Telomere length across different UIP fibrotic-Interstitial Lung Diseases: a prospective Greek case-control study.
Short telomeres are recognized as risk factor for idiopathic pulmonary fibrosis (IPF). We aimed to assess the role of telomere length (TL) in fibrotic-Interstitial Lung Diseases (f-ILDs) associated with a usual interstitial pneumonia (UIP) pattern as well as in IPF acute exacerbation (IPF-AE). TL was measured from peripheral white blood cells using a multiplex quantitative polymerase chain reaction in consecutive patients with f-ILDs, all presenting UIP pattern in the high-resolution chest-computed-tomography and compared to age-matched healthy controls. Seventy-nine individuals were included (mean age 69.77 ± 0.72 years); 24 stable IPF, 18 IPF-AE, 10 combined pulmonary fibrosis and emphysema, 7 Rheumatoid arthritis-UIP-ILDs and 20 controls. TL in all patients was significantly shorter compared to controls [mean T/S ratio (SE) 0.77 (±0.05) vs 2.26 (±0.36), p < 0.001] as well as separately in each one of f-ILD subgroups. IPF-AE patients presented significantly shorter TL compared to stable IPF (p = 0.029). Patients with IPF and shorter than the median TL (0-0.72) showed reduced overall survival (p = 0.004). T/S < 0.72 was associated with increased risk for IPF-AE (OR = 30.787, 95% CI: 2.153, 440.183, p = 0.012) independent of age, gender, smoking and lung function impairment. A protective effect of TL was observed, as it was inversely associated with risk of death both in UIP-f-ILDs (HR = 0.174, 95%CI: 0.036, 0.846, p = 0.030) and IPF patients (HR = 0.096, 95%CI: 0.011, 0.849, p = 0.035). Shorter TL characterizes different UIP f-ILDs. Although no difference was observed in TL among diverse UIP subgroups, IPF-AE presented shorter TL compared to stable IPF. Reduced overall survival and higher hazard ratio of death are associated with shorter TL in IPF.


Post-traumatic stress disorder following traumatic limb amputation in an 8 year-old female child and its management through play therapy.
Posttraumatic mental health issues following traumatic limb amputations in children have been commonly reported worldwide. Traumatic limb amputationsarecatastrophic injuries/events and often have various long term psycho-social impacts on children. We report a case of 8 year-oldfemale child presenting with symptoms of post-traumatic stress disorder (PTSD) following a traumatic amputation of right hand. A non- directive approach in play therapy was used for management of her symptoms. At 12 months follow up, the child is doing well with no impairment in her overall functioning.


Follow-up and Outcomes of Patients With Long-term Cutaneous Vesicostomies at a Single Institution.
To identify and describe the characteristics of a group of patients at our institution who are satisfied with cutaneous vesicostomy for long-term bladder management and never undergo subsequent continence surgery. Using an IRB-approved registry of our patients undergoing reconstructive urinary tract surgery since 1985, we identified patients who underwent vesicostomy creation and were 15 years or older as of October 2017 and performed a retrospective chart review. Sixty-seven patients were included with the most common diagnosis being spina bifida and the average duration of vesicostomy 14.3 years (range 8 months to 35 years). In follow-up, 38 patients (56.7%) had conversations regarding further surgery and 31 (46.3%) had their vesicostomies taken down. Of the 36 patients who still had their vesicostomy at last follow-up, 29 (80.6%) had spina bifida and 14 (38.9%) were satisfied, 1 (2.8%) was unhappy, 4 (11.1%) were deceased and satisfaction was unknown for 17 (47.2 %). Although often intended to be temporary, in our experience many patients keep their vesicostomy for a long time and into adulthood, with generally high satisfaction and low complications. In the properly selected patient, vesicostomy may be a good long-term operation to prevent infection and renal deterioration, though more rigorous studies of these patients are needed.


The bladder is an unreliable witness: The case for urodynamic investigations in female stress urinary incontinence.
For some years, the role of urodynamics (UDS) in female stress urinary incontinence (SUI) has been a topic of intense debate. The findings of the VaLUE and VUSIS-II randomised clinical trials (RCTs) published in 2012 appeared to suggest that UDS is not useful in women with uncomplicated SUI, with the result that several authoritative guidelines were amended and the routine use of UDS in this setting fell sharply. However, many experts have raised concerns about the design of these two RCTs and their subsequent interpretation - including the inappropriate generalisation of the findings beyond uncomplicated cases, which represent only a small minority of the overall patient population. In this paper, we consider a range of issues and confounding factors which raise doubts about how influential these RCTs should have been and reflect on the potential value of UDS both for objective diagnosis and patient counselling in female SUI.


Construction of Low-Impedance and High-Passivated Interphase for Nickel-Rich Cathode by Low-Cost Boron-Containing Electrolyte Additive.
The nickel-rich cathode LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) possesses the advantages of high reversible specific capacity and low cost, thus regarded as a promising cathode material for lithium-ion batteries (LIBs). However, the capacity of the NCM811 decays rapidly at high voltage due to the extremely unstable electrode/electrolyte interphase. The discharge capability at low temperature is also impaired because of the increasing interfacial impedance. Herein, a low-cost film-forming electrolyte additive with multi-function, phenylboronic acid (PBA), was employed to modify the interphasial properties of the NCM811 cathode. Theoretical calculation and experimental results showed that PBA constructed a highly conductive and steady cathode electrolyte interphase (CEI) film through preferential oxidation decomposition, which greatly improved the interfacial properties of the NCM811 cathode at room (25 °C) and low temperature (-10 °C). Specifically, the capacity retention of NCM811/Li cell was increased from 68 % to 87 % after 200 cycles with PBA additive. Moreover, the NCM811/Li cell with PBA additive delivered higher discharge capacity under -10 °C at 0.5 C (173.7 mAh g-1 vs. 111.1 mAh g-1 ). Based on the improvement of NCM811 interphasial properties by additive PBA, the capacity retention of NCM811/graphite full-cell was enhanced from 49 % to 65 % after 200 cycles.


Lipid and carbohydrate effects of a new triphasic oral contraceptive containing norgestimate.
Data are reported from the combined results of two studies assessing the lipid and carbohydrate effects of a triphasic preparation of norgestimate and ethinyl estradiol (Ortho TriCyclen, Tri-Cilest) over a 2-year period in 1,783 healthy women. Mean values for serum levels of high-density lipoprotein cholesterol (HDL-C) were increased significantly, with a percent change at 24 months of 13.2. Values for the ratio of low-density lipoprotein cholesterol to HDL-C were reduced throughout the study period (mean change of -6.4% at cycle 24). There were no clinically significant changes in fasting blood glucose levels or insulin levels or in values for glycosylated hemoglobin. These results are consistent with those of previous studies and indicate that the triphasic preparation of norgestimate and etinyl estradiol is a selective and minimally androgenic oral contraceptive agent. Long-term therapeutic benefit may accrue from the favorable influences on the lipid profile.


A case of double-chambered right ventricle associated with an interventricular septal aneurysm in an elderly patient.
Double-chambered right ventricle is a congential malformation caused by an anomalous muscle band obstructing the right ventricular outflow tract. Most reported cases of this condition have been diagnosed in infants, or adolescents. We encountered a 61-year-old woman with a double-chambered right ventricle, associated with a large interventricular septal aneurysm, which is a rare complication. The right ventricular obstruction was corrected with surgery.


Incidence and outcomes of major trauma patients with thoracic injuries and rib fractures in Aotearoa New Zealand.
Thoracic trauma represents a significant burden of disease in Aotearoa, New Zealand (AoNZ). To date, no study has examined the incidence or outcomes of patients suffering major thoracic trauma, or major trauma and rib fractures in AoNZ. A 6 year retrospective study of all major trauma (Injury Severity Score >12) patients in AoNZ was performed. The National Trauma Registry was searched to identify patients. The National Minimum Data Set was searched for all ICD-10 codes associated with surgical stabilisation of rib fractures (SSRF). Poisson regression was used to determine the change in incidence rate over the study period adjusted for age with the logarithm of population size as the offset variable. The incidence rate ratios (IRR) with 95% confidence intervals (CI) were reported. 12,218 patients sustained major trauma. 7,059 (57.8%) of these patients sustained thoracic injuries. Of these patients, 5,585 (79.1%) sustained rib fractures, and 180 (3.2%) proceeded to SSRF. A flail segment was observed in 16% of patients with rib fractures. Transport was the mechanism of injury in 53% of patients. During the study the incidence (cases per 100,000 people per year) of major trauma increased from 39.5 to 49.3 (IRR 1.05, 95%CI 1.04 to 1.07, <0.001), the incidence of thoracic injuries from 21.3 to 28.7 (1.07, 95% CI 1.05 to 1.08, <0.001) and the incidence of rib fractures from 16.0 to 22.9 (1.08, 95% CI 1.06 to 1.09, <0.001). SSRF was performed in 3.2% of patients with rib fractures and increased from 0.2 to 0.8 cases per 100,000 people per year (1.27, 95% CI 1.15 to 1.41, <0.001) during the study. This study reports the incidence of major trauma patients with thoracic injury, major trauma patients with rib fractures and the incidence of SSRF in AoNZ. Transport related injuries are the predominant mechanism of injury. The incidence of SSRF was low across AoNZ. To improve the quality of care in AoNZ for major trauma patients with rib fractures, consideration should be made to create national guidelines and robust referral pathways to specialist centres that provide multidisciplinary care including performing SSRF.


Cultural Competency and Its Effect on Treatment Outcome of IPT-A in School-Based Health Clinics.
This paper assesses acculturation and ethnic matching of therapist and patient as predictors and moderators of treatment outcome in a 12-week effectiveness study of Interpersonal Psychotherapy for depressed adolescents (IPT-A) versus treatment as usual (TAU). The treatment was delivered in school-based health clinics in which care was provided for a predominantly Latino patient population. Birthplace, length of residence in the United States (U.S.), and therapist-patient ethnic matching were examined as predictors and moderators of treatment outcomes for depression, social functioning, and global functioning scores. Birthplace significantly moderated treatment condition in predicting week 12 depression severity and improvement, and marginally significantly moderated treatment in predicting week 12 depression symptoms, with U.S.-born adolescents who received IPT-A having better outcomes. Birthplace predicted week 12 self-reports of depression, social (overall, school, and family) and global functioning, with U.S.-born adolescents faring worse across treatment conditions. Foreign-born adolescents treated with IPT-A as compared to TAU who lived for a longer period of time in the U.S. demonstrated better overall social functioning as compared to foreign-born adolescents who had lived for a shorter period of time in the U.S. Ethnic matching predicted significant reduction in depression severity and improved overall social functioning, and marginally significant improvement in week 12 depression scores, regardless of treatment condition. IPT-A may be a culturally responsive treatment for depressed Latino youth who are struggling with acculturation issues that affect their significant relationships. Ethnic matching appears beneficial for the general population in reducing depression and improving social functioning.


Diarrhoeal prevalence and handwashing practices of children attending early childhood development centres in KwaZulu-Natal, South Africa.
Diarrhoea, a leading cause of childhood morbidity and mortality, spread through contaminated food or water or from person to person, is a major cause of hospitalisation in South African children. To determine if hygiene practices of parents or guardians and early childhood development centre (ECD) educators contributed to diarrhoea in children attending the centres. The study was conducted at ECD centres in Mpumalanga Township of KwaZulu-Natal province, South Africa. A descriptive cross-sectional study was conducted at 10 ECD centres. Parents or guardians (n = 385) and educators (n = 121) answered self-administered questionnaires. Frequencies, bivariate associations and multivariate regression modelling were conducted. The prevalence of diarrhoea in children ≤ 5 years was 67.3%. Most parents or guardians washed their hands after defecating and handling a child's faeces as well as before preparing food. Handwashing after urination was low. Washing of children's hands after these events was lower. Although all educators reported always washing the child's hands after defecating and before handling or eating food, they were less likely to wash the children's hands after urination (p = 0.003). Childhood diarrhoea was associated with the type of toilet, households with pit latrines having a higher prevalence of diarrhoea (p < 0.001). It was also associated with washing of children's hands after urination (p = 0.014), before handling or eating food (p = 0.001) and with increased number of children in the household (p = 0.001). In this population, the high prevalence of diarrhoea is related to the number of children in a household and handwashing practices. This study highlights the importance of handwashing practices in the prevention of diarrhoea in children.


Can healing be taught?
The recent explosion of opportunities and interest in learning to heal has not been accompanied by sufficiently convincing empirical data to show that healing is teachable. We explore selected examples of teaching modalities and outline their general ethos. Five empirical criteria necessary to demonstrate teachability are outlined. We suggest that no research to date, including a previous claim by one of us (W.F.B.), has surmounted the difficult obstacles that need to be overcome to make such a claim. Some scientific and social implications of the teachability of healing are discussed.


Optimization of the technique of cell migration from explants: Application to human synoviocytes on cryoprecipitate coating.
The explant technique, though easy to carry out, is unpredictable and thus not readily reproducible. Addition of cryoprecipitate, which is rich in fibronectin, serves to optimize this technique of cell migration from explants by improving adhesion.


Reduced susceptibility of Moritella profunda dihydrofolate reductase to trimethoprim is not due to glutamate 28.
The E28D variant of dihydrofolate reductase from Moritella profunda was generated and found to have the same K (i) (within error) for the competitive inhibitor trimethoprim as the wild type enzyme. Contrary to a previous claim in the literature, Glu 28 is therefore not the cause of the reduced affinity for trimethoprim relative to dihydrofolate reductase from Escherichia coli.


Red-green colour blindness in Singaporean children.
X-linked red-green colour blindness is the most common form of colour blindness. Various studies suggest that, worldwide, 2-8% of men are afflicted with this condition. The purpose of this study is to determine the prevalence of red-green colour blindness in Singaporean schoolchildren. A total of 1249 children aged 13-15 years were screened using the Ishihara 24-plate edition book during the School Cohort study of the Risk factors for Myopia visit. A total of 1210 children (96.8%) managed to correctly identify at least 13 of the initial 15 plates and were deemed to have normal colour vision.Thirty-three children (32 boys, one girl) were only able to identify nine or less plates and were considered to be colour blind. Overall, 5.4% (95% confidence interval 3%, 7%) of Chinese, 4.9% (1%, 9%) of Malay and 4.9% (2%, 11%) of Indian boys were colour blind (P = 0.97). Classification plates 16-17 were useful in determining deutran or protan tendencies in only 14 (43%) of the 33 children identified as being colour blind. 5.3% of boys and 0.2% of girls were found to be colour blind in this Singapore-based study. Although the Ishihara test proved useful in identifying colour-blind children, other tests are required to accurately classify the types of red-green colour blindness in these children.


Selection of diagnosis with oncologic relevance information from histopathology free text reports: A machine learning approach.
Histopathology reports are a primary data source for the case definition phase of a Cancer Registry. By reading the histopathology report, the operator that evaluates an oncology case can define the morphology and topography of cancer, and validate the case with the highest diagnosis base. The key problem of the Catania-Messina-Enna Integrated Cancer Registry (RTI) is that these reports are written in natural language and relevant information for cancer evaluation is only a little part of the total annual histopathological reports. In this population-based retrospective cohort study, we try to optimize the working time spent by the RTI operators in seeking and selecting the right information among the histopathology reports in the east Sicily population, by developing a binary classifier on a training set of labeled historical data and validating its outcome by a test set of labeled data created by the operators during the years. Using a machine learning algorithm we built a classification model that evaluates each free text report and returns a score that indicates the probability that it contains oncologic relevant information. The best performing algorithm, among the eight analyzed in this study, was the LightGBM that reached an F1-Score of 98.9%. Using the chosen classifier we shortened the time for case evaluation, improving the timeliness of cancer statistics.


Single-cell RNA sequencing reveals the regenerative potential of thyroid follicular epithelial cells in metastatic thyroid carcinoma.
Thyroid stimulating hormone deficiency is the cornerstone of treatment for metastatic thyroid cancer. Due to the loss of follicular epithelial cells in thyroid cancer, the thyroid gland degenerates to 85% of its original size. When thyroid stimulating hormone is restored, follicular epithelial cells in thyroid cancer regenerate, which is postulated to be related to stem-like cells. By single cell RNA seq, we found a group of rare thyroid follicular epithelial cells in mouse metastatic thyroid cancer, which expressed stem-like genes (CD44V6+ and CD133+) and a large number of differentiated cells (CD44V6+ and CD24+). In mouse and in organoids, the two subsets contribute equally to metastatic thyroid cancer regeneration. The analysis of human metastatic thyroid cancer revealed that the differentiated thyroid follicular epithelial cell subpopulation was similar to that of the stem like epithelial cell subpopulation, and the regeneration potential was also enhanced after thyroid stimulating hormone ablation. Accordingly, we propose that the regeneration of metastatic thyroid cancer is driven by almost all persistent thyroid follicular epithelial cells, not only by few stem-like cells.


Lymphocytic leukemia and exposures to benzene and other solvents in the rubber industry.
Previous epidemiological studies on one cohort of rubber industry workers indicated that observed mortality excesses from lymphocytic leukemia were related to solvent exposures. The results of a detailed examination of the solvent exposure histories of 15 cases of lymphocytic leukemia from this cohort and 30 matched industry controls are presented. Extensive review of historical solvent use, raw materials specifications and job description records were used to reconstruct exposures to specific agents. Cases were 4.5 times as likely as controls to have had direct exposures to both benzene and other solvents. Analysis by manufacturing production source of solvent revealed that cases spent greater proportions of their work experience in jobs with potential exposures to coal tar-based benzene and xylene. No differences were seen for petroleum-derived solvents.


geiger v2.0: an expanded suite of methods for fitting macroevolutionary models to phylogenetic trees.
Phylogenetic comparative methods are essential for addressing evolutionary hypotheses with interspecific data. The scale and scope of such data have increased dramatically in the past few years. Many existing approaches are either computationally infeasible or inappropriate for data of this size. To address both of these problems, we present geiger v2.0, a complete overhaul of the popular R package geiger. We have reimplemented existing methods with more efficient algorithms and have developed several new approaches for accomodating heterogeneous models and data types. This R package is available on the CRAN repository http://cran.r-project.org/web/packages/geiger/. All source code is also available on github http://github.com/mwpennell/geiger-v2. geiger v2.0 depends on the ape package. email@example.com Supplementary data are available at Bioinformatics online.


Examination of transport equations pertaining to permeable elastic tubules such as Henle's loop.
The transport equations applicable to loops of Henle and similar elastic permeable tubules were re-examined to assess the effect of radial transport resistance in the lumen and tubule geometry on solute transport. Active transport at the wall as well as external gradients equivalent to a 2--1,000-fold concentration increase per centimeter of distance were considered. Wall permeabilities and active transport constants were varied up to 2 . 10(-2) cm/s. It is shown that for conditions applicable to the loop of Henle, resistance to radial solute transfer in the lumen is negligible, both for passive and active transmural transport with concomitant water flux, and that axial dispersion further reduces that resistance. These conclusions apply equally to conical and elliptical geometries likely to arise in loop operation. The validity of Poiseuille's equation for these geometries is discussed. Ii is concluded that the one-dimensional transport equations are a valid representation of loop operation.


[Effect of a food ration with a low-protein content on the processes of liver parenchyma recovery in rats after tetrachloromethane damage].
Male Wistar rats weighing 190-200 g were fed a low protein diet. Atrophy of cytoplasm was observed after a 3-week malnutrition. In early periods of liver regeneration (6 hr after CCl4 poisoning), an increase in DNA synthesis was accompanied by an increase in summary concentration of organelle membranes. Though their ploidy was higher than in the control, volume of hepatocytes and summary area of organelles surface membrane was smaller than in standard diet. These data show a reduced capacity for realization of genetic program during the regeneration period in protein-deficient rats.


The Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, an Oral Small Molecule Factor XIa Inhibitor, in Healthy Chinese Volunteers.
There is an unmet need for a safer anticoagulant since bleeding remains a concern with currently approved anticoagulants. Coagulation factor XI (FXI) is an attractive anticoagulant drug target with limited a role in physiological hemostasis. The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of SHR2285, a novel small molecule FXIa inhibitor, in healthy Chinese volunteers. The study consisted of single ascending doses part (part 1: 25-600 mg) and multiple ascending doses part (part 2: 100, 200, 300, and 400 mg). In both parts, subjects were randomized in a 3:1 ratio to receive SHR2285 or placebo orally. Blood, urine and feces samples were collected to describe its pharmacokinetic and pharmacodynamic profile. In total, 103 healthy volunteers completed the study. SHR2285 was well tolerated. SHR2285 was absorbed rapidly with median time to maximum plasma concentration (Tmax) of 1.50 to 3.00 h. The geometric median half-life (t1/2) of SHR2285 varied from 8.74 to 12.1 h across 25-600 mg single dose. Total systemic exposure of metabolite SHR164471 was approximately 1.77- to 3.61-fold that of the parent drug. The plasma concentration of SHR2285 and SHR164471 reached steady state by the morning of Day 7, with low accumulation ratio (0.956-1.20 and 1.18-1.56, respectively). The increase in pharmacokinetic exposure of SHR2285 and SHR164471 was less than dose proportional. Food has minimal effect on the pharmacokinetics of SHR2285 and SHR164471. SHR2285 produced an exposure-dependent prolongation of activated partial thromboplastin time (APTT) and a decrease in FXI activity. The maximum FXI activity inhibition rate (geometric mean) at steady state was 73.27%, 85.58%, 87.77% and 86.27% for 100-400 mg, respectively. SHR2285 was generally safe and well tolerated in healthy subjects across a wide range of doses. SHR2285 exhibited a predictable pharmacokinetic profile and an exposure-related pharmacodynamic profile. gov Identifier NCT04472819; registered on July 15, 2020.


Inconsistency of Association between Coffee Consumption and Cognitive Function in Adults and Elderly in a Cross-Sectional Study (ELSA-Brasil).
Coffee is one of the most consumed beverages worldwide and the effect on cognition appears to be task specific and vary by age. In cohort of 14,563 public service workers (35-74 years old) we assessed coffee consumption habits and examined cognitive function using standardized neuropsychological test battery. By linear regression and generalize linear regression with logarithmic link and gamma distribution we investigated the relation of coffee consumption (never/almost never, ≤1 cup/day, 2-3 cups/day, ≥3 cups/day) in the last 12 months to performance on specific domains of cognition for adults and elderly separately. Among elderly, after adjustments, coffee consumption was associated only with an increase in the mean words remembered on learning, recall, and word recognition tests when comparing the 2-3 cups/day to never/almost never category (arithmetic mean ratio (AMR): 1.03; 95% Confidence Interval (CI): 1.00 to 1.07), and to an increase in the mean words pronounced in semantic verbal fluency test when comparing the ≥3 cups/day to never/almost never category (difference of the mean: 1.23; 95% CI: 0.16 to 2.29). However, coffee consumption was not associated with any cognitive function tests in adults and also was not associated with the phonemic verbal fluency test and trail-making test B in elderly. RESULTS suggest that coffee consumption might be slightly beneficial to memory in elderly but lacks a dose response relationship. Longitudinal analyses are needed to investigate possible, even if subtle, positive effects of coffee drinking on specific cognitive domains in elderly.


Abundant macrophage growth in culture from patients with chronic myelogenous leukemia: a risk factor for graft-versus-host disease after bone marrow transplantation.
Peripheral blood cultures of hemopoietic precursor cells from 30 patients with chronic myelogenous leukemia showed different growth patterns before bone marrow transplantation. A strong increase of free and clustered macrophages was seen in 11/30. Of these 11 patients, 10 developed Graft-versus-Host Disease (GvHD). Of 19 patients without the macrophage pattern, 4 developed GvHD (p = 0.004). Of 14 patients with GvHD, 10 had shown the macrophage pattern before bone marrow transplantation, compared to 1/19 without GvHD (p = 0.004). We postulate that excess macrophages in the bone marrow recipient trigger GvHD by enhancing presentation of recipient antigens to donor T-lymphocytes, and that their presence is predictive of GvHD in CML.


Identification of a Novel Pm65 Allele Conferring a Wide Spectrum of Resistance to Powdery Mildew in Wheat Accession PI 351817.
Powdery mildew is caused by the highly adaptive biotrophic fungus Blumeria graminis f. sp. tritici infecting wheat worldwide. Novel powdery mildew resistance genes are urgently needed that can be used rapidly in wheat cultivar development with minimal disruption of trait advances elsewhere. PI 351817 is a German cultivar exhibiting a wide spectrum of resistance to B. graminis f. sp. tritici isolates collected from different wheat-growing regions of the United States. Evaluation of an F2 population and 237 F2:3 lines derived from OK1059060-2C14 × PI 351817 for responses to B. graminis f. sp. tritici isolate OKS(14)-B-3-1 identified a single dominant gene, designated Pm351817, for powdery mildew resistance in PI 351817. Using bulked segregant analysis (BSA) and simple sequence repeat (SSR) markers, Pm351817 was mapped in the terminal region of the long arm of chromosome 2A. Deep sequencing of the genotyping-by-sequencing libraries of the two parental lines identified a set of single-nucleotide polymorphism (SNP) markers in the 2AL candidate gene region. Those SNP markers was subsequently converted to Kompetitive allele-specific PCR (KASP) markers for genotyping the mapping population. Linkage analysis delimited Pm351817 to a 634-kb interval between Stars-KASP656 (771,207,512 bp) and Stars-KASP662 (771,841,609 bp) on 2AL, based on the Chinese Spring reference sequence IWGSC RefSeq v 2.1. Tests of allelism indicated that Pm351817 is located at the Pm65 locus. Pm351817 shows resistance to all B. graminis f. sp. tritici isolates used in this study and can be used to enhance powdery mildew resistance in the United States. KASP markers flanking Pm351817 can be used to select Pm351817 in wheat breeding programs after further tests for polymorphism.


Disassembly of the lens fiber cell nucleus to create a clear lens: The p27 descent.
The eye lens is unique among tissues: it is transparent, does not form tumors, and the majority of its cells degrade their organelles, including their cell nuclei. A mystery for over a century, there has been considerable recent progress in elucidating mechanisms of lens fiber cell denucleation (LFCD). In contrast to the disassembly and reassembly of the cell nucleus during mitosis, LFCD is a unidirectional process that culminates in destruction of the fiber cell nucleus. Whereas p27Kip1, the cyclin-dependent kinase inhibitor, is upregulated during formation of LFC in the outermost cortex, in the inner cortex, in the nascent organelle free zone, p27Kip1 is degraded, markedly activating cyclin-dependent kinase 1 (Cdk1). This process results in phosphorylation of nuclear Lamins, dissociation of the nuclear membrane, and entry of lysosomes that liberate DNaseIIβ (DLAD) to cleave chromatin. Multiple cellular pathways, including the ubiquitin proteasome system and the unfolded protein response, converge on post-translational regulation of p27Kip1. Mutations that impair these pathways are associated with congenital cataracts and loss of LFCD. These findings highlight new regulatory nodes in the lens and suggest that we are close to understanding this fascinating terminal differentiation process. Such knowledge may offer a new means to confront proliferative diseases including cancer.


A review of porcine reproductive and respiratory syndrome virus in Dutch breeding herds: population dynamics and clinical relevance.
Understanding the spread of porcine reproductive and respiratory syndrome virus (PRRSV) in pig populations is essential to the development of effective PRRS prevention and control strategies. Moreover, knowledge of the field dynamics of PRRSV in pigs will provide insights into the clinical relevance of PRRS, and will enable the targeting of interventions. This review of PRRSV includes discussion on the occurrence of outbreaks, the persistence of infection and the fade-out of infection in Dutch breeding herds. The dynamic character of PRRSV infections in endemically infected herds and the relevance of the disease under Dutch field conditions are also highlighted. Furthermore, several strategies aimed at controlling the spread of PRRSV are discussed.


Changes in the dose of peritoneal dialysis: have these independently affected outcomes?
Over the past decade, there has been a sustained improvement in mortality rates for peritoneal dialysis (PD) patients in the United States and Canada. Although patients with diabetes continue to have higher mortality rates than those without diabetes, the observed improvement in PD patient survival rates has been even more marked among patients with diabetes. There has been an impressive improvement in death rates in older and younger PD patients with diabetes in both the United States and Canada. The observed improvement in mortality rates in US and Canadian PD patients preceded concerns about dialysis adequacy and efforts to increase the dose of PD. Thus, it is too early to see the effect of attention to dialysis dose reflected in published data from these registries. The ongoing improvement in mortality is an encouraging trend for dialysis practitioners and patients because even further improvement can be expected as the prescription of adequate doses of PD become more widespread.


Acquired pellicle engineering with the association of cystatin and vitamin E against enamel erosion.
Evaluate CaneCPI-5 associated with Vitamin E in acquired enamel pellicle (AEP) engineering to prevent dental erosion. 180 human enamel specimens were divided into 12 groups and treated with the following solutions: Cane+VitT and Cane+VitS- CaneCPI-5 + Vit E; Vit+CaneT and Vit+CaneS- Vit E + CaneCPI-5; VitT and VitS- Vit E; CaneT and CaneS- CaneCPI-5; ControlT and ControlS - AmF/NaF/SnCl2; WaterT and WaterS- Deionized water. Groups' name followed by "T" were first treated (200 μl; 2 min) and then incubated in human saliva (200 μl; 1 h) to form the AEP. For groups followed by "S", the AEP was formed and then treatment was applied. The erosive challenge consisted of immersion in 1% citric acid (1 min, 1x/day, for 3 days). The percentage of superficial hardness loss (%SHL) and the relative surface reflection intensity (%SRI) were subjected to normality and homogeneity tests, Shapiro-Wilk and Levene tests, respectively. Subsequently, the data were analyzed using two-way ANOVA, Tukey's test and Pearson's correlation (p < 0.005). For%SHL and%SRI, water controls showed significantly lower protective capacity. Cane+VitT, Cane+VitS, and Vit+CaneS presented the lowest%SHL, and VitT and VitS did not differ from Vit+CaneT, but they were different from the other groups (p = 0.002). The greatest%SRI was found for the Cane+VitT, Vit+CaneT, VitT, Cane+VitS, Vit+CaneS, and VitS groups, which did not significantly differ. CaneT and ControlT, showed similar reflections compared to CaneS and ControlS. CaneCPI-5 and Vitamin E demonstrated a synergistic protective effect against initial erosion. The results open up new possibilities for preventive approaches against erosion through the acquired pellicle engineering, with the combination of CaneCPI-5 and Vitamin E, which demonstrated to be more effective than commercial stannous mouthwash. Further research is warranted to explore the potential of this combination in diverse clinical settings.


Purification, identification, and characterization of elastase on erythrocyte membrane as factor IX-activating enzyme.
In our previous papers, we reported that factor IX (F-IX), when activated by erythrocyte membranes, causes coagulation. We report on purification, identification, and characterization of F-IX-activating enzyme extracted from human erythrocyte membranes. The enzyme whose amino acid sequence is almost in accord with neutrophil elastase was found in normal erythrocyte membrane. The molecular mass was slightly smaller than that of neutrophil elastase. The content of the enzyme in erythrocyte membranes was estimated to be 3.0-3.7 ng per 10(6)erythrocytes. The F-IX sites cleaved by the enzyme were slightly different from those by the ordinary coagulation reaction. The ability of F-IX cleaved by the enzyme to cause coagulation was estimated to be approximately 1/10 as high as that of the F-IX cleaved by activated F-XI. These findings provide evidence that F-IX is activated by erythrocyte membrane, which may serve as a triggering mechanism for blood coagulation.


Colonoscopic treatment of sigmoid volvulus.
Sigmoid volvulus commonly presents with signs of bowel obstruction. In the absence of an exact preoperative diagnosis, these patients have to undergo urgent surgery. We report a case of sigmoid volvulus diagnosed radiologically and managed by endoscopic derotation. When the cause of the obstruction is known to be due to sigmoid volvulus, surgery can be avoided by careful endoscopic derotation of the sigmoid colon.


Embryonic staging table for a direct-developing salamander, Plethodon cinereus (Plethodontidae).
This work presents a refined staging table for the direct-developing red-backed salamander Plethodon cinereus, which is based on the incomplete staging system of James Norman Dent (J Morphol 1942; 71:577-601). This common species from eastern North America is a member of the species-rich lungless salamander family Plethodontidae. The staging table presented here covers several stages omitted by Dent and reveals novel developmental features of P. cinereus embryos. These include putative Leydig cells and open gill clefts, which are found in larvae of metamorphosing species but were previously reported as absent in direct-developing Plethodon. Other features found in larvae of metamorphosing salamander species, such as the palatopterygoid bone and lateral line neuromasts, were not observed in this material. The occurrence of larval and metamorphic features in these embryos has direct bearing on the patterns of life history evolution within the plethodontidae family. This study emphasizes the degree to which typically larval structures are retained in this direct-developing species and provides a staging table for further investigations into the development and evolution of plethodontid salamanders.


Pharmacokinetics and pharmacodynamics of the stable prostacyclin analogue, ZK 36 374, in the cat.
The pharmacokinetics and the pharmacologic effect on blood pressure and heart rate of ZK 36 374 were studied simultaneously in the unanaesthetized cat following intraarterial injection of 20 micrograms/kg of tritium-labelled drug. After a rapid distribution phase the plasma level of radioactive substances declined with a half-life of 44 min. The disposition of the unchanged drug was biphasic with half-lives of 7 min and 36 min. 1.5 min after injection, the systolic and diastolic blood pressures were depressed by 40 and 57% and the heart rate rose by 18%. The kinetics of the pharmacologic action was biphasic and strictly parallel to the plasma drug level. Accordingly, there was a highly significant (p less than 0.001) logarithmic correlation between the blood pressure depression and the concentration of unchanged ZK 36 374 in the plasma. ZK 36 374 was totally metabolized and excreted nearly equally with urine and feces in the form of more than eight metabolites.


Induction by verapamil of a rapid increase in ATP consumption in multidrug-resistant tumor cells.
A marked increase in cellular ATP consumption was induced by verapamil in the multidrug-resistant (MDR) cell line 2780AD, but not in the drug-sensitive parental cell line A2780. A group of structurally unrelated drugs in concentrations known to reverse MDR, but not the verapamil analog tiapamil, a weak modulator of MDR, had similar effects. This effect was saturated at verapamil concentrations of about 1 microM. These data demonstrate that verapamil concentrations in MDR cells are maintained at a low level at the expense of ATP hydrolysis, and provide a first indication of the amount of metabolic energy used in this process.


Sorting out functions of sirtuins in cancer.
The sirtuins (SIRT 1-7) comprise a family of NAD⁺-dependent protein-modifying enzymes with activities in lysine deacetylation, adenosinediphospho(ADP)-ribosylation, and/or deacylation. These enzymes are involved in the cell's stress response systems and in regulating gene expression, DNA damage repair, metabolism and survival. Sirtuins have complex roles in both promoting and/or suppressing tumorigenesis. This review presents recent research progress concerning sirtuins and cancer. On one hand, functional loss of sirtuin genes, particularly SIRT1, involved in maintaining genome integrity and DNA repair will promote tumorigenesis because of genomic instability upon their loss. On the other hand, cancer cells tend to require sirtuins for these same processes to allow them to survive, proliferate, repair the otherwise catastrophic genomic events and evolve. The bifurcated roles of SIRT1, and perhaps several other sirtuins, in cancer may be in part a result of the nature of the genes that are involved in the cell's genome maintenance systems. The in-depth understanding of sirtuin functions may have significant implication in designing precise modulation of selective sirtuin members to aid cancer prevention or treatment under defined conditions.


Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients.
Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevacizumab response in recurrent glioblastoma patients. The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized NanoString platform covering 800 genes. Candidate gene predictors associated with response were analyzed by multivariate logistic and Cox regression analysis. Two genes were independently associated with response: Low expression of angiotensinogen (2-fold decrease in AGT; OR = 2.44; 95% CI: 1.45-4.17; P = 0.0009) and high expression of a HLA class II gene (2-fold increase in HLA-DQA1; OR = 1.22; 95% CI: 1.01-1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive model for response was significantly associated with improved overall survival. Two genes (low angiotensinogen and high HLA-class II expression) were predictive for bevacizumab response and were included in a predictive model for response. This model can be used in clinical practice to identify patients who will benefit from bevacizumab combination therapy.


Silencing Of hsa_circ_0008450 Represses Hepatocellular Carcinoma Progression Through Regulation Of microRNA-214-3p/EZH2 Axis.
Circular RNA (circRNA) hsa_circ_0008450 has been shown to be up-regulated in hepatocellular carcinoma (HCC). However, the functional role of hsa_circ_0008450 and its molecular mechanism are still unknown. We used qRT-PCR and Western blot to examine the expression levels of hsa_circ_0008450, microRNA-214-3p (miR-214-3p), and enhancer of zeste homolog 2 (EZH2) protein. CCK8 assay and wound healing assay were used to detect cell viability and cell migration capability. Cell apoptosis was assessed by flow cytometry. Luciferase reporter assay was used to explore the interaction among hsa_circ_0008450, miR-214-3p, and EZH2. hsa_circ_0008450 was significantly increased in HCC tissues and cells. Furthermore, knockdown of hsa_circ_0008450 in HCC cells inhibited cell proliferation, invasion, and migration. Mechanically, hsa_circ_0008450 promoted the expression of EZH2 protein through sponging miR-214-3p. Knockdown of circ_0008450 suppressed tumorigenesis of HCC cells in vivo. Knockdown of hsa_circ_0008450 inhibits HCC progression by regulating miR-214-3p/EZH2 axis. This study suggests that hsa_circ_0008450 may serve as a novel target for the treatment of HCC.


Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages.
Bacterial lipopolysaccharide (LPS) is a potent activator of antibacterial responses by macrophages. Following LPS stimulation, the tyrosine phosphorylation of several proteins is rapidly increased in macrophages, and this event appears to mediate some responses to LPS. We now report that two of these tyrosine phosphoproteins of 41 and 44 kDa are isoforms of mitogen-activated protein (MAP) kinase. Each of these proteins was reactive with anti-MAP kinase antibodies and comigrated with MAP kinase activity in fractions eluted from a MonoQ anion-exchange column. Following LPS stimulation, column fractions containing the tyrosine phosphorylated forms of p41 and p44 exhibited increased MAP kinase activity. Inhibition of LPS-induced tyrosine phosphorylation of these proteins was accompanied by inhibition of MAP kinase activity. Additionally, induction of p41/p44 tyrosine phosphorylation and MAP kinase activity by LPS appeared to be independent of activation of protein kinase C, even though phorbol esters also induced these responses. These results demonstrate that LPS induces the tyrosine phosphorylation and activation of at least two MAP kinase isozymes. Since MAP kinases appear to modulate cellular processes in response to extracellular signals, these kinases may be important targets for LPS action in macrophages.


Prophylactic and curative effects of Carica papaya Linn. pulp extract against carbon tetrachloride-induced hepatotoxicity in male rats.
Several chemicals and medications induce cellular damage in various organs of the body by activating reactive substances' metabolism leading to various pathological conditions including liver disease. In this study, we evaluated the prophylactic and curative effects of Carica papaya Linn. pulp water extract (PE) against CCl4-induced rat hepatotoxicity. Five groups of rats were created, control, PE, CCl4, (PE-CCl4): The rats were administered with PE pre and during CCl4 injection, and (PE-CCl4-PE): The rats were administered with PE pre, during, and after CCl4. The markers of oxidative stress ("OS": oxidant and antioxidants), inflammation [nuclear factor-κB, tumor necrosis factor-α, and interleukin-6], fibrosis [transforming growth factor-β], and apoptosis [tumor suppressor gene (p53)] were evaluated. Additionally, liver functions, liver histology, and kidney functions were measured. Also, PE characterization was studied. The results showed that PE, in vitro, has a high antioxidant capacity because of the existence of phenolics, flavonoids, tannins, terpenoids, and minerals. Otherwise, the PE administration [groups (PE-CCl4) and (PE-CCl4-PE)] exhibited its prophylactic and therapeutic role versus the hepatotoxicity induced by CCl4 where PE treatment improved liver functions, liver histopathology, and renal functions by decreasing oxidative stress, inflammation, fibrosis, and apoptosis induced by CCl4. Our study elucidated that PE contains high amounts of phenolics, flavonoids, tannins, terpenoids, and ascorbic acid. So, PE exerted significant prophylactic and curative effects against hepatotoxicity induced by CCl4. These were done by enhancing the markers of antioxidants and drug-metabolizing enzymes with reductions in lipid peroxidation, inflammation, fibrosis, and apoptosis. PE administration for healthful rats for 12 weeks had no negative impacts. Consequently, PE is a promising agent for the prohibition and therapy of the toxicity caused by xenobiotics.


Listen-and-repeat training improves perception of second language vowel duration: Evidence from mismatch negativity (MMN) and N1 responses and behavioral discrimination.
The purpose of this study was to examine the efficacy of three days of listen-and-repeat training on the perception and production of vowel duration contrasts. Generalization to an untrained vowel and a non-linguistic sound was also examined. Twelve adults underwent four sessions of listen-and-repeat training over two days with the pseudoword contrast /tite/-/ti:te/. Generalization effects were examined with another vowel contrast, /tote/-/to:te/ and a sinusoidal tone pair as a non-linguistic stimulus. Learning effects were measured with psychophysiological (EEG) event-related potentials (mismatch negativity and N1), behavioral discrimination tasks and production tasks. The results showed clear improvement in all perception measurements for the trained stimuli. The effects also affected the untrained vowel by eliciting an N1 response, and affected the behavioral perception of the non-linguistic stimuli. The MMN response for the untrained linguistic stimuli, however, did not increase. These findings suggest that the training was able to increase the sensitivity of preattentive auditory duration discrimination, but that phoneme-specific spectral information may also be needed to shape the neural representation of phoneme categories.


Mutational analysis of the HIV nef protein.
The nef protein is one of the regulatory proteins encoded by the human immunodeficiency virus (HIV). It has been shown to down-regulate viral transcription and displays features typical of some membrane-associated G proteins. To define the amino acid sequences involved in several of the properties of the nef protein, the corresponding gene has been submitted to a series of site-directed mutations. The mutants have been evaluated using various parameters which seem to correlate with the biological properties of nef. As previously observed for some signal transducing proteins, membrane localization and correct folding are critical for nef activity. Additionally, two domains, putative "P and G sites" which may be involved in nucleotide binding, have been identified.


Role of thromboxane A2 in a microcirculation disorder of the rat inner ear.
Since thromboxane (TX) A2 causes vasoconstriction and platelet aggregation, we evaluation the effect of a TXA2 receptor antagonist (vapiprost) and a TXA2 synthetase inhibitor (Y-20811) on a microcirculation disorder in the rat inner ear that was induced by a photochemical reaction between an intravenous injection of rose bengal (RB) and green light. A gradual decrease of the cochlear action potential (CAP) to an 8 kHz sound stimulus was measured with an electrocochleogram and occurred after the RB injection. The CAP then disappeared 5 min after the injection of RB. Both vapiprost and Y-20811 significantly prolonged the time required to complete suppression of the CAP as compared with saline as control. These findings indicate that TXA2 may play an important role in microcirculation disorders in the rat inner ear.


miR-124a expression contributes to the monophasic pattern of insulin secretion in islets from pregnant rats submitted to a low-protein diet.
To evaluate the role of miR-124a in the regulation of genes involved in insulin exocytosis and its effects on the kinetics of insulin secretion in pancreatic islets from pregnant rats submitted to a low-protein diet. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. Kinetics of the glucose-induced insulin release and measurement of [Ca2+]i in pancreatic islets were assessed by standard protocols. The miR-124a expression and gene transcriptions from pancreatic islets were determined by real-time polymerase chain reaction. In islets from LPP rats, the first phase of insulin release was abrogated. The AUC [Ca2+]i from the LPP group was lower compared with the other groups. miR-124a expression was reduced by a low-protein diet. SNAP-25 mRNA, protein expression, and Rab3A protein content were lower in the LPP rats than in CP rats. Syntaxin 1A and Kir6.2 mRNA levels were decreased in islets from low-protein rats compared with control rats, whereas their protein content was reduced in islets from pregnant rats. Loss of biphasic insulin secretion in islets from LPP rats appears to have resulted from reduced [Ca2+]i due, at least in part, to Kir6.2 underexpression and from the changes in exocytotic elements that are influenced either directly or indirectly by miR-124a.


[Primary central nervous system lymphomas].
Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal lymphoma (nearly always non-Hodgkin's) and accounts for approximately 3 to 4% of primary brain tumors. PCNSL typically affects patients older than 60 years. Clinical features are variable and reflect the location of central nervous system lesion. Magnetic resonance imaging and stereotactic biopsy are the most important tools for diagnostic assessment. Chemotherapy based on high-dose of methotrexate (HD-MTX) and whole brain radiotherapy are the cornerstones of treatment. Radiotherapy is usually omitted in individuals older than 60 years because of high risk of unacceptable delayed neurotoxicity. Treatment of PCNSL should be started as soon as possible after diagnosis because delay in treatment may shorten the patients' survival.


Seniors' life histories and perceptions of illness.
This life history research examined seniors' life experiences and perceived connections to illnesses. From a randomly selected sample of 190 seniors'interviews, 107 deemed to be the most expressive life stories were selected as the focus for this analysis. All seniors lived independently in a Canadian prairie city, were 60 years of age or older, Caucasian, European decent, had a chronic illness, and told of lives touched by the Great Depression and World War II. Given the paucity of research exploring seniors' life histories, these findings increase understanding of how life experiences shape seniors' identities. Four main themes emerged to describe seniors' lives: chaos, tragedy, quest, and romance. Findings reported here show that seniors with optimistic perceptions do not connect their life experiences with illnesses. Seniors with pessimistic perceptions frequently connect their life experiences with present illnesses and are most likely to remember past abuse and coping with abuse.


The first regiospecific, enantiospecific total synthesis of 6-oxoalstophylline and an improved total synthesis of alstonerine and alstophylline as well as the bisindole alkaloid macralstonine.
A Wacker sequence has been modified to rapidly generate ring E of (-)-alstonerine, (+)-6-oxoalstophylline, and (-)-alstophylline via a domino process. This one-pot sequence provides facile entry into the dihydropyranyl enone unit of many Alstonia alkaloids. [structure: see text]


Development of in vitro embryo production systems for red deer (Cervus elaphus). Part 3. In vitro fertilisation using sheep serum as a capacitating agent and the subsequent birth of calves.
The following experiments investigated the use of sheep serum (SS) as a capacitating agent for red deer (Cervus elaphus) sperm during in vitro fertilisation. Red deer oocytes were collected at slaughter and matured in vitro for 24h in TCM-199 supplemented with 10% foetal calf serum, 10 microg ml(-1) FSH and LH, and 1microg ml(-1) of oestradiol. Fertilisation medium was IVF-SOF modified to contain 5mM Ca(2+) and no glucose. Experiment 1 investigated the addition of heparin, BSA (8 mg ml(-1)) or 20% SS. All oocytes were penetrated when IVF-SOF was supplemented with SS compared to 10 and 0% penetration when either heparin or BSA was present (P<0.01). However, 43.8% of these oocytes were polyspermic when the medium contained SS. In Experiment 2, the effect of sperm concentration on penetration rates during in vitro fertilisation was investigated. Total sperm penetration and monospermic penetration rates increased with increased sperm concentrations in a log linear manner (P<0.001) and both approached an asymptote at 0.4 x 10(6) sperm ml(-1) with 93.6 and 77% for total and monospermic penetration, respectively. Polyspermic fertilisation also increased with increasing sperm concentrations (P<0.05) but was variable (range 3.5+/-4.2 to 42.3+/-10.6%), especially at the lower sperm concentrations. Experiment 3 investigated the viability of these oocytes after transfer into red deer recipients. Fifteen 2- and 4-cell embryos were transferred into the oviducts of synchronized recipients 28 h post in vitro insemination. An additional fourteen embryos (8-10 cell) were transferred into synchronised recipients after 48 h of in vitro culture in either SOFaaBSA (n=10) or on red deer epithelial oviduct monolayers (n=4). Five (33% 5/15) of the recipients that received 2- and 4-cell embryos were pregnant at Day 45 (verified by ultrasonography) and four recipients subsequently calved. One recipient receiving an embryo cultured in SOFaaBSA was pregnant at Day 45 and subsequently calved. The birth of five normal calves indicate that full developmental competence of red deer oocytes matured and fertilised in vitro can be achieved by the techniques described.


Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy.
Ovarian carcinoma cells are often infected inefficiently by adenoviruses (Ad) due to low expression of coxsackie-adenovirus receptors (CAR), hindering the application of adenovirus-mediated gene therapy in ovarian cancer. In this study, we explored a class of infectivity-enhanced Ad vectors, which contain CAR-independent targeting motifs RGD (Ad5.RGD), polylysine (Ad5.pK7), or both (Ad5.RGD.pK7), for their utility in ovarian cancer gene therapy using in vitro and in vivo model systems. We found that these vectors infected established ovarian carcinoma cell lines and primary ovarian cancer cells with significantly enhanced infectivity. Among them, Ad5.RGD.pK7 appeared to be most efficient. Further, we evaluated their gene delivery efficiency using two different ovarian cancer mouse models--subcutaneous and intraperitoneal human ovarian cancer xenografts. All of the modified vectors appeared to be more efficient than the unmodified Ad5 vector in both models, although some of the differences are not statistically significant. Of these, Ad5.RGD.pK7 exhibited the highest efficacy in the subcutaneous tumor model, while Ad5.pK7 worked most efficiently in the intraperitoneal tumor model. These preclinical results suggest that Ad5.RGD.pK7 and Ad5.pK7 may be very useful in ovarian cancer gene therapy.


Cetuximab directly inhibits P-glycoprotein function in vitro independently of EGFR binding.
Cancer chemotherapy typically combines anticancer drugs from different mechanisms of action. However, cancer cells could become resistant to chemotherapy via P-gp or other ATP binding cassette proteins. The objective of this study was to evaluate whether cetuximab, monoclonal antibody directed toward epidermal growth factor receptor, could increase intracellular concentration of conventional chemotherapy by interacting with P-gp. Two human ovarian carcinoma (IGROV1) and two human embryonary kidney (HEK) cell lines, overexpressing or weakly expressing P-gp, were used. Their EGFR expressions were compared. Cetuximab effect on P-gp functionality was evaluated by measuring doxorubicin (P-gp fluorescent substrate) intracellular accumulation. Cetuximab ability to increase doxorubicin cytotoxicity was evaluated by MTT test. A quaternary structure model of the P-gp-Cetuximab complex was established. Exposure of cetuximab in therapeutic concentrations range with doxorubicin led to significant doxorubicin accumulation and reversion of doxorubicin resistance in P-gp expressing cells lines. Molecular modeling of P-gp-cetuximab interactions showed that cetuximab is able to bind P-gp extracellular part. Cetuximab increases a P-gp substrate intracellular accumulation in both P-gp expressing cell lines, independently of their EGFR expression. One hypothesis is that cetuximab binding on P-gp could hamper the conformational changes that occur during drugs efflux. Our results offer new possibilities of research on monoclonal antibodies influence in MDR phenomena.


Chronic inflammatory demyelinating polyradiculoneuropathy: long-term course and treatment of 60 patients.
The objective of this study was to assess the long-term course and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We evaluated, according to a predefined protocol, a series of 60 CIDP patients who received a long-term course of steroids and immunosuppressants. Eighteen of them also had monoclonal gammopathy of undetermined significance (MGUS). Mean follow-up was 4.4 years and was similar for CIDP and CIDP-MGUS patients. At the end of the follow-up, improvement was ascertained in 60% of patients (69% CIDP, 39% CIDP-MGUS). Complete remission was achieved in 13%. Out of 26 patients receiving steroids as a monotherapy, 19 improved (73%). The following variables were predictive of a better outcome: female gender, younger age at onset, relapsing-remitting course, and absence of axonal damage at neurophysiologic study. In the multivariate analysis, younger age at onset and demyelination without axonal damage still retained an independent positive value.


Recurrent herpes simplex virus hepatitis after liver retransplantation despite acyclovir therapy.
Herpes virus hepatitis (HSV) represents a form of acute necrotizing hepatitis, which most frequently develops in immunocompromised patients. Therapeutic options include high-dose intravenous acyclovir and liver transplantation. We report the first case of recurrent HSV hepatitis after liver retransplantation, which occurred despite continuous administration of high-dose intravenous antiviral therapy. Because explant histology pointed to initial therapy response, we thought that the reason for recurrence might be due to acyclovir resistance. Most acyclovir resistance is caused by inactivating mutations in the herpes virus thymidine kinase gene. HSV infection was detected by histology and proofed by immunohistochemistry. PCR amplification of the herpes virus thymidine kinase gene was performed on histology specimens to demonstrate the course of viral infection in liver tissue. Genotypic resistance testing of the herpes virus was performed by sequencing the thymidine kinase amplicon. In serial biopsy, HSV-DNA sequences were only detectable when histology revealed herpes hepatitis. Whereas the primary explant exhibited the wild-type thymidine kinase gene, a biopsy of the second graft one month after retransplantation, which showed recurrent herpes virus hepatitis, had a single base insertion within a homopolymeric cytosine stretch. This mutation causes a frame shift leading to a premature stop codon and results in a known acyclovir-resistant herpes strain. In conclusion, we believe that testing for acyclovir-resistant herpes strains should be considered in high-risk patients in whom viral clearance is not achieved serologically to prevent fatal recurrence of disease by using antiviral drugs such as inhibitors of HSV-DNA polymerase or viral helicase primase inhibitors.


Epidemiology and prognosis of ommaya reservoir-related bacterial meningitis in adult patients with leptomeningeal metastases from solid tumors: A 10-year retrospective single-center study in Japan.
Leptomeningeal metastases (LM) from solid tumors have poor prognosis. Intrathecal chemotherapy through the Ommaya reservoir (OR) is one of the options for treating LM; however, OR-related bacterial meningitis (ORRBM) is a severe complication in patients who underwent OR placement. Little is known about the incidence rate and prognosis of ORRBM among patients with LM from solid tumors. We retrospectively reviewed the records of patients who underwent OR placement to treat LM from solid tumors at Kawasaki Municipal Kawasaki Hospital between January 2009, and December 2018. Among 136 patients with OR placement (median age of 64.5 years) including 30,320 Ommaya-days, 18 (13.2%) developed ORRBM (5.9 infections per 10,000 Ommaya-days). The major primary diseases were lung cancer (65.4%). The median times from OR placement and from last OR puncture to ORRBM onset were 20 days and 4.5 days, respectively. Major clinical symptoms were fever (83.3%), headache (50.0%), disturbance of consciousness (50.0%), and nausea (38.9%). Seventeen of 18 patients underwent an OR removal operation. One patient died from ORRBM, and another patient died from heart failure during ORRBM treatment. The median duration of treatment with antibiotics was 16.5 days. The median survival period from the day of OR placement was 146.5 days among patients who developed ORRBM and 142.5 days among patients who did not develop ORRBM. The rate of ORRBM among patients with LM from solid tumors in our hospital was 13.2%. ORRBM may not shorten the patients' survival period with adequate management including removal of the device.


Return to sport after arthroscopic surgery for femoroacetabular impingement.
Femoroacetabular impingement (FAI) is common among the active and young population. The present study analysed the rate of return to sport, related influencing factors, and the sport activity level according to the Hip Outcome Score - Sport-Specific Subscale (HOS-SSS). The literature search was performed in December 2020. All clinical trials investigating HOS-SSS and/or return to sport after arthroscopic treatment for FAI were considered for inclusion. The outcomes of interest were to analyse the rate of return to sport and the sport activity level according to the HOS-SSS in patients who underwent arthroscopic osteoplasty for FAI. Data from 41 studies (4063 procedures) were retrieved. A total of 88.75% (581 of 655) of patients returned to sports within a mean of 37.4 ± 16.5 months. The HOS-SSS score improved from 45.0 ± 10.6 to 73.1 ± 9.5 (P < 0.0001) at last follow-up. The following baseline characteristics evidenced positive association with post-operative activity level: lighter weight (P = 0.01), younger age (P = 0.001), Tönnis angle grade I (P = 0.009), greater HHS (P = 0.01), NAHS (P < 0.0001) and HOS-ADL (P = 0.01). Arthroscopic treatment for FAI resulted in excellent results in terms of return to sport. Moreover, lighter weight and younger age, greater HHS, NAHS, HOS-ADL at baseline were positively associated with post-operative sport activity level. IV, systematic review.


Phytosterolemia and γ-glutamyl transferase in adults with parenteral nutrition: Fish versus vegetal lipids: A randomized clinical trial.
Fish oil (FO)-based lipid emulsions (LEs) have been reported to prevent hepatic dysfunction in patients treated with parenteral nutrition (PN). We studied patients with alterations of γ-glutamyl transferase (GGT) associated with the administration of PN containing olive/soybean (O/S)-based LE. The aim of this study was to determine whether the strategy of reducing the lipid dose by 50%, by changing to an FO-based LE, reduced plasma levels of phytosterols (PS) and GGT more effectively and safely, than the strategy of reducing lipid contribution by 50% while maintaining the same LE composition. A randomized double-blind clinical trial was carried out in patients with normal initial GGT, who after a minimum of 1 wk of daily PN (0.8 g/kg of O/S-based LE) presented with GGT values twice the upper normal value. At the time of randomization 1:1, lipids were reduced to 0.4 g/kg daily. Group A maintained O/S LE and group B changed to FO LE. The primary endpoints were reduction of plasmatic PS and GGT on day 7 after randomization, performed in the study population per protocol by Student's t test and simple linear regression. Secondary outcomes included alkaline phosphatase (AP), alanine transaminase (ALT), and total bilirubin (BIL), and safety variables. Nineteen patients were included. On day 7 after randomization, GGT and AP values were higher in the O/S group (n = 10; GGT: median [Med], 4.99; interquartile range [IQR], 4.09; AP: Med, 2.59 μkat/L; IQR 1.74) than in the FO group (n = 9; GGT: Med, 2.26 μkat/L; IQR, 1.07; AP: Med, 1.2 μkat/L; IQR 1.44). Although there were no differences in ALT and BIL values, the ALT decrease was larger and more statistically significant in the FO group than in the O/S group (P = 0.009). Total PS (Med, 21.10 μg/mL; IQR, 5.50) in the O/S group was higher than in the FO group (Med, 13.4 μg/mL; IQR, 10.65; P = 0.002). Significant decreases in PS and their fractions were observed, with the exception of campesterol and stigmasterol. Plasma accumulation of PS and high values of GGT, AP, and ALT can be prevented with the exclusive administration of FO-based LE.


A focus of tissue necrosis increases renal susceptibility to gentamicin administration.
The purpose of this study was to determine whether a retained focus of necrotic tissue predisposes to aminoglycoside-induced acute renal failure (ARF). Rats were subjected to either (1) 25% liver ligation, creating a focus of ischemic tissue which was left in place; (2) 25% liver resection; or (3) sham liver ligation. Gentamicin, 80 mg/kg bid, was administered for two days after surgery to all three groups. A fourth group was subjected to 25% liver ligation but no gentamicin therapy. Only rats subjected to partial liver ligation plus gentamicin treatment developed ARF, manifested by azotemia (BUN 80 +/- 2; creatinine 1.63 +/- 0.21; mg/dl) and tubular necrosis. This occurred in the absence of any discernible reduction in arterial blood pressure, renal blood flow, excessive weight loss, or ascites formation. The partial liver ligation-gentamicin group had 70% higher renal gentamicin concentrations than the liver resection-gentamicin controls (P = 0.01). To assess whether factors released from necrotic liver might account for these findings, additional rats were infused with: (1) 1 ml of a soluble liver extract alone; (2) 1 ml of liver extract plus gentamicin; or (3) 1 ml of saline plus gentamicin. Only the liver extract/gentamicin group developed ARF (BUN 88 +/- 13; creatinine 1.46 +/- 0.25). This occurred in association with a 110% increase in renal gentamicin uptake (P less than 0.03). In separate experiments, 5 ml liver extract infusions caused ARF (BUN 118 +/- 7; creatinine 2.1 +/- 0.18) without gentamicin treatment. In conclusion, a focus of liver necrosis can predispose to experimental gentamicin nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)


Extradural frontal abscess complicating nasal septal abscess in a child.
Nasal septal abscess (NSA) is an uncommon sequel to minor nasal trauma. Abscess extension beyond the nasal cavity is rarely documented. A case of a 10-year-old boy who presented with a NSA associated with a large extradural frontal abscess is presented and indications for CT scanning in the workup of pediatric patients with NSA is discussed.


Author Correction: KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Primary care physicians' assessment and prevention of HIV infection.
The degree and depth to which primary care physicians counsel patients at risk for human immunodeficiency virus (HIV) infection is a major concern. To determine which factors influence whether physicians counsel patients at risk for HIV, primary care physicians's clinical experience, knowledge, attitudes, and preventive counseling advice in hypothetical case scenarios were assessed. Ninety-nine adult primary care physicians in the Washington, D.C., metropolitan area were interviewed by telephone from May through November 1987. Ninety-one physicians had tested or referred patients for HIV antibody tests. However, 58% could not name the ELISA or Western blot as the tests. The most frequent HIV prevention recommendations were using condoms (67.7%), abstaining from sexual activity (36.4%), getting tested for HIV (30.3%), and safe sex (23.2%). Naming the HIV antibody tests was the most significant predictor of preventive counseling advice; other significant predictors included physicians' personal comfort with counseling homosexual patients and various physician practice and demographic characteristics. Previous studies showed that homophobia was the main inhibitor of effective AIDS counseling. These results suggest that physicians' lack of knowledge and general discomfort in counseling patients about sexual risk factors, rather than homophobia alone, are important barriers to preventive counseling about HIV infection.


Enjoyment of tactile play is associated with lower food neophobia in preschool children.
Previous research has shown that parental reports of food neophobia and tactile sensitivity are associated with lower fruit and vegetable (F/V) intake in children. This study aimed to pilot a behavioral observation measure of tactile play in young children. The primary aim of the study was to see whether children's enjoyment of tactile play was associated with higher F/V consumption, as well as lower food neophobia. Seventy 2- to 5-year-old children (37 males and 33 females) and their parents were recruited through children's centers in the Leicester region of the United Kingdom during July to October 2012. Children's engagement in two tactile play tasks using sticky foods (mashed potatoes and vegetarian gelatin) was observed and rated by both the researcher and parent. Parents were asked to complete a series of questionnaires measuring F/V consumption, food neophobia, and sensory processing. It was found that lower child food neophobia was significantly related to enjoyment of tactile play, whereas child F/V consumption was associated with parental F/V consumption, but not enjoyment of tactile play. The findings strengthen the idea that tactile processing may be associated with the acceptance of food variety, but not the total amount of F/V consumed. Additional research is indicated to determine whether tactile play tasks can be used to lower child food neophobia.


Familial asymmetric crying facies. Its occurrence secondary to hypoplasia of the anguli oris depressor muscles.
Asymmetric crying facies is a common neonatal problem with multiple causes. Asymmetric crying facies occurred in a newborn, secondary to familial hypoplasia of the anguli oris depressor muscle. The differential diagnosis of asymmetric crying facies should include this genetic cause.


K+/H+ antiport in mitochondria.
Mitochondria contain a latent K+/H+ antiporter that is activated by Mg2+-depletion and shows optimal activity in alkaline, hypotonic suspending media. This K+/H+ antiport activity appears responsible for a respiration-dependent extrusion of endogenous K+, for passive swelling in K+ acetate and other media, for a passive exchange of matrix 42K+ against external K+, Na+, or Li+, and for the respiration-dependent ion extrusion and osmotic contraction of mitochondria swollen passively in K+ nitrate. K+/H+ antiport is inhibited by quinine and by dicyclohexylcarbodiimide when this reagent is reacted with Mg2+-depleted mitochondria. There is good suggestive evidence that the K+/H+ antiport may serve as the endogenous K+-extruding device of the mitochondrion. There is also considerable experimental support for the concept that the K+/H+ antiport is regulated to prevent futile influx-efflux cycling of K+. However, it is not yet clear whether such regulation depends on matrix free Mg2+, on membrane conformational changes, or other as yet unknown factors.


[Anatomoradiological patterns of vermiform appendix's arterial supply (author's transl)].
The authors tried to establish the most frequents anatomo-radiological patterns of the irrigation on the vermiform appendix. The search was done in one hundred cases they found six different patterns of arterial irrigation.


Time to stop counting the tablets?
We attempted to assess compliance using both a pharmacologic indicator (low-dose phenobarbital) and a return tablet count in 225 patients who were taking part in three separate studies. There were 216 patients (96%) who kept a follow-up appointment after 28 days; 161 patients appeared to have good compliance (90% to 109%) by return tablet count. Of these 161 patients, 51 (32%) had plasma phenobarbital concentrations (corrected for dose and weight) that were less than 90% of the lowest value previously found in normal volunteers, which suggested poorer compliance. When compared with the age-related volunteer values, 77 (48%) had values that were less than 90% of the lowest volunteer value. There were 6 of 10 patients with apparently excessive (greater than or equal to 110%) compliance by return tablet count and 4 of 12 who failed to return their container who also had phenobarbital concentrations that were less than 90% of the lowest volunteer value. We concluded that return tablet count grossly overestimates compliance.


Insight into transketolase of Pyropia haitanensis under desiccation stress based on integrative analysis of omics and transformation.
Pyropia haitanensis, distributes in the intertidal zone, can tolerate water losses exceeding 90%. However, the mechanisms enabling P. haitanensis to survive harsh conditions remain uncharacterized. To elucidate the mechanism underlying P. haitanensis desiccation tolerance, we completed an integrated analysis of its transcriptome and proteome as well as transgenic Chlamydomonas reinhardtii carrying a P. haitanensis gene. P. haitanensis rapidly adjusted its physiological activities to compensate for water losses up to 60%, after which, photosynthesis, antioxidant systems, chaperones, and cytoskeleton were activated to response to severe desiccation stress. The integrative analysis suggested that transketolase (TKL) was affected by all desiccation treatments. Transgenic C. reinhardtii cells overexpressed PhTKL grew better than the wild-type cells in response to osmotic stress. P. haitanensis quickly establishes acclimatory homeostasis regarding its transcriptome and proteome to ensure its thalli can recover after being rehydrated. Additionally, PhTKL is vital for P. haitanensis desiccation tolerance. The present data may provide new insights for the breeding of algae and plants exhibiting enhanced desiccation tolerance.


Emerging resistance to beta-lactams in Pantoea ananatis isolated from an immunocompetent patient with bacteremia.
We observed an emerging resistance to β-lactams in a P. ananatis bacteremia case. Whole genome sequence analysis detected two β-lactamase genes as well as related genes that regulate the β-lactamase genes in the chromosome. The induction experiment resulted in the expression of the class A β-lactamase gene in the isolate.


The use of borneol as an enhancer for targeting aprotinin-conjugated PEG-PLGA nanoparticles to the brain.
To evaluate the effect of borneol on the brain targeting efficiency of aprotinin-conjugated poly (ethyleneglycol)-poly (L-lactic-co-glycolic acid) nanoparticles (Apr-NP) and the activity of huperzine A (Hup A) loaded nanoparticles to AD rats . Apr-NP was prepared by emulsion and solvent evaporation method. The uptake of Apr-NP alone or combined with borneol by brain capillary endothelial cells (BCECs) was evaluated by incorporating coumarin-6 as a tracer. In vivo imaging and the distribution of Hup A in the brain were measured to investigate the brain delivery of Apr-NP in rats, with or without the oral administration of borneol. Morris water maze was used to evaluate the memory improvement effect of Hup A loaded nanoparticles (Apr-NP-Hup). Co-incubation with borneol could increase the uptake of nanoparticles by BCECs. Nanoparticles delivered into the rat brain were enhanced significantly by the co-administration of borneol. The pharmacological effects of Hup A loaded nanoparticles on improving the memory impairment of AD rats were greatly improved when combined with borneol. Borneol is a promising enhancer for brain-targeting delivery systems. When co-administered with aprotinin-modified nanoparticles, borneol could improve the brain targeting efficiency of nanoparticles significantly.


The relationship between phonological processing skills and word and nonword identification performance in children with mild intellectual disabilities.
Word and nonword identification skills were examined in a sample of 80 elementary school age students with mild intellectual disabilities and mixed etiologies who were described as struggling to learn to read by their teachers. Performance on measures of receptive and expressive vocabulary, measures of phonological awareness, and measures of word and nonword identification were included for analyses. Hierarchical regression analyses indicated that, after controlling for chronological age and vocabulary knowledge, phonological processing accounted for a large and significant amount of unique variance of both word and nonword identification. In addition, the pattern of results found in this study is similar to that obtained with typically developing learners. As with typically developing children, measures of phonological awareness were significantly correlated with measures of both reading achievement and vocabulary knowledge.


Low rates of heterotopic ossification after resurfacing hip arthroplasty with use of prophylactic radiotherapy in select patients.
Recent reports have noted higher rates of heterotopic ossification (HO) with surface replacement arthroplasty (SRA) than with traditional total hip arthroplasty in the absence of postoperative HO prophylaxis. This study reports rates and grades of HO in 44 SRA patients with at least 1 year of follow-up. Heterotopic ossification prophylaxis was used in 32 (73%) of 44 cases. Heterotopic ossification prophylaxis consisted of radiotherapy (22/32), nonsteroidal anti-inflammatory drugs (8/32), or both (2/32). One case of clinically significant HO was documented in the no-prophylaxis group. This strategy of selective HO prophylaxis in patients felt by orthopedic surgeons to be at high risk of HO resulted in low rates of clinically relevant HO after SRA (1/44, 2.3%). Further study is needed to establish optimal selection criteria for HO prophylaxis after SRA.


Meta-Analyses on the Effects of Disease-Modifying Antirheumatic Drugs on the Most Relevant Patient-Reported Outcome Domains in Rheumatoid Arthritis.
Whereas in the treatment of rheumatoid arthritis much evidence exists on the effects of current pharmacologic treatment on clinical outcomes, little is known about the effects on patient-reported outcomes. This systematic review aims to evaluate the effects of disease-modifying antirheumatic drugs (DMARDs) on the patient-relevant domains of pain, fatigue, activity limitation, overall emotional and physical health impact, and work/school/housework ability and productivity. A literature search was conducted to identify randomized controlled trials wherein registered DMARDs were compared with placebo or methotrexate and reported the effects on patient-reported outcomes included in the International Consortium of Health Outcomes Measurement standard set for inflammatory arthritis. Random effects meta-analyses using the standardized mean differences of change scores as the effect measure were performed for the domains of pain, fatigue, and activity limitation, comparing DMARDs with placebo and methotrexate. The other 2 domains were presented narratively. Across the 5 domains, 69 records belonging to 52 studies were identified. All meta-analyses showed a decrease of burden when DMARDs were compared with placebo (standardized mean differences [95% confidence interval] in pain -0.80 [-0.99, -0.61], fatigue -0.48 [-0.64, -0.32], and activity limitation -0.56 [- 0.63, -0.49]) and when compared with methotrexate (-0.55 [-0.70, -0.41), -0.44 [-0.55, -0.33], and - 0.37 [-0.44, -0.30], respectively). DMARDs decrease the burden in all the domains that are relevant to patients. Effect sizes may be influenced by DMARD type. Therefore, in the decision for rheumatoid arthritis treatment, patient-reported outcomes should be taken into account.


Correlation between helical surface waves and guided modes of an infinite immersed elastic cylinder.
Scattering of obliquely incident plane acoustic waves from immersed infinite solid elastic cylinders is a complex phenomenon that involves generation of various types of surface waves on the body of the cylinder. Mitri [F.G. Mitri, Acoustic backscattering enhancement resulting from the interaction of an obliquely incident plane wave with an infinite cylinder, Ultrasonics 50 (2010) 675-682] recently showed that for a solid aluminum cylinder, there exist acoustic backscattering enhancements at a normalized frequency of ka⩽0.1. The incidence angle α(c) at which these enhancements are observed lies between the first (longitudinal) and second (shear) coupling angles of the cylinder. He also confirmed the observations previously reported by the authors that there exist backscattering enhancements of the dipole mode at large angles of incidence where no wave penetration into the cylinder is expected. In this paper, physical explanations are provided for the aforementioned observations by establishing a correlation between helical surface waves generated by oblique insonification of an immersed infinite solid elastic cylinder and the longitudinal and flexural guided modes that can propagate along the cylinder. In particular, it is shown that the backscattering enhancement observed at ka⩽0.1 is due to the excitation of the first longitudinal guided mode travelling at the bar velocity along the cylinder. It is also demonstrated that the dipole resonance mode observed at incidence angles larger than the Rayleigh coupling angle is associated with the first flexural guided mode of the cylinder. The correlation established between the scattering and propagation problems can be used in both numerical and experimental studies of interaction of mechanical waves with cylinders.


Proteoglycan 4 is a diagnostic biomarker for COPD.
The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported. However, CRP is a systemic inflammatory biomarker that is related to many other diseases. The objective of this study is to discover a diagnostic biomarker for COPD. Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study. Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected. CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects. Receiver operating characteristic values of CRP and the identified biomarkers were determined. A validation COPD cohort was used to reexamine the identified biomarker. Correlation of the biomarker with 1-year lung function decline was determined. Proteoglycan 4 (PRG4) was identified as a biomarker in COPD. The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05). PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency. There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R (2)=0.91, P=0.013). PRG4 may be a biomarker for identification of severity in COPD. It was related to the 1-year forced vital capacity decline in COPD patients.


A clinically relevant bi-cellular murine mammary tumor model as a useful tool for evaluating the effect of retinoic acid signaling on tumor progression.
The effect of retinoic acid (RA) on breast cancer progression is controversial. Our objective was to obtain information about breast cancer progression, taking advantage of the ER-negative murine mammary adenocarcinoma model LM38 (LM38-LP constituted by luminal (LEP) and myoepithelial-like cells (MEP), LM38-HP mainly composed of spindle-shaped epithelial cells, and LM38-D2 containing only large myoepithelial cells), and to validate the role of the retinoic acid receptors (RARs) in each cell-type compartment. We studied the expression and functionality of the RARs in LM38 cell lines. We analyzed cell growth and cell cycle distribution, apoptosis, the activity of proteases, motility properties, and expression of the molecules involved in these pathways. We also evaluated tumor growth and dissemination in vivo under retinoid treatment. LM38 cell lines expressed most retinoic receptor isotypes that were functional. However, only the bi-cellular LM38-LP cells responded to retinoids by increasing RARβ2 and CRBP1 expression. The growth of LM38 cell sublines was inhibited by retinoids, first by inducing arrest in MEP cells, then apoptosis in LEP cells. Retinoids induced inhibitory effects on motility, invasiveness, and activity of proteolytic enzymes, mainly in the LM38-LP cell line. In in-vivo assays with the LM38-LP cell line, RA treatment impaired both primary tumor growth and lung metastases dissemination. These in-vivo and in-vitro results show that to achieve maximum effects of RA on tumor progression both the LEP and MEP cell compartments have to be present, suggesting that the interaction between the LEP and MEP cells is crucial to full activation of the RARs.


Granulocyte-colony stimulating factor-producing gallbladder carcinoma-include analysis all case reports: A case report.
It is extremely rare for gallbladder carcinoma to produce granulocyte-colony stimulating factor (G-CSF) and such tumors have a poor prognosis. A 67-year-old man was admitted with continuous fever. Laboratory tests showed a leukocyte count of 27,980/μL, serum C-reactive protein (CRP) of 9.2mg/dL and serum G-CSF of 225pg/mL. Imaging revealed an irregular gallbladder mass about 90mm in diameter with peripheral enhancement that also involved the liver and transverse colon. G-CSF producing gallbladder carcinoma was diagnosed. We performed cholecystectomy, partial resection of segments 4 and 5 of the liver, partial resection of the transverse colon, and gastrostomy. Histopathological examination showed gallbladder carcinoma (pT3, pN0, M0, G2, and pStage IIIA by the UICC classification, version 7). On immunohistochemical staining, tumor cells were positive for G-CSF. The leukocyte count was normalized postoperatively and fever subsided immediately after surgery. Two months later, the leukocyte count rose to 56,820/μL and metastases to the liver and lymph nodes were detected by CT. Chemotherapy (gemcitabine plus cisplatin) was started and the leukocyte count was normalized after the first course. The patient has continued chemotherapy and has survived for 16 months postoperatively. G-CSF producing gallbladder carcinoma has a poor prognosis and most patients die within 12 months of starting therapy. It is rare for patients with recurrence to survive for 16 months after surgery, as in the present case. Multidisciplinary therapy (surgery and chemotherapy) may prolong the survival of patients with G-CSF producing gallbladder carcinoma, especially those with recurrence.


Survival of Listeria monocytogenes in commercial food-processing equipment cleaning solutions and subsequent sensitivity to sanitizers and heat.
To determine the ability of Listeria monocytogenes to survive exposure to commercial food-processing equipment cleaning solutions and subsequent treatment with sanitizers or heat. Cells of five strains of L. monocytogenes were suspended in 1% solutions of eight commercial cleaners (pH 7.1-12.5) or in water (control) and incubated at 4 degrees C for 30 min or 48 h before populations were determined by plating on tryptose phosphate agar. After exposure of cells to cleaning solutions for 30 min, populations of the most resistant strain of L. monocytogenes were reduced by < or = 1.63 log10 cfu ml(-1). In only three highly alkaline cleaning solutions (pH 11.6-12.4) were populations reduced significantly (P < or = 0.05) compared with reductions in water. After 48 h, populations were significantly higher in one cleaning solution (pH 10.4) than in water, while populations in six of the other seven cleaning solutions were reduced by > or = 4.72 log10 cfu ml(-1). Cells exposed to cleaning solutions for 30 min became sensitive to 4.0 or 6.0 mg l(-1) free chlorine and to 50 or 100 mg l(-1) benzalkonium chloride and cetylpyridinium chloride, common components of quaternary ammonium sanitizers. Cells exposed to four of the five test cleaners had D56 degrees C values less than or equal to those of the control cells. Listeria monocytogenes tolerates exposure to a high concentration of alkaline cleaning solutions but consequently becomes sensitized to sanitizers. The elimination of L. monocytogenes surviving exposure to alkaline cleaning solutions widely used for food-processing equipment is essential and the appropriate use of sanitizers for subsequent application to equipment is important in achieving this goal.


Sensor fault detection and minimum detectable fault analysis for dynamic point-the-bit rotary steerable system.
In this paper, the sensor fault detection problem considering the drilling disturbances is studied for the dynamic point-the-bit rotary steerable system. Firstly, the DPRSS is modeled as a linear system with the drilling disturbances, including unknown inputs, measurement noises, and model perturbations. Then, a finite-frequency zonotopic fault detection observer is proposed. The finite-frequency range H- performance and the P-radius criterion are considered to design the observer gains such that the residuals are sensitive to sensor faults and robust against the drilling disturbances simultaneously. Subsequently, the calculation method of minimum detectable faults is presented for the proposed sensor fault detection mechanism. Finally, simulations and experiments are presented to illustrate the effectiveness of the proposed methods.


The effect on incisional hernia of absorbable barbed suture for midline fascial closure in minimally invasive surgery for colorectal and gastric cancers: study protocol for a randomized controlled trial.
Incisional hernia following abdominal surgery is a frequent complication of midline laparotomy. This complication is strongly associated with the technique and material used for suture. While a monofilament absorbable suture is recommended to prevent incisional hernia, it can lead to suture loosening or surgical-knot breakage. Although barbed sutures can be an alternative suture material in abdominal fascial closure, evidence for its safety and effectiveness is lacking. Therefore, we designed a prospective randomized trial to evaluate the safety and efficacy of absorbable barbed sutures for midline fascia closure in minimally invasive surgery for colorectal and gastric cancers in comparison with conventional absorbable monofilament sutures. A total of 312 patients who underwent minimally invasive surgery for colorectal and gastric cancers will be randomly allocated to either the absorbable barbed or monofilament suture group for abdominal fascia closure in a 1:1 ratio. The primary outcome is incisional hernia rate within 3 years after surgery, as verified by physical examination and computed tomography. Postoperative complications, including surgical site infection, postoperative pain, and quality of life, will be compared between two groups as secondary outcomes. The investigator will examine the patients until discharge and at 6, 12, 18, 24, and 36 months postoperatively. This is the first randomized controlled trial to compare absorbable barbed sutures with monofilament sutures for midline fascia closure in minimally invasive surgery. If absorbable barbed sutures demonstrate superior results to those of monofilament sutures, this type of suture material may be recommended as an alternative option for abdominal fascia closure. KCT0007069. Registered on January 30, 2023.


A collection of transcriptomic and proteomic datasets from sesame in response to salt stress.
Soil salinity is a major abiotic factor affecting the growth and development of important crops such as sesame (Sesamum indicum L.). To understand the molecular mechanisms of this oilseed crop in response to salt stress, we examined the transcriptome and proteome profiles of two sesame varieties, with contrasting tolerances to salinity. Here, RNA sequencing and quantitative proteomic analyses of 30 samples from salt-tolerant and -sensitive sesame seedlings under salt stress were carried out. These data can be used for differential gene expression and protein accumulation analyses, based on a genetic aberration or phenotypic differences in sesame responses to salt stress. Our dataset provides an extensive resource for understanding the molecular mechanisms underlying the adaptation of sesame to salt stress, and may constitute useful a resource for increasing the tolerance of major crop plants to raised salinity levels in soils.


Development and validation of the immunosuppressant therapy adherence instrument (ITAS).
A five-item scale was developed that asked respondents to indicate how often they were non-adherent to immunosuppressant therapy (IST) given a particular circumstance. Two hundred and twenty-two recipients completed the instrument. Validity of the scale was assessed by correlating composite item scores with refill record adherence rates (RRARs), serum immunosuppressant (IS) concentrations, graft rejection, and increased serum creatinine (SCr) levels. One scale item was deleted due to lack of response variability. Cronbach's alpha coefficient for the four-item scale was 0.81, demonstrating that the scale has acceptable reliability. All items loaded on a single principal component, suggesting that the scale measures a single adherence construct, which accounted for 64% of the scale items' variance. The four-item scale, adherence measured by IS RRARs, and "target" IS serum concentrations had positive correlations (p < 0.01). Item scores were shown to be negatively related to rejection occurrence and increased SCr (p < 0.05). The immunosuppressant therapy adherence scale is the first published, valid and reliable instrument that measures recipients IST adherence.