Ascaris suum exposure and technical performance parameters in fattening pigs.
The aim of this study was to investigate the effect of a strategic deworming program on Ascaris suum infection levels and technical performance parameters in fattening pigs. Eighteen fattening stables were selected and divided into two groups. Group 1 consisted of 9 stables in which the fattening pigs tested seropositive for Ascaris, indicative for the presence of Ascaris eggs in the stable, whereas group 2 consisted of 9 stables in which the fattening pigs tested seronegative for Ascaris, indicating of a low or absent environmental contamination with Ascaris eggs. The production in each stable was monitored for a period of 7 consecutive fattening rounds. The first of these 7 fattening rounds (i.e. round 0), during which no intervention took place in the deworming strategy applied in the stable, served as a historical control. A deworming program using 200 mg/ml fenbendazole oral suspension in drinking water for 2 days every 6 weeks was implemented for a period of 6 consecutive fattening rounds. For each fattening round and for each stable, technical performance parameters including average daily growth, feed conversion ratio, days in fattening and the percentage of affected livers were obtained from the producers. Blood was collected from 10 randomly selected animals per stable at the end of each fattening round and evaluated for the presence of anti-Ascaris antibodies using 2 different serological tests, namely the AsHb- and the L3-Lung ELISA. The serological results obtained indicated a lower exposure of the animals to Ascaris after the implementation of a strategic deworming program. A significant decline in anti-Ascaris antibody levels was detectable in the stables that originally tested positive for Ascaris and was already visible after one treatment round. The outcomes of hierarchical linear mixed models indicated that the level of L3-Lung antibody reactivity was a significant predictor of decreased ADG, increased FCR and prolonged DIF for the Ascaris-positive herds, indicating an effect of Ascaris infections on productivity.


The Quality of Life of Coronavirus Disease Survivors Living in Rural and Urban Area of Riau Province, Indonesia.
This study assesses the status of health-related quality of life (HRQOL) among coronavirus survivors living in rural and urban districts in Riau province, Indonesia. The cross-sectional study was conducted among 468 and 285 Coronavirus disease (COVID-19) survivors living in rural and urban areas, respectively in August 2021. The St. George Respiratory Questionnaire (SGRQ) was used to measure the HRQOL of COVID-19 survivors. A higher total score domain corresponds to worse quality of life status. Quantile regression with the respect to 50th percentile found a significant association for the factors living in rural areas, being female, having comorbidities, and being hospitalized during treatment, with total score of 4.77, 2.43, 7.22, and 21.27 higher than in their contra parts, respectively. Moreover, having received full vaccination had the score 3.96 in total score. The HRQOL of COVID-19 survivors living in rural areas was significantly lower than in urban areas. Factors such as living in rural areas, female sex, having comorbidities, and history of symptomatic COVID-19 infection were identified as significant predictors for lower quality of life. Meanwhile, having full vaccination is a significant predictor for a better quality of life. The results of this study can provide the targeted recommendations for improvement of HRQOL of COVID-19 survivors.


Th and Treg response induced by Aspergillus fumigatus pulsed dendritic cells in vitro.
Dendritic cells (DCs) can recognize the pathogen-associated molecular patterns (PAMP) of Aspergillus fumigatus (A. fumigatus), activating the immune response. During A. fumigatus infection, a Th and Treg response induced in the fungi-pulsed DCs is not yet well understood. In this study, bone marrow-derived dendritic cells (BMDCs) were separated and proliferated from C57BL/6 mice. A. fumigatus pulsed DCs were generated and cultured with CD4(+) T cells derived from the spleen of C57BL/6 mice in vitro. CD4(+) T cells differentiation after co-culture were analyzed by flow cytometry, ELISA, and real-time PCR analysis. The A. fumigatus pulsed DCs exhibited increased Th1 and Treg frequency, Th1-related cytokines (IFN-γ and IL-12), Treg-related cytokines (TGF-β) and T-bet, and Foxp3 mRNA levels compared with the control group. There was no significant difference between A. fumigatus pulsed DCs group and the control group about Th17 and Th2 frequency. The inactivated conidia of A. fumigatus were able to activate BMDCs and made them capable of triggering T cell responses in vitro. A. fumigatus loaded DCs was a weak inducer of Th17 and Th2, but induced a strong Th1 and Treg response.


Polyphenolic composition, antioxidant and antibacterial activities for two Romanian subspecies of Achillea distans Waldst. et Kit. ex Willd.
The aim of this work was to study the chemical composition, antioxidant and antibacterial properties of Achillea distans Waldst. et Kit. subsp. distans and Achillea distans Waldst. et Kit. subsp. alpina Rochel, from the Rodna Mountains (Romania). The identification and quantification of major phenolic compounds was performed by a HPLC-MS method. The total polyphenolic and flavonoid content was determined spectrophotometrically. The antioxidant activity was evaluated using the DPPH bleaching method, trolox equivalent antioxidant capacity assay (TEAC), hemoglobin ascorbate peroxidase activity inhibition (HAPX) assay, and an Electron Paramagnetic Resonance (EPR) spectroscopy method. A data indicated that A. distans subsp. alpina extract has more antioxidant activity than A. distans subsp. distans extract. Luteolin, apigenin, quercetin, caffeic and chlorogenic acids were present in the two extracts of A. distans, but in different amounts. Three flavonoids were detected only in A. distans subsp. alpina. The polyphenol-richer A. distans subsp. alpina extract showed a higher antioxidant activity than A. distans subsp. distans extract. A. distans subsp. distans extract showed inhibitory activity for Gram-positive bacteria, as evaluated with four species. The quantitative and qualitative differences between the two subspecies of Achillea distans could be used as a potential taxonomic marker in order to distinguish the species.


A review of the pharmacological and psychopharmacological aspects of smoking and smoking cessation in psychiatric patients.
The data reviewed confirm that mentally ill patients smoke twice as many cigarettes as patients without mental illness. The secretion of neurotransmitters such as noradrenaline, serotonin, dopamine, acetylcholine, gamma-amino-butyric acid and glutamate is increased by the binding of nicotine to central nicotine receptors. There are also data showing that serotonin formation and secretion in patients with mental illness are influenced by chronic smoking. Cigarette smoke inhibits the activity of monoamine oxidase B, which is responsible for the catabolism of several brain neurotransmitters. Patients suffering from major depression show a comorbidity between heavy smoking and the disease. In patients with schizophrenia treated with neuroleptics, increased cigarette smoking reduces adverse reactions to the drug therapy presumably because of an increase in metabolism of the neuroleptics. There is also evidence suggesting that quitting smoking is more difficult for mentally ill patients than patients without psychiatric disease. Several studies have been carried out on smoking cessation in psychiatric patients. The alternative method of harm reduction, e.g. reducing the number of cigarettes smoked using nicotine patches or chewing gum, is necessary in patients not able to quit. The data indicate that strategies such as the coupling of smoking prohibition with administration of nicotine preparations are useful in smoking cessation. A no-smoking policy in psychiatric clinics, even when this leads to withdrawal symptoms in the patients affected, has no negative effect on mental illness. Because patients with mental diseases are particularly vulnerable to the marketing strategies of the tobacco industry, this chronically ill section of the population requires special protection by the law-makers.


Long-term stability of mandibular incisors following successful treatment of Class II, Division 1, malocclusions.
The purpose of this study was to evaluate the long-term stability of mandibular anterior alignment in a large group of Class II, Division 1, patients who demonstrated successful occlusal results at the end of active treatment. The specific aim was to search for predictors of relapse and associations between relapse and other post-retention changes. The sample of 78 adolescents was limited to successfully treated cases as judged by subjective evaluation of intercuspation and incisor occlusion of posttreatment study models. Neither cephalometric characteristics nor post-retention occlusion were considered in sample selection. Of these patients, study models and cephalograms were available pretreatment, at the end of active treatment, and a mean of 14 years post-retention. The results demonstrated an increase of incisor irregularity and a reduction of intercanine width and arch length post-retention. At post-retention, 9.0% had irregularity index values of 6.5 mm or more and 47.4% had values equal to 3.5 mm or less. Stepwise backward multiple regression analyses revealed that narrow pretreatment intercanine width and high pretreatment incisor irregularity were significant predictors of relapse. Treatment increase of intercanine width and post-retention decrease of intercanine width and arch length were associated with relapse.


Restoration of conduction and growth of axons through injured spinal cord of neonatal opossum in culture.
The ability of neurons in the central nervous system to grow through a lesion and restore conduction has been analyzed in a developing spinal cord. The preparation consists of the entire central nervous system of the newly born opossum (Monodelphis domestica), isolated and maintained in culture. Cell division, cell migration, and reflexes are maintained in such preparations for up to 8 days in culture. In the present experiments, massive lesions were produced by crushing the spinal cord, which abolished all conduction for a day. By 2-3 days after injury, electrical conduction across the crush could be observed. After 4-5 days, clear recovery had occurred: the amplitude of the conducted volley was comparable to that in acute preparations. In such preparations, the spinal cord had largely regained its normal appearance at the crush site. Axons stained by carbocyanine dyes or horseradish peroxidase had, by 4 days, grown in profusion through the lesion and several millimeters beyond it. These experiments demonstrate that neurons in the central nervous system of newly born mammals, unlike those in adults, can respond to injury by rapid and extensive outgrowth in the absence of peripheral nerve bridges or antibodies that neutralize inhibitory factors of myelin. With rapid and reliable regeneration occurring in vitro, it becomes practicable to assay the effects of molecules that promote or inhibit the restoration of functional connections.


Detection of different tumor growth kinetics in single transgenic mice with oncogene-induced mammary carcinomas by flat-panel volume computed tomography.
Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm(3)) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns.


Myocardial viability independently influences left ventricular diastolic function in the early phase after acute myocardial infarction.
After acute myocardial infarction, a broad range of left ventricular (LV) end-diastolic pressure (LVEDP) is expected because of chamber remodeling. However, intrinsic characteristics of the infarcted tissue (necrosis or viability) may also play a role. We aimed to evaluate whether myocardial viability (Mviab) has an influence on LVEDP. One hundred twenty-three consecutive patients with acute myocardial infarction underwent low-dose dobutamine echocardiography (5-10 microg/kg/min) to assess Mviab. Mviab was quantitatively evaluated by the variation of Delta wall motion score index. Patients underwent left heart catheterization with recording of LVEDP and a complete echocardiographic examination with measurement of LV volumes, ejection fraction, and mass. The overall population (81% male; mean age 58 +/- 10 years) was divided into 2 groups according to the presence (group 1; 66 patients) or absence (group 2; 57 patients) of Mviab. LVEDP was higher in patients without Mviab (16 +/- 8 vs 20 +/- 7 mm Hg; P =.02). The multivariate analysis showed that Delta wall motion score index correlated with LVEDP (P =.01) independent of wall motion score index and LV end-systolic volume. After acute myocardial infarction, LVEDP shows wide variability and is independently associated with Mviab.


Advanced dental disease in people with severe mental illness: systematic review and meta-analysis.
Psychiatric patients have increased comorbid physical illness. There is less information concerning dental disease in this population in spite of risk factors including diet and psychotropic side-effects (such as xerostomia). Aims To compare the oral health of people with severe mental illness with that of the general population. A systematic search for studies from the past 20 years was conducted using Medline, PsycINFO, Embase and article bibliographies. Papers were independently assessed. The primary outcome was total tooth loss (edentulousness), the end-stage of both untreated caries and periodontal disease. We also assessed dental decay through standardised measures: the mean number of decayed, missing and filled teeth (DMFT) or surfaces (DMFS). For studies lacking a control group we used controls of similar ages from a community survey within 10 years of the study. We identified 21 papers of which 14 had sufficient data (n = 2784 psychiatric patients) and suitable controls (n = 31 084) for a random effects meta-analysis. People with severe mental illness had 3.4 times the odds of having lost all their teeth than the general community (95% CI 1.6-7.2). They also had significantly higher scores for DMFT (mean difference 6.2, 95% CI 0.6-11.8) and DMFS (mean difference 14.6, 95% CI 4.1-25.1). Fluoridated water reduced the gap in oral health between psychiatric patients and the general population. Psychiatric patients have not shared in the improving oral health of the general population. Management should include oral health assessment using standard checklists that can be completed by non-dental personnel. Interventions include oral hygiene and management of xerostomia.


Changes of the retinal and choroidal vasculature in cerebral small vessel disease.
Cerebral small vessel disease (CSVD) is associated with changes in the retinal vasculature which can be assessed non-invasively with much higher resolution than the cerebral vasculature. To detect changes at a microvascular level, we used optical coherence tomography angiography which resolves retinal and choroidal vasculature. Participants with CSVD and controls were included. White matter lesions were determined on magnetic resonance imaging (MRI). The retinal and choroidal vasculature were quantified using swept-source optical coherence tomography angiography. Data were analysed using linear regression. We included 30 participants (18 females; patients, n = 20; controls, n = 10) with a mean age of 61 ± 10 years. Patients had a higher mean white matter lesion index and number of lesions than controls (p ≤ 0.002). The intraindividual deviation of choriocapillaris reflectivity differed significantly between age-matched patients (0.234 ± 0.012) and controls (0.247 ± 0.011; p = 0.029). Skeleton density of the deep retinal capillaries was significantly associated with the number of lesions on MRI (β = - 5.3 × 108, 95%-confidence interval [- 10.3 × 108; - 0.2 × 108]) when controlling for age. The choroidal microvasculature and the deep retinal vascular plexus, as quantified by optical coherence tomography angiography, are significantly altered in CSVD. The value of these findings in diagnosing or monitoring CSVD need to be assessed in future studies.


[Electrochemical degradation of sodium pentachlorophenol on a Pd/C gas-diffusion electrode].
Pd/C catalyst was prepared by hydrogen reduction method and used for the Pd/C gas-diffusion electrode. It was characterized by cyclic voltammetry (CV) techniques. The electrochemical degradation of sodium pentachlorophenol (PCP-Na) was investigated in a diaphragm electrolysis device, feeding firstly with hydrogen gas then with air, using the Pd/C gas-diffusion electrode and the carbon/polytetrafluoroethylene (C/PTFE) gas-diffusion electrode as the cathode, respectively. The results indicate that the two-electron reduction from O2 to hydrogen peroxide (H2O2) is produced at the Pd/C gas-diffusion electrode, and the accumulated H2O2 in the cathodic compartment reach to the steady concentration of 9.8 mg/L after 100 min. The Pd/C gas-diffusion cathode can reductively dechlorinate PCP-Na by feeding hydrogen gas, and accelerate the two-electron reduction of O2 to hydrogen peroxide (H2O2) by feeding air. Therefore, both the removal efficiency and the dechlorination degree of PCP-Na exceed 80% after 100 min, and the average removal efficiency of PCP-Na in terms of total organic carbon (TOC) exceeds 75% after 200 min by using Pd/C gas-diffusion cathode,which is better than that of the C/PTFE gas-diffusion cathode. High performance liquid chromatography (HPLC) allows identifying phenol as the dechlorination product.


Cloning of cDNAs encoding the human BAG1 protein and localization of the human BAG1 gene to chromosome 9p12.
cDNAs encoding the human homolog of BAG1, a Bcl-2-binding protein with anti-apoptotic function, were cloned. DNA sequence analysis of human BAG1 cDNAs predicts a protein with an additional 55 amino acids at its NH2-terminus compared to the mouse protein. Immunoblot assays using monoclonal antibodies raised against bacterially produced h-BAG1 protein confirmed the larger size of the human protein (approximately 34 kDa) compared to mouse. PCR analysis of DNA from human x rodent somatic cell hybrids using human BAG1-specific primers localized the gene to human chromosome 9. Cosmid clones of h-BAG1 were obtained and used for fluorescence in situ hybridization analysis of normal metaphase chromosomes, thus localizing h-BAG1 to 9p12, a region associated with hereditary disorders that may involve developmental dysregulation of programmed cell death.


Needs assessment and impact of COVID-19 on pharmacy professionals in 31 commonwealth countries.
The declaration of COVID-19 a pandemic by the World Health Organization on 11 March 2020 marked the beginning of a global health crisis of an unprecedented nature and scale. The approach taken by countries across the world varied widely, however, the delivery of frontline healthcare was consistently recognised as being central to the pandemic response. This study aimed to identify and explore the issues currently facing pharmacy teams across Commonwealth countries during the COVID-19 pandemic. The study also evaluates pharmacy professionals' understanding of key knowledge areas from the COVID-19 webinar hosted by the Commonwealth Pharmacists' Association (CPA). A quantitative survey-based approach was adopted, using a 32-item questionnaire developed from the literature on pharmacy and pandemic response. The survey was hosted on Survey Monkey and pilot tested. The final survey was disseminated by CPA member organisations. A 6-item online questionnaire was sent via email to all attendees of CPA's COVID-19 webinar. Descriptive statistics on frequency distributions and percentages were used to analyse the responses. Data were analysed using Microsoft® Excel (2010). There were 545 responses from pharmacy professionals across 31/54 Commonwealth countries in Africa, Asia, the Americas, Europe and the Pacific. Majority of the respondents reported being at least somewhat worried (90%) and more than 65% were very worried or extremely about the impact of COVID-19 on them personally and professionally. Nearly two-thirds of respondents stated finding it somewhat difficult or very difficult to work effectively during the pandemic. Challenges mostly faced by pharmacy professionals working remotely included; general anxiety about the impact of COVID-19 on their lives (12%), and difficulties in communicating with their co-workers (12%). Most pharmacy professionals had not previously been actively involved in a global health emergency (82%) nor obtained training on global/public health emergency preparedness (62%). Between 45 and 97% of the COVID-19 webinar attendees provided the correct answers to post-webinar questions, suggesting some improvement in knowledge. Our study confirms pharmacy professionals' concerns about practice during a pandemic and provides preliminary data on the challenges and learning needs of the profession. The CPA has since acted on these findings, providing ongoing opportunities to develop and refine resources for the profession as the pandemic evolves. Pharmacy professionals have also demonstrated improved knowledge on the management of COVID-19 and resources available for professionals.


The effect of direct cell injury inflicted by cryotherapy on eyelid sebaceous gland carcinoma cells: An ex-vivo experimental study.
To evaluate the effect of direct cell injury of cryotherapy on eyelid sebaceous gland carcinoma cells by an ex vivo cryotherapy experiment. It was a prospective interventional case series. Six patients with biopsy-proven nodular sebaceous gland carcinoma were included. After excision of the mass, a thin slice of the mass resembling the thickness of the conjunctiva was shaved off and was oriented over the broad end of a tissue forceps. Cryotherapy was applied to both its anterior and posterior aspects by the triple freeze-thaw technique. The mass was then labeled and sent separately for histopathological evaluation by fixation and staining. A total of six patients with a mean age of 58.2 ± 15.5 years were included. There were four females and two males. The mean duration of the lesion was 21.6 ± 17.51 months. All patients had involvement of the upper eyelid. The patients were clinically staged as T2b (n=2), T1a (n=2), T2c (n=1), and T3a (n=1) respectively. There was no regional lymphadenopathy or metastasis in any of the cases. The experimental cryo-tissue containing the cryo-treated lesion revealed the presence of viable tumor cells (>50%) in all six specimens. The direct cell injury caused by cryotherapy may not be sufficient to kill all the residual sebaceous gland carcinoma cells on the tumor bed.


Bordetella pertussis invasive adenylate cyclase. Partial resolution and properties of its cellular penetration.
The existence of an invasive adenylate cyclase in dialyzed urea extracts of the bacterium Bordetella pertussis has been suggested recently. Gel filtration of B. pertussis dialyzed urea extract shows that the invasive enzyme constitutes only a small portion of the total adenylate cyclase activity found in the extract. Its size is different than the size of the two peaks of adenylate cyclase activity identified in the extract. Ca2+ is absolutely required for the penetration of the invasive enzyme, it also controls the rate of intracellular cAMP accumulation in human lymphocytes exposed to dialyzed extract. These characteristics may be attributed to the increase in the size of the invasive enzyme as found by gel filtration chromatography of the extract in the absence of Ca2+. Removal of nonpenetrating adenylate cyclase that adheres to lymphocytes permits a direct assay of the intracellular enzyme. The time course of intracellular accumulation of adenylate cyclase activity is similar to the time course of intracellular accumulation of cAMP, suggesting that the invasive enzyme is rapidly deactivated, but not degraded, since it can be detected upon cell disruption. No appreciable amount of the enzyme is introduced when cells are incubated with extract at 4 degrees C for 120 min, then washed and incubated further at 37 degrees C. Concanavalin A inhibits cAMP accumulation irrespective of the time of its addition, and EGTA prevents penetration of the invasive enzyme even if added 20 min after addition of extract. These findings are different from those observed in other bacterial toxins thought to be internalized by receptor-mediated endocytosis. However, the cellular penetration of B. pertussis adenylate cyclase is cell-selective. It does not occur in human erythrocytes. In addition to human lymphocytes, S49 cyc- murine lymphoma, turkey erythrocytes, and rat oocytes accumulate cAMP in response to B. pertussis extract.


Readiness to Change and Prospective Effects of Weight Management Programs in Pediatric Nonalcoholic Fatty Liver Disease.
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem in pediatrics with limited treatment options. We prospectively assessed outcomes in patients managed in a hepatology clinic (HC) alone vs. those managed in combination with a multidisciplinary weight management program (MWMP). We describe each group's readiness to change at the time of NAFLD diagnosis. Patients diagnosed with NAFLD were given a modified Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) at enrollment (T1) to assess readiness to change. They were then followed at 3-9 months (T2) and at 10-15 months (T3). Linear mixed models were used to evaluate changes in body mass index (BMI), BMI z-score, and transaminases over time and between the two groups. There were no significant treatment group main effects or treatment × time interactions for our primary end points for HC alone (n = 75) or with MWMP (n = 18). There was a significant main effect for time for BMI z-score, with BMI z-scores declining on average by 0.0568 (P = 0.004) from visit to visit. Low SOCRATES subscales scores in HC alone (n = 33) or with MWMP (n = 4) suggested a patient population with low recognition of disease and likelihood of taking steps for change. Patients with obesity and NAFLD had low scores on all three SOCRATES subscales. Despite this, both groups had improvement in BMI z-score without significant difference between the two treatment groups in other primary end points. Further study is needed to identify the most effective patient selection and treatment strategies for pediatric patients with NAFLD, including pharmacotherapy and surgery.


Antibiotic Use for Growth Promotion in Animals: Ecologic and Public Health Consequences.
Antibiotics have successfully treated infectious diseases in man, animals and agricultural plants. However, one consequence of usage at any level, subtherapeutic or therapeutic, has been selection of microorganisms resistant to these valuable agents. Today clinicians worldwide face singly resistant and multiply resistant bacteria which complicate treatment of even common infectious agents. This situation calls for a critical evaluation of the numerous ways in which antibiotics are being used so as to evaluate benefits and risks. About half of the antibiotics produced in the United States arc used in animals, chiefly in subtherapeutic amounts for growth promotion. This usage is for prolonged periods leading to selection of multiply-resistant bacteria which enter a common environmental pool. From there, resistance determinants from different sources spread from one bacterium to another, from one animal host to another, from one area to another. The same resistance determinants have been traced to many different genera associated with humans, animals and foods where they pose a continued threat to public health. Since alternative measures for growth promotion, such as antimicrobials which are not used for human therapy and which do not select for multiple-resistances are available, their use, instead of antibiotics, would remove a major factor contributing to the environmental pool of transferable resistance genes.


Evaluation of fetal pulmonary maturity by gas-chromatographic analysis of amniotic fluid palmitic acid/stearic acid (P/S) ratio.
Gas-chromatographic analysis of the fatty acids (P/S ratio) in 212 samples of amniotic fluid, 35 samples of vernix caseosa and 35 samples of the pellets obtained after centrifugation of the amniotic fluid were carried out to evaluate the effects of contaminants that might be present in amniotic fluid on the P/S ratio. The P/S ratio is used as an index of the degree of maturity of the fetal or neonatal lungs. Analysis of variance applied to the means of the P/S values for each of above materials showed them to be significantly different and attests to the importance of centrifugation for obtaining valid results. We propose a standard procedure of centrifugation for 60 minutes at 3500 X g followed by extraction and gas-chromatography as a rapid, valid way to measure the P/S ratio.


Structural characterization of chromone C-glucosides in a toxic herbal remedy.
Two novel compounds, 8-C-D-glucopyranosyl-7-hydroxy-5-methylchromone-2-carboxylic acid and a 2-O'-p-coumaroyl derivative thereof, were identified in a herbal tea that caused severe vomiting in a South African patient who had taken the traditional remedy to clean his stomach. For structural characterization, electrospray (ES) ionization in combination with collision-induced dissociation (CID) and tandem mass spectrometry (MS/MS) were used, as well as UV and nuclear magnetic resonance (NMR) spectroscopy. Specific ions or neutral losses generated under conditions of ES-MS/CID/MS permitted the establishment of structural features such as the free carboxyl group, the C-hexosidic part and the p-coumaroyl group. NMR spectroscopy was necessary to support the structure of the chromone-type aglycone and the glucosidic parts. Since the compounds are structurally related to aloesin and aloeresin A, which are chemotaxonomic markers of Aloe species, and have not been previously reported, we propose that they were formed by oxidative degradation during preparation of the herbal tea from an Aloe species or during its storage.


Characterization of the genome of the mealybug Planococcus lilacinus, a model organism for studying whole-chromosome imprinting and inactivation.
The co-occurrence of three chromosome-wide phenomena--imprinting, facultative heterochromatization and diffuse centromere--in the mealybug Planococcus lilacinus makes investigation of the genomics of this species an attractive prospect. In order to estimate the complexity of the genome of this species, 300 random stretches of its DNA, constituting approximately 0.1% of the genome, were sequenced. Coding sequences appear to constitute approximately 53.5%, repeat sequences approximately 44.5% and non-coding single-copy sequences approximately 2% of the genome. The proportion of repetitive sequences in the mealybug is higher than that in the fruit fly Drosophila melanogaster (approximately 30%). The mealybug genome (approximately 220 Mb) is about 1.3 times the size of the fly genome (approximately 165 Mb) and its GC content (approximately 35%) less than that of the fly genome (approximately 40%). The relative abundance of various dinucleotides, as analysed by the method of Gentles and Karlin, shows that the dinucleotide signatures of the two species are moderately similar and that in the mealybug there is neither over-representation nor under-representation of any dinucleotide.


Studies of nontraumatic osteonecrosis. Manometric and histologic studies of the femoral head after chronic steroid treatment: an experimental study in rabbits.
High-dose methylprednisolone was administered to adult rabbits over a five- to nine-week period, according to previously described experimental models of nontraumatic osteonecrosis (NON). Manometric studies were performed using a sensitive computer-directed microvolume flow system. Osteocyte viability within the femoral head was assessed by counting empty osteocyte lacunae in five random high-power fields of hematoxylin- and eosin-stained sections. There was no significant elevation of intramedullary pressure or venous outflow resistance in femoral heads of animals receiving steroids, and a significant random loss of osteocytes was observed in these femoral heads. The clinical relevance of these studies is as follows. NON associated with steroids may not simply be the result of progressive ischemia. Ischemia and elevated intramedullary pressure may be epiphenomena, and a direct cytotoxic effect of steroids on osteocytes may be the earliest event in the development of nontraumatic osteonecrosis. The stress test, as it is currently being used in the clinical setting, may be unreliable.


Asymmetric cell division requires specific mechanisms for adjusting global transcription.
Most cells divide symmetrically into two approximately identical cells. There are many examples, however, of asymmetric cell division that can generate sibling cell size differences. Whereas physical asymmetric division mechanisms and cell fate consequences have been investigated, the specific problem caused by asymmetric division at the transcription level has not yet been addressed. In symmetrically dividing cells the nascent transcription rate increases in parallel to cell volume to compensate it by keeping the actual mRNA synthesis rate constant. This cannot apply to the yeast Saccharomyces cerevisiae, where this mechanism would provoke a never-ending increasing mRNA synthesis rate in smaller daughter cells. We show here that, contrarily to other eukaryotes with symmetric division, budding yeast keeps the nascent transcription rates of its RNA polymerases constant and increases mRNA stability. This control on RNA pol II-dependent transcription rate is obtained by controlling the cellular concentration of this enzyme.


Mechanisms of arousal from sleep and their consequences.
In recent years, understanding of the mechanisms by which sleep is maintained and the consequences of abnormal arousal from sleep has improved rapidly. This review describes the recent insights into the nature of sleep and arousal and the particular insights gained in common disease states such as sleep-disordered breathing. Expansion of the definitions of the classic stages of non-REM and REM sleep to include consideration of the role of cyclic alternating pattern sleep as a gating mechanism for arousal and maintenance of stable sleep has led to a significant advancement in understanding the nature of normal and pathologic arousals from sleep. In addition, the effect of arousals from sleep on cerebral cortical electrophysiology and autonomic activation has been further defined, with a potential effect on clinical practice. Arousal from sleep is dependent on wake-promoting influences overwhelming forces promoting sleep. Autonomic activation and cortical arousal can significantly affect and destabilize sleep homeostasis. The understanding of sleep-respiration interactions continues to evolve. The definition of the minimal arousal event is an important research goal. It will be important in clinical practice and research to consider sleep stability domains as a complement to sleep depth staging to allow better understanding of the relative stability and instability of the system and to consider all components of the consequences of arousal.


Morphology of the distal radioulnar joint: cadaveric study with MRI and MR arthrography with the forearm in neutral position, pronation, and supination.
The purpose of this study was to evaluate the physiologic extent and thickness of the cartilage and bare areas of the distal radioulnar joint with gross anatomic examination, MRI, and MR arthrography with the forearm in neutral position, maximal pronation, and maximal supination. MRI and MR arthrography were performed on 10 cadaveric specimens (mean age at death, 82.9 years; range, 56-97 years) with the forearm in neutral position, maximal pronation, and maximal supination. Cartilage surface and thickness were assessed, and degenerative changes and bare areas were evaluated in consensus by two musculoskeletal radiologists. Gross anatomic and histologic examinations were used as the reference standard. MRI in maximal pronation and supination was helpful in evaluation of the ulnar cartilage. In the axial plane, any change in cartilage thickness in the ulnar head was related to chondral degeneration. In the coronal plane, cartilage thickness proved to be an unreliable sign in the assessment of chondral degeneration. The presence of osteophytes in the proximal aspect of the joint was easily detected and proved to be a reliable criterion for joint degeneration. Bare areas were found at the proximal and volar attachments of the joint capsule. Detailed knowledge of the anatomy of the distal radioulnar joint should allow more accurate assessment of degenerative changes and localization of erosions in inflammatory joint disease. Imaging with the forearm in maximal pronation and supination can improve visualization of the cartilage of the ulnar head.


Sensitivity of the nonlinear joint transform correlator: experimental investigations.
Experiments are provided to investigate nonlinear joint transform correlator sensitivity to scaling and rotation changes of input objects for various degrees of nonlinearity applied to the joint power spectrum. The experimental results for the images used here show that a severe nonlinear transformation of the joint power spectrum increases the sensitivity of the correlation peak intensity to scaling and rotation changes of input objects. However, the correlation peak-to-sidelobe ratio of the nonlinear joint transform correlator remains higher than the linear joint transform correlator. These experiments indicate that, in the presence of input signal rotation or scale changes, the performance of the nonlinear joint transform correlator may be better than the linear joint transform correlator. The effect of the modulation transfer function of the spatial light modulator on the nonlinear joint transform correlator performance in the presence of multiple input targets is discussed.


[Rehabilitation of women suffering chronic cystitis in the postmenopausal period with the use of an AMUS-01 - Intramag apparatus equipped with a Rektomassazher device].
The objective of the present study was to develop a rationale for the local treatment of chronic recurring cystitis in the postmenopausel period. To this effect, 76 patients at the mean age of 66.4 years with this pathology were examined and the data obtained were compared with observations of control postmenopausel women receiving traditional local substitution hormonal therapy. In the patients of the study group, this treatment was supplemented by intravaginal vibro-magnetotherapy and the conventional antibacterial therapy was replaced by local electrophoresis. All local physiotherapeutic procedures were performed with the use of a AMUS-01 - Intramag apparatus equipped with a Rektomassazher device an AMUS-01 - Intramag apparatus equipped with a Rektomassazher device. The immunological analysis of vaginal secretion coupled to bacterial and clinical investigations have demonstrated the advantages of the combined local treatment including physiotherapy. The integral efficacy index was by a factor of 1.8 higher than in the control group.


Immune response to second dose of MMR vaccine in Indian children.
MMR vaccine in a two dose schedule has successfully eliminated measles, mumps and rubella from many developed countries. In India, it is not a part of national immunization programme but is included in the State immunization programme of Delhi as a single dose between 15-18 months. This prospective study was carried out to assess the extent of seroprotection against these three diseases in immunized children and to study the immune response to a second dose of MMR. Consecutive children aged 4-6 yr, attending the immunization clinic of a tertiary care hospital in Delhi for routine DT vaccination, were enrolled. Second dose of MMR was given and pre- and post-vaccination antibody levels were compared. The pre-vaccination percentage seropositivity observed in the 103 children recruited, was 20.4 per cent for measles, 87.4 per cent for mumps and 75.7 per cent for rubella. Amongst the 84 children who were followed up after the second dose, the percentage seroprotection for measles rose from 21.4 (18/84) to 72.6 per cent (61/84) and 100 per cent became seroprotected to mumps and rubella. The percentage of children protected against measles was found to be alarmingly low which needs to be investigated. Though the observed protection against mumps and rubella was adequate, its durability was not known. The need for re-appraisal of the current MMR immunization policy is called for by carrying out longitudinal studies on a larger sample.


Density and chain conformation profiles of square-well chains confined in a slit by density-functional theory.
Density and chain conformation profiles of square-well chains between two parallel walls were studied by using density-functional theory. The free energy of square-well chains is separated into two contributions: the hard-sphere repulsion and the attraction. The Heaviside function is used as the weighting function for both of the two parts. The equation of state of Hu et al. is used to calculate the excess free energy of the repulsive part. The equation of state of statistical associating fluid theory for chain molecules with attractive potentials of variable range [A. Gil-Villegas et al. J. Chem. Phys. 106, 4168 (1997)] is used to calculate the excess free energy of the attractive part. Because the wall is inaccessible to a mass center of a longer chain, there exists a sharp fall in the distribution of end-to-end distance near the wall as the chain length increases. When the average density of the system is not too low, the prediction of this work is in good agreement with computer simulation results for the density profiles and the chain conformation over a wide range of chain length, temperature, and attraction strength of the walls. However, when the average density and the temperature are very low, the prediction deviates to a certain degree from the computer simulation results for molecules with long chain length. A more accurate functional approximation is needed.


Improving client-centred care and services: the role of front/back-office configurations.
This paper is a report of a study conducted to explore the application of designing front- and back-office work resulting in efficient client-centred care in healthcare organizations that supply home care, welfare and domestic services. Front/back-office configurations reflect a neglected domain of design decisions in the development of more client-centred processes and structures without incurring major cost increases. Based on a literature search, a framework of four front/back-office configurations was constructed. To illustrate the usefulness of this framework, a single, longitudinal case study was performed in a large organization, which provides home care, welfare and domestic services for a sustained period (2005-2006). The case study illustrates how front/back-office design decisions are related to the complexity of the clients' demands and the strategic objectives of an organization. The constructed framework guides the practical development of front/back-office designs, and shows how each design contributes differently to such performance objectives as quality, speed and efficiency. The front/back-office configurations presented comprise an important first step in elaborating client-centred care and service provision to the operational level. It helps healthcare organizations to become more responsive and to provide efficient client-centred care and services when approaching demand in a well-tuned manner. In addition to its applicability in home care, we believe that a deliberate front/back-office configuration also has potential in other fields of health care.


In vitro comparison of digital and conventional bitewing radiographs for the detection of approximal caries in primary teeth exposed and viewed by a new wireless handheld unit.
The aim of this study was to compare the diagnostic quality of a new wireless handheld unit (ADX4000; Dexcowin Co. Ltd, Korea) on conventional bitewings and its LCD screen for the detection of approximal caries in primary teeth. In total, 108 approximal surfaces of primary teeth were examined in vitro by 3 observers. Conventional films were viewed under subdued lighting conditions on a conventional view box. Digital 3.5 inch images were displayed on the built-in monitor of the ADX4000 and digital 17 inch images were viewed on a 17 inch monitor. The true caries diagnosis was based on histological assessment of the approximal surfaces after sectioning the primary teeth. Receiver operating characteristic (ROC) curve (A(z)) analysis was used to assess the diagnostic quality of imaging modalities. The areas under the ROC curves ranged from 0.786 (digital 17 inch) to 0.813 (digital 3.5 inch). No statistically significant differences were found between the three modalities for detecting approximal caries. It was concluded that the diagnostic quality of conventional film and digital images, which were exposed and viewed by a new wireless handheld unit, was comparable.


Adjuvant treatment with concomitant radiotherapy and chemotherapy in high-risk endometrial cancer: a clinical experience.
The concurrent use of radiotherapy (RT) and chemotherapy (CT) as adjuvant treatment after surgery in high-risk endometrial cancer has been generally considered cautiously. Recently some of us have reported preliminary data on the efficacy and tolerability of concomitant CT and RT. In this paper, we update our experience. A total of 47 patients aged >18 years and <80 years with histological diagnosis of high-risk endometrial endometrioid carcinomas entered the study. Inclusion criteria were stages IC G3, IIB, IIIA (patients with positive washing without other unfavourable prognostic factors were omitted), IIIB and IIIC. The radiation plan consisted of a total dose of 50.4 Gy, given in five fractions per week (1.8 Gy: daily dose) for 6 weeks. Paclitaxel (P) at a dose of 60 mg/m(2) was infused intravenously in 250 mL of normal saline for 1 h once weekly during RT for 5 weeks. Three further cycles of Paclitaxel, at a dose of 80 mg/m(2), have been given weekly at the end of RT. There was no life-threatening toxicity. The overall 5-year relapse-free survival was 81.8% (95% CI, 65.2-90.9). The 5-year percent overall disease-specific survival was 88.4% (95% CI, 71.1-95.6). These results, based on a larger series, support our previous data: Paclitaxel plus RT may represent an effective and well-tolerated treatment in high-risk endometrial cancer patients.


Spontaneous chronic spinal subdural hematoma associated with spinal arachnoiditis and syringomyelia.
Spontaneous chronic spinal subdural hematoma is rare. We describe a case of spontaneous chronic spinal subdural hematoma associated with arachnoiditis and syringomyelia in a 76-year old woman who presented with a 14-year history of progressive myelopathy. MRI scan revealed a thoraco-lumbar subdural cystic lesion and a thoracic syrinx. The patient underwent thoracic laminectomy and decompression of the lesion, which was a subdural hematoma. A myelotomy was performed to drain the syrinx. Pathological examination revealed features consistent with chronic subdural membrane. This report attempts to elucidate the pathogenesis of chronic spinal subdural hematoma. We discuss possible etiological factors in light of the current literature and pathogenesis of both spinal subdural hematoma and syrinx formation.


Outcomes of stereotactic ablative radiotherapy for centrally located early-stage lung cancer.
The use of stereotactic ablative radiotherapy (SABR) in centrally located early-stage lung tumors has been associated with increased toxicity. We studied outcomes after delivery of risk-adapted SABR of central tumors. SABR was delivered in eight fractions of 7.5 Gy to 63 such patients between 2003 and 2009. Of these, 37 patients had a tumor at a central hilar location, whereas 26 patients had tumors abutting the pericardium or mediastinal structures. Survival outcomes were compared with patients with peripheral tumors treated during the same time period using fewer fractions of SABR. Median follow-up was 35 months. Late grade III toxicity was limited to chest wall pain (n = 2) and increased dyspnoea (n = 2). No grade IV/V toxicity was observed, but grade V toxicity could not be excluded with certainty in nine patients who died of cardiopulmonary causes. Distant metastases were the predominant cause of death; cardiovascular deaths were not associated with a paracardial tumor location. No significant differences in outcomes were observed between these 63 patients and 445 other SABR patients treated for peripheral early-stage lung tumors. Three-year local control rates were 92.6% and 90.2% (p = 0.9). Three-year overall survival rates were 64.3% and 51.1% with median survival rates of 47 and 36 months, in favor of the group of patients with central tumors (p = 0.09). Use of risk-adapted SABR delivered in eight fractions of 7.5 Gy did not result in excess toxicity for centrally located early-stage lung tumors, and clinical outcomes were comparable with those seen for peripheral lesions.


MARK1 is a Novel Target for miR-125a-5p: Implications for Cell Migration in Cervical Tumor Cells.
Aberrant miRNA expression is associated with the development of several diseases including cervical cancer. Dysregulation of miR-125a-5p is present in a plethora of tumors, but its role in cervical cancer is not well understood. The aim was to analyze the expression profile of miR-125a-5p in tumor and immortal cell lines with further target prediction, validation and function analysis. MiR-125a-5p expression was determined by real-time RT-PCR from nine cervical cell lines. In silico tools were used to find target transcripts with an miR-125-5p complementary site within the 3'UTR region. Further target selection was based on gene ontology annotation and ΔG analysis. Target validation was performed by transfection of synthetic miR-125a-5p mimics and luciferase assays. Functional evaluation of miR-125a-5p on migration was performed by transwell migration assays. Differential miR-125a-5p expression was observed between immortal and tumor cells regardless of the human papillomavirus (HPV) content. Thermodynamic and ontological analyses showed Microtubule-Affinity-Regulating Kinase1 (MARK1) as a putative target for miR-125a-5p. An inverse correlation was observed among miR-125a-5p expression and MARK1 protein levels in tumor but not in immortal cells. Luciferase assays showed direct miR-125a-5p regulation over MARK1 through recognition of a predicted target site within the 3'-UTR. HeLa and C-33A cervical tumor cells enhanced migration after transfection with miR-125a-5p mimics and stimulation of cell migration was reproduced by siRNA-mediated inhibition of MARK1. The results showed MARK1 as a novel functional target for miR-125a-5p with implications on cell migration of tumor cervical cancer cells.


Subunit exchange of small heat shock proteins. Analysis of oligomer formation of alphaA-crystallin and Hsp27 by fluorescence resonance energy transfer and site-directed truncations.
alphaA-Crystallin, a member of the small heat shock protein (sHsp) family, is a large multimeric protein composed of 30-40 identical subunits. Its quaternary structure is highly dynamic, with subunits capable of freely and rapidly exchanging between oligomers. We report here the development of a fluorescence resonance energy transfer method for measuring structural compatibility between alphaA-crystallin and other proteins. We found that Hsp27 and alphaB-crystallin readily exchanged with fluorescence-labeled alphaA-crystallin, but not with other proteins structurally unrelated to sHsps. Truncation of 19 residues from the N terminus or 10 residues from the C terminus of alphaA-crystallin did not significantly change its subunit organization or exchange rate constant. In contrast, removal of the first 56 or more residues converts alphaA-crystallin into a predominantly small multimeric form consisting of three or four subunits, with a concomitant loss of exchange activity. These findings suggest residues 20-56 are essential for the formation of large oligomers and the exchange of subunits. Similar results were obtained with truncated Hsp27 lacking the first 87 residues. We further showed that the exchange rate is independent of alphaA-crystallin concentration, suggesting subunit dissociation may be the rate-limiting step in the exchange reaction. Our findings reveal a quarternary structure of alphaA-crystallin, consisting of small multimers of alphaA-crystallin subunits in a dynamic equilibrium with the oligomeric complex.


Identification of high- and low-risk second kidney grafts.
The purpose of this study was to identify recipients who are at low or high risk of early cadaveric regraft failure by segregating results of the flow cytometric crossmatch (FCXM) test with previous graft survival time (PGST). Early immunologic kidney regraft failure was analyzed in 103 multicenter recipients by cross-stratifying FCXM negative/positive status with < or =3- and >3-month PGST. T cell and B cell cytotoxicity crossmatches were negative. All were tested retrospectively in the T cell FCXM and 60 of the 103 were also tested in the B cell FCXM. A positive T and B cell FCXM was defined as a mean channel shift of > or = 9 (256 channel log scale) or > or = 40 (1024 channel log scale) for pretransplant crossmatch serum above negative control serum. Recipients received triple immunosuppression therapy and limited-use antilymphocyte induction therapy. Early cadaveric regraft losses were biopsied. Comparably good rates of second kidney graft survival at 3 years were found among three ow risk subsets: 78% for 18 FCXM-positive patients with PGST >3 months, 78% for 49 FCXM-negative patients with PGST >3 months, and 84% for 19 FCXM-negative patients with PGST < or =3 months. in contrast, 53% 3-month and 44% 3-year regraft survival rates occurred in 17 high-risk FCXM-positive recipients with a PGST < or =3 months. The odds ratio for increased relative risk of early second graft loss was 4.5 (confidence interval: 1.32-1.67) for the high-risk versus low-risk subsets (P = 0.009). Within the high-risk subset, 56% (5 of 9) of those who were FCXM T negative B positive experienced early regraft loss. A positive B cell FCXM has an adverse clinical impact only for high-risk regraft recipients. Pretransplant panel reactive antibody levels, pregnancy, number of blood transfusions between grafts, repeat donor HLA mismatches, and regraft recipient HLA mismatches did not correlate with early regraft loss. We conclude that kidney regraft survival rates in low-risk recipients (PGST >3 months/FCXM negative or positive [T and/or B cell] and PGST < or = 3 months/FCXM negative) approach primary graft survival rates and justify retransplantation, but the rate in high-risk regraft candidates (PGST < or =3 months/FCXM positive T and/or B cell) suggests that retransplantation should be performed only with a negative FCXM.


Nuclear receptor LXR: a new partner for sodium-dependent phosphate cotransporters.
New pharmaceutical research approaches are focusing on trying to alleviate the perturbed phosphate (Pi) homeostasis associated with the onset of chronic kidney disease; this includes activation of some of the nuclear receptors. We have recently reported the down regulation of the intestinal and renal sodium-phosphate (NaPi) cotransporters by the liver X receptor (LXR) agonists, and the consequent decrease of the serum Pi levels. In this review, we describe our current knowledge of the different proteins involved in the renal and intestinal actions of LXR.


Recent insights in the development of organ damage caused by hypertension.
Recent recommendations for the management of hypertension have stressed the importance of assessing subclinical target organ damage for the evaluation of cardiovascular risk, the choice of antihypertensive treatment and the follow-up of hypertensive patients. In addition to classic hallmarks of target organ damage (left ventricular hypertrophy, renal dysfunction, microalbuminuria), new concepts emerging from basic research and technical progresses have allowed more accurate and earlier detection of target organ damage affecting the heart (plasma BNP, coronary calcifications), the brain (silent lacunar infarcts, advanced deep white matter lesions, microbleedings) and the vasculature. The latter include markers of diffuse atherosclerosis (carotid intima-media thickness), arterial stiffness (pulse wave velocity, augmentation index) and endothelial dysfunction (increased plasma levels of adhesion molecules). Current studies should help to better define the predictive power of these new phenotypes for the occurrence of overt cardio- and cerebrovascular diseases, their reversibility under antihypertensive treatment and the most adapted therapeutic strategy in at-risk patients. Furthermore, early identification of hypertensive patients more likely to develop target organ damage, will be facilitated by a more global evaluation of cardiovascular risk factors, a better use and wider acceptance of ambulatory BP measurement (including determination of nocturnal dip and blood pressure variability) and, maybe, an increased knowledge of the genetic factors underlying susceptibility to target organ damage. Lastly, randomized studies comparing different classes of antihypertensive drugs should help to test the well-known but frequently challenged concept of additional benefits of some antihypertensive drugs "beyond BP" on prevention and reversal of target organ damage.


T2 mapping of the acetabular cartilage in infants and children with developmental dysplasia of the hip.
T2 mapping is useful for evaluating the cartilage matrix. To determine the variations in the acetabular cartilage T2 relaxation values between healthy individuals and those with developmental dysplasia of the hip (DDH). Thirty-three patients with unilateral DDH underwent 3-T magnetic resonance imaging (MRI) between January 2018 and February 2019. Fifteen volunteers (30 hips) were enrolled as controls. T2 values were measured with the T2 mapping sequence in all layers and were equally divided into three layers (deep, middle, and superficial) with equal thickness. We calculated the mean T2 relaxation values for the full thickness, deep, middle, and superficial layers and compared the values between the different groups. In addition, the inter- and intra-observer agreements were calculated. The T2 relaxation values in the DDH arm were significantly lower in the middle, superficial, and full thickness layers compared with those of the volunteers and contralateral hips. The T2 relaxation values of the deep layers showed no significant difference between the different groups. The acetabular cartilage T2 relaxation values increased from the deep layer to the superficial layer in the control and contralateral groups. Both inter- and intra-observer agreements were good. MRI T2 mapping may help to diagnose developmental disorders of the acetabular cartilage matrix in infants and children with DDH. Abnormal acetabular cartilage T2 relaxation values may be due to the extraordinary stress load of the femoral head.


Lipophagic Panniculitis of Childhood: A Case Report and Comprehensive Review of the Literature.
Lipophagic panniculitis of childhood is a rare condition notable clinically for an inflammatory panniculitis followed by the development of permanent lipoatrophy. In this regard, the term lipoatrophic panniculitis has been used synonymously with lipophagic panniculitis. Additional designations include lipophagic lipoatrophic panniculitis and annular lipoatrophic panniculitis of the ankles. Although lipophagic panniculitis has been associated with a number of autoimmune phenomena, a paucity of reports and limited pathological analyses to date renders this disease an elusive one whose pathogenesis is not yet established. We describe the clinical, histopathologic, and immunohistochemical findings in a case of lipophagic panniculitis of childhood in a 7-year-old boy and present it in the context of a comprehensive review of the literature. Furthermore, we offer a hypothesis regarding the pathogenetic basis of lipophagic panniculitis of childhood, suggesting cellular immunity targeting the adipocyte at the crux of its pathogenesis.


Experimental pseudo arteriovenous malformation. A model for training and research.
There are few experimental models of arteriovenous malformations (AVM). The following study was designed to evaluate an easy-to-perform method in a canine model. Bilateral high-flow carotid to external jugular vein arteriovenous fistulae (AVF) were created in three adult dogs. 21 days after surgery one AVF was occluded by a coated stent, whereas the contralateral side remained patent. Frequent angiograms of the carotid and the vertebral arteries were performed in the nine months after surgery to investigate the effects of long-standing high-flow AVF. Because of a significant steal effect, the fistulae recruited arterial blood flow at a rapid rate from the ipsilateral vertebral artery and to lesser extent from the contralateral side, which was only disclosed after occlusion of the contralateral AVF. These cephalic pseudo AVMs were seen in all three dogs. The model presented is easy to establish and shows angioma-like morphological components comparable to human AVM. It is useful for the testing of new catheters and embolic materials as well as in the training of superselective navigation with micro catheters. However, it is unsuitable for examination of intracranial pathophysiology.


Strain-dependent morphine-induced analgesic and hyperalgesic effects on thermal nociception in domestic fowl (Gallus gallus).
The effects of morphine (30 mg/kg), naloxone (5 mg/kg), and morphine with naloxone on distress vocalizations and thermal nociception were examined in different strains of domestic fowl. Naloxone by itself did not significantly affect vocalizations or thermal nociception. Morphine produced a naloxone-reversible attenuation of vocalizations that was not strain dependent. Morphine produced a strain-dependent analgesic (Rhode Island Red strain) and hyperalgesic (White Leghorn and Cal-White strains) effect on tests of thermal nociception. Both the analgesic and hyperalgesic effects were reversed by naloxone. These opposite effects on thermal nociception may reflect the effects of selective breeding on opioid receptor subtype.


Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges.
Urothelial carcinoma (UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells (UroCSCs), a tumor subpopulation derived from transformation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of UroCSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells.


Long saphenous vein and its anatomical variations.
Vascular ultrasonography has an important role in the diagnosis and management of venous disease. The venous system, however, is more complex and variable compared to the arterial system due to its frequent anatomical variations. This often becomes quite challenging for sonographers. This paper discusses the anatomy of the long saphenous vein and its anatomical variations accompanied by sonograms and illustrations.


General remarks on the role of the vestibular system in weightlessness.
Different methods are described to experimentally achieve weightlessness. Since the function of the otolith system depends on the presence of contact forces opposing gravity, it is disabled in weightlessness and may send misleading positional information to the brain. Without the contributions of the otolith system it is difficult in space to distinguish self-motion from object motion. Furthermore, the disintegration of information from the neck position receptors from those of the otolith system can lead to additional illusory positional sensations. Since the function of the semicircular canal system in previous space flights was found to be essentially undisturbed, the vestibular experiments in the Spacelab-D1 missions concentrated more on the otolith system. The function of other orientational cues from the visual system, the semicircular canal system and proprioception can be studied in isolation from the otolith system in space. In the Spacelab-D1 mission, the space vestibular sled was used as a device for studying linear acceleration. The vestibular helmet "permitted" video and EOG recordings of all eye movements and provided caloric and optokinetic stimulation. Various factors contributing to static and dynamic forms of space sickness are identified.


Notch signalling regulates the contribution of progenitor cells from the chick Hensen's node to the floor plate and notochord.
Hensen's node of the chick embryo contains multipotent self-renewing progenitor cells that can contribute to either the floor plate or the notochord. Floor plate cells are a population of epithelial cells that lie at the ventral midline of the developing neural tube, whereas the notochord is a rod of axial mesoderm that lies directly beneath the floor plate. These two tissues serve as a source of a potent signalling morphogen, sonic hedgehog (Shh), which patterns the dorsoventral axis of the neural tube. We show, through both gain- and loss-of-function approaches, that Notch signalling promotes the contribution of chick axial progenitor cells to the floor plate and inhibits contribution to the notochord. Thus, we propose that Notch regulates the allocation of appropriate numbers of progenitor cells from Hensen's node of the chick embryo to the notochord and the floor plate.


Patellar cartilage: T2 values and morphologic abnormalities at 3.0-T MR imaging in relation to physical activity in asymptomatic subjects from the osteoarthritis initiative.
To study the interrelationship between patella cartilage T2 relaxation time, other knee abnormalities, and physical activity levels in asymptomatic subjects from the Osteoarthritis Initiative (OAI) incidence cohort. The study had institutional review board approval and was HIPAA compliant. One hundred twenty subjects from the OAI without knee pain (age, 45-55 years) and with risk factors for knee osteoarthritis (OA) were studied by using knee radiographs, 3.0-T knee magnetic resonance (MR) images (including intermediate-weighted fast spin-echo and T2 mapping sequences), and the Physical Activity Scale for the Elderly. MR images of the right knee were assessed by two musculoskeletal radiologists for the presence and grade of abnormalities. Segmentation of the patella cartilage was performed, and T2 maps were generated. Statistical significance was determined by using analysis of variance, chi(2) analysis, correlation coefficient tests, the Cohen kappa, and a multiple linear regression model. Cartilage lesions were found in 95 (79.0%) of 120 knees, and meniscal lesions were found in 54 (45%) of 120 knees. A significant correlation between patella cartilage T2 values and the severity and grade of cartilage (P = .0025) and meniscus (P = .0067) lesions was demonstrated. Subjects with high activity levels had significantly higher prevalence and grade of abnormalities and higher T2 values (48.7 msec +/-4.35 vs 45.8 msec +/-3.93; P < .001) than did subjects with low activity levels. Middle-aged asymptomatic individuals with risk factors for knee OA had a high prevalence of cartilage and meniscus knee lesions. Physically active individuals had more knee abnormalities and higher patellar T2 values. Additional studies will be needed to determine causality.


Cyanine 5.5 conjugated nanobubbles as a tumor selective contrast agent for dual ultrasound-fluorescence imaging in a mouse model.
Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan-vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400-800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan-vitamin C lipid system have achieved tumor-selective imaging in vivo.


Prevalence and risk factors of myasthenia gravis recurrence post-thymectomy.
To evaluate the prevalence and the factors associated with recurrence of myasthenia gravis following thymectomy. Six electronic databases which reported on recurrence of myasthenia gravis following thymectomy and/or its risk factors from 1985 to 2018 were searched. Summary prevalence and risk values obtained based on the random effect models were reported. Seventy (70) papers containing 7,287 individuals with myasthenia gravis who received thymectomy as part of their management were retrieved. The patients had a mean follow-up of 4.65 years post-thymectomy. The prevalence of myasthenia gravis recurrence post-thymectomy was 18.0% (95% CI 14.7-22.0%; 1865/7287). Evident heterogeneity was observed (I2=93.6%; p<0.001). Recurrence rate was insignificantly higher in male compared with female patients (31.3 vs. 23.8%; p=0.104). Pooled recurrence rates for thymomatous (33.3%) was higher than the rate among non-thymomatous (20.8%) myasthenia gravis patients (Q=4.19, p=0.041). Risk factors for recurrence include older age, male sex, disease severity, having thymomatous myasthenia gravis, longer duration of the myasthenia gravis before surgery, and having an ectopic thymic tissue. A fifth of individuals with myasthenia gravis experience recurrence after thymectomy. Closer monitoring should be given to at-risk patients and further studies are needed to understand interventions to address these risks.


Combined Adipose-Derived Mesenchymal Stem Cells and Low-Energy Extracorporeal Shock Wave Therapy Protect the Brain From Brain Death-Induced Injury in Rat.
This study tested the hypothesis that combined adipose-derived mesenchymal stem cell (ADMSC) and low-energy extracorporeal shock wave (ECSW) therapy could protect brain from brain death (BD)-induced injury. Adult male Sprague Dawley rats were categorized into group 1 (sham control), group 2 (BD), group 3 (BD + ECSW [0.15 mJ/mm2/300 impulses] applied to the skull surface 3 hours after BD induction), group 4 (BD + ADMSC [1.2 × 106 cell] by intravenous injection 3 hours after BD induction) and group 5 (BD + ECSW + ADMSC). By 6 hours after BD induction, circulating/spleen levels of immune cells (CD3/CD4+, CD8/CD4+, Treg+) and circulating levels of inflammatory cells (MPO/Ly6G/CD11a/b) and soluble mediators (TNF-α/IL-6) were lowest in group 1 and significantly progressively reduced from groups 2 to 5 (all p < 0.0001). Brain protein expressions of inflammatory (TNF-α/NF-κB/MMP-9/IL-1β), apoptotic (caspase-3/PARP/mitochondrial-BAX), oxidative stress/DNA-damage (NOX-1/NOX-2/oxidized protein/γ-H2AX) biomarkers exhibited an identical pattern, whereas anti-oxidant (SIRT1/SIRT3) and mitochondrial-integrity (mitochondrial-cytochrome-C) biomarkers exhibited an opposite pattern to inflammatory biomarkers among the 5 groups (all p < 0.0001). The cellular expressions of inflammatory/brain-edema (F4/80/CD14+/GFAP/AQP4) biomarkers exhibited an identical pattern to inflammation among the 5 groups (all p < 0.0001). In conclusion, ECSW-ADMSC therapy is superior to either alone for attenuating brain from BD-induced damage.


White Matter Lesions Are Not Related to β-Amyloid Deposition in an Autopsy-Based Study.
Population-based studies have investigated the relation between β-amyloid levels in cerebrospinal fluid or plasma and white matter lesions (WMLs). However, these circulating levels of β-amyloid in cerebrospinal fluid or plasma may not reliably reflect the actual degree of amyloid present in the brain. Therefore, we investigated the relation between WMLs and β-amyloid plaques and amyloid angiopathy in brain tissue. WML on MRI or CT were rated in 28 nondemented patients whose neuroimaging was available prior to death. β-amyloid in plaques and arterioles were immunohistochemically stained and quantified in postmortem brain necropsies. WMLs were present in 43% of the total population. Both cortex and periventricular region showed no differences for β-amyloid deposition in either plaques or blood vessel walls in patients with WMLs compared to those without WMLs. Thus, our results indicate that there is no relation between the degree of WMLs and β-amyloid deposition in the brain.


A Combined Epithelial Mesenchymal Transformation and DNA Repair Gene Panel in Colorectal Cancer With Prognostic and Therapeutic Implication.
Epithelial mesenchymal transformation (EMT) and DNA repair status represent intrinsic features of colorectal cancer (CRC) and are associated with patient prognosis and treatment responsiveness. We sought to develop a combined EMT and DNA repair gene panel with potential application in patient classification and precise treatment. We comprehensively evaluated the EMT and DNA repair patterns of 1,652 CRC patients from four datasets. Unsupervised clustering was used for classification. The clinical features, genetic mutation, tumor mutation load, and chemotherapy as well as immunotherapy sensitivity among different clusters were systematically compared. The least absolute shrinkage and selection operator regression method was used to develop the risk model. Three distinct CRC clusters were determined. Clustet1 was characterized by down-regulated DNA repair pathways but active epithelial markers and metabolism pathway and had intermediate prognosis. Clustet2 was characterized by down-regulated both epithelial markers and DNA repair pathways and had poor outcome. Clustet3 presented with activation of DNA repair pathway and epithelial markers had favorable prognosis. Clustet1 might benefit form chemotherapy and Clustet3 had a higher response rate to immunotherapy. An EMT and DNA repair risk model related to prognosis and treatment response was developed. This work developed and validated a combined EMT and DNA repair gene panel for CRC classification, which may be an effective tool for survival prediction and treatment guidance in CRC patients.


[Analysis of the gene mutation in an inherited FVII deficiency patient].
The identify the gene defect of an inherited FVII deficiency patient. The promoter, all the exons and exon-intron boundaries and 3' UTR of F7 gene of the proband were analyzed by direct sequencing. The defected mutations were confirmed by sequencing the complementary strand. The mutations would be screened in the related database and 150 healthy donors to identify the SNP. By splice site prediction, we analyzed the pathogenesis of defected mutations. Genetic analysis revealed G to A transition at 15975 in the intron 6 of F7 gene (IVS6-1G>A) and A to G transition at 16813 in the intron 7 of F7 gene (IVS7+7 A>G). According to the fruitfly, the acceptor site could not be recognized when a G to A substitution took place. The closest candidate splice site was located 132 bp downstream. The distance was probably too far to allow the use of the cryptic splice site and resulted in the skipping of exon6. A to G transition at 16813 in the intron 7 of F7 gene could not change the splice site, but modify a different molecular interaction that is important for the splice process. The heterozygous mutation of IVS6-1G>A combined with polymorphism of IVS7+7 A>G in F7 gene relates to the FVII deficiency.


Label-free LC-HRMS-based enzymatic activity assay for the detection of DDC, MAO and COMT inhibitors.
Pharmacological treatment of Parkinson's disease consists of a combined chemotherapy that mostly relies on levodopa (L-DOPA) administration together with inhibitors of dopa-decarboxylase (DDC), monoamine oxidase (MAO) and catechol-methyltransferase (COMT). Identification of inhibitors specifically targeting these enzymes is still a significative part of the development of new alternative antiparkinsonian drugs. Most of the available methods use measurement of enzymatic reactions through radioactive labeling, antibody-recognized products or coupled enzymatic assays. Mass spectrometry (MS) represents an interesting alternative approach as it allows direct and specific detection and quantification of enzymatic reactions. We describe the development of a simple, reliable, label-free assay based on high-resolution mass spectrometry (HRMS) for the detection and relative quantification of three different enzymatic reactions using non-isolated enzymes. The assay was applied both to reference drugs and plant crude extracts. This method can be used to detect hits in extracts libraries as well as determine relative IC50 of inhibitors.


Inferring evolutionary signals from ecological data in a plant-pathogen metapopulation.
We followed the dynamics of local epidemics in three populations of a natural plant-pathogen system for four sequential years. We characterize the overwintering process with spatial statistics and use a stochastic, spatially explicit, modeling approach with Bayesian parameter estimation to study the spread of the infection during the growing season. Our modeling approach allows us to infer coevolutionary signals from spatiotemporal data on pathogen prevalence. Most importantly, we are able to assess the distribution of resistant hosts within the distribution of all host plants. We show that resistant hosts occur in areas with high pathogen encounter rates, and that the occurrence of resistance correlates with overwintering probability of the pathogen. The estimates for essentially all model parameters are characterized by a large amount of variation over the years and the populations. While the variation in the fraction of resistant hosts and in the force of infection is to a large extent explained by the population, the other model parameters (two parameters describing the shape of the dispersal kernel) vary essentially in an unpredictable manner, suggesting that much of the variation may occur at very fine spatial and temporal scales.


Retrospective comparison of negative pressure wound therapy and silver-coated foam dressings in open-wound treatment in cats.
Objectives The objective of this study was to evaluate negative pressure wound therapy (NPWT) for the treatment of complicated wounds in cats. Methods Twenty cats undergoing open-wound treatment in two clinics were classed according to treatment method: NPWT (group A, n = 10) and polyurethane foam dressing (group B, n = 10). Pairs of patients from each group were matched based on wound conformation, localisation and underlying cause. Cats from both groups were compared in terms of duration of previous treatment, time to closure and complications. Results Signalment, duration of previous treatment, antibiotic and antiseptic treatment, and bacterial status were comparable between groups. Total time to wound closure was significantly shorter ( P = 0.046, strong effect size; Cohen d = 0.8) in group A (25.8 days, range 11.0-57.0 days) compared with group B (39.5 days, range 28.0-75.0 days). NPWT-treated wounds suffered fewer complications and became septic less frequently during treatment compared with wounds treated with a foam dressing. The progression of fat tissue necrosis was particularly well controlled under NPWT, resulting in fewer deaths due to this condition in this group. However, although a strong effect of NPWT on the progression of infection, fever and sepsis was detected (Cramer-V 0.5), this difference was not significant. Conclusions and relevance This study demonstrated that time to healing was considerably shorter, and complication rate lower, in NPWT-treated animals compared with foam dressing-treated cats. In particular, the effective management of infection by NPWT emphasises the value of NPWT in the treatment of cats suffering from infected wounds.


[Ecodialysis: first strategies to limit damages and reduce costs].
In the medical field, the attention to the environmental impact of industrial processes and products is still limited. In recent years there has been an increased sensitivity towards the environment; meanwhile, the economic burden of hazardous waste disposal is becoming evident. Dialysis is a "big producer" of waste and it has been estimated that disposal costs can be up to 10-40% of the cost of disposables. So there are several reasons of interest on "ecodialysis": the high amount of waste defined as "potentially hazardous", which requires a very expensive management and the recyclability potential of the non-contaminated waste, that has not yet been fully explored in dialysis. This primary study has been performed in collaboration with the Politecnico di Torino. Its aim has been to define a schedule of activities by a few brainstorming sessions. This schedule is to be readily performed or it should be developed in detail to optimize, by reducing and recycling, the waste production during the dialysis session. The discussion identified seven basic points for the eco-sustainability of haemodialysis to: [1] reduce packaging; [2] facilitate separation of materials, and [3] their discharge; [4] differentiate materials; [5] clearly highlight the potentially hazardous materials; [6] improve the recyclability of plastic products; [7] propose a path of recovery and reuse. Although a full optimization requires a close cooperation with the manufacturers and is achievable only in the long term, the reduction of one pound of potentially contaminated materials could presently lead, on a national scale, to a saving of several million euros, which can be better employed in investments to improve our treatments.


The evaluation of coronary bypass graft patency: direct and indirect techniques other than coronary arteriography.
Patients having one or more coronary artery bypass graft operations constitute an important part of the practice of cardiac radiology. Bypass graft patency can be determined by indirect and direct methods. The indirect imaging methods include radionuclide ventriculography, thallium-201 scintigraphy, and positron emission tomography. The direct methods include conventional CT, ultrafast CT, MR imaging, digital subtraction angiography, and Doppler sonography. This review discusses the advantages and limitations of these methods and attempts to define the relative importance of each of these techniques in the evaluation of bypass graft patency.


Tracking 10-year competitive winning performance of judo athletes across age groups.
Little information is available concerning early specialization and competitive success in judo across the early training years. Thus, the present objective was to verify the stability of individual competitive performance of a state-level championship for judo athletes who had been previously successful. For this, 406 athletes from six age groups (9 to 20+ years old) of each sex were followed for 10 years. Using recorded data from the São Paulo State Judo Federation beginning in 1999, the scores and standings for these judo players were analyzed. The proportion of medal winners during this period was not constant, differing from the grand mean in all groups of both 204 males and 202 females. At the end of this period, only 7% of the male and 5% of the female athletes had maintained their competitive levels. Successful competitive performance in early judo competition was not associated with success later in adulthood.