Management of non-acute gastrointestinal defects using the over-the-scope clips (OTSCs): a retrospective single-institution experience.
Advanced endoscopic techniques provide novel therapies for complications historically treated with surgical interventions. Over-the-scope clips (OTSCs) have recently been shown to be effective at endoscopic closure of gastrointestinal (GI) defects. We hypothesize that by following classic surgical principles of fistula management, a high rate of long-term success can be achieved with endoscopic closure of non-acute GI tract defects. A retrospective review of a single-institution prospectively maintained database (2012-2015) of all patients referred for the management of GI leaks or fistulae who underwent attempted closure with the OTSC system (Ovesco, Germany) was performed. Acute perforations were excluded. The primary endpoint was long-term success defined by the absence of radiographic or clinical evidence of leak or fistula during follow-up. Patients were stratified by success or failure of OTSC closure and compared with Fisher's exact and Mann-Whitney U tests. We identified 22 patients with 28 defects (22 fistulae and 6 leaks). Most patients were female (59 %) with a mean age of 54 years (±14), median BMI of 29, and prior bariatric procedure (55 %). Comorbidities included smoking history (68 %) and diabetes (23 %). The majority of defects were solitary (64 %), involved the upper GI tract (82 %), and had been present for >30 days (50 %). Multiple therapeutic interventions were necessary in 46 % of defects. There were no adverse outcomes related to OTSC placement or misfiring. Endoscopic adjuncts were used in 61 % of cases. Overall success rate was 82 % (100 % for leaks and 76 % for fistulae) at a median follow-up of 4.7 months (IQR 2.1-8.4 months). Predictors of success and failure could not be distinguished due to limited sample size. Over-the-scope clips can be safely and effectively used in patients presenting with GI leaks and fistulae. Further research is required to characterize the determinants of long-term success and risk factors for failure.


Xenopus tropicalis U6 snRNA genes transcribed by Pol III contain the upstream promoter elements used by Pol II dependent U snRNA genes.
We have cloned and sequenced a 977bp DNA fragment, pXTU6-2, that represents the transcription unit for a Xenopus tropicalis U6 RNA gene. This basic repeating unit is reiterated ca.500-fold per haploid genome. Oocyte injections of pXTU6-2 led to the transcription of a mature-sized U6 RNA that, however, lacked internal 2'-O-methylations. These posttranscriptional modifications of U6 RNA might be cytoplasmic and could require its association with U4 RNA to be accomplished. The low alpha- amanitin sensitivity of U6 RNA synthesis in oocytes suggested that U6 RNA is transcribed by RNA polymerase III, consistent with features of the U6 RNA molecule which also contains a Box A- like intragenic control region. Inspection of X. tropicalis, mouse and human U6 DNA upstream sequences revealed the presence of a TATA box as well as of the proximal and enhancer (octamer motif) elements contained in snRNA genes transcribed by RNA polymerase II. We propose that U6 RNAs are synthesized by a specialized transcription complex consisting of RNA polymerase III and transcription factors, some of which are very likely shared with RNA polymerase II promoters.


Characterization of a DNA topoisomerase encoded by Amsacta moore entomopoxvirus.
We have identified an Amsacta moorei entomopoxvirus (AmEPV) gene encoding a DNA topoisomerase. The 333-amino acid AmEPV topoisomerase displays instructive sequence similarities to the previously identified topoisomerases encoded by five genera of vertebrate poxviruses. One hundred nine amino acids are identical or conserved among the six proteins. The gene encoding AmEPV topoisomerase was expressed in bacteria and the recombinant enzyme was partially purified. AmEPV topoisomerase is a monomeric enzyme that catalyzes the relaxation of supercoiled DNA. Like the vaccinia, Shope fibroma virus, and Orf virus enzymes, the AmEPV topoisomerase forms a covalent adduct with duplex DNA at the target sequence CCCTT decreases. The kinetic and equilibrium parameters of the DNA cleavage reaction of AmEPV topoisomerase (Kobs = 0.08 sec-1; Kcl = 0.22) are similar to those of the vaccinia virus enzyme.


First-Line Treatments for Extensive-Stage Small-Cell Lung Cancer With Immune Checkpoint Inhibitors Plus Chemotherapy: A Network Meta-Analysis and Cost-Effectiveness Analysis.
Immune checkpoint inhibitors (ICIs) plus chemotherapy were unlikely to be considered cost-effective compared with chemotherapy as the first-line treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC) in China due to its high costs. However, the cost-effectiveness of the comparison between the regimens of ICIs plus chemotherapy were remained unclear yet. The aim of this study was to evaluate the efficacy and cost-effectiveness of ICIs plus chemotherapy as the first-line treatment for ES-SCLC from the perspective of the Chinese healthcare system. A network meta-analysis (NMA) was conducted to indirect compare the clinical benefits between the ICIs plus chemotherapy regimens. A decision-analytic model was established to evaluate the cost-effectiveness from the Chinese healthcare system, the clinical efficacy and safety data were obtained from the clinical trials and the results of NMA. Cost and utility values were gathered from the local charges and previously studies. Key outputs of the NMA were overall survival (OS) and progression-free survival (PFS). Incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed to explore the robustness of the model outcomes. Five clinical trials (IMpower133, CASPIAN, KEYNOTE-604, CA184-156, and EA5161) of 1,255 patients received first-line ICIs plus chemotherapy strategies were analyzed in the NMA. NMA showed that nivolumab plus chemotherapy was ranked higher than other strategies. The cost-effectiveness analysis showed that atezolizumab plus chemotherapy achieved relatively higher health benefits and lower costs. One-way sensitivity analyses revealed that the cost of ICIs had the substantial impact on model outcomes. The probabilistic sensitivity analyses suggested that the probability of atezolizumab plus chemotherapy could be considered cost-effective was more than 50% at the willingness-to-pay (WTP) threshold of $31,313/QALY in China. In scenario analyses, when the price of nivolumab reduced 80%, the probability of nivolumab plus chemotherapy being cost-effective was more than 50%. The NMA and cost-effectiveness revealed that atezolizumab plus chemotherapy is the most favorable first-line treatment for previously untreated ES-SCLC patients compared other ICIs plus chemotherapy regimens in China. The price reduction of nivolumab would make nivolumab plus chemotherapy be the most cost-effective option in future possible context.


The relationship between frequency and intensity of fears and a collagen condition.
Encouraged by the positive relationship between joint laxity and panic anxiety, our objective in this study was to compare widespread cultural fears in subjects with and without joint hypermobility syndrome and to assess whether this relationship is sustained for common fears as well. A sample consisting of 1,305 subjects from a rural town were assessed for joint hypermobility syndrome using Beighton's criteria. We assessed fear intensity and frequency using a modified version of the Fear Survey Schedule (FSS-III). Intense fears, defined with a score of 3-4, were compared between hypermobile and nonhypermobile subjects. The analysis was carried out separately for men and women. Nonparametric analysis was applied throughout. Joint hypermobility syndrome was found in 19.9% (141) of women and 6.9% (41) of men. Concerning the fear survey, when we compared the groups with and without joint hypermobility, the mean total scores for both genders were significantly higher for the hypermobile group. When we analyzed each item individually, 43 out of the 44 most severe fears in women and 36 out of the 39 in men, scores were significantly higher in the hypermobile group. We found significant differences between subjects with and without joint hypermobility when assessing specific fears, reinforcing the hypothesis that intensity of fears is greater in subjects with joint hypermobility syndrome. These results show that the association of joint laxity and phobic anxiety is sustained for intense fears and might represent a susceptibility factor for these anxiety conditions.


Accuracy of image-free computer navigated total knee arthroplasty is not compromised in severely deformed varus knees.
In severe varus knee deformity, image-free computer navigated total knee arthroplasty (TKA) may result in a malaligned knee. The aim of this study was to compare the results of 17 severe varus knees (≥ 20°) and 81 varus knees (< 20°) that underwent image-free computer navigated TKA and analyze postoperative malalignment. Computer navigated TKA was performed according to standard protocol, and component angles and mechanical axes were evaluated postoperatively with weight bearing full-length standing radiographs. All severe varus knees were corrected to within 3° of neutral lower limb alignment despite having a mean preoperative varus deformities of 22.4°. Neutral alignment was obtained in 88.9% of the varus group (mean preoperative varus deformity of 11.7°), without significant difference between the two groups. No significant difference was found in either the femoral or tibial component angles, or in the frequency of complications. Severity of varus deformity did not affect the accuracy of image-free computer navigated TKA.


Pharmacogenetic selection of volunteers increases stringency of bioequivalence studies; the case of clopidogrel.
Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. The purpose of the current investigation was to study the effect of selection of volunteers homozygous for the CYP2C19*1 haplotype on the bioavailability of clopidogrel. A regular 2×2 bioequivalence study between two formulations of clopidogrel was performed in volunteers selected and unselected for relevant CYP2C19 haplotypes for the Mexican population. It was found that selection of volunteers homozygous for the CYP2C19*1 haplotype, increased the stringency of bioequivalence statistics and resulted in bioinequivalence of a generic clopidogrel compound that otherwise proved equivalent when tested in an open unselected population. Augmentation of bioequivalence strictness is expected to result from pharmacogenetic selection of volunteers.


Antimicrobial susceptibility testing of Mycobacterium tuberculosis to first-line drugs: comparisons of the MGIT 960 and BACTEC 460 systems.
The reliability of the Mycobacteria Growth Indicator Tube (MGIT) 960 system for rapid antimicrobial susceptibility testing (AST) of Mycobacterium tuberculosis was evaluated. Forty-seven isolates, including 10 fully susceptible and 37 resistant strains, were tested for susceptibility to the critical concentrations of streptomycin (STR), isoniazid (INH), rifampin (RMP), and ethambutol (EMB), as recommended by the manufacturer. Strains resistant to the critical concentrations were tested with higher concentrations. The results were compared to those obtained by a radiometric method (BACTEC 460TB) and by a conventional agar dilution method, which served as the reference method. Based on these data, we suggest that the following antibiotic concentrations give satisfactory results with the MGIT 960 system: STR, 4.0 microg/ml; INH, 0.1 microg/ml; RMP, 1.0 microg/ml; and EMB, 5.0 microg/ml. The time required to obtain susceptibility results averaged 6.9 days by the MGIT 960 system and 5.4 days by the BACTEC 460TB system; these intervals were not significantly different. This study shows that the MGIT 960 system is a reliable, rapid, automated method for testing the susceptibility of M. tuberculosis isolates to first-line drugs.


Quantifying Associations Between Child Health and Neighborhood Social Vulnerability: Does the Choice of Index Matter?
Policymakers have increasingly utilized place-based social disadvantage indices to quantify the impacts of place on health and inform equitable resource allocation. Indices vary in design, content, and purpose but are often used interchangeably, potentially resulting in differential assignments of relative disadvantage depending on index choice. To compare associations between three commonly used disadvantage indices (Social Vulnerability Index (SVI), Area Deprivation Index (ADI), and Child Opportunity Index (COI)) and two epidemiologically distinct child health outcomes-infant well-child check (WCC) attendance and adolescent obesity. Cross-sectional analysis of Duke University Health System electronic health record (EHR) data from January 2014 to December 2019. Children ≤18 years of age with outpatient encounters between January 2014 and December 2019, and who were Durham County residents were eligible. WCC attendance was assessed for infants ages 0-15 months; obesity was assessed for children ages 11-17 years. 2014 Social Vulnerability Index (SVI), 2015 Area Deprivation Index (ADI), and 2015 Child Opportunity Index (COI) 2.0. 1) Infant WCC attendance: attending less than the minimum recommended six WCCs in the first 15 months of life, and 2) Adolescent obesity: BMI ≥ the 95th percentile at both the most recent encounter and an encounter within the prior 9-36 months. Of 10175 patients in the WCC cohort, 20% (n = 2073) had less than six WCCs. Of 14961 patients in the obesity cohort, 20% (n = 2933) had obesity. All three indices were associated with both WCCs (OR for SVI 1.10, 95% CI 1.08-1.12; OR for ADI 1.10, 95% CI 1.08-1.12; OR for COI 1.12, 95% CI 1.10-1.14) and obesity (OR for SVI 1.05, 95% CI 1.04-1.08; OR for ADI 1.08, 95% CI 1.06-1.10; OR for COI 1.07, 95% CI 1.05-1.08). Higher social disadvantage as defined by all three indices was similarly associated with both adolescent obesity and decreased infant WCC attendance. While the COI incorporates a broader set of child-specific variables, the SVI and ADI may often be just as suitable for pediatric research. Users should consider population and outcome characteristics when selecting an index.


Is there a broader role for independent mental capacity advocates in critical care? An exploratory study.
This research explores the current and potential future role of independent mental capacity advocates (IMCAs) in critical care. The Mental Capacity Act (MCA) of 2005 introduced IMCAs as advocates for patients without anyone to represent their best interests, but research suggests that this role is not well understood or implemented. No existing research explores the role of IMCAs in critical care or their potential use when families are judged 'appropriate to act' on the patient's behalf. It is suggested that families may not be best placed to advocate for their sick family member when they themselves are in a state of shock. To investigate existing levels of knowledge and awareness of the MCA and understanding of the role of IMCAs in critical care as a prelude to considering whether the role of IMCAs might usefully be extended. The concept of 'IMCA clinics' is introduced and explored. A small-scale qualitative study using thematic analysis of 15 interviews across two NHS sites and a survey of IMCA services were undertaken. Some knowledge of the MCA was evident across both study sites, but training on MCA remains unsatisfactory, with confusion about the role of IMCAs and when they should become involved. Overall, participants felt that the broader involvement of IMCAs on a regular basis within critical care could be useful. There was evidence of good practice when instructing IMCAs, but further work needs to be conducted to ensure that critical care staff are informed about the referral process. It was clear that expanding the role of an advocate warrants further investigation. Further training on the role of IMCAs within critical care is required, and good practice examples should be shared with other units to improve referral rates to the IMCA service and ensure that vulnerable patients are properly represented.


Palliative urinary diversion in carcinoma of the cervix.
Over a 28-year period, 46 patients with previously treated carcinoma of the cervix developed bilateral ureteral obstruction that was treated with palliative urinary diversion. All but 3 patients had elevated blood urea nitrogen (BUN) levels, and 19 had received no prior treatment. Forty-one percent (19/46) lived 6 months or more and spent 86% of their remaining life out of the hospital. Various factors potentially affecting survival are examined, and guidelines for patient selection are offered.


Interest of biology in the management of pregnancies where a fetal malformation has been detected by ultrasonography.
The results of two French collaborative studies are reported with respect to chromosomal and biochemical analyses following the ultrasonographic detection of a fetal anomaly. Overall, chromosomal anomalies were observed in 14.8%, ranging from 8.6% in isolated single malformations to 40.5% in multiple fetal malformations associated with intrauterine growth retardation. Acetylcholinesterase (AChE) electrophoresis was performed on the amniotic fluid of 64 cases of ultrasonographically diagnosed isolated hydrocephalus. 8 cases of previously unsuspected open neural tube defects were diagnosed by AChE. Digestive microvillar enzyme assays were useful in the precise diagnosis of suspected gastrointestinal anomaly. The correlation of the results of ultrasonography and chromosomal and biochemical analyses is the basis for the diagnosis and the prognosis of pregnancy.


Update on eating disorders: epidemiology, mortality and comorbidity.
In recent years there have been, in clinical practice an increased influx of services dedicated to eating disorders (DCA). This article provides An examination of some epidemiological aspects aimed at assessing a possible increase in the incidence and prevalence of these syndromes, toghether with an analysis of the mortality and comorbidities of DCA. The literature search covered the period 2006-2011. The selected articles were evaluated to establish the correct approach using the checklist proposed by the NICE Guideline Manual. Some recent publications among those examined hypothesize (common impression) a possible increase in eating disorders (especially BN and BED) in the last two decades.


A 3-year follow-up after anterior colporrhaphy compared with collagen-coated transvaginal mesh for anterior vaginal wall prolapse: a randomised controlled trial.
To compare the 1-year (previously published) and 3-year objective and subjective cure rates, and complications, related to the use of a collagen-coated transvaginal mesh for anterior vaginal wall prolapse against a conventional anterior repair. Randomised controlled study. Six departments of obstetrics and gynaecology in Norway, Sweden, Finland, and Denmark. A total of 138 women, of 55 years of age or older, admitted for stage ≥2 anterior vaginal wall prolapse. The women scheduled for primary anterior vaginal wall prolapse surgery were randomised between conventional anterior colporrhaphy and surgery with a collagen-coated prolene mesh. All patients were evaluated using the Pelvic Organ Prolapse Quantification (POP-Q) assessment before and after surgery. Symptoms related to pelvic organ prolapse were evaluated using the Pelvic Floor Impact Questionnaire (PFIQ-7) and the Pelvic Floor Distress Inventory (PFDI-20). Objective cure, defined as POP-Q stage <2 prolapse at the 1- and 3-year follow-ups. Furthermore, mesh exposure and dyspareunia were also recorded. In total, 138 patients (70 from the mesh group versus 68 from the conventional anterior colporrhaphy group) out of 160 (86.3%) participated in the 3-year follow-up. POP-Q revealed an objective anatomic cure for 88.1 and 91.4%, respectively, in the mesh group at the 1- and 3-year follow-ups, compared with 39.9 and 41.2% in the colporrhaphy group. No difference between the groups was observed regarding PFIQ-7, PFDI-20, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) scores. The number of mesh exposures did not change during the study period and all exposures were minor. Our study demonstrates that although the objective outcome was superior in the mesh group, the use of mesh had no impact on the subjective outcome. POP-Q deteriorates after anterior prolapse surgery but remains stable in women with mesh implantation.


Exposure to 1,3-Butadiene in the U.S. Population: National Health and Nutrition Examination Survey 2011-2016.
1,3-Butadiene is a volatile organic compound with a gasoline-like odour that is primarily used as a monomer in the production of synthetic rubber. The International Agency for Research on Cancer has classified 1,3-butadiene as a human carcinogen. We assessed 1,3-butadiene exposure in the U.S. population by measuring its urinary metabolites N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (34HBMA), N-acetyl-S-(1-hydroxymethyl-2-propenyl)-L-cysteine (1HMPeMA), N-acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine (2HBeMA), and N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (4HBeMA). Urine samples from the 2011 to 2016 National Health and Nutrition Examination Survey were analysed for 1,3-butadiene metabolites using ultrahigh-performance liquid chromatography/tandem mass spectrometry. 34HBMA and 4HBeMA were detected in >96% of the samples; 1HMPeMA and 2HBeMA were detected in 0.66% and 9.84% of the samples, respectively. We used sample-weighted linear regression models to examine the influence of smoking status (using a combination of self-reporting and serum-cotinine data), demographic variables, and diet on biomarker levels. The median 4HBeMA among exclusive smokers (31.5 µg/g creatinine) was higher than in non-users (4.11 µg/g creatinine). Similarly, the median 34HBMA among exclusive smokers (391 µg/g creatinine) was higher than in non-users (296 µg/g creatinine). Furthermore, smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was associated with 475%, 849%, and 1143% higher 4HBeMA (p < 0.0001), respectively. Additionally, smoking 1-10, 11-20, and >20 CPD was associated with 33%, 44%, and 102% higher 34HBMA (p < 0.0001). These results provide significant baseline data for 1,3-butadiene exposure in the U.S. population, and demonstrate that tobacco smoke is a major exposure source.


The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition.
Nogo receptor (NgR)-mediated control of axon growth relies on the central nervous system-specific type I transmembrane protein Lingo-1. Interactions between Lingo-1 and NgR, along with a complementary co-receptor, result in neurite and axonal collapse. In addition, the inhibitory role of Lingo-1 is particularly important in regulation of oligodendrocyte differentiation and myelination, suggesting that pharmacological modulation of Lingo-1 function could be a novel approach for nerve repair and remyelination therapies. Here we report on the crystal structure of the ligand-binding ectodomain of human Lingo-1 and show it has a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. The structure, together with biophysical analysis of its solution properties, reveals that in the crystals and in solution Lingo-1 persistently associates with itself to form a stable tetramer and that it is its LRR-Ig-composite fold that drives such assembly. Specifically, in the crystal structure protomers of Lingo-1 associate in a ring-shaped tetramer, with each LRR domain filling an open cleft in an adjacent protomer. The tetramer buries a large surface area (9,200 A2) and may serve as an efficient scaffold to simultaneously bind and assemble the NgR complex components during activation on a membrane. Potential functional binding sites that can be identified on the ectodomain surface, including the site of self-recognition, suggest a model for protein assembly on the membrane.


The role of Renasys-GO™ in the treatment of diabetic lower limb ulcers: a case series.
This case series aims to study the effectiveness of Renasys-GO™ negative pressure wound therapy system in the healing of diabetic lower limb ulcers. An electronic vacuum pump (Renasys-GO™, Smith & Nephew GmbH) was used to apply negative pressure wound therapy on wounds, with pressure settings determined according to clinical indication. Changes in wound dimension, infection status and duration of treatment were recorded over the course of Renasys-GO™ therapy in 10 patients with diabetic lower limb ulcers. Healing was achieved in all wounds, three by secondary closure and seven by split-thickness skin grafting. Eight wounds showed a reduction in wound size. The average duration of treatment with Renasys-GO™ therapy was 15.9 days, and all wounds showed sufficient granulation and were cleared of bacterial infection at the end of therapy. Renasys-GO™ therapy may be beneficial in the treatment of diabetic lower limb ulcers and wounds. In this study, which included wounds presenting as post-surgery ray amputation, metatarsal excision wounds, post-debridement abscesses and ulcers, the Renasys-GO™ therapy prepared all wounds for closure via split-thickness skin grafting or secondary healing by promoting granulation tissue and reducing bacterial infection in approximately 2 weeks.


The Role of Alcohol-Related Behavioral Risk in the Design of HIV Prevention Interventions in the Era of Antiretrovirals: Alcohol Challenge Studies and Research Agenda.
HIV/AIDS remains a significant health threat and alcohol is a robust contributing factor. After 25 years of alcohol challenge studies investigating alcohol-related behavioral risk (ARBR), much has been learned delineating how drinking influences sexual transmission. We examine this research and consider its relevance for interventions in the era of antiretrovirals. We consider prototypic alcohol challenge methods, illustrative findings, and prevention/intervention implications, noting three perspectives: (a) scale up/extend existing interventions, including identifying under-targeted risk groups and intersecting with PrEP/PEP interventions; (b) modify existing interventions by cultivating psychoeducational content related to alcohol expectancies, alcohol myopia, sexual arousal, risk perception, sexual abdication, and condom use resistance; and (c) innovate new interventions through Science of Behavior Change approaches and repurposing ARBR paradigms. Finally, we suggest research directions concluding that until HIV incidence diminishes significantly, psychosocial interventions addressing the nexus of alcohol use, sexual transmission, and adherence to biomedical protocols will be an important priority.


The association of lipodystrophy and oxidative stress biomarkers in HIV-infected men.
The aim of this study was to describe the status of oxidative stress and antioxidant biomarkers and their association with metabolic and body composition components of HIV-lipodystrophy syndrome. In a cross-sectional study of blood samples from HIV-infected men with lipodystrophy syndrome (HIV+LIPO+ = 10), HIV-infected men without lipodystrophy syndrome (HIV+LIPO- = 22), and healthy subjects (control = 12), the following oxidative stress biomarkers were analyzed: total hydroperoxide, thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP). In addition, antioxidant biomarkers, including total glutathione, uric acid, alpha-tocopherol, and metabolic components were tested. Dual-energy x-ray absorciometry (DXA) was used to measure the fat mass. The duration of HIV infection and the duration and type of highly active antiretroviral therapy were similar between the two HIV-infected groups. Higher levels of total hydroperoxide were observed in the HIV+LIPO+ (50 +/- 33 H(2)O(2)/L) group compared to the HIV+LIPO- (19 +/- 13 H(2)O(2)/L) and control (5 +/- 5 H(2)O(2)/L) groups (p < 0.05). Similarly, higher levels of AOPP were observed in the HIV+LIPO+ (326 +/- 173 micromol/L) group compared to the HIV+LIPO- (105 +/- 92 micromol/L) and control groups (80 +/- 20 micromol/L) (p < 0.05). Total hydroperoxide significantly correlated with insulin serum levels in the HIV+LIPO+ (r = 0.47, p < 0.05) and HIV+LIPO- groups (r = 0.29, p < 0.05), while AOPP significantly correlated with insulin serum levels in the HIV+LIPO+ (r = 0.73, p < 0.05) and HIV+LIPO- (r = 0.54, p < 0.05) groups. Therefore, higher lipid and protein oxidation were found in HIV-infected patients with lipodystrophy syndrome, and both were associated with insulin levels.


Comparison of the USCOM ultrasound cardiac output monitor with pulmonary artery catheter thermodilution in patients undergoing liver transplantation.
The aim of the study was to compare the standard technique of cardiac output determination by pulmonary artery catheter thermodilution (PAC-TD) with a noninvasive ultrasound Doppler monitor (USCOM Pty., Ltd., Coffs Harbour, Australia) in surgery for liver transplantation. We wished to determine if the degree of accuracy would allow the ultrasound cardiac output monitor (USCOM) to be used as an alternative monitor in a clinical setting in which wide fluctuations in cardiac output could be expected. This was a prospective method comparison study, with 71 paired measurements obtained in 12 patients undergoing liver transplantation in a university teaching hospital. Bland-Altman analysis of the 2 techniques showed a bias of 0.39 L/minute, with the USCOM cardiac output lower compared with that of PAC-TD. The bias was small and did not vary with the magnitude of the cardiac output. The 95% limits of agreement were -1.47 and 2.25 L/minute. There was good repeatability for USCOM measurements, with a repeatability coefficient of 0.43 for USCOM versus 0.77 for PAC-TD. We conclude that USCOM is acceptable for the clinical determination of noninvasive cardiac output, particularly in situations in which tracking changes over time is more important than knowing the precise value. However, the utility of USCOM is limited by its inability to measure pulmonary artery pressure.


Cytogenetics of chronic myeloid leukaemia.
The standard Philadelphia (Ph) translocation t(9;22), its variants and a proportion of Ph-negative cases are positive for the BCR-ABL fusion gene, as determined by molecular analysis. Extensive deletions of chromosome 9 and 22 derived sequences around the translocation breakpoints on the derivative 9 are seen in 10-30% of patients at diagnosis and may confer a worse prognosis. Additional cytogenetic changes can occur in the few months before or during disease progression and are often specific for blast morphology; however, the molecular basis of the most common additional cytogenetic abnormalities is largely unknown. Cytogenetics is important for monitoring patient response to treatment but is increasingly being replaced by the more sensitive and less invasive techniques of RT-PCR and FISH.


Turbulent Supercritical Fluid Chromatography in Open-Tubular Columns for High-Throughput Separations.
A method utilizing turbulent flow to perform ultrafast separations and screen chiral compounds in supercritical fluid chromatography (SFC) is described. Carbon dioxide at high flow rates (up to 4.0 mL/min) is delivered into gas chromatography (GC) open-tubular columns (OTC, 0.18 mm i.d., 20 m long, ∼0.2 μm stationary film thickness) to establish turbulent flow at Reynolds numbers (Re) as high as 9000. Postcolumn dispersion is eliminated by using a modified UV detector that takes measurements directly on column. Upon crossing the laminar-to-turbulent flow transition regime, a significant reduction in plate height is observed resulting in a nearly 3-fold increase in peak capacity from the laminar regime. This is explained by the massive reduction of the mass transfer resistance in the mobile phase due to a flatter flow profile and faster analyte dispersion across the open-tubular column (OTC) i.d.. Demonstrated in this work is a 9 s separation of four polycyclic aromatic hydrocarbons (PAHs) over a 2.2 s separation window using a poly(dimethylsiloxane-co-methylphenylsiloxane) coated OTC. Additionally, three chiral compounds and three chiral cyclodextrin-incorporated OTCs were evaluated at high temperatures (90-120 °C) and CO2 flow rates (3.3-3.7 mL/min) to demonstrate column stability and application of this method for rapid screening. Turbulent SFC provides a separation method for users desiring to achieve separation speeds above what is currently available with very high-pressure LC systems and do so without the resolution loss commonly observed at maximum allowable speed.


Method selection for liquid chromatography.
The accurate measurement of trace level substances in complex mixtures requires advanced instrumental techniques that generally use some form of separation prior to analysis, such as chromatography. There is an increasing trend for users that do not specialise in separation science to undertake this work. With the plethora of available liquid chromatographic techniques this can lead to the inappropriate selection of separation methods, resulting in data that is incoherent or misleading. Hence, despite the existence of comprehensive guidance for users, there remains a need to provide quick and easy to use educational tools that are applicable across the natural and physical sciences.


[Rare differential diagnosis of a degenerative cervical syndrome: an arteriovenous meningeal fistula of the sigmoid sinus].
A 65-year-old patient was referred to our clinic with persisting, severe tinnitus aurium. Due to the facts that prior otolaryngological as well as neurological assessment had been unremarkable and that the patient showed marked degenerative changes in the cervical spine the referring orthopaedic surgeon suggested the cause to be of vertebral origin. Case history showed that the tinnitus had spontaneously occurred and was pulse synchronous. Overall clinical evaluation of the cervical spine was inconspicuous. A brachialgia or other symptoms typically associated with a degenerative cervical syndrome could not be provoked. On the basis of this atypical clinical picture we performed a digital subtraction angiography (DSA) to exclude pathology in the vicinity of the cerebral vessels. This revealed an arteriovenous fistula of the sigmoid sinus which was then, under the auspices of our neurosurgeons, successfully closed by Gugliemo coil embolism. The patient reported that the tinnitus subsided almost immediately. This case demonstrates that despite the manifold pathology that is associated with degenerative cervical syndrome, pulse synchronous tinnitus aurium needs further clarification. Had the case history been taken more accurately and the quality of the tinnitus assessed earlier, the period between onset of symptoms and correct treatment could have been decreased significantly.


Knockdown of two Cadherin genes confers resistance to Cry2A and Cry1C in Chilo suppressalis.
Bacillus thuringiensis (Bt) Cry toxins play an important role in the management of insect pests. Resistance to Bt toxins has been reported in many pest insects but the mechanism responsible for this resistance in rice crop pests remains largely unknown. Cadherin is one of several Bt toxin receptors. At present, only one cadherin gene, CsCAD1, has been documented in the striped rice stem borer, Chilo suppressalis. We amplified a nearly full-length transcript of another C. suppressalis cadherin gene, CsCAD2, and found that it has a different expression pattern to CsCAD1. CsCAD1 was highly expressed in fifth and sixth instar larvae, especially in the midgut, while the expression levels of CsCA2 were equably in each developmental stage. Newly hatched larvae were fed on rice smeared with synthesized siRNA to knockdown either CsCAD1 or CsCAD2, and then were fed transgenic rice expressing either the Cry2A or Cry1C toxins. The siRNA-treatment groups had lower mortality and higher survival rates than the control group, suggesting that reduced expression of CsCAD1 or CsCAD2 increased resistance to Cry2A and Cry1C. We conclude that CsCAD1 and CsCAD2 interact with Bt toxins in C. suppressalis and that this interaction could be the mechanism underlying Bt resistance in this insect.


Inflammatory Response-Related Long Non-Coding RNA Signature Predicts the Prognosis of Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is a high mortality malignant tumor with genetic and phenotypic heterogeneity, making predicting prognosis challenging. Meanwhile, the inflammatory response is an indispensable player in the tumorigenesis process and regulates the tumor microenvironment, which can affect the prognosis of tumor patients. Using HCC samples in the TCGA-LIHC dataset, we explored lncRNA expression profiles associated with the inflammatory response. The inflammatory response-related lncRNA signature was constructed by univariate Cox regression, LASSO regression, and multivariate Cox regression methods based on inflammatory response-related differentially expressed lncRNAs in HCC. Seven inflammatory response-related lncRNA signatures were identified in predicting HCC prognosis. Kaplan-Meier (K-M) survival analysis indicated that high-risk group HCC patients were associated with poor prognosis. The utility of the inflammatory response-related lncRNA signatures was proved by the AUC and DCA analysis. The nomogram further confirmed the accuracy of the novel signature in predicting HCC patients' prognoses. In validation, our novel signature is more accurate than traditional clinicopathological performance for prognosis prediction of HCC patients. GSEA analysis further elucidated the underlying mechanisms and pathways of HCC progression in the low- and high-risk groups. Moreover, immune cells infiltration responses and immune function analyses revealed a significant difference between high- and low-risk groups in cytolytic activity, MHC class I, type I INF response, type II INF response, inflammation-promoting, and T cell coinhibition. Finally, HHLA2, NRP1, CD276, TNFRSF9, TNFSF4, CD80, and VTCN1 were expressed higher in high-risk groups in the immune checkpoint analysis. A novel inflammatory response-related lncRNA signature (AC145207.5, POLHAS1, AL928654.1, MKLN1AS, AL031985.3, PRRT3AS1, and AC023157.2) is capable of predicting the prognosis of HCC patients and providing new immune targeted therapies insight.


The long-term effects of taxol on explants of developing chick optic tectum in culture.
The long term effects on cellular ultrastructure and survival of exposure to the antimitotic drug taxol were investigated using explant cultures of embryonic chick optic tectum. After 7-8 days of continuous exposure the major changes were similar to those previously reported for shorter periods of exposure (Bird, 1984), i.e. the presence of increased numbers of microtubules in large bundles, associated with networks of filamentous cytoskeletal elements (inter-microtubule substance). With longer periods of exposure microtubule numbers increased further, the inter-microtubule substance became displaced towards the periphery of the microtubule bundles and filamentous cross-bridges between microtubules, other microtubules and membranous organelles became more numerous. Further microtubule accumulation, darkening of the cytoplasmic matrix, compression of endoplasmic cisterns and neuronal cell death were increasingly evident after 15 days and longer, and the numbers of synaptic profiles fell drastically. Few neurons survived beyond 28 days and return of cultures to normal medium after 7-14 days continuous exposure to taxol had limited effects on neuronal survival and none on synaptic profile numbers.


Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients Aged ≥ 75 Years With Non-small-cell Lung Cancer (NSCLC): An Italian, Multicenter, Retrospective Study.
Non-small-cell lung cancer (NSCLC) is predominantly a disease of the elderly population. Over the past few years, immunotherapy with monoclonal antibodies named checkpoint inhibitors (ICIs) greatly improved the clinical management of a significant proportion of patients with metastatic NSCLC. However, pivotal trials excluded older patients, although, given the favorable clinical profile of ICIs, this treatment may be revealed to be a most valuable option also for these patients. To this aim, a multicenter retrospective analysis was performed on patients aged ≥ 75 years with NSCLC treated with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy. Inclusion criteria were: diagnosis of locally advanced or metastatic NSCLC (stage IIIB or IV, according to the American Joint Committee on Cancer (AJCC) classification system, version 8.0); age ≥ 75 years; treatment with anti-PD-1/PD-L1 monoclonal antibodies in first or subsequent lines of treatment; absence of epidermal growth factor receptor-activating mutations or anaplastic lymphoma kinase and ROS-1 rearrangements. The primary endpoints of the study were the efficacy, in terms of overall response rate, progression-free survival, and overall survival, and safety, by means of evaluations of the incidence of immune-related adverse events. Eighty-six patients were considered for the final analysis; 71 (82.6%) were male. The mean age was 78.5 years (range, 75-86 years; SD, 3.12 years). Of the 86 patients, 69 (80.2%) of patients had a performance status of 0 or 1. The overall median progression-free survival was 5.6 months (range 1-36 months; SD, 7.5 months,) whereas the median overall survival was 10.1 months (range, 1.7-34.8 months; SD, 8 months). At the Cox regression analysis, the only parameter significantly associated with survival was the smoking status (P = .008). No difference in survival was found between patients younger and older than 80 years. In the present real-world retrospective cohort, efficacy and toxicity profiles of ICIs in older patients with advanced NSCLC were comparable with those observed in younger patients enrolled in clinical trials.


Automated ribotyping for the identification and characterization of foodborne clostridia.
The DuPont Qualicon RiboPrinter was employed to determine if automated ribotyping could be used to differentiate between and characterize various species of foodborne clostridia. EcoRI digests were used to ribotype 49 isolates that represented seven Clostridium species: C. aerotolerans, C. beirjerinckii, C. botulinum, C. butyricum, C. perfringens, C. putrificum, and C. sporogenes. EcoRV digests were also used to ribotype 17 C. botulinum isolates to determine if an alternate restriction enzyme was more suitable than was EcoRI for toxin typing. It was concluded that the RiboPrinter could be potentially used to identify most of the clostridia represented in the study, but that the system has difficulty distinguishing between C. botulinum and C. sporogenes. The system may also be potentially used to characterize clostridia based on phenotypic characteristics. Toxin typing of clostridia remains problematic, but may be improved by the use of restriction enzyme combinations.


Energy issues in microwave food processing: A review of developments and the enabling potentials of solid-state power delivery.
The enormous magnitude and variety of microwave applications in household, commercial and industrial food processing creates a strong motivation for improving the energy efficiency and hence, sustainability of the process. This review critically assesses key energy issues associated with microwave food processing, focusing on previous energy performance studies, energy performance metrics, standards and regulations. Factors affecting energy-efficiency are categorised into source, load and source-load matching factors. This highlights the need for highly-flexible and controllable power sources capable of receiving real-time feedback on load properties, and effecting rapid control actions to minimise reflections, heating non-uniformities and other imperfections that lead to energy losses. A case is made for the use of solid-state amplifiers as alternatives to conventional power sources, magnetrons. By a full-scale techno-economic analysis, including energy aspects, it is shown that the use of solid-state amplifiers as replacements to magnetrons is promising, not only from an energy and overall technical perspective, but also in terms of economics.


A multi-objective model for sustainable recycling of municipal solid waste.
The efficient management of municipal solid waste is a major problem for large and populated cities. In many countries, the majority of municipal solid waste is landfilled or dumped owing to an inefficient waste management system. Therefore, an optimal and sustainable waste management strategy is needed. This study introduces a recycling and disposal network for sustainable utilisation of municipal solid waste. In order to optimise the network, we develop a multi-objective mixed integer linear programming model in which the economic, environmental and social dimensions of sustainability are concurrently balanced. The model is able to: select the best combination of waste treatment facilities; specify the type, location and capacity of waste treatment facilities; determine the allocation of waste to facilities; consider the transportation of waste and distribution of processed products; maximise the profit of the system; minimise the environmental footprint; maximise the social impacts of the system; and eventually generate an optimal and sustainable configuration for municipal solid waste management. The proposed methodology could be applied to any region around the world. Here, the city of Tehran, Iran, is presented as a real case study to show the applicability of the methodology.


[Quantitative value of the hallux pattern: mother-child correlation].
Mother-child correlations based upon the ridge-counts of the patterns of the hallucal areas of the soles were computed and compared with the results from finger-tips and palms. The results which are to be found in the hallucal areas of the sole join seamless to those known from finger and hand characters and show that the ridge-count of the hallucal pattern is in the same way suitable for quantitative genetic analysis of dermatoglyphics as the generally accepted dermatoglyphic counts.


Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study.
In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD. An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation. Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes. This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD.


Diffusion-weighted and macromolecular contrast enhanced MRI of tumor response to antivascular therapy with ZD6126.
The effects of the anti-vascular agent ZD6126 were studied in volume matched subcutaneous DU-145 human prostate cancer xenografts in SCID mice using two different MRI techniques, diffusion and vascular imaging. Diffusion weighted MRI was performed before and at 24 h, 48 h and 72 h following a single dose of 200 mg/kg. Tumor vascular volume and permeability surface area product (PSP) were determined 24 h post antivascular therapy following an identical dose using dynamic contrast enhanced MRI of the macromolecular contrast agent albumin-gadolinium diethylenetriaminepentaacetate (albumin-GdDTPA). Consistent with the mechanism of action of ZD6126, significantly lower vascular volume was detected at 24 h whereas diffusion changes were evident at 48 h. Diffusion MRI findings correlated well with histological determination of the necrotic fraction in the tumors by 48 h. Both diffusion and vascular imaging are useful noninvasive techniques to detect response of tumors to antivascular therapy with ZD6126 in the DU-145 human prostate cancer xenograft model.


BSA-Sugar Conjugates as Ideal Building Blocks for SPR-Based Glycan Biosensors.
Controlled immobilization of sugar probes is of key importance for the development of glycan biosensors. To this end, a series of BSA-sugar conjugates with different numbers of mannose units are prepared via the squaric acid-mediated coupling reaction. The conjugates can absorb directly on gold substrate without any derivation reactions, thus providing a simple and effective method for the construction of SPR-based glycan biosensors. SPR measurements show that the BSA-mannose conjugate with 11 mannoses exhibit the highest affinity to the lectin concanavalin A with a limit of detection of ca. 1.8 nM. Regeneration and specificity of the obtained glycan biosensors are also investigated.


Where do U.S. households purchase healthy foods? An analysis of food-at-home purchases across different types of retailers in a nationally representative dataset.
Food shopping decisions are pathways between food environment, diet and health outcomes, including chronic diseases such as diabetes and obesity. The choices of where to shop and what to buy are interrelated, though a better understanding of this dynamic is needed. The U.S. Department of Agriculture's nationally representative Food Acquisitions and Purchase Survey food-at-home dataset was joined with other databases of retailer characteristics and Healthy Eating Index-2010 (HEI) of purchases. We used linear regression models with general estimating equations to assess relationships between trip, store, and shopper characteristics with trip HEI scores. We examined HEI component scores for conventional supermarkets and discount/limited assortment retailers with descriptive statistics. Overall, 4962 shoppers made 11,472 shopping trips over one-week periods, 2012-2013. Trips to conventional supermarkets were the most common (53.6%), followed by supercenters (18.6%). Compared to conventional supermarkets, purchases at natural/gourmet stores had significantly higher HEI scores (β = 6.48, 95% CI = [4.45, 8.51], while those from "other" retailers (including corner and convenience stores) were significantly lower (-3.89, [-5.87, -1.92]). Older participants (versus younger) and women (versus men) made significantly healthier purchases (1.19, [0.29, 2.10]). Shoppers with less than some college education made significantly less-healthy purchases, versus shoppers with more education, as did households participating in SNAP, versus those with incomes above 185% of the Federal Poverty Level. Individual, trip, and store characteristics influenced the healthfulness of foods purchased. Interventions to encourage healthy purchasing should reflect these dynamics in terms of how, where, and for whom they are implemented.


Actions of a newly isolated intestinal peptide PHI on pancreatic acini.
In dispersed acini from guinea pig pancreas, PHI, a peptide recently isolated from porcine intestine and found to contain 27 amino acids, inhibited binding of 125I-vasoactive intestinal peptide (125I-VIP), increased cellular cAMP, and stimulated amylase secretion. The increase in amylase secretion caused by a maximally effective concentration of PHI in combination with 8-bromo-cAMP, VIP, or secretin was the same as that caused by PHI alone. In contrast, the increase in amylase secretion caused by PHI plus bombesin, carbachol, or the C-terminal octapeptide of cholecystokinin was significantly greater than the sum of the increase caused by each secretagogue acting alone. From the abilities of PHI to inhibit binding of 125I-VIP, to increase cellular cAMP, and to increase amylase secretion, the apparent affinity of PHI for the VIP-preferring receptors on pancreatic acinar cells is approximately 25 times less than that of VIP but 10 times greater than that of secretin. From the ability of PHI to increase cellular cAMP, the apparent affinity of PHI for the secretin-preferring receptors on pancreatic acinar cells is approximately 300 times less than that of secretin but equal to that of VIP.


Respiratory medication use in primary care among COPD subjects in four Latin American countries.
To assess respiratory medications used, factors predicting treatment and patterns of corticosteroid (CS) use in primary care in Latin America among chronic obstructive pulmonary disease (COPD) patients. COPD was defined as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) < 0.70 or previous medical diagnosis. To determine factors associated with respiratory medication use, crude and adjusted Poisson regression models were performed. Of 1743 patients interviewed, 1540 completed spirometry, 309 had COPD (FEV1/FVC<0.70) and 102 had a prior diagnosis of COPD. Among spirometry-defined COPD patients, 36.6% used respiratory medications: bronchodilators (BD) 24.9%, CS 13.3%, BD+CS 15.2%. In those with a previous diagnosis, 79.4% used respiratory medications: BD 64.7%, CS 37.6%, BD+CS 25.6%. A total of 81/102 (79%) patients with prior diagnosis were using CS despite not having airway obstruction or exacerbation. In spirometry-defined COPD, dyspnoea (OR 2.09, 95%CI 1.13-3.87), severe airway obstruction (OR 3.36, 95%CI 1.40-8.03) and exacerbation in the past year (OR 5.52, 95%CI 2.19-13.89) were associated with increased respiratory medication use. Among those with a previous diagnosis, use of respiratory medications was associated with cough (OR 5.31, 95%CI 1.28-22.12), severe airway obstruction (OR 29.50, 95%CI 3.18-273.30) and fewer years of schooling (OR 0.12, 95%CI 0.03-0.52). In the primary care setting, undertreatment is frequent in spirometry-defined COPD patients, and there is increased use of CS (overtreatment) in patients with a previous diagnosis of COPD.


Identifying intermediate-risk candidates for active surveillance of prostate cancer.
Although already established for very-low and low-risk (LR) prostate cancer (PCa), controversy remains around offering active surveillance (AS) to men with intermediate-risk (IR) PCa. As IR represents a broad spectrum of disease biology, there is a critical need to define eligibility criteria that will enable both patient and physician to accept AS as the best balance of competing risks. In this study, we aimed to identify predictors of progression to enable optimal patient selection. In our AS cohort, men were assigned to risk categories according to the National Comprehensive Cancer Network (NCCN favorable and NCCN unfavorable) and the CAPRA classifications. Clinical, biochemical and pathological characteristics, progression to definitive invasive treatment, and pathologic progression on follow-up biopsies were compared among these groups. A multivariate Cox regression model was used to identify independent predictors of progression on AS. AS was the initial management option for 651 men, including 144 with IR PCa. During the median follow-up of 4.5 years (range: 0.6-19.1), 259 patients (39.7%) underwent definitive treatment. Further, 5- and 10-year predicted rates of intervention for IR patients were 50% and 66%, respectively. Treatment rates were no different between the NCCN LR and NCCN IR groups, but were higher in CAPRA IR compared to CAPRA LR groups (P = 0.025). NCCN unfavorable IR patients had a twofold increased risk of definitive intervention compared to favorable IR (hazard ratio [HR] = 2.07; 95% CI: 1.17-3.65; P = 0.01). In the entire cohort, the percentage of biopsy cores positive (continuous variable; P = 0.006) and ISUP grade 2 or higher on initial biopsy (P = 0.027) were independent predictors of cessation of AS on multivariate analysis. In the intermediate group, only the percentage of positive biopsy cores was an independent predictor (P = 0.021) of AS cessation. Only 1 IR patient developed metastatic disease (0.7%). Actuarial overall survival at 5 and 10 years was 98.6% and 94.1%, respectively. There were 2 PCa deaths at 18.7 and 19.1 years of follow-up. In all AS, increasing percentage of core involvement and presence of Gleason pattern 4 are predictors of increased risk of progression. For IR patients, the NCCN favorable criteria and CAPRA score predict those more likely to remain on AS.


Evaluation of myocardial viability in patients with acute myocardial infarction: Layer-specific analysis of 2-dimensional speckle tracking echocardiography.
The value of layer-specific two-dimensional speckle tracking echocardiography (LS2D-STE) for evaluating viable myocardium (VM) in patients with acute myocardial infarction (AMI) was unclear, this study provides new insights into it and to make a comparison with dualisotope simultaneous acquisition single photon emission computed tomography ( DISA-SPECT). Forty hospitalized patients with AMI and left ventricular systolic dysfunction (left ventricular ejection fraction <50%) underwent LS2D-STE and DISA-SPECT before percutaneous coronary intervention (PCI). The longitudinal, circumferential, and radial peak systolic strains and the peak systolic strain rates of 3 myocardiallayers (endocardium, mid-myocardium, and epicardium), as well as the total wall thickness, were determined by LS2D-STE. Routine echocardiography was followedup at 1, 3, 6 months after PCI, with the improvement of the wall motion as the goldenstandard for evaluating VM. The sensitivity, specificity and accuracy of DISA-SPECT for evaluating VM were 82.1%, 74.3%, and 79.3%, respectively. Among the layer-specific parameters, only endocardial (endo-) longitudinal strain (LS) and endo- longitudinal strain rate (LSr) were used as independent parameters for evaluating VM (P < .05), and the sensitivity, specificity and accuracy of endo-LS and endo-LSr in evaluation of VM were 77.1%, 65.4%, and 72.9% vs 72.9%, 65.4%, and 69.7%. Endo-LS and endo-LSr were superior to total wall thickness LS and LSr (AUC endo-LS 0.767 vs total-LS 0.669; endo-LSr 0.743 vs total-LSr 0.682). The parallel test and the serial test of combination of endo-LS and endo-LSr showed similar sensitivity, specificity and accuracy to DISA-SPECT (P > .05). The endo-LS and endo-LSr analysis of LS2D-STE can evaluate the VM well, and its sensitivity, specificity and accuracy in detection of VM are similar to those of DISA-SPECT, resulting in LS2D-STE being a good option for the assessment of VM.


[Fibrous dysplasia of maxilla and the orthodontic treatment. Case report].
Patients who have malocclusions caused by bone diseases come to see the dentist for the orthodontic treatment. One of these diseases is fibrous dysplasia. The aim of this study was to present the patient with the active form of fibrous dysplasia who reported to the Orthodontic Department of Pomeranian Medical University in Szczecin for treatment. We used the patient's own documentation, photos, radiological view and histopathological investigations. The extraoral, clinical examination revealed the asymmetry of the face on the left side, while the intraoral examination showed the convex lesion similar to an egg on the palate which crosses the medial line and clear "distension" of the alveolar bone in the direction of the oral vestibule. The dysplastic lesions are extensive and cause numerous malocclusions and disorders of the symmetry. The radiological and histopathological examinations were added to the clinical examination. The panoramic radiographs have shown the asymmetry and heterogenic structure of the bone with areas of"ground glass". Computer tomography demonstrated bumpy thickening of the zygomatic bone, maxilla, and a great wing of the sphenoid bone and almost completely filled maxillary sinus. The histopathological examination is the confirmation of the diagnosis of fibrous dysplasia. It demonstrates immature bone. The diagnosis of fibrous dysplasia commands the periodic observation and the postponement of the orthodontic treatment in the stage of active development of lesions, but when the overgrowth impairs the function, there is the necessity to use surgical and radical excision to remove lesions. We must pay particular attention to the possibility of malignant transformation of these lesions.


[Home care effectiveness assessment in a health maintenance organization in Belo Horizonte, Minas Gerais State, Brazil].
A retrospective cohort study was performed to assess the impact of a Case Management Home Care Program supplied by the Unimed-BH medical cooperative on hospitalization-free survival time among eligible patients 60 years or older. A Cox proportional hazards model was fitted to assess the impact of home visits by health professionals on hospitalization-free survival time in a sample of 2,943 elders, while adjusting for patient age, physical dependence, medicines, feeding route, pressure ulcers, supplemental oxygen therapy, cognitive impairment, outpatient visits, and hospitalizations in the preceding quarter. Risk factors for shorter hospitalization-free survival time were: degree of physical dependence, enteral nutrition, supplemental oxygen therapy, pressure ulcers, and hospital admissions in the previous quarter. Higher rates of home visits by physicians and nurses showed a protective dose-response effect on hospitalization-free survival time. The data suggest that regular home visits by physicians and nurses lengthen hospitalization-free survival time among elderly patients enrolled in the program.


Aging in singapore.
This paper outlines the aging trends in Singapore and takes stock of socioeconomic differences between Malay and Chinese elderly persons. It draws attention to the idea that policy response to the graying of Singapore has largely been confined to dealing with the consequences of population aging for the economy on the one hand and to creating social and community support for caregiving for elderly persons on the other. These policies cover employment, healthcare, housing, and social and recreational needs. Although fairly comprehensive, it is the position of this paper that further attention on supplementary programs that will address the particularities of specific ethnic groups will be required in order that the minority ethnic groups may also age gracefully.


Haemolytic uraemic syndrome in children England, Wales, Northern Ireland, and Ireland: A prospective cohort study.
Haemolytic uraemic syndrome (HUS) caused by infection with Shiga toxin-producing Escherichia coli (STEC) is a relatively rare but potentially fatal multisystem syndrome clinically characterised by acute kidney injury. This study aimed to provide robust estimates of paediatric HUS incidence in England, Wales, Northern Ireland, and the Republic of Ireland by using data linkage and case reconciliation with existing surveillance systems, and to describe the characteristics of the condition. Between 2011 and 2014, 288 HUS patients were included in the study, of which 256 (89.5%) were diagnosed as typical HUS. The crude incidence of paediatric typical HUS was 0.78 per 100,000 person-years, although this varied by country, age, gender, and ethnicity. The majority of typical HUS cases were 1 to 4 years old (53.7%) and female (54.0%). Clinical symptoms included diarrhoea (96.5%) and/or bloody diarrhoea (71.9%), abdominal pain (68.4%), and fever (41.4%). Where STEC was isolated (59.3%), 92.8% of strains were STEC O157 and 7.2% were STEC O26. Comparison of the HUS case ascertainment to existing STEC surveillance data indicated an additional 166 HUS cases were captured during this study, highlighting the limitations of the current surveillance system for STEC for monitoring the clinical burden of STEC and capturing HUS cases.


Do Gold Humanism Honor Society Inductees Differ From Their Peers in Empathy, Patient-Centeredness, Tolerance of Ambiguity, Coping Style, and Perception of the Learning Environment?
Construct: Induction into the Gold Humanism Honor Society (GHHS) during medical school is recognized as an indicator of humanistic orientation and behavior. Various attitudes and interpersonal orientations including empathy and patient-centeredness have been posited to translate into behaviors constituting humanistic care. To our knowledge there has never been a longitudinal, multi-institutional empirical study of the attitudinal and interpersonal orientations correlated with GHHS membership status. We used the American Medical Association Learning Environment Study (LES) data set to explore attitudinal correlates associated with students whose behaviors are recognized by their peers as being exceptionally humanistic. Specifically, we examined whether empathy, patient-centeredness, tolerance of ambiguity, coping style, and perceptions of the learning environment are associated with GHHS membership status. We further considered to what extent GHHS members arrive in medical school with these attitudinal correlates and to what extent they change and evolve differentially among GHHS members compared to their non-GHHS peers. Between 2011 and 2015, 585 students from 13 North American medical schools with GHHS chapters participated in the LES, a longitudinal cohort study using a battery of validated psychometric measures including the Jefferson Scale of Empathy, Patient-Practitioner Orientation Scale and Tolerance of Ambiguity Questionnaire. In the final survey administration, students self-identified as GHHS inductees or not (non-GHHS). T tests, effect sizes, and longitudinal generalized mixed-effects models examined the differences between GHHS and non-GHHS students. Students inducted into GHHS scored significantly higher on average over 4 years than non-GHHS inductees on clinical empathy, patient-centered beliefs, and tolerance of ambiguity. GHHS students reported higher levels of empathy and patient-centeredness at medical school matriculation. This difference persists in the 4th year of medical school and when controlling for time, race, gender, and school. GHHS inductees enter medical school with different attitudes and beliefs than their non-GHHS classmates. Although humanistic attitudes and beliefs vary over time during students' 4 years, the gap between the two groups remains constant. Medical schools may want to consider selecting for specific humanistic traits during admissions as well as fostering the development of humanism through curricular interventions.


Role of azathioprine in preventing recurrences in a patient of recurrent erythema nodosum leprosum.
The pathogenesis of erythema nodosum leprosum (ENL) involves both immune complex deposition and dysfunction of cell mediated immunity. Tumour necrosis factor-alpha (TNF-alpha) plays an important role in its pathogenesis. Thalidomide and corticosteroids are the mainstay of treatment for ENL. However, there are often severe limitations to their use. We report a case of recurrent ENL treated successfully with azathioprine. A 15-year-old unmarried girl with lepromatous leprosy had recurrent ENL for 2 years. She was treated with WHO-MB MDT and prednisolone in doses of 40-90 mg a day for 2-12 weeks. Her condition was inadequately controlled. The patient was therefore treated with thalidomide 300 mg and prednisolone 40 mg. The symptoms subsided after 5 days and ENL lesions healed in 2 weeks. Prednisolone was reduced by 10 mg per week and stopped, while thalidomide was reduced to 100 twice daily after 4 weeks. Azathioprine 100 mg (2 mg/kg per day) daily orally was added to prevent recurrences. Thalidomide was further reduced and stopped after another 4 weeks while she continued with azathioprine in the same doses for 8 months. There was no recurrence of ENL lesions and no side effects of the therapy. MB-MDT was stopped 1 year ago, and she is on follow-up without any relapse. Azathioprine, therefore, appears to be an effective and safe drug to prevent recurrences of ENL.


A simple reliable agglutination test for screening P-fimbriated Escherichia coli in children with urinary tract infections gives valuable clinical information.
Most urinary tract infections (UTI) are caused by Escherichia coli (E. coli) and the pathogenetic mechanisms of this bacterium have been thoroughly studied. Lipopolysaccharide (LPS), capsular polysaccharides and fimbrial structures are among the more important virulence markers. P-fimbriae, with a specificity for the carbohydrate structure of the P blood group system (alpha-D-Gal-1,4-beta-D-Gal) have attracted particular interest, as non-fimbriated E. coli rarely give rise to pyelonephritis, unless the normal defence mechanisms of the urinary tract are impaired. We have evaluated a commercial test (Orion Diagnostica, PF test), developed to detect P-fimbriae on E. coli from clinical isolates. It is based on latex particles with covalently bound receptors (alpha-D-Gal-1,4-beta-D-gal). In this study a high correlation was found between pyelonephritis, as judged by clinical and biochemical criteria, and a positive PF test.


Pirprofen.
Pirprofen, a nonsteroidal antiinflammatory drug (NSAID) undergoing Phase III investigation as Rengasil (Ciba-Geigy Corp.), is useful in the management of both rheumatoid arthritis and osteoarthritis and as an analgesic. In doses of 600-800 mg/d, pirprofen has been found to be as effective as, but not superior to, aspirin 3.6 g/d in relieving the more common symptoms of rheumatoid arthritis. Pirprofen is as effective as, but not superior to, other available NSAIDs in terms of efficacy, tolerability, and incidence of adverse effects. The recommended dosage in osteoarthritis is 450-600 mg/d. As with all NSAIDs, including aspirin, the side effects most commonly seen with pirprofen are gastrointestinal in nature. Peptic ulceration and occult gastrointestinal blood loss have been reported in a small percentage of patients receiving pirprofen. Central-nervous-system-related side effects that are frequently associated with high-dose aspirin therapy appear less frequently with pirprofen. Although it does not offer distinct advantages over other NSAIDs, pirprofen offers an effective therapeutic alternative for patients who are unable to tolerate aspirin or other existing compounds.


Machine Learning Approach for Predicting Systemic Lupus Erythematosus in an Oman-Based Cohort.
This study aimed to design a machine learning-based prediction framework to predict the presence or absence of systemic lupus erythematosus (SLE) in a cohort of Omani patients. Data of 219 patients from 2006 to 2019 were extracted from Sultan Qaboos University Hospital's electronic records. Among these, 138 patients had SLE, while the remaining 81 had other rheumatologic diseases. Clinical and demographic features were analysed to focus on the early stages of the disease. Recursive feature selection was implemented to choose the most informative features. The CatBoost classification algorithm was utilised to predict SLE, and the SHAP explainer algorithm was applied on top of the CatBoost model to provide individual prediction reasoning, which was then validated by rheumatologists. CatBoost achieved an area under the receiver operating characteristic curve score of 0.95 and a sensitivity of 92%. The SHAP algorithm identified four clinical features (alopecia, renal disorders, acute cutaneous lupus and haemolytic anaemia) and the patient's age as having the greatest contribution to the prediction. An explainable framework to predict SLE in patients and provide reasoning for its prediction was designed and validated. This framework enables clinicians to implement early interventions that will lead to positive healthcare outcomes.


In silico comparative genomic analysis of two non-small cell lung cancer subtypes and their potentials for cancer classification.
Lung adenocarcinoma (AC) and squamous cell lung carcinoma (SCC) are two main subtypes of non-small cell lung cancer. In order to understand their biological differences, we conducted an in silico comparative genomic analysis of their expression profiles. We utilized the published microarray data of 18 SCC samples and 40 AC samples to discriminate genes differentially expressed in SCC and AC. Genes were employed to construct a functional module network and build a support vector machine classifier. Another set of published non-small cell lung cancer microarray data was used to test the predictive accuracy of support vector machine classifier. Our analysis showed that SCC shows an elevated expression of genes related to cell division and DNA replication while AC presents an elevated expression of the genes related to protein transport and cell junction. ROC analysis demonstrates that the support vector machine classifier has a high classification accuracy for AC and SCC. AC and SCC are distinctively different in certain biological network modules. This proposes different pathological mechanisms involved in these two non-small cell lung cancer subtypes.


Copper-dependent inhibition of cytochrome c oxidase by Abeta(1-42) requires reduced methionine at residue 35 of the Abeta peptide.
By altering key amino acid residues of the Alzheimer's disease-associated amyloid-beta peptide, we investigated the mechanism through which amyloid-beta inhibits cytochrome c oxidase (EC 22.214.171.124). Native amyloid-beta inhibited cytochrome oxidase by up to 65%, and the level of inhibition was determined by the period of amyloid-beta ageing before the cytochrome oxidase assay. Substituting tyrosine-10 with alanine did not affect maximal enzyme inhibition, but the altered peptide required a longer period of ageing. By contrast, oxidizing the sulfur of methionine-35 to a sulfoxide, or substituting methionine-35 with valine, completely abrogated the peptide's inhibitory potential towards cytochrome oxidase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that the loss of inhibitory potential towards cytochrome oxidase with the methionine-35-altered peptides did not correlate with a substantially different distribution of amyloid-beta oligomeric species. Although the amyloid-beta-mediated inhibition of cytochrome oxidase was completely dependent on the presence of divalent Cu2+, it was not supported by monovalent Cu+, and experiments with catalase and H2O2 indicated that the mechanism of cytochrome oxidase inhibition does not involve amyloid-beta-mediated H2O2 production. We propose that amyloid-beta-mediated inhibition of cytochrome oxidase is dependent on the peptide's capacity to bind, then reduce Cu2+, and that it may involve the formation of a redox active amyloid-beta-methionine radical.


Rehospitalization rates of patients with schizophrenia discharged on haloperidol, risperidone or clozapine.
The purpose of this study was to evaluate the rehospitalization rates of patients discharged from the Institute of Psychiatry of the Hospital das Clínicas of the Universidade de São Paulo Medical School while being treated with haloperidol, risperidone or clozapine. This is a naturalistic study designed to monitor rehospitalization rates for patients discharged on haloperidol (n=43), risperidone (n=22) or clozapine (n=31). Time to readmission over the course of three years was measured by the product-limit (Kaplan-Meier) method. Risk factors associated with rehospitalizations were examined. At 36 months, remained in the community 74% of the haloperidol-treated patients, 59% of the risperidone-treated patients and 84% of the clozapine-treated patients. The haloperidol group showed a higher proportion of women, a late age of onset and shorter length of illness than the other groups, whereas the opposite was observed in the clozapine group. This study suggests that the rehospitalization rates of patients taking clozapine are lower than the rate for patients treated with haloperidol and risperidone. However confounding variables such as gender distribution and age of onset represent limitations that should be taken into account for the interpretation of the results.


[Effects of subchronic exposure of laboratory mice to benzylbutyl phthalate (BBP) on the quantity and quality of male germ cells].
The aim of the study was to investigate the effect of 8-weeks exposure of male mice to benzyl butyl phthalate (BBP) on the sperm count and quality of gametes. Pzh:Sfis male mice exposed per os to 450 mg/kg bw (1/16 LD50) and to 1800 mg/kg bw (1/4 LD50) of BBP in olive oil were used in the study. Control mice were treated with olive oil only. Groups of animals were killed 4 and 8 weeks after the start of exposure and 4 weeks after he end of exposure. Sperm count, motility, morphology and DNA damage in gametes were estimated in the study. Sperm counts were diminished 4 and 8 weeks after the start of exposure to BBP. In the same time decrease in sperm motility and dose-dependent increase in the frequency of abnormal sperm heads and slight increase in DNA damage were noted. 4 weeks after the end of exposure, slight decrease in sperm counts in the group of 1/4 LD50 was observed, only. Correlation between sperm count and testes and epididymes weight were noted. Themost sensitive to BBP exposure occurred spermatozoa and spermatids.


Evolution of endovascular mechanical thrombectomy for acute ischemic stroke.
Acute ischemic stroke (AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, but key limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy.


The impact of initial treatment delay using primary angioplasty on mortality among patients with acute myocardial infarction: from the Korea acute myocardial infarction registry.
The impact of treatment delays to reperfusion on patient mortality after primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) is controversial. We analyzed 5,069 patients included in the Korea Acute Myocardial Infarction Registry (KAMIR) between November 2005 and January 2007. We selected 1,416 patients who presented within 12 hr of symptom onset and who were treated with primary PCI. The overall mortality at one month was 4.4%. The medians of door-to-balloon time, symptom onset-to-balloon time, and symptom onset-to-door time were 90 (interquartile range, 65-136), 274 (185-442), and 163 min (90-285), respectively. One-month mortality was not increased significantly with any increasing delay in door-to-balloon time (4.3% for < or =90 min, 4.4% for >90 min; p=0.94), symptom onset-to-balloon time (3.9% for < or =240 min, 4.8% for >240 min; p=0.41), and symptom onset-to-door time (3.3% for < or =120 min, 5.0% for >120 min; p=0.13). These time variables had no impact on one-month mortality in any subgroup. Thus, this first nationwide registry data in Korea showed a good result of primary PCI, and the patient prognosis may not depend on the initial treatment delay using the current protocols.


TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway.
The RNA binding protein TRA2A, a member of the transformer 2 homolog family, plays a crucial role in the alternative splicing of pre-mRNA. However, it remains unclear whether TRA2A is involved in non-coding RNA regulation and, if so, what are the functional consequences. By analyzing expression profiling data, we found that TRA2A is highly expressed in esophageal cancer and is associated with disease-free survival and overall survival time. Subsequent gain- and loss-of-function studies demonstrated that TRA2A promotes proliferation and migration of esophageal squamous cell carcinoma and adenocarcinoma cells. RNA immunoprecipitation and RNA pull-down assay indicated that TRA2A can directly bind specific sites on MALAT1 in cells. In addition, ectopic expression or depletion of TRA2A leads to MALAT expression changes accordingly, thus modulates EZH2/β-catenin pathway. Together, these findings elucidated that TRA2A triggers carcinogenesis via MALAT1 mediated EZH2/β-catenin axis in esophageal cancer cells.


Growth inhibition of Lewis lung carcinoma by an inorganic dye, Ruthenium Red.
The growth of subcutaneously transplanted Lewis lung carcinoma in BDF1 mice was inhibited by an inorganic dye, Ruthenium Red. The mean volume of the tumors of the mice which were given Ruthenium Red by daily ip injection of 5 mg/kg on days 1 approximately 10 was 28 and 39% of that of the controls at days 18 and 23 after transplantation, respectively. The median survival time (MST) of the treated mice was 27.8 days while that of the control was 23.0 days. The higher MST (32.5 days) was obtained when the dye was given at 2.5 mg/kg for 1 approximately 20 days, although the tumor volume in this group of mice was 51% of that of the control at day 18.


Positive Youth Development and Depression: An Examination of Gender Differences in Croatia and Spain.
Depression is a major public health issue and the literature has consistently showed that the rates of depression increase dramatically during youth transition to adulthood, and gender differences merge in this period. Positive youth development (PYD) framework is focused on strengths that make young people more resistant to negative outcomes, like depression, and more capable to choose a positive life direction. The aim of the study was to examine the relationship between the 5Cs of PYD and depression in Croatia and Spain, as well as to analyze gender differences. This research was conducted within the PYD Cross-National Project. High school and university students from Eastern Croatia and Southern Spain participated in the study (M age = 19.37, SD = 2.11; 62.3% female). There were 584 students from Croatia and 768 students from Spain, who filled in self-reports of PYD and depression (i.e., PYD-SF and PHQ-9, respectively). Results showed that male participants presented more Competence and Confidence, while female participants reported more Connection, Caring, Character, overall PYD, but also more depressive symptoms. Furthermore, Confidence and Connection were negative correlates of depressive symptoms, with neither Spain nor Croatia showing remarkable gender differences. These results may have some implications concerning the promotion of the 5Cs of PYD as a recommendable approach to promote youth mental health in Croatia and Spain from a gender perspective. Youth mental health services and initiatives that engage the partnership of youth contexts, such as the family, schools and neighborhoods, should not only address risk factors for mental health problems, but also protecting factors as the 5Cs, thus providing a more inclusive and sustainable support for youth well-being.


Prognostic significance of Ki-67 expression in rectal carcinoid tumors.
Rectal carcinoid tumors can be resected with endoscopy, and it is important to assess their prognostic factors. We evaluated the potential of Ki-67 expression as a prognostic factor in rectal carcinoid tumors. We retrospectively reviewed the medical records of 37 patients with rectal carcinoid tumors who got endoscopic resection from January 2001 to January 2011 at Inje University Seoul Paik Hospital. We analyzed their endoscopic and histologic findings, Ki-67 expression, clinical outcome, and prognosis. The mean age (±SD) of the patients was 56.3±10.7 years, and the male : female ratio was 3.6 : 1. The mean tumor size was 0.5±0.4 cm, 33 patients showed grade 1 tumors (89.2%) and the average Ki-67 expression was 0.7±1.2%. Thirty five patients underwent endoscopic mucosal resection, and two required endoscopic submucosal dissection. Eight patients had positive margins after resection, but no cases of lymphovascular invasion were identified. The median follow-up duration was 21.4±25.4 months, and no recurrences were observed. In low grade rectal carcinoid tumors which are lack of central depression on colonoscopy, the expression of a molecular marker of malignant potential, Ki-67, was low. Therefore, endoscopic resection seemed to be a safe and effective treatment for these tumors.


Auxiliary liver transplantation in the pig without portal blood: a study of a new technique for application to the heterotopic hepatic xenotransplant.
An auxiliary liver transplantation surgical technique in the pig, in which the graft only receives blood flow via the hepatic artery since an end-to-side portacaval shunt is performed in the donor animal prior to the transplantation, is described. The functional impairment of the receptor liver was done by a ligature of the choledoch, provoking death by sepsis in six of the transplanted animals at 8.16 +/- 6.61 days post transplantation. The auxiliary liver never suffered atrophy and prevented jaundice. It can be concluded that this simple surgical technique could be applied to the heterotopic xenotransplantation when the complications inherent in the immunological aggression are eliminated.


Modulation of ATP and drug binding by monoclonal antibodies against P-glycoprotein.
The role of P-glycoprotein in mediating the drug-resistance phenotype in multidrug resistant cells is now well documented. It is thought to function as an energy-dependent drug-efflux pump of broad specificity. Structurally, P-glycoprotein is an internally duplicated molecule containing two large multi-spanning transmembrane domains and two cytoplasmic ATP binding domains. In this report we demonstrate that monoclonal antibodies C219, C494, and C32 directed against short linear regions of the P-glycoprotein molecule inhibit ATP binding to P-glycoprotein in vitro. We also provide direct evidence that both predicted ATP-binding domains bind ATP and that there is co-operativity between the two sites. In addition, the capacity of P-glycoprotein to bind the calcium channel blocker, azidopine, is inhibited differentially by the antibodies. These observations are the first evidence linking specific perturbations of the P-glycoprotein molecule with ATP and drug binding.


Deciphering the human immunome.
Technological advances in next-generation DNA sequencing offer great potential to probe the human immune system. On 3 April 2015, leading immunologists and bioinformatics scientists met to consider how best to harness these advances for decoding the human immunome.


A public health approach to mobilizing community partners for injury prevention: A scoping review.
Reducing injuries in adults requires work with diverse stakeholders across many sectors and at multiple levels. At the local level, public health professionals need to effectively bring together, facilitate, and support community partners to initiate evidence-based efforts. However, there has been no formal review of the literature to inform how these professionals can best create action among community partners to address injuries in adults. Thus, this scoping review aims to identify theories, models or frameworks that are applicable to a community-based approach to injury prevention. Searches of scientific and less formal literature identified 13,756 relevant items published in the English language between 2000 and 2016 in North America, Europe and Australia. After screening and review, 10 publications were included that (1) identified a theory, framework or model related to mobilizing partners; and (2) referred to community-based adult injury prevention. Findings show that use of theories, frameworks and models in community-based injury prevention programs is rare and often undocumented. One theory and various conceptual models and frameworks exist for mobilizing partners to jointly prevent injuries; however, there are few evaluations of the processes to create community action. Successful community-based injury prevention must build on what is already understood about creating partnership action. Evaluating local public health professional injury prevention practice based on available theories, models and frameworks will identify successes and challenges to inform process improvements. We propose a logic model to more specifically guide and evaluate how public health can work locally with community partners.


Feasibility of self-directed learning in clerkships.
Self-directed learning has been well described in preclinical settings. However, studies report conflicting results when self-directed initiatives are implemented in clinical clerkships. To explore the feasibility of self-directed learning stimulated by clinical encounter-cards (CECs) in clinical clerkships. Two focus groups of year-four and year-five students were interviewed about the usefulness of CECs to their learning in clerkships. The CECs were then introduced in two cohorts of 248 year-four and 250 year-five medical students and evaluated on a nine-point scale with regard to usefulness and feasibility. The pilot groups reported that the CECs had positive effects in terms of engaging in diagnostic reasoning, reflection on management plans, and professional identity formation. However, the two large cohorts of students rated the usefulness of the CECs on learning in clerkship low (year-four: mean 2.92, SD 1.54; year-five: mean 2.28, SD 1.06) along with preceptor support (year-four: mean 2.68, SD 1.62; year-five: mean 2.59, SD 1.78, p = 0.34). Self-directed CECs can have a positive effect on participation and clinical reasoning but are highly dependent on the context of use. Self-directed learning initiatives that aim to increase participation in communities of practice may not be feasible without major faculty development initiatives.


Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors.
The most important goal in the treatment of patients with diabetes is to prevent the risk of cardiovascular disease (CVD), the first cause of mortality in these subjects. Thiazolidinediones (TZDs), a class of antidiabetic drugs, act as insulin sensitizers increasing insulin-dependent glucose disposal and reducing hepatic glucose output. TZDs including pioglitazone, rosiglitazone and troglitazone, by activating PPAR-γ have shown pleiotropic effects in reducing vascular risk factors and atherosclerosis. However, troglitazone was removed from the market due to its hepatoxicity, and rosiglitazone and pioglitazone both have particular warnings due to being associated with heart diseases. Specific genetic variations in genes involved in the pathways regulated by TDZs have demonstrated to modify the variability in treatment with these drugs, especially in their side effects. Therefore, pharmacogenomics and pharmacogenetics are an important tool in further understand intersubject variability per se but also to assess the therapeutic potential of such variability in drug individualization and therapeutic optimization.


[Efficacy of two bariatric surgeries in type 2 diabetic patients with a body mass index of 25-27.5].
To evaluate the therapeutic effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic duodenal-jejunal bypass with sleeve gastrectomy (SADJB-SG) in patients with type 2 diabetes mellitus and a low body mass index (BMI) of 25-27.5. Thirty-one type 2 diabetic patients with a BMI of 25-27.5 underwent bariatric surgeries in the General Hospital of Guangzhou Military Command between August, 2013 and August, 2015. The patients receiving LRYGB (17 cases) and SADJB-SG (14 cases) were compared for physical indexes, glucose metabolism and of pancreatic islet function at 1 year after the surgeries. No mortality occurred in the patients after the operations. At 1 year after the operation, the patients in LRYGB group showed significant improvements in body weight, BMI, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), oral glucose tolerance test 2 h (OGTT2h), C-peptide, fasting insulin (FINS), and postprandial 2 hour insulin (2 hPINS) (P<0.05); in SADJB-SG group, significant improvements were observed in the body weigh, BMI, HbA1c, FPG, OGTT2h, and FINS after the operation (P<0.05). The postoperative improvements in body weigh, BMI, HbA1c, FPG, OGTT2h, C-peptide, and 2hPINS were comparable between SADJB-SG group and LRYGB group (P>0.05), but the incidence of postoperative anastomotic ulcer was lower in SADJB-SG group. SADJB-SG and LRYGB produce similar therapeutic effects in type 2 diabetic patients with a low BMI, but SADJB-SG is associated with a low incidence of postoperative complications and is therefore more suitable in such patients.


The Protective Effects of Ciji-Hua'ai-Baosheng II Formula on Chemotherapy-Treated H22 Hepatocellular Carcinoma Mouse Model by Promoting Tumor Apoptosis.
Ciji-Hua'ai-Baosheng II Formula (CHB-II-F) is a traditional Chinese medical formula that has been shown in clinical practice to relieve side effects of chemotherapy and improve quality of life for cancer patients. In order to understand the mechanism of its protective effects on chemotherapy, mice with transplanted H22 hepatocellular carcinoma were employed in this study. Ninety-two mice were injected subcutaneously with H22 HCC cell suspension into the right anterior armpit. After mice were treated with 5-fluorine pyrimidine (5-FU), they were divided into six groups as untreated group, 5-FU group, 5-FU plus Yangzheng Xiaoji Capsule group and three groups of 5-FU plus different concentrations of CHB-II-F. Twenty mice were euthanized after 7 days of treatment in untreated and medium concentration of CHB-II-F groups and all other mice were euthanized after 14 days of treatment. Herbal components/metabolites were analyzed by UPLC-MS. Tumors were evaluated by weight and volume, morphology of light and electron microscope, and cell cycle. Apoptosis were examined by apoptotic proteins expression by western blot. Four major components/metabolites were identified from serum of mice treated with CHB-II-F and they are β-Sitosterol, Salvianolic acid, isobavachalcone, and bakuchiol. Treatment of CHB-II-F significantly increased body weights of mice and decreased tumor volume compared to untreated group. Moreover, CHB-II-F treatment increased tumor cells in G0-G1 transition instead of in S phase. Furthermore, CHB-II-F treatment increased the expression of pro-apoptotic proteins and decreased the expression anti-apoptotic protein. Therefore, CHB-II-F could improve mice general condition and reduce tumor cell malignancy. Moreover, CHB-II-F regulates apoptosis of tumor cells, which could contribute its protective effect on chemotherapy.